Medical Devices; Quality System Regulation Amendments, 10119-10134 [2022-03227]
Download as PDF
Federal Register / Vol. 87, No. 36 / Wednesday, February 23, 2022 / Proposed Rules
(i) Related Information
(1) For more information about this AD,
contact Dorie Resnik, Aerospace Engineer,
Boston ACO Branch, 1200 District Avenue,
Burlington, Massachusetts 01803; telephone
781–238–7693; email 9-AVS-AIR-BACOCOS@faa.gov.
(2) For service information identified in
this AD, contact Sikorsky’s Engineering
Group Sikorsky Aircraft Corporation, 124
Quarry Road, Trumbell, CT, 06611, United
States; phone: (800) 946–4337; email: wcs_
cust_service_eng.gr-sik@lmco.com; website:
www.sikorsky360.com. You may view this
referenced service information at the FAA,
Office of the Regional Counsel, Southwest
Region, 10101 Hillwood Pkwy, Room 6N–
321, Fort Worth, TX 76177. For information
on the availability of this material at the
FAA, call (817) 222–5110.
Issued on February 16, 2022.
Lance T. Gant,
Director, Compliance & Airworthiness
Division, Aircraft Certification Service.
[FR Doc. 2022–03769 Filed 2–22–22; 8:45 am]
BILLING CODE 4910–13–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 4 and 820
RIN 0910–AH99
Medical Devices; Quality System
Regulation Amendments
Food and Drug Administration,
HHS.
ACTION:
Proposed rule.
The Food and Drug
Administration (FDA, the Agency, or
we) is proposing to amend the device
current good manufacturing practice
(CGMP) requirements of the Quality
System (QS) Regulation to align more
closely with the international consensus
standard for devices by converging with
the quality management system (QMS)
requirements used by other regulatory
authorities from other jurisdictions (i.e.,
other countries). We propose to do so
through incorporating by reference an
international standard specific for
device quality management systems set
by the International Organization for
Standardization (ISO), the 2016 edition
of ISO 13485 (ISO 13485). Through this
rulemaking we also propose additional
requirements to align with existing
requirements in the Federal Food, Drug,
and Cosmetic Act (FD&C Act) and its
implementing regulations, and make
conforming edits to the Code of Federal
Regulations (CFR) to clarify the device
khammond on DSKJM1Z7X2PROD with PROPOSALS
SUMMARY:
VerDate Sep<11>2014
17:39 Feb 22, 2022
Submit either electronic or
written comments on the proposed rule
by May 24, 2022. Submit written
comments (including recommendations)
on the collection of information under
the Paperwork Reduction Act of 1995
(PRA) by March 25, 2022.
ADDRESSES: You may submit comments
as follows. Please note that late,
untimely filed comments will not be
considered. Electronic comments must
be submitted on or before May 24, 2022.
The https://www.regulations.gov
electronic filing system will accept
comments until 11:59 p.m. Eastern Time
at the end of May 24, 2022. Comments
received by mail/hand delivery/courier
(for written/paper submissions) will be
considered timely if they are
postmarked or the delivery service
acceptance receipt is on or before that
date.
DATES:
Electronic Submissions
[Docket No. FDA–2021–N–0507]
AGENCY:
CGMP requirements for combination
products. This action, if finalized, will
continue our efforts to align our
regulatory framework with that used by
other regulatory authorities to promote
consistency in the regulation of devices
and provide timelier introduction of
safe, effective, high-quality devices for
patients.
Jkt 256001
Submit electronic comments in the
following way:
• Federal eRulemaking Portal:
https://www.regulations.gov. Follow the
instructions for submitting comments.
Comments submitted electronically,
including attachments, to https://
www.regulations.gov will be posted to
the docket unchanged. Because your
comment will be made public, you are
solely responsible for ensuring that your
comment does not include any
confidential information that you or a
third party may not wish to be posted,
such as medical information, your or
anyone else’s Social Security number, or
confidential business information, such
as a manufacturing process. Please note
that if you include your name, contact
information, or other information that
identifies you in the body of your
comments, that information will be
posted on https://www.regulations.gov.
• If you want to submit a comment
with confidential information that you
do not wish to be made available to the
public, submit the comment as a
written/paper submission and in the
manner detailed (see ‘‘Written/Paper
Submissions’’ and ‘‘Instructions’’).
Written/Paper Submissions
Submit written/paper submissions as
follows:
PO 00000
Frm 00039
Fmt 4702
Sfmt 4702
10119
• Mail/Hand Delivery/Courier (for
written/paper submissions): Dockets
Management Staff (HFA–305), Food and
Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments
submitted to the Dockets Management
Staff, FDA will post your comment, as
well as any attachments, except for
information submitted, marked and
identified, as confidential, if submitted
as detailed in ‘‘Instructions.’’
Instructions: All submissions received
must include the Docket No. FDA–
2021–N–0507 for ‘‘Medical Devices;
Quality System Regulation
Amendments.’’ Received comments,
those filed in a timely manner (see
ADDRESSES), will be placed in the docket
and, except for those submitted as
‘‘Confidential Submissions,’’ publicly
viewable at https://www.regulations.gov
or at the Dockets Management Staff
between 9 a.m. and 4 p.m., Monday
through Friday, 240–402–7500.
• Confidential Submissions—To
submit a comment with confidential
information that you do not wish to be
made publicly available, submit your
comments only as a written/paper
submission. You should submit two
copies total. One copy will include the
information you claim to be confidential
with a heading or cover note that states
‘‘THIS DOCUMENT CONTAINS
CONFIDENTIAL INFORMATION.’’ The
Agency will review this copy, including
the claimed confidential information, in
its consideration of comments. The
second copy, which will have the
claimed confidential information
redacted/blacked out, will be available
for public viewing and posted on
https://www.regulations.gov. Submit
both copies to the Dockets Management
Staff. If you do not wish your name and
contact information to be made publicly
available, you can provide this
information on the cover sheet and not
in the body of your comments and you
must identify this information as
‘‘confidential.’’ Any information marked
as ‘‘confidential’’ will not be disclosed
except in accordance with 21 CFR 10.20
and other applicable disclosure law. For
more information about FDA’s posting
of comments to public dockets, see 80
FR 56469, September 18, 2015, or access
the information at: https://
www.govinfo.gov/content/pkg/FR-201509-18/pdf/2015-23389.pdf.
Docket: For access to the docket to
read background documents or the
electronic and written/paper comments
received, go to https://
www.regulations.gov and insert the
docket number, found in brackets in the
heading of this document, into the
‘‘Search’’ box and follow the prompts
E:\FR\FM\23FEP1.SGM
23FEP1
10120
Federal Register / Vol. 87, No. 36 / Wednesday, February 23, 2022 / Proposed Rules
and/or go to the Dockets Management
Staff, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852, 240–402–7500.
I. Executive Summary
A. Purpose of the Proposed Rule
Submit comments on information
collection under the PRA to the Office
of Management and Budget (OMB) at
https://www.reginfo.gov/public/do/
PRAMain. Find this particular
information collection by selecting
‘‘Currently under Review—Open for
Public Comments’’ or by using the
search function. The title of this
proposed collection is ‘‘Medical
Devices; Quality Management System.’’
FOR FURTHER INFORMATION CONTACT:
With regard to the proposed rule: Keisha
Thomas or Melissa Torres, Center for
Devices and Radiological Health, Food
and Drug Administration, 10903 New
Hampshire Ave., Silver Spring, MD
20903, 301–796–2001, Proposed-DeviceQMSR-Rule@fda.hhs.gov.
With regard to the information
collection: Amber Sanford, Office of
Operations, Food and Drug
Administration, Three White Flint
North 10A–12M, 11601 Landsdown St.,
North Bethesda, MD 20852, 301–796–
8867, PRAStaff@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
khammond on DSKJM1Z7X2PROD with PROPOSALS
Table of Contents
I. Executive Summary
A. Purpose of the Proposed Rule
B. Summary of the Major Provisions of the
Proposed Rule
C. Legal Authority
D. Costs and Benefits
II. Table of Abbreviations/Commonly Used
Acronyms in This Document
III. Background
A. Introduction
B. Need for the Regulation
C. FDA’s Current Regulatory Framework
D. History of the Rulemaking
E. Incorporation by Reference
IV. Legal Authority
V. Description of the Proposed Rule
A. Scope (Proposed § 820.1)
B. Definitions (Proposed § 820.3)
C. Incorporation by Reference (Proposed
§ 820.7)
D. Proposed Requirements for a Quality
Management System (Proposed § 820.10)
E. Proposed Clarification of Concepts
(Proposed § 820.15)
F. Proposed Supplementary Provisions
(Proposed Subpart B)
G. Proposed Conforming Amendments
VI. Proposed Effective Date and
Implementation Strategy
VII. Preliminary Economic Analysis of
Impacts
VIII. Analysis of Environmental Impact
IX. Paperwork Reduction Act of 1995
X. Federalism
XI. Consultation and Coordination With
Indian Tribal Governments
XII. References
VerDate Sep<11>2014
17:39 Feb 22, 2022
Jkt 256001
FDA has historically recognized the
benefits of harmonization with other
regulatory authorities and over time has
taken a number of actions to promote
consistency with its regulatory
counterparts. As part of such activities,
FDA is proposing to revise its device
CGMP requirements as set forth in the
QS regulation, codified in part 820 (21
CFR part 820). Through this proposed
rulemaking, FDA intends to converge its
requirements with quality management
system requirements used by other
regulatory authorities. FDA seeks to
accomplish this primarily by
incorporating by reference the 2016
edition of International Organization for
Standardization (ISO) 13485 (ISO
13485). This rule, if finalized, would
harmonize quality management system
requirements for devices with
requirements used by other regulatory
authorities. Such harmonization should
provide patients more efficient access to
necessary devices, leading to
improvement of life quality of the
consumers.
B. Summary of the Major Provisions of
the Proposed Rule
We are proposing to amend the
current part 820, primarily, through
incorporating by reference the quality
management system requirements of
ISO 13485. We have determined that the
requirements in ISO 13485 are, when
taken in totality, substantially similar to
the requirements of the current part 820,
providing a similar level of assurance in
a firm’s quality management system and
ability to consistently manufacture
devices that are safe and effective and
otherwise in compliance with the FD&C
Act. As such, we propose to withdraw
the requirements in the current part 820,
except that we propose to retain the
scope of the current regulation and to
retain and modify, as indicated below,
a number of the definitions in the
current part 820. We are also proposing
to amend the title of the regulation and
add FDA-specific requirements and
provisions that clarify certain concepts
used in ISO 13485. The result will be
referred to as the Quality Management
System Regulation (QMSR). These
additions will ensure that the
incorporation by reference of ISO 13485
does not create inconsistencies with
other applicable FDA requirements.
FDA is also proposing conforming edits
to part 4 (21 CFR part 4) to clarify the
device QMS requirements for
combination products. These edits
would not impact the CGMP
PO 00000
Frm 00040
Fmt 4702
Sfmt 4702
requirements for combination products.
The rule, if finalized, would converge
QS regulation with the QMS
requirements of ISO 13485, while
continuing to provide the same level of
assurance of safety and effectiveness
under the FD&C Act and its
implementing regulations. The Agency
solicits comments on specific subject
areas related to this proposed rule that
FDA should consider in seeking to
converge U.S. requirements with
requirements used by other regulatory
authorities in ways that are consistent
with FDA’s authority under the FD&C
Act.
C. Legal Authority
We are proposing to issue this rule
under the same authority that FDA
initially invoked to issue the current
part 820 and combination product
regulations, as well as the general
administrative provisions of the FD&C
Act (21 U.S.C. 351, 352, 360, 360c,
360d, 360e, 360h, 360i, 360j, 360l, 371,
374, 381, 383; 42 U.S.C. 216, 262, 263a,
264).
D. Costs and Benefits
We estimate that the proposed rule
will result in an annualized net cost
savings (benefits) of approximately $439
million over 10 years at a discount rate
of 3 percent. When we assume a
discount rate of 7 percent, the
annualized net cost savings are
approximately $533 million. The benefit
of the proposed rule is estimated in
terms of reduction of compliance effort,
and consequently cost savings, for
medical device establishments that
currently comply with both standards.
The costs of the rule include initial
training of personnel, and information
technology and documentation update
for the medical device industry and the
FDA. There is also a one-time cost of
reading and learning the rule for the
medical device establishments.
If finalized, in addition to the cost
savings to the medical device industry,
the qualitative benefits of the proposed
rule include quicker access to newly
developed medical devices for patients,
leading to improvement of life quality of
the consumers. The proposed rule, if
finalized, would also align the current
part 820 with other related programs
potentially contributing to additional
cost savings.
II. Table of Abbreviations/Commonly
Used Acronyms in This Document
E:\FR\FM\23FEP1.SGM
23FEP1
Federal Register / Vol. 87, No. 36 / Wednesday, February 23, 2022 / Proposed Rules
Abbreviation/acronym
What it means
ANSI ..................................................................................
CD .....................................................................................
CFR ...................................................................................
CGMP ................................................................................
DGMP ................................................................................
DMR ..................................................................................
FD&C Act ..........................................................................
FDA ...................................................................................
GHTF .................................................................................
GMP ..................................................................................
IBR ....................................................................................
IMDRF ...............................................................................
ISO ....................................................................................
ISO 13485 .........................................................................
ISO 9000 ...........................................................................
MDSAP ..............................................................................
NARA ................................................................................
OMB ..................................................................................
QMS ..................................................................................
QMSR ................................................................................
QS .....................................................................................
QSIT ..................................................................................
SMDA ................................................................................
UDI ....................................................................................
khammond on DSKJM1Z7X2PROD with PROPOSALS
III. Background
A. Introduction
QMSs specify requirements to help
manufacturers ensure that their
products consistently meet applicable
customer and regulatory requirements
and specifications (Ref. 1). In the United
States, authority for the QS regulation
for devices is found under section 520(f)
of the FD&C Act (21 U.S.C. 360j(f)),
which the FD&C Act refers to as CGMP
requirements. FDA issued a final rule
for CGMP requirements in the Federal
Register of July 21, 1978 (43 FR 31508),
which created part 820 (Ref. 2).
As described below, FDA significantly
revised part 820 in a final rule
published in the Federal Register of
October 7, 1996 (61 FR 52602, effective
June 1, 1997) (1996 Final Rule),
establishing the current QS regulation.
As revised, part 820 includes
requirements related to the methods
used in, and the facilities and controls
used for, designing, manufacturing,
packaging, labeling, storing, installing,
and servicing of devices intended for
human use. These requirements are
intended to assure that devices are safe
and effective and otherwise in
compliance with the FD&C Act. FDA
has not undertaken a significant
revision of part 820 since the 1996 Final
Rule. Part 820 has been an effective
regulation, providing assurance that
devices are safe and effective and
otherwise in compliance with
applicable sections of the FD&C Act.
Also in 1996, ISO issued the first
version of ISO 13485, ‘‘Quality
systems—Medical devices—Particular
requirements for the application of ISO
VerDate Sep<11>2014
17:39 Feb 22, 2022
Jkt 256001
10121
American National Standards Institute.
Committee Draft.
Code of Federal Regulations.
Current Good Manufacturing Practice.
Device Good Manufacturing Practice.
Device Master Record.
Federal Food, Drug, and Cosmetic Act.
Food and Drug Administration.
Global Harmonization Task Force.
Good Manufacturing Practice.
Incorporated by Reference.
International Medical Device Regulators Forum.
International Organization for Standardization.
International Organization for Standardization 13485:2016.
Quality Management Systems—Fundamentals and Vocabulary,’’ ISO 9000:2015.
Medical Device Single Audit Program.
National Archives and Records Administration.
Office of Management and Budget.
Quality Management System.
Quality Management System Regulation.
Quality System.
Quality System Inspection Technique.
Safe Medical Devices Act of 1990.
Unique Device Identification.
9001,’’ as a voluntary consensus
standard to specify, in conjunction with
the application of ISO 9001, the QMS
requirements for the design/
development and, when relevant,
installation and servicing of medical
devices (Refs. 3 and 4). Over time, ISO
13485 has evolved into a stand-alone
standard outlining QMS requirements
for devices (Ref. 1). With each revision,
ISO 13485 has become more closely
aligned with, and similar to, the
requirements in part 820. This
alignment and similarity are particularly
true for the 2016 version of ISO 13485.
Recognizing this progression, FDA sees
an opportunity for regulatory
harmonization by proposing to amend
the current part 820 regulation to
explicitly incorporate the QMS
requirements of ISO 13485. ISO 13485
is used internationally by many
regulatory authorities either as a
foundation for or as that country’s QMS
requirements for device manufacturers
and is utilized in regulatory
harmonization programs such as the
Medical Device Single Audit Program
(MDSAP), in which FDA and regulatory
authorities from four other countries
participate (Ref. 5).
The current part 820 applies to many
different devices and thus does not
prescribe in detail how a manufacturer
must design and manufacture a specific
device. Rather, the regulation was
developed to be a mandatory and
flexible framework, requiring
manufacturers to develop and follow
procedures and processes, as
appropriate to a given device, according
to the state-of-the-art for manufacturing
PO 00000
Frm 00041
Fmt 4702
Sfmt 4702
and designing such device. Successful
compliance with this regulation
provides the manufacturer with a
framework for achieving quality
throughout the organization (Ref. 1).
While part 820 effectively addresses
the requirements for a QMS, FDA has
long recognized the value of, and has
been exploring ways to effect, global
harmonization for the regulation of
devices. For example, FDA has actively
participated in the development of
internationally harmonized documents
and standards on risk management since
their inception, including the
development of the Global
Harmonization Task Force (GHTF)
guidance document, ‘‘Implementation of
Risk Management Principles and
Activities Within a Quality Management
System,’’ dated May 20, 2005, which
outlines the integration of a risk
management system into a QMS (Ref. 6).
FDA also participated in the
development of the various versions of
ISO 14971 ‘‘Medical Devices—
Application of Risk Management to
Medical Devices’’ (Ref. 7).
In 2012, FDA developed a voluntary
audit report submission pilot program,
which is no longer operational, in
which FDA accepted a manufacturer’s
ISO 13485:2003 audit report (Ref. 8).
Through this program, FDA established
the feasibility and use of ISO 13485
audit reports in lieu of FDA’s routine
inspections covering the QS regulation
requirements. Additionally, FDA
participates in the International Medical
Device Regulators Forum (IMDRF), a
voluntary group of medical device
regulators from around the world
E:\FR\FM\23FEP1.SGM
23FEP1
khammond on DSKJM1Z7X2PROD with PROPOSALS
10122
Federal Register / Vol. 87, No. 36 / Wednesday, February 23, 2022 / Proposed Rules
focused on regulatory harmonization
and convergence (Ref. 9). IMDRF
developed MDSAP in 2012. Under
MDSAP, audits are conducted based on
core ISO 13485 requirements with
additional country-specific
requirements. In determining whether to
participate in MDSAP and which FDAspecific provisions were needed for the
United States, FDA conducted a
thorough review and comparison of ISO
13485 and part 820 and concluded that
very few FDA-specific requirements
needed to be added to this audit model,
demonstrating not only the similarities
between the current part 820 and ISO
13485, but the comprehensive QMS
approach provided by ISO 13485. This
has allowed FDA to participate in
MDSAP and accept certain MDSAP
audits as a substitute for its own routine
surveillance of device quality systems
(Ref. 5).
Through our participation in MDSAP,
FDA has gained experience with ISO
13485 and determined that it provides
a comprehensive and effective approach
to establish a QMS for devices. As such,
FDA is proposing to amend the device
CGMP requirements of the QS
regulation by incorporating by reference
the 2016 edition of ISO 13485 as well
as proposing additional regulations that
help connect and align ISO 13485 with
other FDA requirements. The 2016
version of ISO 13485 provides
requirements for a QMS that allow a
manufacturer to demonstrate its ability
to provide devices and related services
that consistently meet customer
requirements and regulatory
requirements applicable to such devices
and services (Ref. 1). These
requirements can be used by ‘‘an
organization involved in one or more
stages of the life cycle of a medical
device, including design and
development, production, storage and
distribution, installation, servicing and
final decommissioning and disposal of
medical devices’’ (Ref. 1).
FDA believes that globally
harmonizing the regulation of devices
will help provide consistent, safe, and
effective devices, contributing to public
health through timelier access for
patients. Harmonizing differing
regulations would remove unnecessary
duplicative regulatory requirements and
impediments to market access and
remove barriers to patient access and
costs. The more flexible approach to
quality, based on risk management,
found within ISO 13485 will meet the
needs of patients to have access to
quality devices in consonance with the
progress of science and technology (Ref.
9).
VerDate Sep<11>2014
17:39 Feb 22, 2022
Jkt 256001
B. Need for the Regulation
Currently, device manufacturers
registered with the FDA must comply
with the current part 820. In addition to
the current part 820, registered
manufacturers in many other
jurisdictions and domestic
manufacturers that export devices must
comply with ISO 13485, which is
substantially similar to the current part
820. As a result, there is redundant
effort for some manufacturers in
complying with both the current part
820 and ISO 13485. The redundancy of
effort to comply with two substantially
similar requirements creates
inefficiency. In order to address this
inefficiency, we propose to incorporate
by reference ISO 13485 requirements so
that compliance with ISO 13485 would
satisfy requirements of current part 820.
Although the requirements under the
current part 820 are effective and very
similar to those in ISO 13485,
incorporating ISO 13485 by reference
would further the Agency’s goals for
regulatory simplicity and global
harmonization and should reduce
burdens on regulated industry, thereby
providing patients more efficient access
to necessary devices (Ref. 9).
C. FDA’s Current Regulatory Framework
The FD&C Act, as amended, and its
implementing regulations establish a
comprehensive system for the regulation
of devices intended for human use. The
device CGMP requirements in the
current part 820 were authorized by
section 520(f) of the FD&C Act, which
was among the authorities added to the
FD&C Act by the Medical Device
Amendments of 1976 (Pub. L. 94–295).
Under section 520(f) of the FD&C Act,
FDA issued the current part 820
regulation, which was last revised in
1996.
In addition, section 520(f)(1)(B) of the
FD&C Act directs the Agency to afford
the Device Good Manufacturing Practice
Advisory Committee (DGMP Advisory
Committee) an opportunity to submit
recommendations for proposed CGMP
regulations, to afford an opportunity for
an oral hearing, and to ensure that such
regulations conform, to the extent
practicable, with internationally
recognized standards defining quality
management systems, or parts of the
standards, for devices (see 21 U.S.C.
360j(f)(1)(B)). The DGMP Advisory
Committee reviews regulations
proposed for promulgation regarding
good manufacturing practices and
makes recommendations to the Agency
regarding the feasibility and
reasonableness of the proposed
regulations. The Agency will convene a
PO 00000
Frm 00042
Fmt 4702
Sfmt 4702
DGMP Advisory Committee meeting
and afford an opportunity for an oral
hearing to discuss this proposal prior to
FDA’s finalization of this rule.
Further, the provisions of sections
501(a)(2)(B) and (h) of the FD&C Act (21
U.S.C. 351(a)(2)(B) and (h)) require the
manufacture of drugs and devices to
comply with CGMP requirements, and
section 520(f) of the FD&C Act
specifically authorizes the issuance of
CGMP regulations for devices, including
device constituent parts of products that
constitute a combination of a drug,
device, and/or biological product, as
defined in § 3.2(e) (21 CFR 3.2(e))
(‘‘combination products’’). Combination
products that include device constituent
parts have a distinct regulatory
framework for CGMP requirements
because the product, by definition, also
includes non-device constituent parts
(e.g., a drug or a biological product). In
the Federal Register of January 22, 2013
(78 FR 4307), we issued a final rule
codifying the CGMP requirements
applicable to combination products at
part 4. We issued the part 4 regulations,
in part, under sections 501(a)(2)(B) and
(h) and 520(f) of the FD&C Act and are
proposing to amend part 4 under the
same authorities.
In that final rule, we explained that
the CGMP requirements specific to each
constituent part of a combination
product also apply to the combination
product itself because, by definition,
combination products consist of drugs,
devices, and/or biological products (see
78 FR 4307 at 4320, citing § 3.2(e)). We
also explained that, because the
constituent parts of a combination
product retain their regulatory status (as
a drug or device, for example) after they
are combined, all combination products
are subject to at least two sets of CGMP
requirements, but that those for drugs
overlap considerably with the part 820
requirements for devices (see 78 FR
4307 at 4320). Part 4 clarifies the
applicability of the various CGMP
requirements to provide a streamlined
option for practical implementation for
co-packaged and single-entity
combination products (see 78 FR 4307
at 4320 and § 4.4 (21 CFR 4.4)). Because
of the similarity of the drug and device
CGMP requirements, FDA considers
demonstrating compliance with one of
these two sets of regulations (e.g., device
CGMP requirements) along with
demonstrating compliance with the
specified provisions from the other set
(e.g., drug CGMP requirements)
identified in part 4 as demonstrating
compliance with all CGMP
requirements from both sets (see 78 FR
4307 at 4320 and § 4.4).
E:\FR\FM\23FEP1.SGM
23FEP1
khammond on DSKJM1Z7X2PROD with PROPOSALS
Federal Register / Vol. 87, No. 36 / Wednesday, February 23, 2022 / Proposed Rules
D. History of the Rulemaking
This proposed rulemaking is the first
revision of the current part 820 since
1996. As previously described, FDA has
had a longstanding interest and history
of participation in efforts to harmonize
its regulatory requirements with the
requirements used by other regulatory
authorities from various jurisdictions
(i.e., other countries). This rulemaking
is a continuation of these efforts and, if
finalized, will harmonize FDA’s quality
management system regulation with
requirements of the international
standard ISO 13485, which is used by
other regulatory authorities.
Harmonizing the FDA standard with the
ISO standard would have benefits for
manufacturers because many firms
producing devices for sale within the
United States and abroad have to
comply with both standards. If
finalized, this rule would require
compliance with an aligned set of
requirements, instead of two different
requirements.
On July 21, 1978, FDA issued a final
rule in the Federal Register (43 FR
31508), establishing CGMP
requirements for medical devices under
section 520(f) of the FD&C Act. This rule
became effective on December 18, 1978,
and is codified under part 820.
The Safe Medical Devices Act of 1990
(SMDA) (Pub. L. 101–629) amended
section 520(f) of the FD&C Act to
provide FDA with the authority to add
preproduction design controls to the
CGMP regulation. This change in law
was based on findings that a significant
proportion of device recalls were
attributable to faulty product design.
The SMDA also added section 803 to
the FD&C Act, which, among other
things, authorizes the Agency to enter
into agreements with foreign countries
to facilitate commerce in devices, and in
such agreements, FDA must encourage
the mutual recognition of GMP
regulations under section 520(f) of the
FD&C Act (see 21 U.S.C. 383(b)(1)).
To implement the SMDA changes to
section 520(f) of the FD&C Act, FDA
revised part 820 by the 1996 Final Rule
(61 FR 52602). This final rule revised
the CGMP requirements for medical
devices and promulgated the QS
regulation under part 820 in its current
form. As part of this revision, FDA
added the design controls authorized by
the SMDA in addition to other changes
to achieve consistency with QMS
requirements worldwide. At the time,
the Agency sought to harmonize the
CGMP regulations, to the extent
possible, with the requirements for
quality management systems contained
in then-applicable international
VerDate Sep<11>2014
17:39 Feb 22, 2022
Jkt 256001
standards. In particular, FDA worked
closely with the GHTF and ISO
Technical Committee 210 (TC 210) to
develop a regulation consistent with
both ISO 9001:1994, Quality Systems—
Model for Quality Assurance in Design,
Development, Production, Installation,
and Servicing; and the ISO committee
draft (CD) revision of ISO/CD 13485
Quality Systems—Medical Devices—
Supplementary Requirements to ISO
9001 (see 61 FR 52602 at 52604).
E. Incorporation by Reference
FDA is proposing to incorporate by
reference ISO 13485:2016 Medical
devices—Quality management
systems—Requirements for regulatory
purposes, Third Edition 2016–03–01.
ISO is an independent, nongovernmental international organization
with a membership of national
standards bodies. ISO 13485 specifies
requirements for a QMS that can be
used by a manufacturer involved in one
or more stages of the life cycle of a
medical device, including design and
development, production, storage and
distribution, installation, servicing and
final decommissioning and disposal of
medical devices, or provision of
associated activities.
You may view the material at the
Dockets Management Staff, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852,
240–420–7500. The material can also be
found in a read-only format at the
American National Standards Institute
(ANSI) Incorporated by Reference (IBR)
Portal, https://ibr.ansi.org/Standards/
iso1.aspx, or you may purchase a copy
of the material from the International
Organization for Standardization, BIBC
II, Chemin de Blandonnet 8, CP 401,
1214 Vernier, Geneva, Switzerland;
+41–22–749–01–11; customerservice@
iso.org, https://www.iso.org/store.html.
ISO 13485 provides a comprehensive
approach to establish a QMS for medical
devices.
FDA is proposing to incorporate by
reference the current 2016 version of
ISO 13485. Any future revisions to this
standard would need to be evaluated to
determine the impact of the changes and
whether this rule, if finalized, should be
amended. If deemed necessary and
appropriate, FDA will update the final
regulation in accordance with the
Administrative Procedure Act (5 U.S.C.
553) and obtain approval of any changes
to the incorporation by reference in
accordance with 1 CFR part 51.
IV. Legal Authority
We are proposing to issue this rule
under the same authority that FDA
initially invoked to issue the current
Quality System Regulation (part 820)
PO 00000
Frm 00043
Fmt 4702
Sfmt 4702
10123
and Regulation of Combination Products
(part 4), as well as the general
administrative provisions of the FD&C
Act: 21 U.S.C. 351, 352, 360, 360c, 360d,
360e, 360h, 360i, 360j, 360l, 371, 374,
381, 383; 42 U.S.C. 216, 262, 263a, 264.
V. Description of the Proposed Rule
We are proposing to amend the
current part 820, primarily to
incorporate by reference ISO 13485,
Medical Devices—Quality Management
System Requirements for Regulatory
Purposes. While the current part 820
provides sufficient and effective
requirements for the establishment and
maintenance of a QMS, regulatory
expectations for a QMS have evolved
since the current part 820 was
implemented over 20 years ago. By
proposing to incorporate ISO 13485 by
reference, we are seeking to explicitly
require current internationally
recognized regulatory expectations for
QMS for devices subject to FDA’s
jurisdiction. The resulting regulation
will be referred to as the QMSR.
The current part 820 requirements
are, when taken in totality, substantially
similar to the requirements of ISO
13485. Where ISO 13485 diverges from
the current part 820, these differences
are generally consistent with the overall
intent and purposes behind FDA’s
regulation of QMSs. Almost all
requirements in the current part 820
correspond to requirements within ISO
13485. Therefore, we are proposing to
amend the current part 820 by
withdrawing the majority of the
requirements for establishing and
maintaining a QS. Despite these
changes, this proposal does not
fundamentally alter the requirements for
a QS that exist in the current part 820.
The rule, if finalized, would converge
QS regulation with the QMS
requirements of ISO 13485, while
continuing to provide the same level of
assurance of safety and effectiveness
under the FD&C Act and its
implementing regulations.
However, we recognize that reliance
on ISO 13485 without clarification or
modification could create
inconsistencies with FDA’s statutory
and regulatory framework. Therefore, as
detailed in this rulemaking, we are
proposing additional definitions,
clarifying concepts, and additional
requirements, all of which would
require compliance within a
manufacturer’s QMS in addition to ISO
13485. The Agency solicits comments
on specific subject areas related to this
proposed rule that FDA should consider
in seeking to converge U.S.
requirements with requirements used by
other regulatory authorities in ways that
E:\FR\FM\23FEP1.SGM
23FEP1
10124
Federal Register / Vol. 87, No. 36 / Wednesday, February 23, 2022 / Proposed Rules
are consistent with FDA’s authority
under the FD&C Act.
Our approach to this rulemaking is to
simplify and streamline the regulation.
Where possible, we either are proposing
to accept the incorporated requirement
without modification or are proposing a
requirement that will supersede the
correlating requirement in ISO 13485.
There are a few exceptions where we are
proposing to clarify concepts or
augment specific clauses in ISO 13485,
but overall, we are not proposing to
modify the clauses in ISO 13485. (see
table 1). This philosophy also helps
further regulatory convergence.
As discussed further in section VI.,
this rule is only proposing to amend the
current part 820 and does not impact
our inspectional authority under section
704 of the FD&C Act (21 U.S.C. 374). We
are also proposing conforming edits to
part 4 to clarify the device QMS
requirements for combination products.
These edits would not impact the CGMP
requirements for combination products.
TABLE 1—HIGH-LEVEL SUMMARY OF 21 CFR PART 820 PROPOSED RULE DIFFERENCES AND ADDITIONS
Current part 820 1
ISO 13485 requirements 1
Proposed rule
Subpart A—General Provisions ................................
Clause 1. Scope, Clause 4. Quality Management
System.
Clause 4. Quality Management System, Clause 5.
Management Responsibility, Clause 6. Resource
Management, Clause 8. Measurement, Analysis,
and Improvement.
Clause 7. Product Realization ..................................
Clause 4. Quality Management System ...................
Clause 7. Product Realization ..................................
Clause 7. Product Realization ..................................
Clause 4. Quality Management System, Clause 6.
Resource Management, Clause 7. Product Realization.
Clause 7. Product Realization, Clause 8. Measurement, Analysis, and Improvement.
Clause 8. Measurement, Analysis, and Improvement.
Clause 8. Measurement, Analysis, and Improvement.
Clause 7. Product Realization ..................................
Clause 7. Product Realization ..................................
Requirements substantively similar.
Clause 4. Quality Management System ...................
Clause 7. Product Realization ..................................
Clause 7. Product Realization, Clause 8. Measurement, Analysis, and Improvement.
Differences addressed in 820.35.
Differences addressed in 820.35.
Requirements substantively similar.
Subpart B—QS Requirements ..................................
Subpart
Subpart
Subpart
Subpart
Subpart
C—Design Controls .....................................
D—Document Controls 2 ..............................
E—Purchasing Controls ..............................
F—Identification and Traceability ................
G—Production and Process Controls ..........
Subpart H—Acceptance Activities .............................
Subpart I—Nonconforming Product ..........................
Subpart J—Corrective and Preventive Action ...........
Subpart K—Labeling and Packaging Control ...........
Subpart L—Handling, Storage, Distribution, and Installation.
Subpart M—Records .................................................
Subpart N—Servicing ................................................
Subpart O—Statistical Techniques ...........................
Requirements substantively similar.
Requirements substantively similar.
Differences addressed in 820.35.
Requirements substantively similar.
Requirements substantively similar.
Requirements substantively similar.
Requirements substantively similar.
Requirements substantively similar.
Requirements substantively similar.
Differences addressed in 820.45.
Requirements substantively similar.
1 This table is not intended to be a requirement-by-requirement analysis, but a higher-level mapping of the totality of the subparts and clauses
of the standard and the QS regulation for reference purposes only.
2 It’s important to note that while there are differences specifically identified in subpart D, document requirements exist in most subparts and
clauses of the standard and the QS Regulation.
khammond on DSKJM1Z7X2PROD with PROPOSALS
A. Scope (Proposed § 820.1)
FDA is not proposing to modify
which establishments or products are
subject to part 820. As before, the
requirements would apply to
manufacturers of finished devices;
however, FDA notes that the legal
authority exists to cover manufacturers
of components or parts of finished
devices under this regulation should the
need arise (see 61 FR 52602 at 52606).
The proposed modifications to the
scope of the requirements are nonsubstantive, and include the following:
1. Clarify that conflicting regulations
that are more specific are controlling
only to the extent of the conflict.
The current § 820.1(b) states that
when there is a conflict between
regulations in part 820 and a
specifically applicable regulation
located in chapter I of title 21 of the
CFR, the regulations that specifically
apply to the device in question
supersede other generally applicable
VerDate Sep<11>2014
17:39 Feb 22, 2022
Jkt 256001
requirements. A reader might interpret
this provision to mean that the
specifically applicable regulation
renders the rest of the part 820
regulation completely inapplicable. The
proposed amendment is intended to
clarify that the generally applicable part
820 regulations apply to the extent they
do not otherwise conflict with the
specifically applicable regulation.
Moreover, to the extent that any clauses
of ISO 13485 conflict with any
provisions of the FD&C Act and/or its
implementing regulations, the FD&C Act
and/or its implementing regulations will
control.
2. Rearrange some of the content and
add paragraph breaks for clarity and
improved flow, for example, separating
requirements for manufacturers of
components or parts into a paragraph
different from the one describing
manufacturers of finished devices.
3. Remove the paragraph listing
authority because the CFR already lists
PO 00000
Frm 00044
Fmt 4702
Sfmt 4702
the legal authority for the regulation as
a separate entry.
4. Relocate the enforcement provision
to a new separate paragraph in § 820.10.
B. Definitions (Proposed § 820.3)
Definitions of key terms related to
quality management systems appear in
the current § 820.3 and in Clause 3 of
ISO 13485. We have reviewed the
definitions in ISO 13485 to determine
their suitability for FDA’s purposes. We
find that most of the definitions in
Clause 3 are acceptable; thus, unless
identified in this section, we are not
proposing any modifications to the
terms and definitions in Clause 3 and
are proposing to remove the correlating
terms and definitions from the current
part 820. In some cases, however, the
current § 820.3 definitions include
terms that ISO 13485 does not and vice
versa. Further, there are some
definitions in ISO 13485 that do not
align with requirements in the FD&C
Act and its implementing regulations.
E:\FR\FM\23FEP1.SGM
23FEP1
khammond on DSKJM1Z7X2PROD with PROPOSALS
Federal Register / Vol. 87, No. 36 / Wednesday, February 23, 2022 / Proposed Rules
To account for these differences and
ensure consistency with such law and
regulations, we are proposing to retain
and/or revise certain definitions that are
in the current part 820. We are also
proposing to withdraw certain terms
and definitions from the current part
820 that do not have a corollary in ISO
13485 because they are not needed to
understand and implement the
proposed part 820. Among the
definitions being withdrawn from the
current part 820 is the term ‘‘establish’’.
Though the term establish is not defined
in the ISO standard, section 0.2 states
that when a requirement is required to
be ‘‘documented’’, it is also required to
be established, implemented, and
maintained. We believe the clarification
of this concept within the standard is
sufficient to convey the current
requirement for manufacturers to
establish and maintain the regulatory
requirements of a QMS.
1. Terms that do not appear in ISO
13485 but that are necessary for the
purposes of part 820 (terms additional
to ISO 13485) (Proposed § 820.3(a)).
For the terms that do not appear in
ISO 13485, but are necessary to ensure
alignment with the FD&C Act and its
implementing regulations, we are
proposing to retain the definitions of
such terms with minor revisions, as
indicated below.
We are proposing to retain the
definition of Act (see § 820.3(a)) in
current part 820, except we propose to
expand the term to more precisely
reflect the specific act to which the
definition refers because FDA has the
authority to promulgate regulations
under other acts. The addition of
‘‘Federal Food, Drug, and Cosmetic’’ to
this term will help avoid potential
ambiguity if we amend part 820 in the
future under a different authority.
We are also proposing to replace the
term ‘‘management with executive
responsibility’’ (see § 820.3(n)) in the
current part 820 with the term ‘‘top
management’’, which is used in ISO
13485, but is defined in ‘‘Quality
Management Systems—Fundamentals
and Vocabulary,’’ ISO 9000:2015 (ISO
9000) (Ref. 10). We propose to
accomplish this by revising the name of
the term to ‘‘top management’’ but
retaining the definition in the current
part 820. This will maintain the
principle and requirement that the most
senior employees of a manufacturer are
responsible for establishing and making
changes to the quality policy and
ensuring the manufacturer follows the
policy. FDA expects medical device
manufacturers, led by top management,
to embrace a culture of quality as a key
component in ensuring safe and
VerDate Sep<11>2014
17:39 Feb 22, 2022
Jkt 256001
effective medical devices that otherwise
comply with the FD&C Act. A culture of
quality meets regulatory requirements
through a set of behaviors, attitudes,
activities, and processes. Top
management ensures that applicable
regulatory requirements are met through
the integration of QS processes.
We are retaining the majority of the
definition of ‘‘rework’’; however, we are
proposing to remove the term ‘‘device
master record (DMR)’’ (§ 820.3(j)) from
the regulation. The device master record
is not a term used in ISO 13485 and so
this definition does not need to be
retained. FDA believes the concept of a
DMR is adequately covered under the
requirements for a medical device file
under Clause 4.2.3 of ISO 13485. We are
retaining the definition of ‘‘process
validation’’ (§ 820.3(z)(1)) and clarifying
the concept. FDA recognizes the terms
‘‘process validation’’ and ‘‘validation of
processes’’, the term used in ISO 13485,
as synonymous. We are also proposing
to include a definition for the term
‘‘customer’’, as it is important for
interpretation of the proposed rule.
Although FDA historically has not used
the term ‘‘customer’’, we find it is a
useful term and can encompass many
types of individuals and organizations
throughout the device manufacturing
process, such as component
manufacturers, contract manufacturers,
and end users. Requirements related to
customers are generally consistent with
the overall intent and purposes behind
FDA’s regulation of device QMSs,
which is to assure that finished devices
will be safe and effective and otherwise
in compliance with the FD&C Act.
When considering the requirements
related to customer property in ISO
7.5.10, FDA expects that manufacturers
comply with this provision to the extent
necessary to assure the safety and
effectiveness of the devices being
manufactured. For example, a
manufacturer is expected to ensure that
the integrity of a component provided
by a contract manufacturer is not
compromised before it is incorporated
into the device being manufactured. To
the extent any customer property
requirements may be interpreted to go
beyond the safety and effectiveness of
the devices being manufactured, FDA
does not intend to enforce this provision
for such activities.
We are retaining without change the
terms and definitions for ‘‘component’’
(§ 820.3(c)); ‘‘finished device’’
(§ 820.3(l)); ‘‘human cell, tissue, or
cellular or tissue-based product (HCT/P)
regulated as a device’’ (820.3(bb));
‘‘design validation’’ (§ 820.3(z)(2));
‘‘remanufacturer’’ (§ 820.3(w));
‘‘nonconformity’’ (§ 820.3(q)); and
PO 00000
Frm 00045
Fmt 4702
Sfmt 4702
10125
‘‘verification’’ (820.3(aa)) because these
terms are necessary for implementing
part 820.
2. Terms that are defined in ISO
13485, which we propose not to
incorporate and are proposing
definitions that supersede the definition
of the similar term in the standard
(Proposed § 820.3(b)).
There are a number of terms and
definitions in ISO 13485 that would
create inconsistencies with the FD&C
Act and its implementing regulations.
FDA cannot incorporate any definitions
of terms that are inconsistent with how
the FD&C Act defines such terms
because FDA cannot, nor does it seek to,
amend its statutory definitions by
rulemaking. As such, we clarify that the
definitions of terms in section 201 of the
FD&C Act (21 U.S.C. 321) supersede the
definitions in ISO 13485. In particular,
the definitions of ‘‘device’’ and
‘‘labeling’’ in sections 201(h) and (m) of
the FD&C Act, respectively, supersede
the correlating definitions for ‘‘medical
device’’ and ‘‘labelling’’ in ISO 13485.
In addition, we are proposing to retain
the definition of ‘‘manufacturer’’
(§ 820.3(o)) and retain with modification
the definition of ‘‘product’’ (§ 820.3(r))
from the current part 820 because the
ISO 13485 definitions of these terms do
not align with the established range of
these terms by FDA. The definitions in
proposed part 820 would supersede that
of the correlating term in ISO 13485.
With regards to the definition of
‘‘manufacturer’’, we are proposing to
retain our current definition because it
is more comprehensive than the
definition in ISO 13485. For example,
FDA’s definition contains a list of
functions that when performed meet the
definition of manufacturer. The
comparable ISO 13485 definition does
not include this level of detail in its
definition. This definition is expanded
upon in the notes to the ISO definition,
which are guidance—not requirements.
By explicitly including the functions
that a manufacturer performs in the
proposed definition, the Agency intends
to maintain its original interpretation of
this term and to clarify the functions
that continue to be subject to the
requirements of part 820.
A similar logic has been applied to
the definition of ‘‘product’’. FDA’s
definition of product includes a list of
items considered to be ‘‘product’’ for the
purposes of part 820 that is not included
in the definition in ISO 13485, but some
of which are included in the notes to the
ISO definition.
Additionally, we note that consistent
with the clarification in clause 0.2,
which specifies that ‘‘when the term
‘product’ is used, it can also mean
E:\FR\FM\23FEP1.SGM
23FEP1
10126
Federal Register / Vol. 87, No. 36 / Wednesday, February 23, 2022 / Proposed Rules
khammond on DSKJM1Z7X2PROD with PROPOSALS
‘service’,’’ for the requirements of clause
7.4 Purchasing we expect that when
ensuring purchased products conform to
requirements, oversight for purchased
services are also included.
C. Incorporation by Reference (Proposed
§ 820.7)
As stated above, FDA is proposing to
incorporate by reference the
International Standard, ISO 13485:2016
Medical devices—Quality management
systems—Requirements for regulatory
purposes, Third Edition 2016–03–01.
ISO 13485 provides a comprehensive
approach to establish a quality
management system for medical
devices. If this proposed rule is
finalized, it will provide most of the
CGMP requirements for devices. We
note that the definitions in ISO 9000
apply to ISO 13485; however, to the
extent that there is any conflict between
ISO 9000 and the FD&C Act and its
implementing regulations, the FD&C Act
and its implementing regulations would
control.
While we recognize that adopting ISO
13485 could seem like a significant
change, the current part 820 and ISO
13485 are substantially similar, and this
effort promotes international
harmonization. The substance of the
ISO 13485 requirements and the
activities and actions required for
compliance are primarily the same as
under the current part 820. ISO 13485
has a greater emphasis on risk
management activities and risk-based
decision making than the current part
820. Risk management for device
manufacturers is the essential
systematic practice of identifying,
analyzing, evaluating, controlling, and
monitoring risk throughout the product
lifecycle to ensure that the devices they
manufacture are safe and effective. The
current part 820 explicitly addresses
risk management activities only in the
risk analysis requirement within design
validation in § 820.30(g); whereas, risk
management is more broadly integrated
in ISO 13485. FDA, however, has
expected that manufacturers, led by top
management, integrate risk management
activities throughout their QMS and
across the total product lifecycle. FDA
discussed risk management and riskbased decision making in several
sections of the 1996 Final Rule
establishing the current QS
requirements. For example, while not
specified in the requirements for
Corrective and Preventive Action
(§ 820.100), FDA states that it ‘‘expect[s]
the manufacturer to develop procedures
for assessing the risk, the actions that
need to be taken for different levels of
risk, and how to correct or prevent the
VerDate Sep<11>2014
17:39 Feb 22, 2022
Jkt 256001
problem from recurring, depending on
that risk assessment’’ (61 FR 52602 at
52634). Additionally, FDA states that
‘‘[w]hen conducting a risk analysis,
manufacturers are expected to identify
possible hazards associated with the
design in both normal and fault
conditions. The risks associated with
the hazards, including those resulting
from user error, should then be
calculated in both normal and fault
conditions. If any risk is judged
unacceptable, it should be reduced to
acceptable levels by the appropriate
means’’ (61 FR 52602 at 52620). FDA
has, therefore, expected risk
management throughout a QMS and the
total product lifecycle.
Nonetheless, although the integration
of risk management principles
throughout ISO 13485 does not
represent a shift in philosophy, the
explicit integration of risk management
throughout the clauses of ISO 13485
more explicitly establishes a
requirement for risk management to
occur throughout a QMS and should
help industry develop more effective
total product life-cycle risk management
systems. Effective risk management
systems provide the framework for
sound decision making within a QMS
and provide assurance that the devices
will be safe and effective (see section
520(f) of the FD&C Act).
D. Proposed Requirement for a Quality
Management System (Proposed
§ 820.10)
The current § 820.5 requires that
manufacturers establish and maintain a
quality management system that meets
the requirements of part 820. We
propose to relocate this requirement
within the codified and to revise this
provision to require that a quality
management system that complies with
ISO 13485, as modified by the proposed
part 820, be documented. These
requirements will serve as the minimum
requirements for establishing a QMS
that complies with the final version of
this proposed rule. In general, when ISO
13485 refers to documenting evidence
we recommend that manufacturers
record quantitative data, as appropriate,
because such information will assist
manufacturers in monitoring the
performance of their processes and
effectiveness of their process controls.
In addition, there are many clauses
throughout ISO 13485 that refer to
‘‘applicable regulatory requirements.’’
We propose to include the FDA
requirements that must be completed
when the listed term or clause is used,
in order to assist manufacturers in
understanding how ISO 13485 relates to
other regulatory requirements for
PO 00000
Frm 00046
Fmt 4702
Sfmt 4702
devices. We are only proposing to
identify certain instances of the phrase
‘‘applicable regulatory requirements’’
and therefore the proposed list is not
intended to be comprehensive.
Regulated manufacturers are responsible
for identifying and meeting all
applicable requirements, even if such
requirements are not specifically called
out in the proposed § 820.10.
We also propose to clarify that Clause
7.3 Design and Development applies
only to the manufacturers of the class I
devices that are listed in this provision
in addition to all manufacturers of class
II and III devices. This retains the scope
of current § 820.30(a). We are not
proposing to modify which devices are
subject to these requirements and are
only revising this provision to reflect
the location of similar requirements in
ISO 13485. We also note that this is
consistent with clause 1 of ISO 13485,
which recognizes that there may be
exclusions by the regulatory authority
from the Design and Development
requirement and directs the
manufacturer to document such in its
justification for exclusion.
Finally, we are proposing to add a
requirement to ensure that devices that
support or sustain life, the failure of
which to perform when properly used
in accordance with instructions for use
provided in the labeling can be
reasonably expected to result in a
significant injury, comply with the
traceability requirements set forth in in
Clause 7.5.9.2 for implantable medical
devices. Such products currently are
subject to similar requirements in
§ 820.65 for traceability; however, in
ISO 13485 only implantable devices are
subject to this requirement.
E. Proposed Clarification of Concepts
(Proposed § 820.15)
We are including clarifications for
three concepts to explain how these
concepts in ISO 13485 relate to our
statutory and regulatory framework for
medical devices.
Organization. ISO 13485 uses the
term ‘‘organization’’ to describe the
entity who is creating a QMS that
conforms to the requirements in ISO
13485. Instead, we propose to clarify the
term ‘‘organization’’ to also include the
meaning of the term ‘‘manufacturer’’ as
it is defined in proposed § 820.3.
Safety and performance. ISO 13485
often refers to ‘‘safety and performance’’
as a standard to measure medical
devices. We propose that where the
standard uses ‘‘safety and performance,’’
readers shall construe that phrase to
mean the same as ‘‘safety and
effectiveness’’ in section 520(f) of the
FD&C Act. We understand that some
E:\FR\FM\23FEP1.SGM
23FEP1
Federal Register / Vol. 87, No. 36 / Wednesday, February 23, 2022 / Proposed Rules
people could disagree about how the
two standards compare, whether one is
more stringent than the other, or even
equivalent. In proposing this
clarification, we do not intend to take a
position on the matter of comparison.
Instead, we propose this clarification to
avoid confusion and ensure that
implementation of a QMS is aligned
with the standard of safety and
effectiveness in section 520(f) of the
FD&C Act and otherwise established for
devices in FD&C Act.
Validation of processes. ISO 13485
uses the term ‘‘validation of processes’’
and does not contain its own definition
of the term. We propose to clarify the
term ‘‘validation of processes’’ as used
in ISO 13485 to refer to ‘‘process
validation,’’ as that term is defined in
part 820. We are retaining the definition
of process validation (§ 820.3(z)(1))
because ISO 13485 does not define
‘‘validation of processes,’’ but the use is
the same as that expected for process
validation under part 820. This will also
allow for alignment between ISO 13485
and other requirements in the FD&C Act
and its implementing regulations.
khammond on DSKJM1Z7X2PROD with PROPOSALS
F. Proposed Supplementary Provisions
(Proposed Subpart B)
As stated above, we are proposing
additional requirements to ensure
consistency and alignment with other
requirements in the FD&C Act and its
implementing regulations. FDA
considers the following requirements
necessary for implementation of a QMS
that is consistent with applicable
requirements but are not specified in
ISO 13485. These requirements include
control of records and device labeling
and packaging controls.
FDA notes that the current part 820
contains requirements for record types
that are not specifically identified in
ISO 13485, such as, quality system
record, device master record, design
history file, and device history record.
We are not proposing to retain separate
requirements for these record types as
we believe the elements that comprise
those records are largely required to be
documented by other ISO 13485
Clauses, such as Clause 4.2 and its
subclauses.
1. Proposal for Control of Records
(Proposed § 820.35)
We propose additional requirements
to help ensure that records are
established and maintained in a manner
that is useful to FDA and manufacturers.
First, we propose to include signature
and date requirements for records
subject to Clause 4.2.5 of ISO 13485.
Such requirements provide clarity on
the information FDA needs to ensure
VerDate Sep<11>2014
17:39 Feb 22, 2022
Jkt 256001
validity of records. Records are not
necessarily limited to hardcopy
documents that are physically signed.
Manufacturers can choose to develop
electronic records and electronic
methods for signing and dating such
records, if that best suits their business
practices. Our focus is on whether the
substance of the requirements is met
and not the physicality of the record or
signature methodology. Second, FDA is
proposing specific requirements to
ensure that the information required by
part 803 (21 CFR part 803), Medical
Device Reporting, is captured on certain
records of complaints and servicing
activities. Third, we propose to require
that firms document the Unique Device
Identification (UDI) for each medical
device or batch of medical devices in
accordance with 21 CFR part 830 in its
records. Last, we are proposing to retain
the clarification from the current part
820 (§ 820.180) about confidentiality of
records FDA receives. This reminds
firms that FDA protects such records in
accordance with 21 CFR part 20. If this
rule is finalized as proposed,
manufacturers must meet the
requirements in ISO 13485 Clause 4.2.5
and also meet the requirements of the
eventual § 820.35.
We also note that ISO 13485 Clause
4.2.5 requires that records be ‘‘readily
identifiable and retrievable.’’ FDA
considers this phrase to be substantially
similar to the requirement in current
part 820 (§ 820.180) that records be
‘‘reasonably accessible’’ and ‘‘readily
available.’’ In the 1996 Final Rule, the
Agency explained that ‘‘FDA expects
that such records will be made available
during the course of an inspection. If the
foreign manufacturer maintains records
at remote locations, such records would
be expected to be produced by the next
working day or 2, at the latest. FDA has
clarified that records can be kept at
other than the inspected establishment,
provided that they are made ‘readily
available’ for review and copying.’’ (61
FR 52602 at 52637). FDA will consider
records that a manufacturer makes
available in accordance with this
statement to be ‘‘readily identifiable and
retrievable.’’
2. Proposed Controls for Device
Labeling and Packaging (Proposed
§ 820.45)
Each year, device recalls are initiated
related to product labeling and
packaging. Clause 7.5.1(e) of ISO 13485
states that ‘‘defined operations for
labelling and packaging shall be
implemented.’’ However, ISO 13485
fails to provide additional requirements
for labeling and packaging and does not
specifically address the inspection of
PO 00000
Frm 00047
Fmt 4702
Sfmt 4702
10127
labeling by the manufacturer. Therefore,
FDA proposes to retain requirements
from the current part 820 that would
strengthen controls for labeling and
packaging operations, given that many
device recalls are related to labeling and
packaging. FDA believes that these
provisions will better assure the
manufacture of safe and effective
devices. If this rule is finalized as
proposed, regulated industry must meet
the requirements in ISO 13485 7.5.1 and
the proposed § 820.45.
G. Proposed Conforming Amendments
We are proposing to amend part 4 to
reflect the amendments made to part
820 in incorporating ISO 13485 by
reference. As explained above, part 4
provides a streamlined option to
demonstrate compliance with the
multiple, applicable sets of CGMP
requirements for certain combination
products (i.e., single-entity and copackaged combination products). To do
so, one option part 4 presents for singleentity and co-packaged combination
products with device constituent parts
is to demonstrate compliance with the
requirements of one other applicable set
of requirements along with specified
provisions of part 820 (rather than all
provisions). We are not proposing to
change the underlying activities
required of manufacturers that pursue
this streamlined option. Instead, we are
proposing conforming amendments to
the part 4 references to the
corresponding clauses in ISO 13485. To
that end, we are taking comment on the
proposed conforming amendments and
whether additional changes are
necessary to assure compliance with
part 4. The QS requirements outlined in
part 4 are not fundamentally different
than the corresponding requirements in
ISO 13485.
VI. Proposed Effective Date and
Implementation Strategy
FDA proposes that any final rule
based on this proposal become effective
1 year after the date of publication of the
final rule in the Federal Register. This
approach is intended to provide
adequate time for manufacturers to
make any changes necessary to comply
with the requirements of ISO 13485. We
welcome comment on this approach.
Although this rule does not impact
FDA’s authority to conduct inspections
under section 704 of the FD&C Act, FDA
intends to replace its current inspection
approach for medical devices, the
Quality System Inspection Technique
(QSIT), with an inspection approach
that will be consistent with the
requirements of the proposed part 820
as finalized. Similar to the current QSIT
E:\FR\FM\23FEP1.SGM
23FEP1
10128
Federal Register / Vol. 87, No. 36 / Wednesday, February 23, 2022 / Proposed Rules
inspection approach, these inspections
would involve the collection of
information to support observations
noted during the inspection and those
included on a Form FDA 483, as
appropriate and necessary. FDA
inspections will not result in the
issuance of certificates of conformance
to ISO 13485, nor is FDA developing a
certification program for ISO 13485. In
addition, manufacturers with a
certificate of conformance to ISO 13485
are not exempt from FDA inspections.
If this rule is finalized, FDA intends
to engage in a variety of implementation
activities including, among other
activities, updating information
technology systems, training of
personnel, finalizing the inspection
approach, and revising relevant
regulations and other documents
impacted by this rulemaking.
VII. Preliminary Economic Analysis of
Impacts
We have examined the impacts of the
proposed rule under Executive Order
12866, Executive Order 13563, the
Regulatory Flexibility Act (5 U.S.C.
601–612), and the Unfunded Mandates
Reform Act of 1995 (Pub. L. 104–4).
Executive Orders 12866 and 13563
direct us to assess all costs and benefits
of available regulatory alternatives and,
when regulation is necessary, to select
regulatory approaches that maximize
net benefits (including potential
economic, environmental, public health
and safety, and other advantages;
distributive impacts; and equity). We
believe that this proposed rule is an
economically significant regulatory
action as defined by Executive Order
12866.
The Regulatory Flexibility Act
requires us to analyze regulatory options
that would minimize any significant
impact of a rule on small entities.
Because of the burden of the proposed
rule on very small medical device
establishment (as defined in the
analysis), we propose to certify that the
proposed rule will not have a significant
economic impact on a substantial
number of small entities.
The Unfunded Mandates Reform Act
of 1995 (section 202(a)) requires us to
prepare a written statement, which
includes an assessment of anticipated
costs and benefits, before proposing
‘‘any rule that includes any Federal
mandate that may result in the
expenditure by State, local, and tribal
governments, in the aggregate, or by the
private sector, of $100,000,000 or more
(adjusted annually for inflation) in any
one year.’’ The current threshold after
adjustment for inflation is $158 million,
using the most current (2020) Implicit
Price Deflator for the Gross Domestic
Product. This proposed rule would not
result in an expenditure in any year that
meets or exceeds this amount.
We estimated the benefits in terms of
cost savings. These cost savings are
primarily due to the potential reduction
in redundant effort in compliance of
similar regulations and standards by
medical device establishments. The
annualized costs savings of medical
device establishments are estimated at
approximately $533 million at a 7
percent discount rate, and
approximately $439 million at a 3
percent discount rate. In addition, if
finalized, we believe that there will be
added benefits through quicker access to
newly developed medical devices for
patients, leading to improvement of life
quality for the consumers. The cost of
the proposed rule primarily consists of
a one-time initial expenditure for
updating systems and protocols, and
training personnel for medical device
establishments, which currently do not
comply with ISO 13485. The cost
estimate for these establishments is
annualized at $7.0 million at a 7 percent
discount rate, and approximately $5.8
million at a 3 percent discount rate.
TABLE 2—SUMMARY OF BENEFITS, COSTS AND DISTRIBUTIONAL EFFECTS OF PROPOSED RULE
[Millions $]
Units
Primary
estimate
Low
estimate
High
estimate
$533
439
..................
..................
..................
$267
220
..................
..................
..................
Qualitative ............................................................
6.96
5.73
..................
..................
..................
Transfers:
Federal Annualized Monetized $M/year ..............
Category
Benefits: 1
Annualized Monetized $M/year ...........................
Annualized Quantified ..........................................
Qualitative ............................................................
Costs:
Annualized Monetized $M/year ...........................
khammond on DSKJM1Z7X2PROD with PROPOSALS
Annualized Quantified ..........................................
Year
dollars
Discount
rate
(%)
Period
covered
(years)
$1,332
1,097
..................
..................
..................
2020
2020
..................
..................
..................
7
3
7
3
..................
10
10
..................
..................
..................
6.96
5.73
..................
..................
..................
6.96
5.73
..................
..................
..................
2020
2020
..................
..................
..................
7
3
7
3
..................
10
10
..................
..................
..................
..................
..................
..................
..................
7
..................
..................
..................
..................
..................
3
..................
From/To ...............................................................
From:
Other Annualized Monetized $M/year .................
..................
..................
..................
..................
7
..................
..................
..................
..................
..................
3
..................
From/To ...............................................................
Notes
Benefit are cost savings.
Benefit are cost savings.
To:
From:
To:
Effects:
State, Local or Tribal Government:
Small Business:
Wages:
Growth:
1 Estimated benefits are in terms of cost savings for medical device establishments that conform to the current part 820. Other benefits that are not quantified potentially include quicker delivery and more efficient access to necessary devices for patients, leading to improvement of quality of life for consumers.
Note: All figures are in millions of dollars.
VerDate Sep<11>2014
18:36 Feb 22, 2022
Jkt 256001
PO 00000
Frm 00048
Fmt 4702
Sfmt 4702
E:\FR\FM\23FEP1.SGM
23FEP1
Federal Register / Vol. 87, No. 36 / Wednesday, February 23, 2022 / Proposed Rules
We have developed a comprehensive
Preliminary Economic Analysis of
Impacts that assesses the impacts of the
proposed rule. The full preliminary
analysis of economic impacts is
available in the docket for this proposed
rule (Ref. 11) and at https://
www.fda.gov/about-fda/reports/
economic-impact-analyses-fdaregulations.
VIII. Analysis of Environmental Impact
We have determined under 21 CFR
25.30(j) that this action is of a type that
does not individually or cumulatively
have a significant effect on the human
environment. Therefore, neither an
environmental assessment nor an
environmental impact statement is
required.
IX. Paperwork Reduction Act of 1995
This proposed rule contains
information collection provisions that
are subject to review by the OMB under
the PRA (44 U.S.C. 3501–3521). A
description of these provisions is given
in the Description section with an
estimate of the annual recordkeeping
burden. Included in the estimate is the
time for reviewing instructions,
10129
used by other regulatory authorities.
FDA seeks to accomplish this primarily
by incorporating by ISO 13485. This
rule, if finalized, would harmonize QMS
requirements for devices with
requirements used by other regulatory
authorities.
Description of Respondents:
Respondents to this information
collection are any manufacturers
engaged in the design, manufacture,
packaging, labeling, storage, installation,
or servicing of a finished device,
including, but not limited to,
organizations that perform the functions
of contract sterilization, installation,
relabeling, remanufacturing, repacking,
or specification development, as well as
initial distributors of foreign entities
that perform these functions.
Manufacturers of components or parts
of finished devices may voluntarily use
appropriate provisions of the proposed
regulation as guidance.
Respondents are also manufacturers
of human cells, tissues, and cellular and
tissue-based products (HCT/Ps), as
defined in 21 CFR 1271.3(d), that are
devices.
We estimate the burden of this
collection of information as follows:
searching existing data sources,
gathering and maintaining the data
needed, and completing and reviewing
each collection of information.
FDA invites comments on these
topics: (1) Whether the proposed
collection of information is necessary
for the proper performance of FDA’s
functions, including whether the
information will have practical utility;
(2) the accuracy of FDA’s estimate of the
burden of the proposed collection of
information, including the validity of
the methodology and assumptions used;
(3) ways to enhance the quality, utility,
and clarity of the information to be
collected; and (4) ways to minimize the
burden of the collection of information
on respondents, including through the
use of automated collection techniques,
when appropriate, and other forms of
information technology.
Title: Medical Devices; Quality
Management System; OMB Control
Number 0910–0073—Revision.
Description: FDA is proposing to
revise its device CGMP requirements as
set forth in the QS regulation, codified
in part 820. Through this proposed
rulemaking, FDA intends to converge its
requirements with QMS requirements
TABLE 3—ESTIMATED ONE-TIME RECORDKEEPING BURDEN
Number of
recordkeepers
Activity
Average
burden per
recordkeeping
Total records
Total hours
Total capital
costs
Learn the rule—one-time burden .............
Initial one-time burden for those respondents whose processes do not already
comply with ISO 13485 ........................
20,346
1
20,346
2.6
52,900
$7,600,000
4,445
1
4,445
64
284,480
43,000,000
Total ..................................................
........................
........................
........................
........................
337,380
50,600,000
The currently approved number of
respondents to the collection is 27,074;
however we expect nominal
fluctuations in the number of registered
medical device facilities and have
reduced that number to 20,346 based on
a current review of data and to be
consistent with the Preliminary
Regulatory Impact Analysis for this
proposed rule (see Ref. 11).
khammond on DSKJM1Z7X2PROD with PROPOSALS
Number of
records per
recordkeeper
All medical device establishments
that will be covered under the
rulemaking undergo a one-time burden
to learn the rulemaking. We model the
one-time learning cost as the time
required by medical device
establishments’ regulatory affairs expert
to access and read the proposed rule,
approximately 2.6 hours (rounded). The
average total access and learning cost for
all affected entities is approximately
$7,600,000 (see Ref. 11).
VerDate Sep<11>2014
17:39 Feb 22, 2022
Jkt 256001
In addition to learning the rule
requirements, medical device
establishments that are not in
compliance with ISO 13485 when the
rulemaking is implemented would incur
one-time initial costs related to training
of a regulatory compliance expert,
updating information technology, and
updating documents related to policy
and procedures. The additional
estimated cost burden for medical
device establishments that are not in
compliance with ISO 13485 when the
rulemaking is implemented is
approximately $43,000,000 (see Ref. 11).
The estimated hour burden of these
additional one-time activities is
included under ‘‘Initial one-time burden
for those respondents whose processes
do not already comply with ISO 13485’’
in table 3. In the Preliminary Regulatory
Impact Analysis for this rulemaking, we
PO 00000
Frm 00049
Fmt 4702
Sfmt 4702
estimate there are 4,445 respondents
that do not currently comply with ISO
13485 and that the average burden per
recordkeeping is approximately 64
hours (Ref. 11). Because we do not have
robust data on the number of firms that
currently comply with ISO 13485, we
are using very small domestic medical
device manufacturing establishments to
represent those who will proportionally
bear a greater burden of one-time costs
by the proposed rule. As such, for this
analysis, and as discussed in the
Preliminary Regulatory Impact Analysis,
we assume that very small medical
device manufacturing establishments
currently do not sell their products
abroad and do not comply with ISO
13485 (Ref. 11).
E:\FR\FM\23FEP1.SGM
23FEP1
10130
Federal Register / Vol. 87, No. 36 / Wednesday, February 23, 2022 / Proposed Rules
TABLE 4—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1 2
Number of
recordkeepers
Activity; 21 CFR section
Number of
records per
recordkeeper
Total annual
records
Average
burden per
recordkeeping
Total hours
Quality Management System (proposed § 820.10 and ISO
13485) ..............................................................................
Control of records (proposed § 820.35) ...............................
20,346
20,346
1
1
20,346
20,346
348
2
7,080,408
40,692
Total ..............................................................................
........................
........................
........................
........................
7,121,100
1 There
are no capital costs or operating and maintenance costs associated with this annual collection of information.
have been rounded.
khammond on DSKJM1Z7X2PROD with PROPOSALS
2 Numbers
The current burden associated with
recordkeeping requirements in part 820
is 9,021,752 hours annually. We assume
a commensurate level of burden for the
proposed recordkeeping activities (350
hours for the Average Burden per
Recordkeeping).
As mentioned previously in this
section, we expect nominal fluctuations
in the number of registered medical
device facilities and have reduced that
number from 27,074 to 20,346 based on
a current review of data and to be
consistent with the Preliminary
Regulatory Impact Analysis for this
proposed rule (see Ref. 11). This
adjustment results in a reduction of
1,900,652 total hours annually.
Quality Management System
(proposed § 820.10 and ISO 13485):
Under proposed § 820.10, an
organization subject to proposed part
820 must document a QMS that
complies with the requirements of ISO
13485, as incorporated by reference in
proposed § 820.7, and proposed part
820.
Under proposed § 820.10(c),
manufacturers of class II, class III, and
certain class I devices, as listed in
proposed § 820.10(c)(ii), must comply
with the requirements in Design and
Development, Clause 7.3 and its
Subclauses in ISO 13485. This
amendment does not substantively
change the current recordkeeping
requirement.
Under proposed § 820.10(d),
manufacturers of devices that support or
sustain life, the failure of which to
perform when properly used in
accordance with instructions for use
provided in the labeling can be
reasonably expected to result in a
significant injury, must comply with the
requirements in Traceability for
Implantable Devices, Clause 7.5.9.2 in
ISO 13485, in addition to all other
requirements in this part, as
appropriate. This amendment does not
substantively change the current
recordkeeping requirement.
Control of records (proposed
§ 820.35): In addition to the
requirements of Clause 4.2.5 in ISO
VerDate Sep<11>2014
17:39 Feb 22, 2022
Jkt 256001
13485, Control of Records, the
manufacturer must obtain the signature
for each individual who approved or reapproved the record, and the date of
such approval, on that record and
include the information in certain
records as listed in proposed § 820.35.
In addition to Clause 8.2.2 in ISO
13485, Complaint Handling, the
manufacturer must record the listed
information, at a minimum, for
complaints that must be reported to
FDA under part 803, complaints that a
manufacturer determines must be
investigated, and complaints that the
manufacturer investigated regardless of
those requirements. The reporting
requirements of part 803 are approved
under OMB control number 0910–0437.
Estimated burden for the recordkeeping
requirement in proposed § 820.35(a) is
included as part of the estimate for
‘‘Control of records (proposed § 820.35)’’
in table 4.
In adhering to Clause 7.5.4 in ISO
13485, Servicing Activities, the
manufacturer must record the
information listed in proposed
§ 820.35(b), at a minimum, for servicing
activities.
Under proposed § 820.35(c), in
addition to the requirements of Clauses
7.5.1, 7.5.8, and 7.5.9 of ISO 13485, the
UDI must be recorded for each medical
device or batch of medical devices. The
estimated recordkeeping burden
associated with UDI is included as part
of the estimate for ‘‘Control of records
(proposed § 820.35)’’ in table 4.
Because the records required by
proposed § 820.35 should be readily
available to the respondents, we
estimate the average burden per
response for proposed § 820.35 to be no
more than 2 hours. This estimate is in
addition to the requirements of the
applicable ISO 13485 Clauses, the
burden for which is included under
‘‘Quality Management System (proposed
§ 820.10 and ISO 13485)’’ in table 4.
Device labeling and packaging
controls (proposed § 820.45): In addition
to the requirements of Clause 7.5.1 of
ISO 13485, Control of production and
service provision, manufacturers must
PO 00000
Frm 00050
Fmt 4702
Sfmt 4702
ensure labeling and packaging has been
examined for accuracy prior to release
or storage (§ 820.45(a)), the release of the
labeling for use must be documented in
accordance with Clause 4.2.5 of ISO
13485 (§ 820.45(b)), and results of the
labeling inspection in proposed
§ 820.45(c) must be documented in
accordance with Clause 4.2.5 of ISO
13485. The estimated recordkeeping
burden for ISO 13485, Clause 4.2.5, is
part of the estimate for ‘‘Quality
Management System (proposed § 820.10
and ISO 13485)’’ in table 4. There is no
additional hour burden associated with
proposed § 820.45.
To ensure that comments on
information collection are received,
OMB recommends that written
comments be submitted through https://
www.reginfo.gov/public/do/PRAMain
(see ADDRESSES). All comments should
be identified with the title of the
information collection.
In compliance with the PRA (44
U.S.C. 3501, et seq.), we have submitted
the information collection provisions of
this proposed rule to OMB for review.
These information collection
requirements will not be effective until
FDA publishes a final rule, OMB
approves the information collection
requirements, and the rule goes into
effect. FDA will announce OMB
approval of these requirements in the
Federal Register.
X. Federalism
We have analyzed this proposed rule
in accordance with the principles set
forth in Executive Order 13132. We
have determined that this proposed rule
does not contain policies that have
substantial direct effects on the States,
on the relationship between the
National Government and the States, or
on the distribution of power and
responsibilities among the various
levels of government. Accordingly, we
conclude that the rule does not contain
policies that have federalism
implications as defined in the Executive
Order and, consequently, a federalism
summary impact statement is not
required.
E:\FR\FM\23FEP1.SGM
23FEP1
Federal Register / Vol. 87, No. 36 / Wednesday, February 23, 2022 / Proposed Rules
XI. Consultation and Coordination With
Indian Tribal Governments
We have analyzed this proposed rule
in accordance with the principles set
forth in Executive Order 13175. We
have tentatively determined that the
rule does not contain policies that
would have a substantial direct effect on
one or more Indian Tribes, on the
relationship between the Federal
Government and Indian Tribes, or on
the distribution of power and
responsibilities between the Federal
Government and Indian Tribes. The
Agency solicits comments from tribal
officials on any potential impact on
Indian Tribes from this proposed action.
khammond on DSKJM1Z7X2PROD with PROPOSALS
XII. References
The following references marked with
an asterisk (*) are on display at the
Dockets Management Staff (see
ADDRESSES) and are available for
viewing by interested persons between
9 a.m. and 4 p.m., Monday through
Friday; they also are available
electronically at https://
www.regulations.gov. References
without asterisks are not on public
display at https://www.regulations.gov
because they have copyright restriction.
Some may be available at the website
address, if listed. References without
asterisks are available for viewing only
at the Dockets Management Staff. FDA
has verified the website addresses, as of
the date this document publishes in the
Federal Register, but websites are
subject to change over time.
* 1. ISO 13485:2016, ‘‘Medical devices—
Quality management systems—
Requirements for regulatory purposes,’’
Third Edition, March 1, 2016.
* 2. FDA, ‘‘Regulations Establishing Good
Manufacturing Practices for the
Manufacture, Packing, Storage, and
Installation of Medical Devices.’’ Federal
Register, 43: 31508–31532, July 21, 1978.
3. ISO 13485:1996, ‘‘Quality systems—
Medical devices—Particular
requirements for the application of ISO
9001,’’ December 1996 (withdrawn).
(Referenced at: https://www.iso.org/
standard/22098.html.)
4. ISO 9001:1994, ‘‘Quality Systems—Model
for Quality Assurance in Design,
Development, Production, Installation,
and Servicing,’’ June 1994 (withdrawn).
(Referenced at: https://www.iso.org/
standard/25946.html.)
* 5. FDA, ‘‘Medical Device Single Audit
Program (MDSAP).’’ (Available at:
https://www.fda.gov/medical-devices/
cdrh-international-programs/medicaldevice-single-audit-program-mdsap.)
6. Global Harmonization Task Force.
Guidance document, ‘‘Implementation of
Risk Management Principles and
Activities Within a Quality Management
System,’’ May 20, 2005. (Available at:
https://www.imdrf.org/docs/ghtf/final/
VerDate Sep<11>2014
17:39 Feb 22, 2022
Jkt 256001
sg3/technical-docs/ghtf-sg3-n15r8-riskmanagement-principles-qms050520.pdf.)
7. ISO 14971, ‘‘Medical Devices—
Application of Risk Management to
Medical Devices.’’ (Available at: https://
www.iso.org/standard/72704.html.)
* 8. ‘‘Guidance for Industry, Third Parties
and Food and Drug Administration Staff:
Medical Device ISO 13485:2003
Voluntary Audit Report Submission Pilot
Program’’ effective June 5, 2012. Federal
Register, March 19, 2012 (Available at:
https://www.federalregister.gov/citation/
77-FR-16036).
9. International Medical Device Regulators
Forum, https://www.imdrf.org/.
10. International Standard, ISO 9000
‘‘Quality Management Systems—
Fundamentals and Vocabulary,’’ ISO
9000:2015. (Available at: ISO
9000:2015(en), Quality management
systems—Fundamentals and
vocabulary.)
* 11. ‘‘Preliminary Regulatory Impact
Analysis, Initial Regulatory Flexibility
Analysis, and Unfunded Mandates
Reform Act Analysis; Medical Devices;
Quality System Regulation
Amendments.’’ (Available at: https://
www.fda.gov/about-fda/reports/
economic-impact-analyses-fdaregulations.)
List of Subjects
21 CFR Part 4
Biologics, Drugs, Human cells and
tissue-based products, Incorporation by
reference, Medical devices.
21 CFR Part 820
Incorporation by reference, Medical
devices, Reporting and recordkeeping
requirements.
Therefore, under the Federal Food,
Drug, and Cosmetic Act and under the
authority delegated to the Commissioner
of Food and Drugs, it is proposed that
21 CFR parts 4 and 820 be amended as
follows:
PART 4—REGULATION OF
COMBINATION PRODUCTS
1. The authority citation for part 4
continues to read as follows:
■
Authority: 21 U.S.C. 321, 331, 351, 352,
353, 355, 360, 360b–360f, 360h–360j, 360l,
360hh–360ss, 360aaa–360bbb, 371(a), 372–
374, 379e, 381, 383, 394; 42 U.S.C. 216, 262,
263a, 264, 271.
2. In § 4.2,
a. Revise the definition of ‘‘Device’’;
and
■ b. Remove the definition of ‘‘QS
regulation’’, and add in its place a
definition for ‘‘QMSR for devices’’.
The revision and addition read as
follows:
■
■
§ 4.2 How does FDA define key terms and
phrases in this subpart?
*
PO 00000
*
*
Frm 00051
*
Fmt 4702
*
Sfmt 4702
10131
Device has the meaning set forth in
§ 3.2(f) of this chapter. A device that is
a constituent part of a combination
product is considered a finished device
within the meaning of the Quality
Management System Regulation
(QMSR).
*
*
*
*
*
QMSR for devices refers to the
requirements under part 820 of this
chapter.
*
*
*
*
*
■ 3. In § 4.4, revise paragraph (b)(1) and
the introductory text to paragraph (b)(2)
and add paragraph (f) to read as follows:
§ 4.4 How can I comply with these current
good manufacturing practice requirements
for a co-packaged or single-entity
combination product?
*
*
*
*
*
(b) * * *
(1) If the combination product
includes a device constituent part and a
drug constituent part, and the current
good manufacturing practice operating
system has been shown to comply with
the drug CGMPs, the following clauses
of ISO 13485 within the QMSR
requirements for devices must also be
shown to have been satisfied; upon
demonstration that these requirements
have been satisfied, no additional
showing of compliance with respect to
the QMSR requirements for devices
need be made:
(i) Management responsibility. Clause
4.1, Clause 5 and its subclauses and
Clause 6.1 of ISO 13485;
(ii) Design and development. Clause
7.3 and its subclauses of ISO 13485;
(iii) Purchasing. Clause 7.4 and its
subclauses of ISO 13485;
(iv) Improvement. Clause 8.4, Clause
8.5 and its subclauses of ISO 13485;
(v) Installation activities. Clause 7.5.3
of ISO 13485; and
(vi) Servicing activities. Clause 7.5.4
of ISO 13485 and § 820.35(b).
(2) If the combination product
includes a device constituent part and a
drug constituent part, and the current
good manufacturing practice operating
system has been shown to comply with
the QMS requirements for devices, the
following provisions of the drug CGMPs
must also be shown to have been
satisfied; upon demonstration that these
requirements have been satisfied, no
additional showing of compliance with
respect to the drug CGMPs need be
made:
*
*
*
*
*
(f) Certain material is incorporated by
reference into this section with the
approval of the Director of the Federal
Register under 5 U.S.C. 552(a) and 1
CFR part 51. All approved material is
available for inspection at the Food and
E:\FR\FM\23FEP1.SGM
23FEP1
10132
Federal Register / Vol. 87, No. 36 / Wednesday, February 23, 2022 / Proposed Rules
Drug Administration, Dockets
Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240–
402–7500, and at the National Archives
and Records Administration (NARA).
For information on the availability of
this material at NARA, call 202–741–
6030, email fr.inspection@nara.gov, or
go to www.archives.gov/federal-register/
cfr/ibr-locations.html. It is available
from the following source(s):
(1) The International Organization for
Standardization (ISO), BIBC II, Chemin
de Blandonnet 8, CP 401, 1214 Vernier,
Geneva, Switzerland; +41–22–749–01–
11; customerservice@iso.org, https://
www.iso.org/store.html.
(i) ISO 13485, ‘‘Medical devices—
Quality management systems—
Requirements for regulatory purposes,’’
third edition, dated March 2016,
(ii) [Reserved]
(2) [Reserved]
■ 4. Revise part 820 to read as follows:
PART 820—QUALITY MANAGEMENT
SYSTEM REGULATION
Subpart A—General Provisions
Sec.
820.1 Scope.
820.3 Definitions.
820.5 [Reserved]
820.7 Incorporation by reference.
820.10 Requirements for a quality
management system.
820.15 Clarification of concepts.
Subpart B—Supplemental Provisions
820.20–820.30 [Reserved]
820.35 Control of records.
820.40 [Reserved]
820.45 Device labeling and packaging
controls.
Subparts C–O—[Reserved]
Authority: 21 U.S.C. 351, 352, 360, 360c,
360d, 360e, 360h, 360i, 360j, 360l, 371, 374,
381, 383; 42 U.S.C. 216, 262, 263a, 264.
Subpart A—General Provisions
khammond on DSKJM1Z7X2PROD with PROPOSALS
§ 820.1
Scope.
(a) Applicability. Current good
manufacturing practice (CGMP)
requirements are set forth in this quality
management system regulation (QMSR).
The requirements in this part govern the
methods used in, and the facilities and
controls used for, the design,
manufacture, packaging, labeling,
storage, installation, and servicing of all
finished devices intended for human
use. The requirements in this part are
intended to assure that finished devices
will be safe and effective and otherwise
in compliance with the Federal Food,
Drug, and Cosmetic Act. Any
manufacturers engaged in the design,
manufacture, packaging, labeling,
storage, installation, or servicing of a
VerDate Sep<11>2014
17:39 Feb 22, 2022
Jkt 256001
finished device must establish and
maintain a quality management system
that is appropriate for its specific
device(s). Manufacturers subject to this
part include, but are not limited to,
manufacturers that perform the
functions of contract sterilization,
installation, relabeling,
remanufacturing, repacking, or
specification development, as well as
initial distributors of foreign entities
that perform these functions. If a
manufacturer engages in only some
operations subject to the requirements
in this part, and not in others, that
manufacturer need only comply with
those requirements applicable to the
operations in which it is engaged.
(1) Finished devices. The provisions
of this part shall apply to any finished
device, as defined in this part, intended
for human use, that is manufactured,
imported, or offered for import in any
State or Territory of the United States,
the District of Columbia, or the
Commonwealth of Puerto Rico.
(2) Components or parts. The
provisions of this part do not apply to
manufacturers of components or parts of
finished devices, but such
manufacturers are encouraged to
consider provisions of this regulation as
appropriate.
(3) Blood and blood components. The
provisions of this part do not apply to
manufacturers of blood and blood
components used for transfusion or for
further manufacturing. Such
manufacturers are subject to subchapter
F of this chapter.
(4) HCT/Ps. The provisions of this
part apply to manufacturers of human
cells, tissues, and cellular and tissuebased products (HCT/Ps), as defined in
§ 1271.3(d) of this chapter, that are
devices (subject to premarket review or
notification, or exempt from
notification, under an application
submitted under the device provisions
of the Federal Food, Drug, and Cosmetic
Act or under a biological product
license application under section 351 of
the Public Health Service Act). HCT/Ps
regulated as devices are also subject to
the donor-eligibility requirements set
forth in part 1271, subpart C of this
chapter and applicable current good
tissue practice requirements in part
1271, subpart D of this chapter. In the
event of a conflict between applicable
regulations in part 1271 and in other
parts of this chapter, the regulation
specifically applicable to the device in
question shall supersede the more
general regulation.
(b) Conflicts with other requirements
under the Federal Food, Drug, and
Cosmetic Act. The QMSR for devices in
this part supplements regulations in
PO 00000
Frm 00052
Fmt 4702
Sfmt 4702
other parts of this chapter except where
explicitly stated otherwise. In the event
of a conflict between applicable
regulations in this part and in other
parts of this chapter, the regulations
specifically applicable to the device in
question shall supersede the more
generally applicable regulations to the
extent they conflict. Moreover, to the
extent that any clauses of ISO 13485
(incorporated by reference, see § 820.7)
conflict with any provisions of the
Federal Food, Drug, and Cosmetic Act
and/or its other implementing
regulations, the Federal Food, Drug, and
Cosmetic Act and/or its other
implementing regulations will control.
(c) Foreign manufacturers. If it
appears that an owner, operator, or
agent of any factory, warehouse, or
establishment who offers devices for
import into the United States delays,
denies, or limits an inspection, or
refuses to permit entry or inspection of
the foreign facility for the purpose of
determining compliance with this part,
or the methods used in, and the
facilities and controls used for, the
manufacture, packing, storage,
installation, processing, or held in such
factory, warehouse, or establishment
that are offered for import into the
United States do not conform to the
requirements of section 520(f) of the
Federal Food, Drug, and Cosmetic Act
and this part, then the devices
manufactured at that facility are
adulterated under section 501(h) or (j) of
the Federal Food, Drug, and Cosmetic
Act and will be refused admission to the
United States under section 801(a) of
the Federal Food, Drug, and Cosmetic
Act.
(d) Exemptions or variances. (1) A
manufacturer subject to any requirement
under section 520(f)(1) of the Federal
Food, Drug, and Cosmetic Act,
including any requirements under this
part, may petition for an exemption or
variance from such requirement in
accordance with section 520(f)(2) of the
Federal Food, Drug, and Cosmetic Act.
Petitions for an exemption or variance
shall be submitted in accordance with
the procedures set forth in § 10.30 of
this chapter.
(2) FDA may initiate and grant a
variance from any requirement(s) in this
part when the Agency determines that
such variance is in the best interest of
the public health. Such variance will
remain in effect only so long as there
remains a public health need for the
device and the device would not likely
be made sufficiently available without
the variance.
E:\FR\FM\23FEP1.SGM
23FEP1
Federal Register / Vol. 87, No. 36 / Wednesday, February 23, 2022 / Proposed Rules
khammond on DSKJM1Z7X2PROD with PROPOSALS
§ 820.3
Definitions.
The definitions in ISO 13485
(incorporated by reference, see § 820.7)
apply to this part, except as specified in
paragraph (b) of this section, and do not
affect the meaning of similar terms
defined in this title.
(a) The following terms are necessary
for the purposes of this part and do not
appear in ISO 13485:
Component means any raw material,
substance, piece, part, software,
firmware, labeling, or assembly that is
intended to be included as part of the
finished, packaged, and labeled device.
Customer means persons or
organizations, including users, that
could or do receive a product or a
service that is intended for or required
by this person or organization. A
customer can be internal or external to
the organization.
Design validation means establishing
by objective evidence that device
specifications conform with user needs
and intended use(s).
Federal Food, Drug, and Cosmetic Act
means the Federal Food, Drug, and
Cosmetic Act, 21 U.S.C. 321 et seq., as
amended.
Finished device means any device or
accessory to any device that is suitable
for use or capable of functioning,
whether or not it is packaged, labeled,
or sterilized.
Human cell, tissue, or cellular or
tissue-based product (HCT/P) regulated
as a device means an HCT/P as defined
in § 1271.3(d) of this chapter that does
not meet the criteria in § 1271.10(a) of
this chapter and that is also regulated as
a device.
Nonconformity means the
nonfulfillment of a specified
requirement.
Process agent means any material or
substance used in or used to facilitate
the manufacturing process, a
concomitant constituent, or a byproduct
constituent produced during the
manufacturing process, which is present
in or on the finished device as a residue
or impurity not by design or intent of
the manufacturer.
Process validation means establishing
by objective evidence that a process
consistently produces a result or
product meeting its predetermined
specifications.
Remanufacturer means any person
who processes, conditions, renovates,
repackages, restores, or does any other
act to a finished device that significantly
changes the finished device’s
performance or safety specifications, or
intended use.
Rework means action taken on a
nonconforming product so that it will
VerDate Sep<11>2014
17:39 Feb 22, 2022
Jkt 256001
fulfill the specified requirements before
it is released for distribution.
Top management means those senior
employees of a manufacturer who have
the authority to establish or make
changes to the manufacturer’s quality
policy and quality management system.
Verification means confirmation by
examination and provision of objective
evidence that specified requirements
have been fulfilled.
(b) All definitions in section 201 of
the Federal Food, Drug, and Cosmetic
Act shall apply to the regulation of
quality management systems under this
part and shall supersede the correlating
terms and definitions in ISO 13485 (e.g.,
the definitions of device and labeling in
sections 201(h) and (m) of the Federal
Food, Drug, and Cosmetic Act apply to
this part and supersede the definitions
for the correlating terms in ISO 13485
(labelling and medical device)). In
addition, the following terms and
definitions supersede the correlating
term and definition in ISO 13485:
Manufacturer means any person who
designs, manufactures, fabricates,
assembles, or processes a finished
device. Manufacturer includes, but is
not limited to, those who perform the
functions of contract sterilization,
installation, relabeling,
remanufacturing, repacking, or
specification development, and initial
distributors of foreign entities
performing these functions.
Product means components, process
agents, in-process devices, finished
devices, and returned devices.
§ 820.5
[Reserved]
§ 820.7
Incorporation by reference.
Certain material is incorporated by
reference into this part with the
approval of the Director of the Federal
Register under 5 U.S.C. 552(a) and 1
CFR part 51. All approved material is
available for inspection at the Food and
Drug Administration, Dockets
Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240–
402–7500, and at the National Archives
and Records Administration (NARA).
For information on the availability of
this material at NARA, call 202–741–
6030, email fr.inspection@nara.gov, or
go to www.archives.gov/federal-register/
cfr/ibr-locations.html. It is available
from the following source(s):
(a) The International Organization for
Standardization (ISO), BIBC II, Chemin
de Blandonnet 8, CP 401, 1214 Vernier,
Geneva, Switzerland; +41–22–749–01–
11; customerservice@iso.org, https://
www.iso.org/store.html.
(1) ISO 13485, ‘‘Medical devices—
Quality management systems—
PO 00000
Frm 00053
Fmt 4702
Sfmt 4702
10133
Requirements for regulatory purposes,’’
third edition, dated March 2016; IBR
approved for §§ 820.1; 820.3; 820.10;
820.15; 820.35; 820.45.
(2) [Reserved]
(b) [Reserved]
§ 820.10 Requirements for a quality
management system.
A manufacturer subject to this part as
described by § 820.1(a) must:
(a) Document. Document a quality
management system that complies with
the requirements of ISO 13485
(incorporated by reference, see § 820.7)
and this part; and
(b) Applicable regulatory
requirements. Comply, as appropriate,
with the other applicable regulatory
requirements in this title, including, but
not limited to the following, to fully
comply with the listed ISO 13485
Clause:
(1) For Clause 7.5.8 in ISO 13485,
Identification, the manufacturer must
document a system to assign unique
device identification to the medical
device in accordance with the
requirements of part 830.
(2) For Clause 7.5.9.1 in ISO 13485,
Traceability—General, the manufacturer
must document procedures for
traceability in accordance with the
requirements of part 821, if applicable.
(3) For Clause 8.2.3 in ISO 13485,
Reporting to regulatory authorities, the
manufacturer must notify FDA of
complaints that meet the reporting
criteria of part 803 of this chapter.
(4) For Clauses 7.2.3, 8.2.3, and 8.3.3,
advisory notices shall be handled in
accordance with the requirements of
part 806.
(c) Design and Development.
Manufacturers of class II, class III, and
those class I devices listed below must
comply with the requirements in Design
and Development, Clause 7.3 and its
Subclauses in ISO 13485. The class I
devices are as follows:
(1) Devices automated with computer
software; and
(2) The devices listed in the following
table:
TABLE 1 TO PARAGRAPH (c)(2)
Section
868.6810
878.4460
880.6760
892.5650
Device
..
..
..
..
892.5740 ..
Catheter, Tracheobronchial Suction.
Glove, Non-powdered Surgeon’s.
Restraint, Protective.
System, Applicator, Radionuclide,
Manual.
Source, Radionuclide Teletherapy.
(d) Devices that support or sustain
life. Manufacturers of devices that
support or sustain life, the failure of
which to perform when properly used
in accordance with instructions for use
E:\FR\FM\23FEP1.SGM
23FEP1
10134
Federal Register / Vol. 87, No. 36 / Wednesday, February 23, 2022 / Proposed Rules
provided in the labeling can be
reasonably expected to result in a
significant injury, must comply with the
requirements in Traceability for
Implantable Devices, Clause 7.5.9.2 in
ISO 13485, in addition to all other
requirements in this part, as
appropriate.
(e) Enforcement. The failure to
comply with any applicable
requirement in this part renders a
device adulterated under section 501(h)
of the Federal Food, Drug, and Cosmetic
Act. Such a device, as well as any
person responsible for the failure to
comply, is subject to regulatory action.
§ 820.15
Clarification of concepts.
Manufacturers subject to this part
shall construe the following terms in
ISO 13485 (incorporated by reference,
see § 820.7) as follows:
(a) Organization shall have the
meaning of ‘‘manufacturers’’ as defined
in this part.
(b) Safety and performance shall have
the meaning of ‘‘safety and
effectiveness’’ for the purposes of this
part. The phrase ‘‘safety and
performance’’ does not relieve a
manufacturer from any obligation to
implement controls or other measures
that provide reasonable assurance of
safety and effectiveness.
(c) Validation of processes shall have
the meaning of ‘‘process validation’’ as
defined in this part.
Subpart B—Supplemental Provisions
§ 820.20–§ 820.30
khammond on DSKJM1Z7X2PROD with PROPOSALS
§ 820.35
[Reserved]
Control of records.
In addition to the requirements of
Clause 4.2.5 in ISO 13485 (incorporated
by reference, see § 820.7), Control of
Records, the manufacturer must obtain
the signature for each individual who
approved or re-approved the record, and
the date of such approval, on that record
and include the below information in
certain records as follows:
(a) Records of complaints. In addition
to Clause 8.2.2 in ISO 13485, Complaint
Handling, the manufacturer must record
the following information, at a
minimum, for complaints that must be
reported to FDA under part 803 of this
chapter, complaints that a manufacturer
determines must be investigated, and
complaints that the manufacturer
investigated regardless of those
requirements:
(1) The name of the device;
(2) The date the complaint was
received;
(3) Any unique device identifier (UDI)
or universal product code (UPC), and
any other device identification(s);
VerDate Sep<11>2014
17:39 Feb 22, 2022
Jkt 256001
(4) The name, address, and phone
number of the complainant;
(5) The nature and details of the
complaint;
(6) Any corrective action taken; and
(7) Any reply to the complainant.
(b) Records of servicing activities. In
adhering to Clause 7.5.4 in ISO 13485,
Servicing Activities, the manufacturer
must record the following information,
at a minimum, for servicing activities:
(1) The name of the device serviced;
(2) Any unique device identifier (UDI)
or universal product code (UPC), and
any other device identification(s);
(3) The date of service;
(4) The individual(s) who serviced the
device;
(5) The service performed; and
(6) Any test and inspection data.
(c) Unique device identification. In
addition to the requirements of Clauses
7.5.1, 7.5.8, and 7.5.9 in ISO 13485, the
UDI must be recorded for each medical
device or batch of medical devices.
(d) Confidentiality. Records deemed
confidential by the manufacturer may be
marked to aid FDA in determining
whether information may be disclosed
under the public information regulation
in part 20 of this chapter.
§ 820.40
[Reserved]
§ 820.45 Device labeling and packaging
controls.
In addition to the requirements of
Clause 7.5.1 of ISO 13485 (incorporated
by reference, see § 820.7), Control of
production and service provision, each
manufacturer must establish and
maintain procedures that provide a
detailed description of the activities to
ensure the integrity, inspection, storage,
and operations for labeling and
packaging, during the customary
conditions of processing, storage,
handling, distribution, and where
appropriate, use of the device.
(a) The manufacturer must ensure
labeling and packaging has been
examined for accuracy prior to release
or storage, where applicable, to include
the following:
(1) The correct unique device
identifier (UDI) or universal product
code (UPC), or any other device
identification(s);
(2) Expiration date;
(3) Storage instructions;
(4) Handling instructions; and
(5) Any additional processing
instructions.
(b) The release of the labeling for use
must be documented in accordance with
Clause 4.2.5 of ISO 13485.
(c) The manufacturer must ensure
labeling and packaging operations have
been established and maintained to
PO 00000
Frm 00054
Fmt 4702
Sfmt 4702
prevent errors, including, but not
limited to, inspection of the labeling
and packaging immediately before use
to assure that all devices have correct
labeling and packaging, as specified in
the medical device file. Results of such
labeling inspection must be documented
in accordance with Clause 4.2.5 of ISO
13485.
Subparts C–O—[Reserved]
Dated: February 8, 2022.
Janet Woodcock,
Acting Commissioner of Food and Drugs.
[FR Doc. 2022–03227 Filed 2–22–22; 8:45 am]
BILLING CODE 4164–01–P
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Parts 60 and 63
[EPA–HQ–OAR–2021–0619; FRL–8602–01–
OAR]
RIN 2060–AV43
Review of Standards of Performance
for Lead Acid Battery Manufacturing
Plants and National Emission
Standards for Hazardous Air Pollutants
for Lead Acid Battery Manufacturing
Area Sources Technology Review
Environmental Protection
Agency (EPA).
ACTION: Proposed rule.
AGENCY:
This proposal presents the
results of the Environmental Protection
Agency’s (EPA’s) review of the New
Source Performance Standards (NSPS)
for Lead Acid Battery Manufacturing
Plants and the technology review (TR)
for the National Emission Standards for
Hazardous Air Pollutants (NESHAP) for
Lead Acid Battery Manufacturing Area
Sources as required under the Clean Air
Act (CAA). The EPA is proposing
revised lead (Pb) emission limits for grid
casting, paste mixing, and lead
reclamation operations for both the area
source NESHAP (for new and existing
sources) and under a new NSPS subpart
(for lead acid battery facilities that begin
construction, reconstruction, or
modification after February 23, 2022). In
addition, the EPA is proposing the
following amendments for both the area
source NESHAP (for new and existing
sources) and under a new NSPS subpart
(for lead acid battery facilities that begin
construction, reconstruction or
modification after February 23, 2022):
Performance testing once every 5 years
to demonstrate compliance; work
practices to minimize emissions of
fugitive lead dust; increased inspection
SUMMARY:
E:\FR\FM\23FEP1.SGM
23FEP1
Agencies
[Federal Register Volume 87, Number 36 (Wednesday, February 23, 2022)]
[Proposed Rules]
[Pages 10119-10134]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2022-03227]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 4 and 820
[Docket No. FDA-2021-N-0507]
RIN 0910-AH99
Medical Devices; Quality System Regulation Amendments
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
proposing to amend the device current good manufacturing practice
(CGMP) requirements of the Quality System (QS) Regulation to align more
closely with the international consensus standard for devices by
converging with the quality management system (QMS) requirements used
by other regulatory authorities from other jurisdictions (i.e., other
countries). We propose to do so through incorporating by reference an
international standard specific for device quality management systems
set by the International Organization for Standardization (ISO), the
2016 edition of ISO 13485 (ISO 13485). Through this rulemaking we also
propose additional requirements to align with existing requirements in
the Federal Food, Drug, and Cosmetic Act (FD&C Act) and its
implementing regulations, and make conforming edits to the Code of
Federal Regulations (CFR) to clarify the device CGMP requirements for
combination products. This action, if finalized, will continue our
efforts to align our regulatory framework with that used by other
regulatory authorities to promote consistency in the regulation of
devices and provide timelier introduction of safe, effective, high-
quality devices for patients.
DATES: Submit either electronic or written comments on the proposed
rule by May 24, 2022. Submit written comments (including
recommendations) on the collection of information under the Paperwork
Reduction Act of 1995 (PRA) by March 25, 2022.
ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. Electronic comments
must be submitted on or before May 24, 2022. The https://www.regulations.gov electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of May 24, 2022. Comments received
by mail/hand delivery/courier (for written/paper submissions) will be
considered timely if they are postmarked or the delivery service
acceptance receipt is on or before that date.
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on https://www.regulations.gov.
If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2021-N-0507 for ``Medical Devices; Quality System Regulation
Amendments.'' Received comments, those filed in a timely manner (see
ADDRESSES), will be placed in the docket and, except for those
submitted as ``Confidential Submissions,'' publicly viewable at https://www.regulations.gov or at the Dockets Management Staff between 9 a.m.
and 4 p.m., Monday through Friday, 240-402-7500.
Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts
[[Page 10120]]
and/or go to the Dockets Management Staff, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852, 240-402-7500.
Submit comments on information collection under the PRA to the
Office of Management and Budget (OMB) at https://www.reginfo.gov/public/do/PRAMain. Find this particular information collection by
selecting ``Currently under Review--Open for Public Comments'' or by
using the search function. The title of this proposed collection is
``Medical Devices; Quality Management System.''
FOR FURTHER INFORMATION CONTACT: With regard to the proposed rule:
Keisha Thomas or Melissa Torres, Center for Devices and Radiological
Health, Food and Drug Administration, 10903 New Hampshire Ave., Silver
Spring, MD 20903, 301-796-2001, [email protected].
With regard to the information collection: Amber Sanford, Office of
Operations, Food and Drug Administration, Three White Flint North 10A-
12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-8867,
[email protected].
SUPPLEMENTARY INFORMATION:
Table of Contents
I. Executive Summary
A. Purpose of the Proposed Rule
B. Summary of the Major Provisions of the Proposed Rule
C. Legal Authority
D. Costs and Benefits
II. Table of Abbreviations/Commonly Used Acronyms in This Document
III. Background
A. Introduction
B. Need for the Regulation
C. FDA's Current Regulatory Framework
D. History of the Rulemaking
E. Incorporation by Reference
IV. Legal Authority
V. Description of the Proposed Rule
A. Scope (Proposed Sec. 820.1)
B. Definitions (Proposed Sec. 820.3)
C. Incorporation by Reference (Proposed Sec. 820.7)
D. Proposed Requirements for a Quality Management System
(Proposed Sec. 820.10)
E. Proposed Clarification of Concepts (Proposed Sec. 820.15)
F. Proposed Supplementary Provisions (Proposed Subpart B)
G. Proposed Conforming Amendments
VI. Proposed Effective Date and Implementation Strategy
VII. Preliminary Economic Analysis of Impacts
VIII. Analysis of Environmental Impact
IX. Paperwork Reduction Act of 1995
X. Federalism
XI. Consultation and Coordination With Indian Tribal Governments
XII. References
I. Executive Summary
A. Purpose of the Proposed Rule
FDA has historically recognized the benefits of harmonization with
other regulatory authorities and over time has taken a number of
actions to promote consistency with its regulatory counterparts. As
part of such activities, FDA is proposing to revise its device CGMP
requirements as set forth in the QS regulation, codified in part 820
(21 CFR part 820). Through this proposed rulemaking, FDA intends to
converge its requirements with quality management system requirements
used by other regulatory authorities. FDA seeks to accomplish this
primarily by incorporating by reference the 2016 edition of
International Organization for Standardization (ISO) 13485 (ISO 13485).
This rule, if finalized, would harmonize quality management system
requirements for devices with requirements used by other regulatory
authorities. Such harmonization should provide patients more efficient
access to necessary devices, leading to improvement of life quality of
the consumers.
B. Summary of the Major Provisions of the Proposed Rule
We are proposing to amend the current part 820, primarily, through
incorporating by reference the quality management system requirements
of ISO 13485. We have determined that the requirements in ISO 13485
are, when taken in totality, substantially similar to the requirements
of the current part 820, providing a similar level of assurance in a
firm's quality management system and ability to consistently
manufacture devices that are safe and effective and otherwise in
compliance with the FD&C Act. As such, we propose to withdraw the
requirements in the current part 820, except that we propose to retain
the scope of the current regulation and to retain and modify, as
indicated below, a number of the definitions in the current part 820.
We are also proposing to amend the title of the regulation and add FDA-
specific requirements and provisions that clarify certain concepts used
in ISO 13485. The result will be referred to as the Quality Management
System Regulation (QMSR). These additions will ensure that the
incorporation by reference of ISO 13485 does not create inconsistencies
with other applicable FDA requirements. FDA is also proposing
conforming edits to part 4 (21 CFR part 4) to clarify the device QMS
requirements for combination products. These edits would not impact the
CGMP requirements for combination products. The rule, if finalized,
would converge QS regulation with the QMS requirements of ISO 13485,
while continuing to provide the same level of assurance of safety and
effectiveness under the FD&C Act and its implementing regulations. The
Agency solicits comments on specific subject areas related to this
proposed rule that FDA should consider in seeking to converge U.S.
requirements with requirements used by other regulatory authorities in
ways that are consistent with FDA's authority under the FD&C Act.
C. Legal Authority
We are proposing to issue this rule under the same authority that
FDA initially invoked to issue the current part 820 and combination
product regulations, as well as the general administrative provisions
of the FD&C Act (21 U.S.C. 351, 352, 360, 360c, 360d, 360e, 360h, 360i,
360j, 360l, 371, 374, 381, 383; 42 U.S.C. 216, 262, 263a, 264).
D. Costs and Benefits
We estimate that the proposed rule will result in an annualized net
cost savings (benefits) of approximately $439 million over 10 years at
a discount rate of 3 percent. When we assume a discount rate of 7
percent, the annualized net cost savings are approximately $533
million. The benefit of the proposed rule is estimated in terms of
reduction of compliance effort, and consequently cost savings, for
medical device establishments that currently comply with both
standards. The costs of the rule include initial training of personnel,
and information technology and documentation update for the medical
device industry and the FDA. There is also a one-time cost of reading
and learning the rule for the medical device establishments.
If finalized, in addition to the cost savings to the medical device
industry, the qualitative benefits of the proposed rule include quicker
access to newly developed medical devices for patients, leading to
improvement of life quality of the consumers. The proposed rule, if
finalized, would also align the current part 820 with other related
programs potentially contributing to additional cost savings.
II. Table of Abbreviations/Commonly Used Acronyms in This Document
[[Page 10121]]
------------------------------------------------------------------------
Abbreviation/acronym What it means
------------------------------------------------------------------------
ANSI......................... American National Standards Institute.
CD........................... Committee Draft.
CFR.......................... Code of Federal Regulations.
CGMP......................... Current Good Manufacturing Practice.
DGMP......................... Device Good Manufacturing Practice.
DMR.......................... Device Master Record.
FD&C Act..................... Federal Food, Drug, and Cosmetic Act.
FDA.......................... Food and Drug Administration.
GHTF......................... Global Harmonization Task Force.
GMP.......................... Good Manufacturing Practice.
IBR.......................... Incorporated by Reference.
IMDRF........................ International Medical Device Regulators
Forum.
ISO.......................... International Organization for
Standardization.
ISO 13485.................... International Organization for
Standardization 13485:2016.
ISO 9000..................... Quality Management Systems--Fundamentals
and Vocabulary,'' ISO 9000:2015.
MDSAP........................ Medical Device Single Audit Program.
NARA......................... National Archives and Records
Administration.
OMB.......................... Office of Management and Budget.
QMS.......................... Quality Management System.
QMSR......................... Quality Management System Regulation.
QS........................... Quality System.
QSIT......................... Quality System Inspection Technique.
SMDA......................... Safe Medical Devices Act of 1990.
UDI.......................... Unique Device Identification.
------------------------------------------------------------------------
III. Background
A. Introduction
QMSs specify requirements to help manufacturers ensure that their
products consistently meet applicable customer and regulatory
requirements and specifications (Ref. 1). In the United States,
authority for the QS regulation for devices is found under section
520(f) of the FD&C Act (21 U.S.C. 360j(f)), which the FD&C Act refers
to as CGMP requirements. FDA issued a final rule for CGMP requirements
in the Federal Register of July 21, 1978 (43 FR 31508), which created
part 820 (Ref. 2).
As described below, FDA significantly revised part 820 in a final
rule published in the Federal Register of October 7, 1996 (61 FR 52602,
effective June 1, 1997) (1996 Final Rule), establishing the current QS
regulation. As revised, part 820 includes requirements related to the
methods used in, and the facilities and controls used for, designing,
manufacturing, packaging, labeling, storing, installing, and servicing
of devices intended for human use. These requirements are intended to
assure that devices are safe and effective and otherwise in compliance
with the FD&C Act. FDA has not undertaken a significant revision of
part 820 since the 1996 Final Rule. Part 820 has been an effective
regulation, providing assurance that devices are safe and effective and
otherwise in compliance with applicable sections of the FD&C Act.
Also in 1996, ISO issued the first version of ISO 13485, ``Quality
systems--Medical devices--Particular requirements for the application
of ISO 9001,'' as a voluntary consensus standard to specify, in
conjunction with the application of ISO 9001, the QMS requirements for
the design/development and, when relevant, installation and servicing
of medical devices (Refs. 3 and 4). Over time, ISO 13485 has evolved
into a stand-alone standard outlining QMS requirements for devices
(Ref. 1). With each revision, ISO 13485 has become more closely aligned
with, and similar to, the requirements in part 820. This alignment and
similarity are particularly true for the 2016 version of ISO 13485.
Recognizing this progression, FDA sees an opportunity for regulatory
harmonization by proposing to amend the current part 820 regulation to
explicitly incorporate the QMS requirements of ISO 13485. ISO 13485 is
used internationally by many regulatory authorities either as a
foundation for or as that country's QMS requirements for device
manufacturers and is utilized in regulatory harmonization programs such
as the Medical Device Single Audit Program (MDSAP), in which FDA and
regulatory authorities from four other countries participate (Ref. 5).
The current part 820 applies to many different devices and thus
does not prescribe in detail how a manufacturer must design and
manufacture a specific device. Rather, the regulation was developed to
be a mandatory and flexible framework, requiring manufacturers to
develop and follow procedures and processes, as appropriate to a given
device, according to the state-of-the-art for manufacturing and
designing such device. Successful compliance with this regulation
provides the manufacturer with a framework for achieving quality
throughout the organization (Ref. 1).
While part 820 effectively addresses the requirements for a QMS,
FDA has long recognized the value of, and has been exploring ways to
effect, global harmonization for the regulation of devices. For
example, FDA has actively participated in the development of
internationally harmonized documents and standards on risk management
since their inception, including the development of the Global
Harmonization Task Force (GHTF) guidance document, ``Implementation of
Risk Management Principles and Activities Within a Quality Management
System,'' dated May 20, 2005, which outlines the integration of a risk
management system into a QMS (Ref. 6). FDA also participated in the
development of the various versions of ISO 14971 ``Medical Devices--
Application of Risk Management to Medical Devices'' (Ref. 7).
In 2012, FDA developed a voluntary audit report submission pilot
program, which is no longer operational, in which FDA accepted a
manufacturer's ISO 13485:2003 audit report (Ref. 8). Through this
program, FDA established the feasibility and use of ISO 13485 audit
reports in lieu of FDA's routine inspections covering the QS regulation
requirements. Additionally, FDA participates in the International
Medical Device Regulators Forum (IMDRF), a voluntary group of medical
device regulators from around the world
[[Page 10122]]
focused on regulatory harmonization and convergence (Ref. 9). IMDRF
developed MDSAP in 2012. Under MDSAP, audits are conducted based on
core ISO 13485 requirements with additional country-specific
requirements. In determining whether to participate in MDSAP and which
FDA-specific provisions were needed for the United States, FDA
conducted a thorough review and comparison of ISO 13485 and part 820
and concluded that very few FDA-specific requirements needed to be
added to this audit model, demonstrating not only the similarities
between the current part 820 and ISO 13485, but the comprehensive QMS
approach provided by ISO 13485. This has allowed FDA to participate in
MDSAP and accept certain MDSAP audits as a substitute for its own
routine surveillance of device quality systems (Ref. 5).
Through our participation in MDSAP, FDA has gained experience with
ISO 13485 and determined that it provides a comprehensive and effective
approach to establish a QMS for devices. As such, FDA is proposing to
amend the device CGMP requirements of the QS regulation by
incorporating by reference the 2016 edition of ISO 13485 as well as
proposing additional regulations that help connect and align ISO 13485
with other FDA requirements. The 2016 version of ISO 13485 provides
requirements for a QMS that allow a manufacturer to demonstrate its
ability to provide devices and related services that consistently meet
customer requirements and regulatory requirements applicable to such
devices and services (Ref. 1). These requirements can be used by ``an
organization involved in one or more stages of the life cycle of a
medical device, including design and development, production, storage
and distribution, installation, servicing and final decommissioning and
disposal of medical devices'' (Ref. 1).
FDA believes that globally harmonizing the regulation of devices
will help provide consistent, safe, and effective devices, contributing
to public health through timelier access for patients. Harmonizing
differing regulations would remove unnecessary duplicative regulatory
requirements and impediments to market access and remove barriers to
patient access and costs. The more flexible approach to quality, based
on risk management, found within ISO 13485 will meet the needs of
patients to have access to quality devices in consonance with the
progress of science and technology (Ref. 9).
B. Need for the Regulation
Currently, device manufacturers registered with the FDA must comply
with the current part 820. In addition to the current part 820,
registered manufacturers in many other jurisdictions and domestic
manufacturers that export devices must comply with ISO 13485, which is
substantially similar to the current part 820. As a result, there is
redundant effort for some manufacturers in complying with both the
current part 820 and ISO 13485. The redundancy of effort to comply with
two substantially similar requirements creates inefficiency. In order
to address this inefficiency, we propose to incorporate by reference
ISO 13485 requirements so that compliance with ISO 13485 would satisfy
requirements of current part 820. Although the requirements under the
current part 820 are effective and very similar to those in ISO 13485,
incorporating ISO 13485 by reference would further the Agency's goals
for regulatory simplicity and global harmonization and should reduce
burdens on regulated industry, thereby providing patients more
efficient access to necessary devices (Ref. 9).
C. FDA's Current Regulatory Framework
The FD&C Act, as amended, and its implementing regulations
establish a comprehensive system for the regulation of devices intended
for human use. The device CGMP requirements in the current part 820
were authorized by section 520(f) of the FD&C Act, which was among the
authorities added to the FD&C Act by the Medical Device Amendments of
1976 (Pub. L. 94-295). Under section 520(f) of the FD&C Act, FDA issued
the current part 820 regulation, which was last revised in 1996.
In addition, section 520(f)(1)(B) of the FD&C Act directs the
Agency to afford the Device Good Manufacturing Practice Advisory
Committee (DGMP Advisory Committee) an opportunity to submit
recommendations for proposed CGMP regulations, to afford an opportunity
for an oral hearing, and to ensure that such regulations conform, to
the extent practicable, with internationally recognized standards
defining quality management systems, or parts of the standards, for
devices (see 21 U.S.C. 360j(f)(1)(B)). The DGMP Advisory Committee
reviews regulations proposed for promulgation regarding good
manufacturing practices and makes recommendations to the Agency
regarding the feasibility and reasonableness of the proposed
regulations. The Agency will convene a DGMP Advisory Committee meeting
and afford an opportunity for an oral hearing to discuss this proposal
prior to FDA's finalization of this rule.
Further, the provisions of sections 501(a)(2)(B) and (h) of the
FD&C Act (21 U.S.C. 351(a)(2)(B) and (h)) require the manufacture of
drugs and devices to comply with CGMP requirements, and section 520(f)
of the FD&C Act specifically authorizes the issuance of CGMP
regulations for devices, including device constituent parts of products
that constitute a combination of a drug, device, and/or biological
product, as defined in Sec. 3.2(e) (21 CFR 3.2(e)) (``combination
products''). Combination products that include device constituent parts
have a distinct regulatory framework for CGMP requirements because the
product, by definition, also includes non-device constituent parts
(e.g., a drug or a biological product). In the Federal Register of
January 22, 2013 (78 FR 4307), we issued a final rule codifying the
CGMP requirements applicable to combination products at part 4. We
issued the part 4 regulations, in part, under sections 501(a)(2)(B) and
(h) and 520(f) of the FD&C Act and are proposing to amend part 4 under
the same authorities.
In that final rule, we explained that the CGMP requirements
specific to each constituent part of a combination product also apply
to the combination product itself because, by definition, combination
products consist of drugs, devices, and/or biological products (see 78
FR 4307 at 4320, citing Sec. 3.2(e)). We also explained that, because
the constituent parts of a combination product retain their regulatory
status (as a drug or device, for example) after they are combined, all
combination products are subject to at least two sets of CGMP
requirements, but that those for drugs overlap considerably with the
part 820 requirements for devices (see 78 FR 4307 at 4320). Part 4
clarifies the applicability of the various CGMP requirements to provide
a streamlined option for practical implementation for co-packaged and
single-entity combination products (see 78 FR 4307 at 4320 and Sec.
4.4 (21 CFR 4.4)). Because of the similarity of the drug and device
CGMP requirements, FDA considers demonstrating compliance with one of
these two sets of regulations (e.g., device CGMP requirements) along
with demonstrating compliance with the specified provisions from the
other set (e.g., drug CGMP requirements) identified in part 4 as
demonstrating compliance with all CGMP requirements from both sets (see
78 FR 4307 at 4320 and Sec. 4.4).
[[Page 10123]]
D. History of the Rulemaking
This proposed rulemaking is the first revision of the current part
820 since 1996. As previously described, FDA has had a longstanding
interest and history of participation in efforts to harmonize its
regulatory requirements with the requirements used by other regulatory
authorities from various jurisdictions (i.e., other countries). This
rulemaking is a continuation of these efforts and, if finalized, will
harmonize FDA's quality management system regulation with requirements
of the international standard ISO 13485, which is used by other
regulatory authorities. Harmonizing the FDA standard with the ISO
standard would have benefits for manufacturers because many firms
producing devices for sale within the United States and abroad have to
comply with both standards. If finalized, this rule would require
compliance with an aligned set of requirements, instead of two
different requirements.
On July 21, 1978, FDA issued a final rule in the Federal Register
(43 FR 31508), establishing CGMP requirements for medical devices under
section 520(f) of the FD&C Act. This rule became effective on December
18, 1978, and is codified under part 820.
The Safe Medical Devices Act of 1990 (SMDA) (Pub. L. 101-629)
amended section 520(f) of the FD&C Act to provide FDA with the
authority to add preproduction design controls to the CGMP regulation.
This change in law was based on findings that a significant proportion
of device recalls were attributable to faulty product design. The SMDA
also added section 803 to the FD&C Act, which, among other things,
authorizes the Agency to enter into agreements with foreign countries
to facilitate commerce in devices, and in such agreements, FDA must
encourage the mutual recognition of GMP regulations under section
520(f) of the FD&C Act (see 21 U.S.C. 383(b)(1)).
To implement the SMDA changes to section 520(f) of the FD&C Act,
FDA revised part 820 by the 1996 Final Rule (61 FR 52602). This final
rule revised the CGMP requirements for medical devices and promulgated
the QS regulation under part 820 in its current form. As part of this
revision, FDA added the design controls authorized by the SMDA in
addition to other changes to achieve consistency with QMS requirements
worldwide. At the time, the Agency sought to harmonize the CGMP
regulations, to the extent possible, with the requirements for quality
management systems contained in then-applicable international
standards. In particular, FDA worked closely with the GHTF and ISO
Technical Committee 210 (TC 210) to develop a regulation consistent
with both ISO 9001:1994, Quality Systems--Model for Quality Assurance
in Design, Development, Production, Installation, and Servicing; and
the ISO committee draft (CD) revision of ISO/CD 13485 Quality Systems--
Medical Devices--Supplementary Requirements to ISO 9001 (see 61 FR
52602 at 52604).
E. Incorporation by Reference
FDA is proposing to incorporate by reference ISO 13485:2016 Medical
devices--Quality management systems--Requirements for regulatory
purposes, Third Edition 2016-03-01. ISO is an independent, non-
governmental international organization with a membership of national
standards bodies. ISO 13485 specifies requirements for a QMS that can
be used by a manufacturer involved in one or more stages of the life
cycle of a medical device, including design and development,
production, storage and distribution, installation, servicing and final
decommissioning and disposal of medical devices, or provision of
associated activities.
You may view the material at the Dockets Management Staff, 5630
Fishers Lane, Rm. 1061, Rockville, MD 20852, 240-420-7500. The material
can also be found in a read-only format at the American National
Standards Institute (ANSI) Incorporated by Reference (IBR) Portal,
https://ibr.ansi.org/Standards/iso1.aspx, or you may purchase a copy of
the material from the International Organization for Standardization,
BIBC II, Chemin de Blandonnet 8, CP 401, 1214 Vernier, Geneva,
Switzerland; +41-22-749-01-11; [email protected], https://www.iso.org/store.html. ISO 13485 provides a comprehensive approach to
establish a QMS for medical devices.
FDA is proposing to incorporate by reference the current 2016
version of ISO 13485. Any future revisions to this standard would need
to be evaluated to determine the impact of the changes and whether this
rule, if finalized, should be amended. If deemed necessary and
appropriate, FDA will update the final regulation in accordance with
the Administrative Procedure Act (5 U.S.C. 553) and obtain approval of
any changes to the incorporation by reference in accordance with 1 CFR
part 51.
IV. Legal Authority
We are proposing to issue this rule under the same authority that
FDA initially invoked to issue the current Quality System Regulation
(part 820) and Regulation of Combination Products (part 4), as well as
the general administrative provisions of the FD&C Act: 21 U.S.C. 351,
352, 360, 360c, 360d, 360e, 360h, 360i, 360j, 360l, 371, 374, 381, 383;
42 U.S.C. 216, 262, 263a, 264.
V. Description of the Proposed Rule
We are proposing to amend the current part 820, primarily to
incorporate by reference ISO 13485, Medical Devices--Quality Management
System Requirements for Regulatory Purposes. While the current part 820
provides sufficient and effective requirements for the establishment
and maintenance of a QMS, regulatory expectations for a QMS have
evolved since the current part 820 was implemented over 20 years ago.
By proposing to incorporate ISO 13485 by reference, we are seeking to
explicitly require current internationally recognized regulatory
expectations for QMS for devices subject to FDA's jurisdiction. The
resulting regulation will be referred to as the QMSR.
The current part 820 requirements are, when taken in totality,
substantially similar to the requirements of ISO 13485. Where ISO 13485
diverges from the current part 820, these differences are generally
consistent with the overall intent and purposes behind FDA's regulation
of QMSs. Almost all requirements in the current part 820 correspond to
requirements within ISO 13485. Therefore, we are proposing to amend the
current part 820 by withdrawing the majority of the requirements for
establishing and maintaining a QS. Despite these changes, this proposal
does not fundamentally alter the requirements for a QS that exist in
the current part 820. The rule, if finalized, would converge QS
regulation with the QMS requirements of ISO 13485, while continuing to
provide the same level of assurance of safety and effectiveness under
the FD&C Act and its implementing regulations.
However, we recognize that reliance on ISO 13485 without
clarification or modification could create inconsistencies with FDA's
statutory and regulatory framework. Therefore, as detailed in this
rulemaking, we are proposing additional definitions, clarifying
concepts, and additional requirements, all of which would require
compliance within a manufacturer's QMS in addition to ISO 13485. The
Agency solicits comments on specific subject areas related to this
proposed rule that FDA should consider in seeking to converge U.S.
requirements with requirements used by other regulatory authorities in
ways that
[[Page 10124]]
are consistent with FDA's authority under the FD&C Act.
Our approach to this rulemaking is to simplify and streamline the
regulation. Where possible, we either are proposing to accept the
incorporated requirement without modification or are proposing a
requirement that will supersede the correlating requirement in ISO
13485. There are a few exceptions where we are proposing to clarify
concepts or augment specific clauses in ISO 13485, but overall, we are
not proposing to modify the clauses in ISO 13485. (see table 1). This
philosophy also helps further regulatory convergence.
As discussed further in section VI., this rule is only proposing to
amend the current part 820 and does not impact our inspectional
authority under section 704 of the FD&C Act (21 U.S.C. 374). We are
also proposing conforming edits to part 4 to clarify the device QMS
requirements for combination products. These edits would not impact the
CGMP requirements for combination products.
Table 1--High-Level Summary of 21 CFR Part 820 Proposed Rule Differences and Additions
----------------------------------------------------------------------------------------------------------------
Current part 820 \1\ ISO 13485 requirements \1\ Proposed rule
----------------------------------------------------------------------------------------------------------------
Subpart A--General Provisions..... Clause 1. Scope, Clause 4. Requirements substantively similar.
Quality Management System.
Subpart B--QS Requirements........ Clause 4. Quality Requirements substantively similar.
Management System, Clause
5. Management
Responsibility, Clause 6.
Resource Management,
Clause 8. Measurement,
Analysis, and Improvement.
Subpart C--Design Controls........ Clause 7. Product Requirements substantively similar.
Realization.
Subpart D--Document Controls \2\.. Clause 4. Quality Differences addressed in 820.35.
Management System.
Subpart E--Purchasing Controls.... Clause 7. Product Requirements substantively similar.
Realization.
Subpart F--Identification and Clause 7. Product Requirements substantively similar.
Traceability. Realization.
Subpart G--Production and Process Clause 4. Quality Requirements substantively similar.
Controls. Management System, Clause
6. Resource Management,
Clause 7. Product
Realization.
Subpart H--Acceptance Activities.. Clause 7. Product Requirements substantively similar.
Realization, Clause 8.
Measurement, Analysis,
and Improvement.
Subpart I--Nonconforming Product.. Clause 8. Measurement, Requirements substantively similar.
Analysis, and Improvement.
Subpart J--Corrective and Clause 8. Measurement, Requirements substantively similar.
Preventive Action. Analysis, and Improvement.
Subpart K--Labeling and Packaging Clause 7. Product Differences addressed in 820.45.
Control. Realization.
Subpart L--Handling, Storage, Clause 7. Product Requirements substantively similar.
Distribution, and Installation. Realization.
Subpart M--Records................ Clause 4. Quality Differences addressed in 820.35.
Management System.
Subpart N--Servicing.............. Clause 7. Product Differences addressed in 820.35.
Realization.
Subpart O--Statistical Techniques. Clause 7. Product Requirements substantively similar.
Realization, Clause 8.
Measurement, Analysis,
and Improvement.
----------------------------------------------------------------------------------------------------------------
\1\ This table is not intended to be a requirement-by-requirement analysis, but a higher-level mapping of the
totality of the subparts and clauses of the standard and the QS regulation for reference purposes only.
\2\ It's important to note that while there are differences specifically identified in subpart D, document
requirements exist in most subparts and clauses of the standard and the QS Regulation.
A. Scope (Proposed Sec. 820.1)
FDA is not proposing to modify which establishments or products are
subject to part 820. As before, the requirements would apply to
manufacturers of finished devices; however, FDA notes that the legal
authority exists to cover manufacturers of components or parts of
finished devices under this regulation should the need arise (see 61 FR
52602 at 52606).
The proposed modifications to the scope of the requirements are
non-substantive, and include the following:
1. Clarify that conflicting regulations that are more specific are
controlling only to the extent of the conflict.
The current Sec. 820.1(b) states that when there is a conflict
between regulations in part 820 and a specifically applicable
regulation located in chapter I of title 21 of the CFR, the regulations
that specifically apply to the device in question supersede other
generally applicable requirements. A reader might interpret this
provision to mean that the specifically applicable regulation renders
the rest of the part 820 regulation completely inapplicable. The
proposed amendment is intended to clarify that the generally applicable
part 820 regulations apply to the extent they do not otherwise conflict
with the specifically applicable regulation. Moreover, to the extent
that any clauses of ISO 13485 conflict with any provisions of the FD&C
Act and/or its implementing regulations, the FD&C Act and/or its
implementing regulations will control.
2. Rearrange some of the content and add paragraph breaks for
clarity and improved flow, for example, separating requirements for
manufacturers of components or parts into a paragraph different from
the one describing manufacturers of finished devices.
3. Remove the paragraph listing authority because the CFR already
lists the legal authority for the regulation as a separate entry.
4. Relocate the enforcement provision to a new separate paragraph
in Sec. 820.10.
B. Definitions (Proposed Sec. 820.3)
Definitions of key terms related to quality management systems
appear in the current Sec. 820.3 and in Clause 3 of ISO 13485. We have
reviewed the definitions in ISO 13485 to determine their suitability
for FDA's purposes. We find that most of the definitions in Clause 3
are acceptable; thus, unless identified in this section, we are not
proposing any modifications to the terms and definitions in Clause 3
and are proposing to remove the correlating terms and definitions from
the current part 820. In some cases, however, the current Sec. 820.3
definitions include terms that ISO 13485 does not and vice versa.
Further, there are some definitions in ISO 13485 that do not align with
requirements in the FD&C Act and its implementing regulations.
[[Page 10125]]
To account for these differences and ensure consistency with such
law and regulations, we are proposing to retain and/or revise certain
definitions that are in the current part 820. We are also proposing to
withdraw certain terms and definitions from the current part 820 that
do not have a corollary in ISO 13485 because they are not needed to
understand and implement the proposed part 820. Among the definitions
being withdrawn from the current part 820 is the term ``establish''.
Though the term establish is not defined in the ISO standard, section
0.2 states that when a requirement is required to be ``documented'', it
is also required to be established, implemented, and maintained. We
believe the clarification of this concept within the standard is
sufficient to convey the current requirement for manufacturers to
establish and maintain the regulatory requirements of a QMS.
1. Terms that do not appear in ISO 13485 but that are necessary for
the purposes of part 820 (terms additional to ISO 13485) (Proposed
Sec. 820.3(a)).
For the terms that do not appear in ISO 13485, but are necessary to
ensure alignment with the FD&C Act and its implementing regulations, we
are proposing to retain the definitions of such terms with minor
revisions, as indicated below.
We are proposing to retain the definition of Act (see Sec.
820.3(a)) in current part 820, except we propose to expand the term to
more precisely reflect the specific act to which the definition refers
because FDA has the authority to promulgate regulations under other
acts. The addition of ``Federal Food, Drug, and Cosmetic'' to this term
will help avoid potential ambiguity if we amend part 820 in the future
under a different authority.
We are also proposing to replace the term ``management with
executive responsibility'' (see Sec. 820.3(n)) in the current part 820
with the term ``top management'', which is used in ISO 13485, but is
defined in ``Quality Management Systems--Fundamentals and Vocabulary,''
ISO 9000:2015 (ISO 9000) (Ref. 10). We propose to accomplish this by
revising the name of the term to ``top management'' but retaining the
definition in the current part 820. This will maintain the principle
and requirement that the most senior employees of a manufacturer are
responsible for establishing and making changes to the quality policy
and ensuring the manufacturer follows the policy. FDA expects medical
device manufacturers, led by top management, to embrace a culture of
quality as a key component in ensuring safe and effective medical
devices that otherwise comply with the FD&C Act. A culture of quality
meets regulatory requirements through a set of behaviors, attitudes,
activities, and processes. Top management ensures that applicable
regulatory requirements are met through the integration of QS
processes.
We are retaining the majority of the definition of ``rework'';
however, we are proposing to remove the term ``device master record
(DMR)'' (Sec. 820.3(j)) from the regulation. The device master record
is not a term used in ISO 13485 and so this definition does not need to
be retained. FDA believes the concept of a DMR is adequately covered
under the requirements for a medical device file under Clause 4.2.3 of
ISO 13485. We are retaining the definition of ``process validation''
(Sec. 820.3(z)(1)) and clarifying the concept. FDA recognizes the
terms ``process validation'' and ``validation of processes'', the term
used in ISO 13485, as synonymous. We are also proposing to include a
definition for the term ``customer'', as it is important for
interpretation of the proposed rule. Although FDA historically has not
used the term ``customer'', we find it is a useful term and can
encompass many types of individuals and organizations throughout the
device manufacturing process, such as component manufacturers, contract
manufacturers, and end users. Requirements related to customers are
generally consistent with the overall intent and purposes behind FDA's
regulation of device QMSs, which is to assure that finished devices
will be safe and effective and otherwise in compliance with the FD&C
Act. When considering the requirements related to customer property in
ISO 7.5.10, FDA expects that manufacturers comply with this provision
to the extent necessary to assure the safety and effectiveness of the
devices being manufactured. For example, a manufacturer is expected to
ensure that the integrity of a component provided by a contract
manufacturer is not compromised before it is incorporated into the
device being manufactured. To the extent any customer property
requirements may be interpreted to go beyond the safety and
effectiveness of the devices being manufactured, FDA does not intend to
enforce this provision for such activities.
We are retaining without change the terms and definitions for
``component'' (Sec. 820.3(c)); ``finished device'' (Sec. 820.3(l));
``human cell, tissue, or cellular or tissue-based product (HCT/P)
regulated as a device'' (820.3(bb)); ``design validation'' (Sec.
820.3(z)(2)); ``remanufacturer'' (Sec. 820.3(w)); ``nonconformity''
(Sec. 820.3(q)); and ``verification'' (820.3(aa)) because these terms
are necessary for implementing part 820.
2. Terms that are defined in ISO 13485, which we propose not to
incorporate and are proposing definitions that supersede the definition
of the similar term in the standard (Proposed Sec. 820.3(b)).
There are a number of terms and definitions in ISO 13485 that would
create inconsistencies with the FD&C Act and its implementing
regulations. FDA cannot incorporate any definitions of terms that are
inconsistent with how the FD&C Act defines such terms because FDA
cannot, nor does it seek to, amend its statutory definitions by
rulemaking. As such, we clarify that the definitions of terms in
section 201 of the FD&C Act (21 U.S.C. 321) supersede the definitions
in ISO 13485. In particular, the definitions of ``device'' and
``labeling'' in sections 201(h) and (m) of the FD&C Act, respectively,
supersede the correlating definitions for ``medical device'' and
``labelling'' in ISO 13485.
In addition, we are proposing to retain the definition of
``manufacturer'' (Sec. 820.3(o)) and retain with modification the
definition of ``product'' (Sec. 820.3(r)) from the current part 820
because the ISO 13485 definitions of these terms do not align with the
established range of these terms by FDA. The definitions in proposed
part 820 would supersede that of the correlating term in ISO 13485.
With regards to the definition of ``manufacturer'', we are
proposing to retain our current definition because it is more
comprehensive than the definition in ISO 13485. For example, FDA's
definition contains a list of functions that when performed meet the
definition of manufacturer. The comparable ISO 13485 definition does
not include this level of detail in its definition. This definition is
expanded upon in the notes to the ISO definition, which are guidance--
not requirements. By explicitly including the functions that a
manufacturer performs in the proposed definition, the Agency intends to
maintain its original interpretation of this term and to clarify the
functions that continue to be subject to the requirements of part 820.
A similar logic has been applied to the definition of ``product''.
FDA's definition of product includes a list of items considered to be
``product'' for the purposes of part 820 that is not included in the
definition in ISO 13485, but some of which are included in the notes to
the ISO definition.
Additionally, we note that consistent with the clarification in
clause 0.2, which specifies that ``when the term `product' is used, it
can also mean
[[Page 10126]]
`service','' for the requirements of clause 7.4 Purchasing we expect
that when ensuring purchased products conform to requirements,
oversight for purchased services are also included.
C. Incorporation by Reference (Proposed Sec. 820.7)
As stated above, FDA is proposing to incorporate by reference the
International Standard, ISO 13485:2016 Medical devices--Quality
management systems--Requirements for regulatory purposes, Third Edition
2016-03-01. ISO 13485 provides a comprehensive approach to establish a
quality management system for medical devices. If this proposed rule is
finalized, it will provide most of the CGMP requirements for devices.
We note that the definitions in ISO 9000 apply to ISO 13485; however,
to the extent that there is any conflict between ISO 9000 and the FD&C
Act and its implementing regulations, the FD&C Act and its implementing
regulations would control.
While we recognize that adopting ISO 13485 could seem like a
significant change, the current part 820 and ISO 13485 are
substantially similar, and this effort promotes international
harmonization. The substance of the ISO 13485 requirements and the
activities and actions required for compliance are primarily the same
as under the current part 820. ISO 13485 has a greater emphasis on risk
management activities and risk-based decision making than the current
part 820. Risk management for device manufacturers is the essential
systematic practice of identifying, analyzing, evaluating, controlling,
and monitoring risk throughout the product lifecycle to ensure that the
devices they manufacture are safe and effective. The current part 820
explicitly addresses risk management activities only in the risk
analysis requirement within design validation in Sec. 820.30(g);
whereas, risk management is more broadly integrated in ISO 13485. FDA,
however, has expected that manufacturers, led by top management,
integrate risk management activities throughout their QMS and across
the total product lifecycle. FDA discussed risk management and risk-
based decision making in several sections of the 1996 Final Rule
establishing the current QS requirements. For example, while not
specified in the requirements for Corrective and Preventive Action
(Sec. 820.100), FDA states that it ``expect[s] the manufacturer to
develop procedures for assessing the risk, the actions that need to be
taken for different levels of risk, and how to correct or prevent the
problem from recurring, depending on that risk assessment'' (61 FR
52602 at 52634). Additionally, FDA states that ``[w]hen conducting a
risk analysis, manufacturers are expected to identify possible hazards
associated with the design in both normal and fault conditions. The
risks associated with the hazards, including those resulting from user
error, should then be calculated in both normal and fault conditions.
If any risk is judged unacceptable, it should be reduced to acceptable
levels by the appropriate means'' (61 FR 52602 at 52620). FDA has,
therefore, expected risk management throughout a QMS and the total
product lifecycle.
Nonetheless, although the integration of risk management principles
throughout ISO 13485 does not represent a shift in philosophy, the
explicit integration of risk management throughout the clauses of ISO
13485 more explicitly establishes a requirement for risk management to
occur throughout a QMS and should help industry develop more effective
total product life-cycle risk management systems. Effective risk
management systems provide the framework for sound decision making
within a QMS and provide assurance that the devices will be safe and
effective (see section 520(f) of the FD&C Act).
D. Proposed Requirement for a Quality Management System (Proposed Sec.
820.10)
The current Sec. 820.5 requires that manufacturers establish and
maintain a quality management system that meets the requirements of
part 820. We propose to relocate this requirement within the codified
and to revise this provision to require that a quality management
system that complies with ISO 13485, as modified by the proposed part
820, be documented. These requirements will serve as the minimum
requirements for establishing a QMS that complies with the final
version of this proposed rule. In general, when ISO 13485 refers to
documenting evidence we recommend that manufacturers record
quantitative data, as appropriate, because such information will assist
manufacturers in monitoring the performance of their processes and
effectiveness of their process controls.
In addition, there are many clauses throughout ISO 13485 that refer
to ``applicable regulatory requirements.'' We propose to include the
FDA requirements that must be completed when the listed term or clause
is used, in order to assist manufacturers in understanding how ISO
13485 relates to other regulatory requirements for devices. We are only
proposing to identify certain instances of the phrase ``applicable
regulatory requirements'' and therefore the proposed list is not
intended to be comprehensive. Regulated manufacturers are responsible
for identifying and meeting all applicable requirements, even if such
requirements are not specifically called out in the proposed Sec.
820.10.
We also propose to clarify that Clause 7.3 Design and Development
applies only to the manufacturers of the class I devices that are
listed in this provision in addition to all manufacturers of class II
and III devices. This retains the scope of current Sec. 820.30(a). We
are not proposing to modify which devices are subject to these
requirements and are only revising this provision to reflect the
location of similar requirements in ISO 13485. We also note that this
is consistent with clause 1 of ISO 13485, which recognizes that there
may be exclusions by the regulatory authority from the Design and
Development requirement and directs the manufacturer to document such
in its justification for exclusion.
Finally, we are proposing to add a requirement to ensure that
devices that support or sustain life, the failure of which to perform
when properly used in accordance with instructions for use provided in
the labeling can be reasonably expected to result in a significant
injury, comply with the traceability requirements set forth in in
Clause 7.5.9.2 for implantable medical devices. Such products currently
are subject to similar requirements in Sec. 820.65 for traceability;
however, in ISO 13485 only implantable devices are subject to this
requirement.
E. Proposed Clarification of Concepts (Proposed Sec. 820.15)
We are including clarifications for three concepts to explain how
these concepts in ISO 13485 relate to our statutory and regulatory
framework for medical devices.
Organization. ISO 13485 uses the term ``organization'' to describe
the entity who is creating a QMS that conforms to the requirements in
ISO 13485. Instead, we propose to clarify the term ``organization'' to
also include the meaning of the term ``manufacturer'' as it is defined
in proposed Sec. 820.3.
Safety and performance. ISO 13485 often refers to ``safety and
performance'' as a standard to measure medical devices. We propose that
where the standard uses ``safety and performance,'' readers shall
construe that phrase to mean the same as ``safety and effectiveness''
in section 520(f) of the FD&C Act. We understand that some
[[Page 10127]]
people could disagree about how the two standards compare, whether one
is more stringent than the other, or even equivalent. In proposing this
clarification, we do not intend to take a position on the matter of
comparison. Instead, we propose this clarification to avoid confusion
and ensure that implementation of a QMS is aligned with the standard of
safety and effectiveness in section 520(f) of the FD&C Act and
otherwise established for devices in FD&C Act.
Validation of processes. ISO 13485 uses the term ``validation of
processes'' and does not contain its own definition of the term. We
propose to clarify the term ``validation of processes'' as used in ISO
13485 to refer to ``process validation,'' as that term is defined in
part 820. We are retaining the definition of process validation (Sec.
820.3(z)(1)) because ISO 13485 does not define ``validation of
processes,'' but the use is the same as that expected for process
validation under part 820. This will also allow for alignment between
ISO 13485 and other requirements in the FD&C Act and its implementing
regulations.
F. Proposed Supplementary Provisions (Proposed Subpart B)
As stated above, we are proposing additional requirements to ensure
consistency and alignment with other requirements in the FD&C Act and
its implementing regulations. FDA considers the following requirements
necessary for implementation of a QMS that is consistent with
applicable requirements but are not specified in ISO 13485. These
requirements include control of records and device labeling and
packaging controls.
FDA notes that the current part 820 contains requirements for
record types that are not specifically identified in ISO 13485, such
as, quality system record, device master record, design history file,
and device history record. We are not proposing to retain separate
requirements for these record types as we believe the elements that
comprise those records are largely required to be documented by other
ISO 13485 Clauses, such as Clause 4.2 and its subclauses.
1. Proposal for Control of Records (Proposed Sec. 820.35)
We propose additional requirements to help ensure that records are
established and maintained in a manner that is useful to FDA and
manufacturers. First, we propose to include signature and date
requirements for records subject to Clause 4.2.5 of ISO 13485. Such
requirements provide clarity on the information FDA needs to ensure
validity of records. Records are not necessarily limited to hardcopy
documents that are physically signed. Manufacturers can choose to
develop electronic records and electronic methods for signing and
dating such records, if that best suits their business practices. Our
focus is on whether the substance of the requirements is met and not
the physicality of the record or signature methodology. Second, FDA is
proposing specific requirements to ensure that the information required
by part 803 (21 CFR part 803), Medical Device Reporting, is captured on
certain records of complaints and servicing activities. Third, we
propose to require that firms document the Unique Device Identification
(UDI) for each medical device or batch of medical devices in accordance
with 21 CFR part 830 in its records. Last, we are proposing to retain
the clarification from the current part 820 (Sec. 820.180) about
confidentiality of records FDA receives. This reminds firms that FDA
protects such records in accordance with 21 CFR part 20. If this rule
is finalized as proposed, manufacturers must meet the requirements in
ISO 13485 Clause 4.2.5 and also meet the requirements of the eventual
Sec. 820.35.
We also note that ISO 13485 Clause 4.2.5 requires that records be
``readily identifiable and retrievable.'' FDA considers this phrase to
be substantially similar to the requirement in current part 820 (Sec.
820.180) that records be ``reasonably accessible'' and ``readily
available.'' In the 1996 Final Rule, the Agency explained that ``FDA
expects that such records will be made available during the course of
an inspection. If the foreign manufacturer maintains records at remote
locations, such records would be expected to be produced by the next
working day or 2, at the latest. FDA has clarified that records can be
kept at other than the inspected establishment, provided that they are
made `readily available' for review and copying.'' (61 FR 52602 at
52637). FDA will consider records that a manufacturer makes available
in accordance with this statement to be ``readily identifiable and
retrievable.''
2. Proposed Controls for Device Labeling and Packaging (Proposed Sec.
820.45)
Each year, device recalls are initiated related to product labeling
and packaging. Clause 7.5.1(e) of ISO 13485 states that ``defined
operations for labelling and packaging shall be implemented.'' However,
ISO 13485 fails to provide additional requirements for labeling and
packaging and does not specifically address the inspection of labeling
by the manufacturer. Therefore, FDA proposes to retain requirements
from the current part 820 that would strengthen controls for labeling
and packaging operations, given that many device recalls are related to
labeling and packaging. FDA believes that these provisions will better
assure the manufacture of safe and effective devices. If this rule is
finalized as proposed, regulated industry must meet the requirements in
ISO 13485 7.5.1 and the proposed Sec. 820.45.
G. Proposed Conforming Amendments
We are proposing to amend part 4 to reflect the amendments made to
part 820 in incorporating ISO 13485 by reference. As explained above,
part 4 provides a streamlined option to demonstrate compliance with the
multiple, applicable sets of CGMP requirements for certain combination
products (i.e., single-entity and co-packaged combination products). To
do so, one option part 4 presents for single-entity and co-packaged
combination products with device constituent parts is to demonstrate
compliance with the requirements of one other applicable set of
requirements along with specified provisions of part 820 (rather than
all provisions). We are not proposing to change the underlying
activities required of manufacturers that pursue this streamlined
option. Instead, we are proposing conforming amendments to the part 4
references to the corresponding clauses in ISO 13485. To that end, we
are taking comment on the proposed conforming amendments and whether
additional changes are necessary to assure compliance with part 4. The
QS requirements outlined in part 4 are not fundamentally different than
the corresponding requirements in ISO 13485.
VI. Proposed Effective Date and Implementation Strategy
FDA proposes that any final rule based on this proposal become
effective 1 year after the date of publication of the final rule in the
Federal Register. This approach is intended to provide adequate time
for manufacturers to make any changes necessary to comply with the
requirements of ISO 13485. We welcome comment on this approach.
Although this rule does not impact FDA's authority to conduct
inspections under section 704 of the FD&C Act, FDA intends to replace
its current inspection approach for medical devices, the Quality System
Inspection Technique (QSIT), with an inspection approach that will be
consistent with the requirements of the proposed part 820 as finalized.
Similar to the current QSIT
[[Page 10128]]
inspection approach, these inspections would involve the collection of
information to support observations noted during the inspection and
those included on a Form FDA 483, as appropriate and necessary. FDA
inspections will not result in the issuance of certificates of
conformance to ISO 13485, nor is FDA developing a certification program
for ISO 13485. In addition, manufacturers with a certificate of
conformance to ISO 13485 are not exempt from FDA inspections.
If this rule is finalized, FDA intends to engage in a variety of
implementation activities including, among other activities, updating
information technology systems, training of personnel, finalizing the
inspection approach, and revising relevant regulations and other
documents impacted by this rulemaking.
VII. Preliminary Economic Analysis of Impacts
We have examined the impacts of the proposed rule under Executive
Order 12866, Executive Order 13563, the Regulatory Flexibility Act (5
U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L.
104-4). Executive Orders 12866 and 13563 direct us to assess all costs
and benefits of available regulatory alternatives and, when regulation
is necessary, to select regulatory approaches that maximize net
benefits (including potential economic, environmental, public health
and safety, and other advantages; distributive impacts; and equity). We
believe that this proposed rule is an economically significant
regulatory action as defined by Executive Order 12866.
The Regulatory Flexibility Act requires us to analyze regulatory
options that would minimize any significant impact of a rule on small
entities. Because of the burden of the proposed rule on very small
medical device establishment (as defined in the analysis), we propose
to certify that the proposed rule will not have a significant economic
impact on a substantial number of small entities.
The Unfunded Mandates Reform Act of 1995 (section 202(a)) requires
us to prepare a written statement, which includes an assessment of
anticipated costs and benefits, before proposing ``any rule that
includes any Federal mandate that may result in the expenditure by
State, local, and tribal governments, in the aggregate, or by the
private sector, of $100,000,000 or more (adjusted annually for
inflation) in any one year.'' The current threshold after adjustment
for inflation is $158 million, using the most current (2020) Implicit
Price Deflator for the Gross Domestic Product. This proposed rule would
not result in an expenditure in any year that meets or exceeds this
amount.
We estimated the benefits in terms of cost savings. These cost
savings are primarily due to the potential reduction in redundant
effort in compliance of similar regulations and standards by medical
device establishments. The annualized costs savings of medical device
establishments are estimated at approximately $533 million at a 7
percent discount rate, and approximately $439 million at a 3 percent
discount rate. In addition, if finalized, we believe that there will be
added benefits through quicker access to newly developed medical
devices for patients, leading to improvement of life quality for the
consumers. The cost of the proposed rule primarily consists of a one-
time initial expenditure for updating systems and protocols, and
training personnel for medical device establishments, which currently
do not comply with ISO 13485. The cost estimate for these
establishments is annualized at $7.0 million at a 7 percent discount
rate, and approximately $5.8 million at a 3 percent discount rate.
Table 2--Summary of Benefits, Costs and Distributional Effects of Proposed Rule
[Millions $]
--------------------------------------------------------------------------------------------------------------------------------------------------------
Units
------------------------------------
Category Primary Low High Period Notes
estimate estimate estimate Year Discount covered
dollars rate (%) (years)
--------------------------------------------------------------------------------------------------------------------------------------------------------
Benefits: \1\
Annualized Monetized $M/year...... $533 $267 $1,332 2020 7 10 Benefit are cost savings.
439 220 1,097 2020 3 10 Benefit are cost savings.
Annualized Quantified............. .......... .......... .......... .......... 7 .......... ........................................
.......... .......... .......... .......... 3 .......... ........................................
Qualitative....................... .......... .......... .......... .......... .......... .......... ........................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
Costs:
Annualized Monetized $M/year...... 6.96 6.96 6.96 2020 7 10
5.73 5.73 5.73 2020 3 10
Annualized Quantified............. .......... .......... .......... .......... 7 .......... ........................................
.......... .......... .......... .......... 3 .......... ........................................
Qualitative....................... .......... .......... .......... .......... .......... .......... ........................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
Transfers:
Federal Annualized Monetized $M/ .......... .......... .......... .......... 7 .......... ........................................
year.
-----------------------------------------------------------------------------------------------------------------
.......... .......... .......... .......... 3 .......... ........................................
------------------------------------------------------------------------
From/To........................... From:
To:
-----------------------------------------------------------------------------------------------------------------
Other Annualized Monetized $M/year .......... .......... .......... .......... 7 .......... ........................................
-----------------------------------------------------------------------------------------------------------------
.......... .......... .......... .......... 3 .......... ........................................
------------------------------------------------------------------------
From/To........................... From:
To:
--------------------------------------------------------------------------------------------------------------------------------------------------------
Effects:
State, Local or Tribal Government:..................................................................................................................
Small Business:.....................................................................................................................................
Wages:..............................................................................................................................................
Growth:.............................................................................................................................................
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Estimated benefits are in terms of cost savings for medical device establishments that conform to the current part 820. Other benefits that are not
quantified potentially include quicker delivery and more efficient access to necessary devices for patients, leading to improvement of quality of life
for consumers.
Note: All figures are in millions of dollars.
[[Page 10129]]
We have developed a comprehensive Preliminary Economic Analysis of
Impacts that assesses the impacts of the proposed rule. The full
preliminary analysis of economic impacts is available in the docket for
this proposed rule (Ref. 11) and at https://www.fda.gov/about-fda/reports/economic-impact-analyses-fda-regulations.
VIII. Analysis of Environmental Impact
We have determined under 21 CFR 25.30(j) that this action is of a
type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
IX. Paperwork Reduction Act of 1995
This proposed rule contains information collection provisions that
are subject to review by the OMB under the PRA (44 U.S.C. 3501-3521). A
description of these provisions is given in the Description section
with an estimate of the annual recordkeeping burden. Included in the
estimate is the time for reviewing instructions, searching existing
data sources, gathering and maintaining the data needed, and completing
and reviewing each collection of information.
FDA invites comments on these topics: (1) Whether the proposed
collection of information is necessary for the proper performance of
FDA's functions, including whether the information will have practical
utility; (2) the accuracy of FDA's estimate of the burden of the
proposed collection of information, including the validity of the
methodology and assumptions used; (3) ways to enhance the quality,
utility, and clarity of the information to be collected; and (4) ways
to minimize the burden of the collection of information on respondents,
including through the use of automated collection techniques, when
appropriate, and other forms of information technology.
Title: Medical Devices; Quality Management System; OMB Control
Number 0910-0073--Revision.
Description: FDA is proposing to revise its device CGMP
requirements as set forth in the QS regulation, codified in part 820.
Through this proposed rulemaking, FDA intends to converge its
requirements with QMS requirements used by other regulatory
authorities. FDA seeks to accomplish this primarily by incorporating by
ISO 13485. This rule, if finalized, would harmonize QMS requirements
for devices with requirements used by other regulatory authorities.
Description of Respondents: Respondents to this information
collection are any manufacturers engaged in the design, manufacture,
packaging, labeling, storage, installation, or servicing of a finished
device, including, but not limited to, organizations that perform the
functions of contract sterilization, installation, relabeling,
remanufacturing, repacking, or specification development, as well as
initial distributors of foreign entities that perform these functions.
Manufacturers of components or parts of finished devices may
voluntarily use appropriate provisions of the proposed regulation as
guidance.
Respondents are also manufacturers of human cells, tissues, and
cellular and tissue-based products (HCT/Ps), as defined in 21 CFR
1271.3(d), that are devices.
We estimate the burden of this collection of information as
follows:
Table 3--Estimated One-Time Recordkeeping Burden
--------------------------------------------------------------------------------------------------------------------------------------------------------
Number of Average burden
Activity Number of records per Total records per Total hours Total capital
recordkeepers recordkeeper recordkeeping costs
--------------------------------------------------------------------------------------------------------------------------------------------------------
Learn the rule--one-time burden......................... 20,346 1 20,346 2.6 52,900 $7,600,000
Initial one-time burden for those respondents whose 4,445 1 4,445 64 284,480 43,000,000
processes do not already comply with ISO 13485.........
-----------------------------------------------------------------------------------------------
Total............................................... .............. .............. .............. .............. 337,380 50,600,000
--------------------------------------------------------------------------------------------------------------------------------------------------------
The currently approved number of respondents to the collection is
27,074; however we expect nominal fluctuations in the number of
registered medical device facilities and have reduced that number to
20,346 based on a current review of data and to be consistent with the
Preliminary Regulatory Impact Analysis for this proposed rule (see Ref.
11).
All medical device establishments that will be covered under the
rulemaking undergo a one-time burden to learn the rulemaking. We model
the one-time learning cost as the time required by medical device
establishments' regulatory affairs expert to access and read the
proposed rule, approximately 2.6 hours (rounded). The average total
access and learning cost for all affected entities is approximately
$7,600,000 (see Ref. 11).
In addition to learning the rule requirements, medical device
establishments that are not in compliance with ISO 13485 when the
rulemaking is implemented would incur one-time initial costs related to
training of a regulatory compliance expert, updating information
technology, and updating documents related to policy and procedures.
The additional estimated cost burden for medical device establishments
that are not in compliance with ISO 13485 when the rulemaking is
implemented is approximately $43,000,000 (see Ref. 11).
The estimated hour burden of these additional one-time activities
is included under ``Initial one-time burden for those respondents whose
processes do not already comply with ISO 13485'' in table 3. In the
Preliminary Regulatory Impact Analysis for this rulemaking, we estimate
there are 4,445 respondents that do not currently comply with ISO 13485
and that the average burden per recordkeeping is approximately 64 hours
(Ref. 11). Because we do not have robust data on the number of firms
that currently comply with ISO 13485, we are using very small domestic
medical device manufacturing establishments to represent those who will
proportionally bear a greater burden of one-time costs by the proposed
rule. As such, for this analysis, and as discussed in the Preliminary
Regulatory Impact Analysis, we assume that very small medical device
manufacturing establishments currently do not sell their products
abroad and do not comply with ISO 13485 (Ref. 11).
[[Page 10130]]
Table 4--Estimated Annual Recordkeeping Burden \1\ \2\
----------------------------------------------------------------------------------------------------------------
Number of Average burden
Activity; 21 CFR section Number of records per Total annual per Total hours
recordkeepers recordkeeper records recordkeeping
----------------------------------------------------------------------------------------------------------------
Quality Management System 20,346 1 20,346 348 7,080,408
(proposed Sec. 820.10 and ISO
13485).........................
Control of records (proposed 20,346 1 20,346 2 40,692
Sec. 820.35).................
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 7,121,100
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this annual collection of
information.
\2\ Numbers have been rounded.
The current burden associated with recordkeeping requirements in
part 820 is 9,021,752 hours annually. We assume a commensurate level of
burden for the proposed recordkeeping activities (350 hours for the
Average Burden per Recordkeeping).
As mentioned previously in this section, we expect nominal
fluctuations in the number of registered medical device facilities and
have reduced that number from 27,074 to 20,346 based on a current
review of data and to be consistent with the Preliminary Regulatory
Impact Analysis for this proposed rule (see Ref. 11). This adjustment
results in a reduction of 1,900,652 total hours annually.
Quality Management System (proposed Sec. 820.10 and ISO 13485):
Under proposed Sec. 820.10, an organization subject to proposed part
820 must document a QMS that complies with the requirements of ISO
13485, as incorporated by reference in proposed Sec. 820.7, and
proposed part 820.
Under proposed Sec. 820.10(c), manufacturers of class II, class
III, and certain class I devices, as listed in proposed Sec.
820.10(c)(ii), must comply with the requirements in Design and
Development, Clause 7.3 and its Subclauses in ISO 13485. This amendment
does not substantively change the current recordkeeping requirement.
Under proposed Sec. 820.10(d), manufacturers of devices that
support or sustain life, the failure of which to perform when properly
used in accordance with instructions for use provided in the labeling
can be reasonably expected to result in a significant injury, must
comply with the requirements in Traceability for Implantable Devices,
Clause 7.5.9.2 in ISO 13485, in addition to all other requirements in
this part, as appropriate. This amendment does not substantively change
the current recordkeeping requirement.
Control of records (proposed Sec. 820.35): In addition to the
requirements of Clause 4.2.5 in ISO 13485, Control of Records, the
manufacturer must obtain the signature for each individual who approved
or re-approved the record, and the date of such approval, on that
record and include the information in certain records as listed in
proposed Sec. 820.35.
In addition to Clause 8.2.2 in ISO 13485, Complaint Handling, the
manufacturer must record the listed information, at a minimum, for
complaints that must be reported to FDA under part 803, complaints that
a manufacturer determines must be investigated, and complaints that the
manufacturer investigated regardless of those requirements. The
reporting requirements of part 803 are approved under OMB control
number 0910-0437. Estimated burden for the recordkeeping requirement in
proposed Sec. 820.35(a) is included as part of the estimate for
``Control of records (proposed Sec. 820.35)'' in table 4.
In adhering to Clause 7.5.4 in ISO 13485, Servicing Activities, the
manufacturer must record the information listed in proposed Sec.
820.35(b), at a minimum, for servicing activities.
Under proposed Sec. 820.35(c), in addition to the requirements of
Clauses 7.5.1, 7.5.8, and 7.5.9 of ISO 13485, the UDI must be recorded
for each medical device or batch of medical devices. The estimated
recordkeeping burden associated with UDI is included as part of the
estimate for ``Control of records (proposed Sec. 820.35)'' in table 4.
Because the records required by proposed Sec. 820.35 should be
readily available to the respondents, we estimate the average burden
per response for proposed Sec. 820.35 to be no more than 2 hours. This
estimate is in addition to the requirements of the applicable ISO 13485
Clauses, the burden for which is included under ``Quality Management
System (proposed Sec. 820.10 and ISO 13485)'' in table 4.
Device labeling and packaging controls (proposed Sec. 820.45): In
addition to the requirements of Clause 7.5.1 of ISO 13485, Control of
production and service provision, manufacturers must ensure labeling
and packaging has been examined for accuracy prior to release or
storage (Sec. 820.45(a)), the release of the labeling for use must be
documented in accordance with Clause 4.2.5 of ISO 13485 (Sec.
820.45(b)), and results of the labeling inspection in proposed Sec.
820.45(c) must be documented in accordance with Clause 4.2.5 of ISO
13485. The estimated recordkeeping burden for ISO 13485, Clause 4.2.5,
is part of the estimate for ``Quality Management System (proposed Sec.
820.10 and ISO 13485)'' in table 4. There is no additional hour burden
associated with proposed Sec. 820.45.
To ensure that comments on information collection are received, OMB
recommends that written comments be submitted through https://www.reginfo.gov/public/do/PRAMain (see ADDRESSES). All comments should
be identified with the title of the information collection.
In compliance with the PRA (44 U.S.C. 3501, et seq.), we have
submitted the information collection provisions of this proposed rule
to OMB for review. These information collection requirements will not
be effective until FDA publishes a final rule, OMB approves the
information collection requirements, and the rule goes into effect. FDA
will announce OMB approval of these requirements in the Federal
Register.
X. Federalism
We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. We have determined that
this proposed rule does not contain policies that have substantial
direct effects on the States, on the relationship between the National
Government and the States, or on the distribution of power and
responsibilities among the various levels of government. Accordingly,
we conclude that the rule does not contain policies that have
federalism implications as defined in the Executive Order and,
consequently, a federalism summary impact statement is not required.
[[Page 10131]]
XI. Consultation and Coordination With Indian Tribal Governments
We have analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13175. We have tentatively
determined that the rule does not contain policies that would have a
substantial direct effect on one or more Indian Tribes, on the
relationship between the Federal Government and Indian Tribes, or on
the distribution of power and responsibilities between the Federal
Government and Indian Tribes. The Agency solicits comments from tribal
officials on any potential impact on Indian Tribes from this proposed
action.
XII. References
The following references marked with an asterisk (*) are on display
at the Dockets Management Staff (see ADDRESSES) and are available for
viewing by interested persons between 9 a.m. and 4 p.m., Monday through
Friday; they also are available electronically at https://www.regulations.gov. References without asterisks are not on public
display at https://www.regulations.gov because they have copyright
restriction. Some may be available at the website address, if listed.
References without asterisks are available for viewing only at the
Dockets Management Staff. FDA has verified the website addresses, as of
the date this document publishes in the Federal Register, but websites
are subject to change over time.
* 1. ISO 13485:2016, ``Medical devices--Quality management systems--
Requirements for regulatory purposes,'' Third Edition, March 1,
2016.
* 2. FDA, ``Regulations Establishing Good Manufacturing Practices
for the Manufacture, Packing, Storage, and Installation of Medical
Devices.'' Federal Register, 43: 31508-31532, July 21, 1978.
3. ISO 13485:1996, ``Quality systems--Medical devices--Particular
requirements for the application of ISO 9001,'' December 1996
(withdrawn). (Referenced at: https://www.iso.org/standard/22098.html.)
4. ISO 9001:1994, ``Quality Systems--Model for Quality Assurance in
Design, Development, Production, Installation, and Servicing,'' June
1994 (withdrawn). (Referenced at: https://www.iso.org/standard/25946.html.)
* 5. FDA, ``Medical Device Single Audit Program (MDSAP).''
(Available at: https://www.fda.gov/medical-devices/cdrh-international-programs/medical-device-single-audit-program-mdsap.)
6. Global Harmonization Task Force. Guidance document,
``Implementation of Risk Management Principles and Activities Within
a Quality Management System,'' May 20, 2005. (Available at: https://www.imdrf.org/docs/ghtf/final/sg3/technical-docs/ghtf-sg3-n15r8-risk-management-principles-qms-050520.pdf.)
7. ISO 14971, ``Medical Devices--Application of Risk Management to
Medical Devices.'' (Available at: https://www.iso.org/standard/72704.html.)
* 8. ``Guidance for Industry, Third Parties and Food and Drug
Administration Staff: Medical Device ISO 13485:2003 Voluntary Audit
Report Submission Pilot Program'' effective June 5, 2012. Federal
Register, March 19, 2012 (Available at: https://www.federalregister.gov/citation/77-FR-16036).
9. International Medical Device Regulators Forum, https://www.imdrf.org/.
10. International Standard, ISO 9000 ``Quality Management Systems--
Fundamentals and Vocabulary,'' ISO 9000:2015. (Available at: ISO
9000:2015(en), Quality management systems--Fundamentals and
vocabulary.)
* 11. ``Preliminary Regulatory Impact Analysis, Initial Regulatory
Flexibility Analysis, and Unfunded Mandates Reform Act Analysis;
Medical Devices; Quality System Regulation Amendments.'' (Available
at: https://www.fda.gov/about-fda/reports/economic-impact-analyses-fda-regulations.)
List of Subjects
21 CFR Part 4
Biologics, Drugs, Human cells and tissue-based products,
Incorporation by reference, Medical devices.
21 CFR Part 820
Incorporation by reference, Medical devices, Reporting and
recordkeeping requirements.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
the authority delegated to the Commissioner of Food and Drugs, it is
proposed that 21 CFR parts 4 and 820 be amended as follows:
PART 4--REGULATION OF COMBINATION PRODUCTS
0
1. The authority citation for part 4 continues to read as follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360, 360b-
360f, 360h-360j, 360l, 360hh-360ss, 360aaa-360bbb, 371(a), 372-374,
379e, 381, 383, 394; 42 U.S.C. 216, 262, 263a, 264, 271.
0
2. In Sec. 4.2,
0
a. Revise the definition of ``Device''; and
0
b. Remove the definition of ``QS regulation'', and add in its place a
definition for ``QMSR for devices''.
The revision and addition read as follows:
Sec. 4.2 How does FDA define key terms and phrases in this subpart?
* * * * *
Device has the meaning set forth in Sec. 3.2(f) of this chapter. A
device that is a constituent part of a combination product is
considered a finished device within the meaning of the Quality
Management System Regulation (QMSR).
* * * * *
QMSR for devices refers to the requirements under part 820 of this
chapter.
* * * * *
0
3. In Sec. 4.4, revise paragraph (b)(1) and the introductory text to
paragraph (b)(2) and add paragraph (f) to read as follows:
Sec. 4.4 How can I comply with these current good manufacturing
practice requirements for a co-packaged or single-entity combination
product?
* * * * *
(b) * * *
(1) If the combination product includes a device constituent part
and a drug constituent part, and the current good manufacturing
practice operating system has been shown to comply with the drug CGMPs,
the following clauses of ISO 13485 within the QMSR requirements for
devices must also be shown to have been satisfied; upon demonstration
that these requirements have been satisfied, no additional showing of
compliance with respect to the QMSR requirements for devices need be
made:
(i) Management responsibility. Clause 4.1, Clause 5 and its
subclauses and Clause 6.1 of ISO 13485;
(ii) Design and development. Clause 7.3 and its subclauses of ISO
13485;
(iii) Purchasing. Clause 7.4 and its subclauses of ISO 13485;
(iv) Improvement. Clause 8.4, Clause 8.5 and its subclauses of ISO
13485;
(v) Installation activities. Clause 7.5.3 of ISO 13485; and
(vi) Servicing activities. Clause 7.5.4 of ISO 13485 and Sec.
820.35(b).
(2) If the combination product includes a device constituent part
and a drug constituent part, and the current good manufacturing
practice operating system has been shown to comply with the QMS
requirements for devices, the following provisions of the drug CGMPs
must also be shown to have been satisfied; upon demonstration that
these requirements have been satisfied, no additional showing of
compliance with respect to the drug CGMPs need be made:
* * * * *
(f) Certain material is incorporated by reference into this section
with the approval of the Director of the Federal Register under 5
U.S.C. 552(a) and 1 CFR part 51. All approved material is available for
inspection at the Food and
[[Page 10132]]
Drug Administration, Dockets Management Staff, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852, 240-402-7500, and at the National Archives
and Records Administration (NARA). For information on the availability
of this material at NARA, call 202-741-6030, email
[email protected], or go to www.archives.gov/federal-register/cfr/ibr-locations.html. It is available from the following source(s):
(1) The International Organization for Standardization (ISO), BIBC
II, Chemin de Blandonnet 8, CP 401, 1214 Vernier, Geneva, Switzerland;
+41-22-749-01-11; [email protected], https://www.iso.org/store.html.
(i) ISO 13485, ``Medical devices--Quality management systems--
Requirements for regulatory purposes,'' third edition, dated March
2016,
(ii) [Reserved]
(2) [Reserved]
0
4. Revise part 820 to read as follows:
PART 820--QUALITY MANAGEMENT SYSTEM REGULATION
Subpart A--General Provisions
Sec.
820.1 Scope.
820.3 Definitions.
820.5 [Reserved]
820.7 Incorporation by reference.
820.10 Requirements for a quality management system.
820.15 Clarification of concepts.
Subpart B--Supplemental Provisions
820.20-820.30 [Reserved]
820.35 Control of records.
820.40 [Reserved]
820.45 Device labeling and packaging controls.
Subparts C-O--[Reserved]
Authority: 21 U.S.C. 351, 352, 360, 360c, 360d, 360e, 360h,
360i, 360j, 360l, 371, 374, 381, 383; 42 U.S.C. 216, 262, 263a, 264.
Subpart A--General Provisions
Sec. 820.1 Scope.
(a) Applicability. Current good manufacturing practice (CGMP)
requirements are set forth in this quality management system regulation
(QMSR). The requirements in this part govern the methods used in, and
the facilities and controls used for, the design, manufacture,
packaging, labeling, storage, installation, and servicing of all
finished devices intended for human use. The requirements in this part
are intended to assure that finished devices will be safe and effective
and otherwise in compliance with the Federal Food, Drug, and Cosmetic
Act. Any manufacturers engaged in the design, manufacture, packaging,
labeling, storage, installation, or servicing of a finished device must
establish and maintain a quality management system that is appropriate
for its specific device(s). Manufacturers subject to this part include,
but are not limited to, manufacturers that perform the functions of
contract sterilization, installation, relabeling, remanufacturing,
repacking, or specification development, as well as initial
distributors of foreign entities that perform these functions. If a
manufacturer engages in only some operations subject to the
requirements in this part, and not in others, that manufacturer need
only comply with those requirements applicable to the operations in
which it is engaged.
(1) Finished devices. The provisions of this part shall apply to
any finished device, as defined in this part, intended for human use,
that is manufactured, imported, or offered for import in any State or
Territory of the United States, the District of Columbia, or the
Commonwealth of Puerto Rico.
(2) Components or parts. The provisions of this part do not apply
to manufacturers of components or parts of finished devices, but such
manufacturers are encouraged to consider provisions of this regulation
as appropriate.
(3) Blood and blood components. The provisions of this part do not
apply to manufacturers of blood and blood components used for
transfusion or for further manufacturing. Such manufacturers are
subject to subchapter F of this chapter.
(4) HCT/Ps. The provisions of this part apply to manufacturers of
human cells, tissues, and cellular and tissue-based products (HCT/Ps),
as defined in Sec. 1271.3(d) of this chapter, that are devices
(subject to premarket review or notification, or exempt from
notification, under an application submitted under the device
provisions of the Federal Food, Drug, and Cosmetic Act or under a
biological product license application under section 351 of the Public
Health Service Act). HCT/Ps regulated as devices are also subject to
the donor-eligibility requirements set forth in part 1271, subpart C of
this chapter and applicable current good tissue practice requirements
in part 1271, subpart D of this chapter. In the event of a conflict
between applicable regulations in part 1271 and in other parts of this
chapter, the regulation specifically applicable to the device in
question shall supersede the more general regulation.
(b) Conflicts with other requirements under the Federal Food, Drug,
and Cosmetic Act. The QMSR for devices in this part supplements
regulations in other parts of this chapter except where explicitly
stated otherwise. In the event of a conflict between applicable
regulations in this part and in other parts of this chapter, the
regulations specifically applicable to the device in question shall
supersede the more generally applicable regulations to the extent they
conflict. Moreover, to the extent that any clauses of ISO 13485
(incorporated by reference, see Sec. 820.7) conflict with any
provisions of the Federal Food, Drug, and Cosmetic Act and/or its other
implementing regulations, the Federal Food, Drug, and Cosmetic Act and/
or its other implementing regulations will control.
(c) Foreign manufacturers. If it appears that an owner, operator,
or agent of any factory, warehouse, or establishment who offers devices
for import into the United States delays, denies, or limits an
inspection, or refuses to permit entry or inspection of the foreign
facility for the purpose of determining compliance with this part, or
the methods used in, and the facilities and controls used for, the
manufacture, packing, storage, installation, processing, or held in
such factory, warehouse, or establishment that are offered for import
into the United States do not conform to the requirements of section
520(f) of the Federal Food, Drug, and Cosmetic Act and this part, then
the devices manufactured at that facility are adulterated under section
501(h) or (j) of the Federal Food, Drug, and Cosmetic Act and will be
refused admission to the United States under section 801(a) of the
Federal Food, Drug, and Cosmetic Act.
(d) Exemptions or variances. (1) A manufacturer subject to any
requirement under section 520(f)(1) of the Federal Food, Drug, and
Cosmetic Act, including any requirements under this part, may petition
for an exemption or variance from such requirement in accordance with
section 520(f)(2) of the Federal Food, Drug, and Cosmetic Act.
Petitions for an exemption or variance shall be submitted in accordance
with the procedures set forth in Sec. 10.30 of this chapter.
(2) FDA may initiate and grant a variance from any requirement(s)
in this part when the Agency determines that such variance is in the
best interest of the public health. Such variance will remain in effect
only so long as there remains a public health need for the device and
the device would not likely be made sufficiently available without the
variance.
[[Page 10133]]
Sec. 820.3 Definitions.
The definitions in ISO 13485 (incorporated by reference, see Sec.
820.7) apply to this part, except as specified in paragraph (b) of this
section, and do not affect the meaning of similar terms defined in this
title.
(a) The following terms are necessary for the purposes of this part
and do not appear in ISO 13485:
Component means any raw material, substance, piece, part, software,
firmware, labeling, or assembly that is intended to be included as part
of the finished, packaged, and labeled device.
Customer means persons or organizations, including users, that
could or do receive a product or a service that is intended for or
required by this person or organization. A customer can be internal or
external to the organization.
Design validation means establishing by objective evidence that
device specifications conform with user needs and intended use(s).
Federal Food, Drug, and Cosmetic Act means the Federal Food, Drug,
and Cosmetic Act, 21 U.S.C. 321 et seq., as amended.
Finished device means any device or accessory to any device that is
suitable for use or capable of functioning, whether or not it is
packaged, labeled, or sterilized.
Human cell, tissue, or cellular or tissue-based product (HCT/P)
regulated as a device means an HCT/P as defined in Sec. 1271.3(d) of
this chapter that does not meet the criteria in Sec. 1271.10(a) of
this chapter and that is also regulated as a device.
Nonconformity means the nonfulfillment of a specified requirement.
Process agent means any material or substance used in or used to
facilitate the manufacturing process, a concomitant constituent, or a
byproduct constituent produced during the manufacturing process, which
is present in or on the finished device as a residue or impurity not by
design or intent of the manufacturer.
Process validation means establishing by objective evidence that a
process consistently produces a result or product meeting its
predetermined specifications.
Remanufacturer means any person who processes, conditions,
renovates, repackages, restores, or does any other act to a finished
device that significantly changes the finished device's performance or
safety specifications, or intended use.
Rework means action taken on a nonconforming product so that it
will fulfill the specified requirements before it is released for
distribution.
Top management means those senior employees of a manufacturer who
have the authority to establish or make changes to the manufacturer's
quality policy and quality management system.
Verification means confirmation by examination and provision of
objective evidence that specified requirements have been fulfilled.
(b) All definitions in section 201 of the Federal Food, Drug, and
Cosmetic Act shall apply to the regulation of quality management
systems under this part and shall supersede the correlating terms and
definitions in ISO 13485 (e.g., the definitions of device and labeling
in sections 201(h) and (m) of the Federal Food, Drug, and Cosmetic Act
apply to this part and supersede the definitions for the correlating
terms in ISO 13485 (labelling and medical device)). In addition, the
following terms and definitions supersede the correlating term and
definition in ISO 13485:
Manufacturer means any person who designs, manufactures,
fabricates, assembles, or processes a finished device. Manufacturer
includes, but is not limited to, those who perform the functions of
contract sterilization, installation, relabeling, remanufacturing,
repacking, or specification development, and initial distributors of
foreign entities performing these functions.
Product means components, process agents, in-process devices,
finished devices, and returned devices.
Sec. 820.5 [Reserved]
Sec. 820.7 Incorporation by reference.
Certain material is incorporated by reference into this part with
the approval of the Director of the Federal Register under 5 U.S.C.
552(a) and 1 CFR part 51. All approved material is available for
inspection at the Food and Drug Administration, Dockets Management
Staff, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, 240-402-7500,
and at the National Archives and Records Administration (NARA). For
information on the availability of this material at NARA, call 202-741-
6030, email [email protected], or go to www.archives.gov/federal-register/cfr/ibr-locations.html. It is available from the following
source(s):
(a) The International Organization for Standardization (ISO), BIBC
II, Chemin de Blandonnet 8, CP 401, 1214 Vernier, Geneva, Switzerland;
+41-22-749-01-11; [email protected], https://www.iso.org/store.html.
(1) ISO 13485, ``Medical devices--Quality management systems--
Requirements for regulatory purposes,'' third edition, dated March
2016; IBR approved for Sec. Sec. 820.1; 820.3; 820.10; 820.15; 820.35;
820.45.
(2) [Reserved]
(b) [Reserved]
Sec. 820.10 Requirements for a quality management system.
A manufacturer subject to this part as described by Sec. 820.1(a)
must:
(a) Document. Document a quality management system that complies
with the requirements of ISO 13485 (incorporated by reference, see
Sec. 820.7) and this part; and
(b) Applicable regulatory requirements. Comply, as appropriate,
with the other applicable regulatory requirements in this title,
including, but not limited to the following, to fully comply with the
listed ISO 13485 Clause:
(1) For Clause 7.5.8 in ISO 13485, Identification, the manufacturer
must document a system to assign unique device identification to the
medical device in accordance with the requirements of part 830.
(2) For Clause 7.5.9.1 in ISO 13485, Traceability--General, the
manufacturer must document procedures for traceability in accordance
with the requirements of part 821, if applicable.
(3) For Clause 8.2.3 in ISO 13485, Reporting to regulatory
authorities, the manufacturer must notify FDA of complaints that meet
the reporting criteria of part 803 of this chapter.
(4) For Clauses 7.2.3, 8.2.3, and 8.3.3, advisory notices shall be
handled in accordance with the requirements of part 806.
(c) Design and Development. Manufacturers of class II, class III,
and those class I devices listed below must comply with the
requirements in Design and Development, Clause 7.3 and its Subclauses
in ISO 13485. The class I devices are as follows:
(1) Devices automated with computer software; and
(2) The devices listed in the following table:
Table 1 to Paragraph (c)(2)
------------------------------------------------------------------------
Section Device
------------------------------------------------------------------------
868.6810.......................... Catheter, Tracheobronchial Suction.
878.4460.......................... Glove, Non-powdered Surgeon's.
880.6760.......................... Restraint, Protective.
892.5650.......................... System, Applicator, Radionuclide,
Manual.
892.5740.......................... Source, Radionuclide Teletherapy.
------------------------------------------------------------------------
(d) Devices that support or sustain life. Manufacturers of devices
that support or sustain life, the failure of which to perform when
properly used in accordance with instructions for use
[[Page 10134]]
provided in the labeling can be reasonably expected to result in a
significant injury, must comply with the requirements in Traceability
for Implantable Devices, Clause 7.5.9.2 in ISO 13485, in addition to
all other requirements in this part, as appropriate.
(e) Enforcement. The failure to comply with any applicable
requirement in this part renders a device adulterated under section
501(h) of the Federal Food, Drug, and Cosmetic Act. Such a device, as
well as any person responsible for the failure to comply, is subject to
regulatory action.
Sec. 820.15 Clarification of concepts.
Manufacturers subject to this part shall construe the following
terms in ISO 13485 (incorporated by reference, see Sec. 820.7) as
follows:
(a) Organization shall have the meaning of ``manufacturers'' as
defined in this part.
(b) Safety and performance shall have the meaning of ``safety and
effectiveness'' for the purposes of this part. The phrase ``safety and
performance'' does not relieve a manufacturer from any obligation to
implement controls or other measures that provide reasonable assurance
of safety and effectiveness.
(c) Validation of processes shall have the meaning of ``process
validation'' as defined in this part.
Subpart B--Supplemental Provisions
Sec. 820.20-Sec. 820.30 [Reserved]
Sec. 820.35 Control of records.
In addition to the requirements of Clause 4.2.5 in ISO 13485
(incorporated by reference, see Sec. 820.7), Control of Records, the
manufacturer must obtain the signature for each individual who approved
or re-approved the record, and the date of such approval, on that
record and include the below information in certain records as follows:
(a) Records of complaints. In addition to Clause 8.2.2 in ISO
13485, Complaint Handling, the manufacturer must record the following
information, at a minimum, for complaints that must be reported to FDA
under part 803 of this chapter, complaints that a manufacturer
determines must be investigated, and complaints that the manufacturer
investigated regardless of those requirements:
(1) The name of the device;
(2) The date the complaint was received;
(3) Any unique device identifier (UDI) or universal product code
(UPC), and any other device identification(s);
(4) The name, address, and phone number of the complainant;
(5) The nature and details of the complaint;
(6) Any corrective action taken; and
(7) Any reply to the complainant.
(b) Records of servicing activities. In adhering to Clause 7.5.4 in
ISO 13485, Servicing Activities, the manufacturer must record the
following information, at a minimum, for servicing activities:
(1) The name of the device serviced;
(2) Any unique device identifier (UDI) or universal product code
(UPC), and any other device identification(s);
(3) The date of service;
(4) The individual(s) who serviced the device;
(5) The service performed; and
(6) Any test and inspection data.
(c) Unique device identification. In addition to the requirements
of Clauses 7.5.1, 7.5.8, and 7.5.9 in ISO 13485, the UDI must be
recorded for each medical device or batch of medical devices.
(d) Confidentiality. Records deemed confidential by the
manufacturer may be marked to aid FDA in determining whether
information may be disclosed under the public information regulation in
part 20 of this chapter.
Sec. 820.40 [Reserved]
Sec. 820.45 Device labeling and packaging controls.
In addition to the requirements of Clause 7.5.1 of ISO 13485
(incorporated by reference, see Sec. 820.7), Control of production and
service provision, each manufacturer must establish and maintain
procedures that provide a detailed description of the activities to
ensure the integrity, inspection, storage, and operations for labeling
and packaging, during the customary conditions of processing, storage,
handling, distribution, and where appropriate, use of the device.
(a) The manufacturer must ensure labeling and packaging has been
examined for accuracy prior to release or storage, where applicable, to
include the following:
(1) The correct unique device identifier (UDI) or universal product
code (UPC), or any other device identification(s);
(2) Expiration date;
(3) Storage instructions;
(4) Handling instructions; and
(5) Any additional processing instructions.
(b) The release of the labeling for use must be documented in
accordance with Clause 4.2.5 of ISO 13485.
(c) The manufacturer must ensure labeling and packaging operations
have been established and maintained to prevent errors, including, but
not limited to, inspection of the labeling and packaging immediately
before use to assure that all devices have correct labeling and
packaging, as specified in the medical device file. Results of such
labeling inspection must be documented in accordance with Clause 4.2.5
of ISO 13485.
Subparts C-O--[Reserved]
Dated: February 8, 2022.
Janet Woodcock,
Acting Commissioner of Food and Drugs.
[FR Doc. 2022-03227 Filed 2-22-22; 8:45 am]
BILLING CODE 4164-01-P