Agency Information Collection Activities; Submission for Office of Management and Budget Review; Comment Request; Current Good Manufacturing Practices for Positron Emission Tomography Drugs, 46537-46543 [2019-19030]
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Federal Register / Vol. 84, No. 171 / Wednesday, September 4, 2019 / Notices
development of type 2 diabetes. This
proposed project’s primary purposes are
to (1) increase knowledge of recruitment
strategies, specifically introductory
sessions, used by CDC-recognized
organizations to increase enrollment in
the National DPP LCP (Phase 1), and (2)
evaluate introductory sessions,
specifically a CDC-developed
behaviorally-informed introductory
session known as the Be Your Best
(BYB) Discovery Session, on enrollment
compared with other types of
introductory sessions that organizations
currently use (Phase 2).
CDC is requesting OMB approval to
collect information needed for this
evaluation. For Phase 1 of this project,
the Introductory Session Landscape
Assessment, CDC is seeking approval to
disseminate a brief Landscape
Assessment (survey) to all National DPP
CDC-recognized organizations
(approximately 1,700) and their affiliate
class locations (up to 540). The survey
will initially be disseminated
electronically (web-based survey), and
then a hard copy will be mailed to nonrespondents. The overall evaluation
46537
hard copies to introductory session
attendees. The BYB Discovery Session
Implementation Fidelity Checklist and
the Registration and Attendance
Tracking Form will be designed in
Microsoft Excel and distributed to
participating LCP staff using secure FTP
upload for LCP personnel to complete
electronically.
Information collected will be
analyzed to evaluate the effectiveness of
the BYB Discovery Session intervention
in increasing enrollment in the National
DPP LCP compared with already
occurring introductory sessions (i.e.,
standard care), with a secondary aim of
better understanding how it is
implemented and the context of its
implementation. This data collection is
important because if the BYB Discovery
Session is determined to be an effective
recruitment strategy compared with
other existing introductory sessions, it
should be promoted to maximize the
National DPP’s potential to reduce type
2 diabetes incidence. CDC requests
approval for 1,572 Burden Hours
annually. There are no costs to
respondents other than their time.
objectives of the Introductory Session
Landscape Assessment are to increase
knowledge of recruitment strategies
(specifically introductory sessions) used
by CDC-recognized organizations to
increase enrollment in LCPs;
understand how CDC-recognized
organizations are using introductory
sessions (including session content and
delivery); and inform the subsequent
Phase 2 Introductory Session Evaluation
that will evaluate the BYB Discovery
Session compared with other types of
introductory sessions.
For the Phase 2 Introductory Session
Evaluation, CDC is seeking approval to
disseminate the following data
collection tools: (1) Pre-Session Survey
(to be completed by up to 2,640
introductory session attendees), (2) PostSession Survey (to be completed by up
to 2,640 introductory session attendees),
(3) Registration and Attendance
Tracking Form (to be completed by up
to 132 LCP staff), and (4) Discovery
Session Implementation Fidelity
Checklist (to be completed by up to 66
LCP staff). The Pre-Session and PostSession Surveys will be distributed as
ESTIMATED ANNUALIZED BURDEN HOURS
Number of
respondents
Average
burden per
response
(in hours)
Total
burden
(in hours)
Form name
LCP Staff ...........................................
Introductory Session Attendees (Individuals).
Introductory Session Attendees (Individuals).
LCP Staff ...........................................
Landscape Assessment ...................
Pre-Session Survey .........................
2,240
2,640
1
1
15/60
10/60
560
440
Post-Session Survey ........................
2,640
1
10/60
440
Registration Attendance and Tracking Form.
BYB Discovery Session Implementation Fidelity Checklist.
132
1
15/60
33
66
1
90/60
99
...........................................................
........................
........................
........................
1,572
LCP Staff ...........................................
Total ...........................................
Jeffrey M. Zirger,
Lead, Information Collection Review Office,
Office of Scientific Integrity, Office of Science,
Centers for Disease Control and Prevention.
[FR Doc. 2019–19017 Filed 9–3–19; 8:45 am]
BILLING CODE 4163–18–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2013–N–0242]
Agency Information Collection
Activities; Submission for Office of
Management and Budget Review;
Comment Request; Current Good
Manufacturing Practices for Positron
Emission Tomography Drugs
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Number of
responses per
respondent
Type of respondents
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing
that a proposed collection of
SUMMARY:
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information has been submitted to the
Office of Management and Budget
(OMB) for review and clearance under
the Paperwork Reduction Act of 1995.
DATES: Fax written comments on the
collection of information by October 4,
2019.
ADDRESSES: To ensure that comments on
the information collection are received,
OMB recommends that written
comments be faxed to the Office of
Information and Regulatory Affairs,
OMB, Attn: FDA Desk Officer, Fax: 202–
395–7285, or emailed to oira_
submission@omb.eop.gov. All
comments should be identified with the
OMB control number 0910–0667. Also
include the FDA docket number found
in brackets in the heading of this
document.
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Federal Register / Vol. 84, No. 171 / Wednesday, September 4, 2019 / Notices
FOR FURTHER INFORMATION CONTACT:
Domini Bean, Office of Operations,
Food and Drug Administration, Three
White Flint North, 10A–12M, 11601
Landsdown St., North Bethesda, MD
20852, 301–796–5733, PRAStaff@
fda.hhs.gov.
SUPPLEMENTARY INFORMATION: In
compliance with 44 U.S.C. 3507, FDA
has submitted the following proposed
collection of information to OMB for
review and clearance.
Current Good Manufacturing Practice
(CGMP) for Positron Emission
Tomography (PET) Drugs
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OMB Control Number 0910–0667—
Extension
PET is a medical imaging modality
involving the use of a unique type of
radiopharmaceutical drug product. Our
CGMP regulations at part 212 (21 CFR
part 212) are intended to ensure that
PET drug products meet the
requirements of the Federal Food, Drug,
and Cosmetic Act (FD&C Act) regarding
safety, identity, strength, quality, and
purity. The CGMP requirements for PET
drugs are issued under the provisions of
the Food and Drug Administration
Modernization Act of 1997 (FDAMA)
(Pub. L. 105–115). These CGMP
requirements are designed according to
the unique characteristics of PET drugs,
including their short half-lives, and the
fact that most PET drugs are produced
at locations close to the patients to
whom the drugs are administered.
The CGMP regulations require the
establishment of written procedures as
well as recordkeeping related to ongoing
manufacturing of individual PET drugs,
testing, and product release activities,
including any third-party disclosure
requirements for producing PET drugs.
To estimate time spent to comply with
the requirements, we relied on informal
communications with PET producers,
FDA staff visits to PET facilities, our
familiarity with PET and general
pharmaceutical manufacturing practices
with application and supplement
submissions, and various reports FDA
received from 2016 through 2018.
I. Investigational and Research PET
Drugs
Section 212.5(b) provides that for
investigational PET drugs produced
under an investigational new drug
application (IND) and research PET
drugs produced with approval of a
Radioactive Drug Research Committee
(RDRC), the requirement (FD&C Act) to
follow CGMP is met by complying with
the regulations under part 212 or
complying with United States
Pharmacopeia (USP) 32 Chapter 823.
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We believe that PET production
facilities producing drugs under INDs
and RDRCs are already substantially
complying with the recordkeeping
requirements of USP 32 Chapter 823
(see section 121(b) of FDAMA). Some
IND and RDRC PET facilities also
produce approved NDA (new drug
application) and abbreviated new drug
application (ANDA) PET drugs. While
we do not have sufficient information to
estimate burdens for all IND and RDRC
PET facilities, our estimates have
included those facilities that also
produce NDA and ANDA PET drugs.
Those facilities are included under
academic and small firms.
II. Recordkeeping Burden
A. One-Time Burden for Corporate
Firms
We estimate corporate firms will have
to employ one-time and ongoing annual
recordkeeping. There are three major
PET manufacturing corporations and
most of the quality, manufacturing, and
testing procedures are developed at the
corporate level and then issued to the
individual sites located in various States
across the country. There are an
estimated 115 such sites under three
major corporations. Thus, the burden
has been calculated for 3 recordkeepers
instead of 115 individual sites.
It would take approximately 8 hours
for each corporate firm to create one
master batch record per drug, and an
average of three PET drugs have been
taken into consideration. We also
estimate that approximately 3 firms will
create and maintain approximately 27
records associated with production and
quality testing for an average of 3 drugs,
with a total recordkeeping burden of
approximately 216 hours.
Sections 212.20(c), 212.30(b),
212.50(d), and 212.60(f) (21 CFR
212.20(c), 212.30(b), 212.50(d), and
212.60(f)) contain standard operating
procedures (SOPs) dealing with
equipment operation, maintenance, and
cleaning, including maintenance of
physical facilities.
It would take approximately 5 hours
for each corporate firm to establish and
maintain procedures for equipment and
facility maintenance. We estimate that
the 3 corporate firms will establish and
maintain 39 procedures, with a total
recordkeeping burden of approximately
195 hours.
Sections 212.20(c) and 212.40(a) and
(b) contain requirements on SOPs
regarding receiving, testing, and
accepting components. We estimate that
the burden for corporate firms to create
procedures for acceptance of raw
materials and components would be
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approximately 8 hours and that there
will be approximately three corporate
firms performing these activities, with a
total recordkeeping burden of
approximately 48 hours. The burden for
corporate firms to create component
specification data sheets would be
approximately 2 hours with
approximately 3 corporate firms
performing these activities, with a total
recordkeeping burden of approximately
150 hours for approximately 25
component specification sheets for each
firm.
Sections 212.20(c) and 212.71(a) and
(b) require that PET drug firms establish
procedures for investigating
‘‘deviations’’ and ‘‘out of specifications
failures’’ of products during
manufacturing and testing that do not
conform to specifications and to
conduct these investigations and record
them as needed. We estimate that it will
take approximately 8 hours for three
corporate firms to establish one
procedure, with a total recordkeeping
burden of approximately 24 hours.
Sections 212.20(c) and 212.90(a)
require that written procedures
regarding distribution of PET drug
products be established and maintained.
We estimate that it will take
approximately 8 hours for each
corporate firm to establish written
procedures regarding distribution of
PET drugs with a total of approximately
three records, with a total recordkeeping
burden of approximately 24 hours.
Sections 212.20(c) and 212.100(a), (b),
and (c) require that PET drug firms
establish and maintain written
procedures for handling complaints and
procedures for field alert reports (FARs).
We estimate that each corporate firm
will create three written procedures to
establish complaints and FARs process
and it will take approximately 24 hours
for each corporate firm. A total of 72
hours will be required to create 27
procedures by 3 corporate firms.
B. One-Time Burden for Academia,
Small Firms, and Precursors
There is a total of 52 sites combined
for academic and small commercial
firms, including some IND and RDRC
sites. There are nine starting material/
precursors/sterile raw material
manufacturing entities who are required
to follow selected regulations from part
212, according to the PET drug
definition under section 121(a) of
FDAMA and codified in section
201(ii)(1)(A) of the FD&C Act (21 U.S.C.
321(ii)(1)(A)). We will refer to them as
high-risk component manufacturing
firms in the tables and other sections of
this document.
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It would take approximately 8 hours
for each firm to perform the same
activities as corporate firms regarding
creating master batch records and
manufacturing and quality procedures.
We estimate that there will be a total of
approximately 488 records, with a total
recordkeeping burden of approximately
3,904 hours.
It would take approximately 8 hours
for each firm to create equipment and
facility related procedures as corporate
firms. We also estimate that there will
be a total of approximately 793 records,
with a total recordkeeping burden of
approximately 6,344 hours.
We also estimate that the burden for
each firm to create and maintain
specification sheets would be
approximately 2 hours and that there
will be a total of approximately 61 firms
performing these activities, with a total
recordkeeping burden of approximately
3,050 hours. Furthermore, the burden
for these firms to create and maintain
procedures for acceptance of raw
materials and components would be
approximately 8 hours and that there
will be a total of approximately 61 firms
performing these activities, with a total
recordkeeping burden of approximately
976 hours.
It would take approximately 8 hours
for each firm to perform the same
activities as corporate firms. We
estimate that there will be a total of
approximately 61 records, with a total
recordkeeping burden of approximately
488 hours.
We estimate that 61 academia, small
firms, and high-risk component
manufacturers will create about one
procedure related to deviations and out
of specifications and that each firm will
expend approximately 8 hours, for a
total of 488 hours. Similarly, 488 hours
will be spent for procedures on
distribution of PET drugs. There will be
3 procedures created by each firm
related to customer complaints, recalls,
and FARs, with a total of 156 records
from 52 sites and a total of 1,248 hours.
C. Annual Burden for Corporate Firms
In this section, we considered 115
individual corporate sites under the 3
major corporations in our estimates.
These activities will be related to
individual PET drugs manufactured at
each of the sites located across the
country. We estimate that it would take
30 minutes each to fill 144 batches
(approximately 4 batches/month), for a
total of 8,280 hours. In the second row
of table 3, we have also estimated that
on an annual basis, some new batch
records or quality records may have to
be created for newly introduced or
existing drugs. It would take each firm
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approximately 24 hours for three new
quality procedure/master batch records,
with a total recordkeeping burden of
approximately 216 hours for nine
records from three corporate
organizations.
We estimate that 115 individual
corporate sites belonging to 3 major
corporate entities will create 164
records for equipment maintenance,
cleaning, calibration, and facilities
maintenance records, with a total
recordkeeping burden of 9,430 hours.
Sections 212.20(c) and 212.40(a) and
(b) also set out requirements for raw
material and component shipments
received at the manufacturing facility on
an ongoing basis. We estimate that the
burden for each firm to create incoming
raw material acceptance records for 2
shipments per month and 30 minutes
per shipment will be 1,380 hours for
2,760 records from 115 sites.
Sections 212.60(g), 212.61(b), and
212.70(d)(2) and (3) set out
requirements for documenting
laboratory testing results from each PET
drug manufactured referred to in
laboratory testing, including final
release testing. Each firm must keep
records of different tests for each of their
products. We estimate that
approximately 115 corporate sites will
document 144 records of cumulative
quality control (QC) test results (one
record with 5 to 6 tests included), with
a total recordkeeping burden of
approximately 8,280 hours.
We estimate that each firm will take
approximately 1 hour to record out-ofspecification (OOS) events and perform
investigations for each incident. We also
estimate an average of 2 ‘‘Out of
Specification’’ investigations per firm,
with a total of 230 records for ‘‘OOS’’
investigations from 115 sites, which
results in a burden of 460 hours. This
estimate includes any reprocessing or
special release events, which are very
rare.
Section 212.100(b) and (c) requires
that PET drug firms document how each
complaint is handled. We estimate that
this will take approximately 2 hours for
each site to document and investigate
one complaint. We estimated 2
complaints per year per site, with a total
expended hour of 460 hours for 115
individual sites. We believe the estimate
is appropriate since not all sites receive
complaints.
We also estimate annual
recordkeeping for PET drug firms to
perform quality assurance (QA) and
release of manufactured PET drugs from
the 115 corporate sites to be 4,140
hours, for a total of 144 released batches
estimating 15 minutes per batch.
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Section 212.90(b) requires that
corporate firms maintain distribution
records. We estimate that it will take
each firm approximately 15 minutes to
create a distribution record for each
batch of PET drug products, with a total
burden of approximately 4,140 hours for
144 released batches from 115 sites.
D. Annual Burden for Academia and
Small Firms
It is estimated that each firm will
expend the same amount of time to
perform the same activities as corporate
firms. Approximately 52 academia and
small firms will fill 1,248 batch and
production records, totaling 624 hours.
For any new master batch record or
quality procedures we have estimated
156 total records (3 per site), with a total
of 1,248 hours.
For calibration and cleaning records
like filling information in log books for
each piece of equipment and
documenting calibration records in each
PET production firm, we estimate
approximately 30 minutes on average
for each piece of equipment for all
firms. The calibration efforts are once
per year per equipment, with estimated
10 pieces of equipment per site. We
estimate that 52 academic and small
firms will record a total of 884 hours for
34 records per site and a total of 1,768
records.
For §§ 212.20(c) and 212.40(a) and (b),
approximately 1,768 raw material and
component acceptance records will be
filled on an ongoing annual basis. We
estimate that the burden for each firm to
create incoming raw material
acceptance records for 12 shipments per
year and 30 minutes per shipment will
be 312 hours for 624 records from 52
sites.
We also estimate that approximately
52 academia and small firms will
document 1,248 laboratory QC tests for
24 batches of drugs, with a total
recordkeeping burden of approximately
624 hours.
We estimate that each firm will take
approximately 1 hour each to record
OOS and customer complaint events
and perform investigations. We also
estimate that an average of two ‘‘Out of
Specification’’ and customer complaints
and investigations per firm, with a total
of 208 hours for each category. This
estimate has included any reprocessing
or special batch release events, which
have been rarely observed.
We also estimate annual
recordkeeping for PET drug firms to
perform QA and release of
manufactured PET drugs from 52 sites
to be 312 hours, for a total of 24 batches
per site released if estimating 15
minutes per batch.
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Section 212.90(b) requires that
corporate firms maintain distribution
records. We estimate that it will take
approximately 15 minutes to create a
distribution record for each batch of
PET drug products, with a total burden
of approximately 312 hours for 24
batches per site.
for a total of 108 batches released,
estimating 15 minutes per batch.
We further estimate that it would take
each precursor 15 minutes to create and
maintain distribution records and that
there will be approximately 108 records,
with a total recordkeeping burden of
approximately 27 hours.
E. Annual Burden for High-Risk
Component Manufacturers
III. Process Verification
Section 212.50(f)(2) requires that any
process verification activities and
results be recorded. Process verification
is usually performed as a one-time
activity before a product is approved or
if any major manufacturing process or
equipment changes are made. This effort
to conduct process verification has been
estimated under annual new creation of
master batch records and manufacturing
and quality procedures in section II of
this document.
According to section 121(a) of
FDAMA, the PET drug definition
includes any non-radioactive or
radioactive reagents, kits, nuclidic
generators, target materials,
synthesizers, and so forth. FDA
performs risk assessments of each
manufacturer and inspects such
manufacturers. Sterile manufacturers
and complex labels fall under this
category, including sterile raw material
or reagent manufactures. We have
estimated nine such facilities based on
inspections so far and have included
them in this section. These
manufacturers must comply with
selected sections of part 212 since they
are not final PET drug manufacturers.
We will refer to them as high-risk
component manufacturers in general in
this document.
We estimate that it would take 9 highrisk component manufacturers about 30
minutes to fill each manufacturing batch
records (12 per year) and that there will
be a total of approximately 108 records,
with a total recordkeeping burden of
approximately 54 hours.
We also estimate that it will take nine
component manufacturers 30 minutes to
fill and create equipment and facilities
related records, with a total
recordkeeping burden of 72 hours.
We estimate that 9 high-risk
component manufacturers will
document 54 components, containers,
and closures for incoming acceptance
tests, with a total recordkeeping burden
of approximately 27 hours.
We estimate that 9 high-risk
component manufacturers will
document 12 QC records related to 12
batches, with a total recordkeeping
burden of approximately 54 hours.
We also estimate annual
recordkeeping for PET drug firms to
perform QA and release manufactured
PET drugs from 9 sites to be 27 hours,
IV. Conditional Final Releases
Section 212.70(f) requires PET drug
producers to document any conditional
final releases of a product. We believe
that conditional final releases will be
uncommon, and we have them
estimated under annual ‘‘OOS’’
investigations and final QA release
efforts for each manufactured batch.
V. Reprocessing Procedures
Sections 212.20(c) and 212.71(d)
require PET drug producers to establish
and document procedures for
reprocessing PET drugs. We rarely see
any reprocessing option being submitted
for application of such drugs and, if
reprocessing occurs, we have estimated
such rare events under annual QA
release efforts.
VI. Third-Party Disclosure Burden
Section 212.70(e) requires that PET
drug producers notify all receiving
facilities if a batch fails sterility tests.
FDA receives FARs reports based on
confirmed sterility failures of released
PET drugs. Based on our experience of
such reporting, we estimated a total of
12 failures from all 167 sites (corporate,
small firms, and academia). Therefore,
we have estimated that 12 PET drug
producers will file 2 reports to FDA and
send a notification to the affected
clinical/receiving site per year. PET
drug producers would transmit the
notice by email or Fax and submit the
FARs notice to FDA electronically, with
2.5 hours per incident in total.
In the Federal Register of November
30, 2018 (83 FR 61653), FDA published
a 60-day notice requesting public
comment on the proposed collection of
information. Three comments were
received and are summarized here.
One comment questioned the
necessity of this proposed collection.
One comment suggested that FDA allow
both paper recordkeeping and
simplified electronic report submission.
Two comments questioned some of
FDA’s burden collection estimates. Two
comments questioned whether Annual
Product Review (APR) is being required
by the regulations. Two comments
pertained to an inadvertent oversight in
section VI. Third-Party Disclosure.
FDA believes that this proposed
collection is necessary in keeping with
the Agency’s mission of ensuring the
safety and efficacy of human drugs.
Regarding the estimates included, FDA
has taken a generalized approach for
these estimates, assuming that corporate
firms will take on certain burdens for all
facilities under their purview, rather
than calculating all burdens per facility,
and understanding that due to variation
among facilities the number of batches
and products being produced will vary.
We have also only included estimates
for tasks that are included within part
212 and note that some of the comments
referenced tasks, such as APR, that are
outside that scope. Electronic
recordkeeping is also outside the scope
of this regulation. Regarding the
typographical error in section VI. Third
Party Disclosure, on page 9350, we
estimate that it will take PET drug
producers 2 hours to submit to FDA
notices of sterility test failures. We
intended to estimate 2.5 hours as
accurately shown in Table 6, page 9352.
In section VI of this document, we have
included this change. We appreciate
these comments and will continue to
consider the burden estimate. If
commenters believe certain estimates
are insufficient, we request comments
on specific estimates for these
requirements and why alternative
estimates would be more accurate.
The estimated burden of the
information collection, therefore, is as
follows:
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TABLE 1—ESTIMATED ONE-TIME RECORDKEEPING BURDEN FOR CORPORATE FIRMS 1
Number of
recordkeepers
Activity/type of respondent/21 CFR section
Batch Production and Control Records (§§ 212.20(c) and
(e) and 212.50(a) and (b)) ...............................................
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Number of
records per
recordkeeper
3
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Average
burden per
recordkeeper
One-time
records
9
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Total hours 2
216
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TABLE 1—ESTIMATED ONE-TIME RECORDKEEPING BURDEN FOR CORPORATE FIRMS 1—Continued
Number of
recordkeepers
Activity/type of respondent/21 CFR section
Equipment and Facilities Records (SOP) (§§ 212.20(c),
212.30(b) 212.50(d), and 212.60(f)) .................................
Records of Components, Containers, and Closures (SOP)
(§§ 212.20(c) and 212.40(a) and (b)) ...............................
Records of Components, Containers, and Closures (specifications data sheets) (§§ 212.20(c) and 212.40(a) and
(b)) ....................................................................................
Out-of-Specification Investigations (SOP) (§§ 212.20(c)
and 212.71(a)) ..................................................................
Distribution Records (SOP) (§§ 212.20(c) and 212.90(a)) ..
Complaints, Recalls (§§ 212.20(c) and 212.100(a)) ............
Total ..............................................................................
1 There
Number of
records per
recordkeeper
Average
burden per
recordkeeper
One-time
records
Total hours 2
3
13
39
5
195
3
2
6
8
48
3
25
75
2
150
3
3
3
1
1
3
3
3
9
8
8
8
24
24
72
........................
........................
........................
........................
729
are no capital costs or operating and maintenance costs associated with this collection of information.
rounded to the nearest whole number.
2 Number
TABLE 2—ESTIMATED ONE-TIME RECORDKEEPING BURDEN FOR ACADEMIA, SMALL FIRMS, AND HIGH-RISK COMPONENT
MANUFACTURERS 1
Number of
recordkeepers
Activity/type of respondent/21 CFR section
Batch Production and Control Records (§§ 212.20(c) and
(e) and 212.50(a) and (b)) ...............................................
Equipment and Facilities Records (SOP) (§§ 212.20(c),
212.30(b) 212.50(d), and 212.60(f)) .................................
Records of Components, Containers, and Closures (specification only) (§§ 212.20(c) and 212.40(a) and (b)) .........
Records of Components, Containers, and Closures (SOP)
(§§ 212.20(c) and 212.40(a) and (b)) ...............................
Out-of-Specification Investigations (SOP) (§§ 212.20(c)
and 212.71(a)) ..................................................................
Distribution Records (SOP) (§§ 212.20(c) and 212.90(a)) ..
Complaints, Recalls (§§ 212.20(c) and 212.100(a)) ............
Total ..............................................................................
1 There
Number of
records per
recordkeeper
Average
burden per
recordkeeper
One-time
records
Total hours 2
61
8
488
8
3,904
61
13
793
8
6,344
61
25
1,525
2
3,050
61
2
122
8
976
61
61
52
1
1
3
61
61
156
8
8
8
488
488
1,248
........................
........................
........................
........................
16,498
are no capital costs or operating and maintenance costs associated with this collection of information.
rounded to the nearest whole number.
2 Number
TABLE 3—ESTIMATED ANNUAL RECORDKEEPING BURDEN FOR CORPORATE FIRMS 1
Number of
recordkeepers
jbell on DSK3GLQ082PROD with NOTICES
Activity/21 CFR section
Batch Production (Creating Manufacturing Records (creating batch-related records per year) (§§ 212.20(c) and
(e) and 212.50(a) and (b)) ...............................................
Creating Any New Batch Records/Quality Records for
New or Existing Drugs (§§ 212.20(c) and (e) and
212.50(a) and (b)) ............................................................
Equipment and Facilities Records (calibration and cleaning
records systems) (§§ 212.30(b), 212.50(d), and
212.60(f)) ..........................................................................
Records of Components, Containers, and Closures
(§§ 212.20(c) and 212.40(a) and (b)) ...............................
Laboratory Testing Records (record laboratory test results)
(§§ 212.60(g), 212.61(b), and 212.70(d)(2) and (3)) ........
Out-of-Specification Investigations (record events and investigations) (§ 212.71(b)) ................................................
Complaints (§§ 212.100(b) and (c)) .....................................
QA and Release of Batches ................................................
Distribution Records (§ 212.90(b)) .......................................
Total ..............................................................................
1 There
Number of
records per
recordkeeper
Total
annual
records
Average
burden per
recordkeeper
115
144
16,560
* 0.50
8,280
3
9
27
8
216
115
164
18,860
* 0.50
9,430
115
24
2,760
* 0.50
1,380
115
144
16,560
* 0.50
8,280
115
115
115
115
2
2
144
144
230
230
16,560
16,560
2
2
+ 0.25
+ 0.25
460
460
4,140
4,140
........................
........................
........................
........................
36,786
are no capital costs or operating and maintenance costs associated with this collection of information.
rounded to the nearest whole number.
2 Number
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Federal Register / Vol. 84, No. 171 / Wednesday, September 4, 2019 / Notices
* (30 minutes).
+ (15 minutes).
TABLE 4—ESTIMATED ANNUAL RECORDKEEPING BURDEN FOR ACADEMIA AND SMALL FIRMS 1
Number of
recordkeepers
Activity/21 CFR section
Batch Production (creating manufacturing records) (filling
batch related records per year) (§§ 212.20(c) and (e)
and 212.50(a) and (b)) .....................................................
Creating Any New Batch Records/Procedures for New
Drugs (§§ 212.20(c) and (e) and 212.50(a) and (b)) .......
Equipment and Facilities Records (calibration and cleaning
records) (§§ 212.30(b), 212.50(d), and 212.60(f)) ...........
Records of Components, Containers, and Closures (incoming acceptance tests) (§§ 212.20(c) and 212.40(a)
and (b)) .............................................................................
Laboratory Testing Records (QC test results)
(§§ 212.60(g), 212.61(b) and 212.70(d)(2) and (3)) .........
Out-of-Specification Investigations (record events and investigations) (§ 212.71(b)) ................................................
Complaints (Record events and investigations)
(§§ 212.100(b) and (c)) .....................................................
QA and Release of Batches ................................................
Distribution Records (§ 212.90(b)) .......................................
Total ..............................................................................
Number of
records per
recordkeeper
Total
annual
records
Average
burden per
recordkeeper
Total hours 2
52
24
1,248
* 0.50
624
52
3
156
8
1,248
52
34
1,768
* 0.50
884
52
12
624
* 0.50
312
52
24
1,248
* 0.50
624
52
2
104
2
208
52
52
52
2
24
24
104
1,248
1,248
2
+ 0.25
+ 0.25
208
312
312
........................
........................
........................
........................
4,732
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
rounded to the nearest whole number.
* (30 minutes).
+ (15 minutes).
2 Number
TABLE 5—ESTIMATED ANNUAL RECORDKEEPING BURDEN FOR HIGH RISK COMPONENT MANUFACTURERS 1
Number of
recordkeepers
Activity/21 CFR section
Batch Production (creating manufacturing records and
batch related records per year) (§§ 212.20(c) and (e)
and 212.50(a) and (b)) .....................................................
Equipment and Facilities Records (calibration and cleaning
records systems) (§§ 212.30(b), 212.50(d), and
212.60(f)) ..........................................................................
Records of Components, Containers, and Closures (incoming acceptance test) (§§ 212.20(c) and 212.40(a)
and (b)) .............................................................................
Laboratory Testing Records (record QC test results)
(§§ 212.60(g), 212.61(b) and 212.70(d)(2) and (3)) .........
Out-of-Specification Investigations (Record events and investigations) (§ 212.71(b)) ................................................
QA and Release of Batches ................................................
Distribution Records (§ 212.90(b)) .......................................
Total ..............................................................................
Number of
records per
recordkeeper
Average
burden per
recordkeeper
Total annual
records
Total hours 2
9
12
108
* 0.50
54
9
16
144
* 0.50
72
9
6
54
* 0.50
27
9
12
108
* 0.50
54
9
9
9
1
12
12
9
108
108
1
+ 0.25
+ 0.25
9
27
27
........................
........................
........................
........................
270
1 There
are no capital costs or operating and maintenance costs associated with this collection of information.
rounded to the nearest whole number.
* (30 minutes).
+ (15 minutes).
2 Number
jbell on DSK3GLQ082PROD with NOTICES
TABLE 6—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1
Number of
sterility
failure
incidents
Activity/21 CFR section
Sterility Test Failure Notices (§ 212.70(e)) ..........................
1 There
2 There
Number of
disclosures
per
respondent
12
Total annual
disclosures
23
36
are no capital costs or operating and maintenance costs associated with this collection of information.
are two reports sent to FDA per incident and notification to receiving site.
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Average
burden per
disclosure
2.5
Total hours
90
Federal Register / Vol. 84, No. 171 / Wednesday, September 4, 2019 / Notices
These burden estimates reflect
adjustments since last OMB approval.
Previously we had based the estimated
number of respondents on the number
of individual production sites, however
we believe using the number of
registered organizations better reflects
the burden attributable to information
collection. This results in an overall
decrease to the collection.
Dated: August 26, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019–19030 Filed 9–3–19; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
Docket No. FDA–2019–N–1517]
Agency Information Collection
Activities; Submission for Office of
Management and Budget Review;
Comment Request; Abbreviated New
Animal Drug Applications
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA) is announcing
that a proposed collection of
information has been submitted to the
Office of Management and Budget
(OMB) for review and clearance under
the Paperwork Reduction Act of 1995.
DATES: Fax written comments on the
collection of information by October 4,
2019.
ADDRESSES: To ensure that comments on
the information collection are received,
OMB recommends that written
comments be faxed to the Office of
Information and Regulatory Affairs,
OMB, Attn: FDA Desk Officer, Fax: 202–
395–7285, or emailed to oira_
submission@omb.eop.gov. All
comments should be identified with the
OMB control number 0910–0669. Also
include the FDA docket number found
in brackets in the heading of this
document.
SUMMARY:
jbell on DSK3GLQ082PROD with NOTICES
FOR FURTHER INFORMATION CONTACT:
JonnaLynn Capezzuto, Office of
Operations, Food and Drug
Administration, Three White Flint
North, 10A–12M, 11601 Landsdown St.,
North Bethesda, MD 20852, 301–796–
3794, PRAStaff@fda.hhs.gov.
SUPPLEMENTARY INFORMATION: In
compliance with 44 U.S.C. 3507, FDA
has submitted the following proposed
VerDate Sep<11>2014
19:08 Sep 03, 2019
Jkt 247001
collection of information to OMB for
review and clearance.
Abbreviated New Animal Drug
Applications—Section 512(b)(2) and
(n)(1) of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 360b(b)(2) and
(n)(1))
OMB Control Number 0910–0669—
Extension
Under section 512(b)(2) of the Federal
Food, Drug, and Cosmetic Act (FD&C
Act), any person may file an abbreviated
new animal drug application (ANADA)
seeking approval of a generic copy of an
approved new animal drug. The
information required to be submitted as
part of an ANADA is described in
section 512(n)(1) of the FD&C Act.
Among other things, an ANADA is
required to contain information to show
that the proposed generic drug is
bioequivalent to, and has the same
labeling as, the approved new animal
drug. We allow applicants to submit a
complete ANADA or to submit
information in support of an ANADA
for phased review. Applicants may
submit Form FDA 356v with a complete
ANADA or a phased-review submission
to ensure efficient and accurate
processing of information. We use the
information submitted, among other
things, to assess bioequivalence to the
originally approved drug and thus, the
safety and effectiveness of the generic
new animal drug.
We believe the demonstration of
bioequivalence required by the statute
does not need to be established on the
basis of in vivo studies (blood level
bioequivalence or clinical endpoint
bioequivalence) for soluble powder oral
dosage form products and certain Type
A medicated articles. We are adding to
this information collection applicant
requests to waive the requirement to
establish bioequivalence through in vivo
studies (biowaiver requests) for soluble
powder oral dosage form products or
certain Type A medicated articles based
upon either of two methods. We will
consider granting a biowaiver request if
it can be shown that the generic soluble
powder oral dosage form product or
Type A medicated article contains the
same active and inactive ingredient(s)
and is produced using the same
manufacturing processes as the
approved comparator product or article.
Alternatively, we will consider granting
a biowaiver request without direct
comparison to the pioneer product’s
formulation and manufacturing process
if it can be shown that the active
pharmaceutical ingredient(s) (API) is the
same as the pioneer product, is soluble,
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46543
and that there are no ingredients in the
formulation likely to cause adverse
pharmacologic effects. We use the
information submitted by applicants in
the biowaiver request as the basis for
our decision whether to grant the
request.
Additionally, we have found that
various uses of veterinary master files
have increased the efficiency of the drug
development and drug review processes
for both us and the animal
pharmaceutical industry. A veterinary
master file is a repository for submission
to FDA’s Center for Veterinary Medicine
of confidential detailed information
about facilities, processes, or articles
used in the manufacturing, processing,
packaging, and storing of one or more
veterinary drugs. Veterinary master files
are used by the animal pharmaceutical
industry in support of information being
submitted for new animal drug
applications (NADAs), ANADAs,
investigational new animal drug (INAD)
files, and generic investigational new
animal drug (JINAD) files. In previous
information collection requests, we
included the time necessary to compile
and submit such information to
veterinary master files within the
burden estimates provided for
applications and amended applications
(for NADAs and INAD files) and
abbreviated applications and amended
abbreviated applications (for ANADAs
and JINAD files), respectively. We
recently combined the time necessary to
compile and submit such information to
veterinary master files within the
burden estimates provided in the
collection of information supporting
new animal drug applications (OMB
control number 0910–0032).
The reporting associated with
ANADAs and related submissions is
necessary to ensure that new animal
drugs are in compliance with section
512(b)(2) of the FD&C Act. As noted, we
use the information submitted, among
other things, to assess bioequivalence to
the originally approved drug and thus,
the safety and effectiveness of the
generic new animal drug.
Description of Respondents: The
respondents for this collection of
information are veterinary
pharmaceutical manufacturers.
In the Federal Register of April 18,
2019 (84 FR 16270), FDA published a
60-day notice requesting public
comment on the proposed collection of
information. No comments were
received.
FDA estimates the burden of this
collection of information as follows:
E:\FR\FM\04SEN1.SGM
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]]>Agencies
[Federal Register Volume 84, Number 171 (Wednesday, September 4, 2019)]
[Notices]
[Pages 46537-46543]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-19030]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2013-N-0242]
Agency Information Collection Activities; Submission for Office
of Management and Budget Review; Comment Request; Current Good
Manufacturing Practices for Positron Emission Tomography Drugs
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing that a
proposed collection of information has been submitted to the Office of
Management and Budget (OMB) for review and clearance under the
Paperwork Reduction Act of 1995.
DATES: Fax written comments on the collection of information by October
4, 2019.
ADDRESSES: To ensure that comments on the information collection are
received, OMB recommends that written comments be faxed to the Office
of Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer,
Fax: 202-395-7285, or emailed to [email protected]. All
comments should be identified with the OMB control number 0910-0667.
Also include the FDA docket number found in brackets in the heading of
this document.
[[Page 46538]]
FOR FURTHER INFORMATION CONTACT: Domini Bean, Office of Operations,
Food and Drug Administration, Three White Flint North, 10A-12M, 11601
Landsdown St., North Bethesda, MD 20852, 301-796-5733,
[email protected].
SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has
submitted the following proposed collection of information to OMB for
review and clearance.
Current Good Manufacturing Practice (CGMP) for Positron Emission
Tomography (PET) Drugs
OMB Control Number 0910-0667--Extension
PET is a medical imaging modality involving the use of a unique
type of radiopharmaceutical drug product. Our CGMP regulations at part
212 (21 CFR part 212) are intended to ensure that PET drug products
meet the requirements of the Federal Food, Drug, and Cosmetic Act (FD&C
Act) regarding safety, identity, strength, quality, and purity. The
CGMP requirements for PET drugs are issued under the provisions of the
Food and Drug Administration Modernization Act of 1997 (FDAMA) (Pub. L.
105-115). These CGMP requirements are designed according to the unique
characteristics of PET drugs, including their short half-lives, and the
fact that most PET drugs are produced at locations close to the
patients to whom the drugs are administered.
The CGMP regulations require the establishment of written
procedures as well as recordkeeping related to ongoing manufacturing of
individual PET drugs, testing, and product release activities,
including any third-party disclosure requirements for producing PET
drugs. To estimate time spent to comply with the requirements, we
relied on informal communications with PET producers, FDA staff visits
to PET facilities, our familiarity with PET and general pharmaceutical
manufacturing practices with application and supplement submissions,
and various reports FDA received from 2016 through 2018.
I. Investigational and Research PET Drugs
Section 212.5(b) provides that for investigational PET drugs
produced under an investigational new drug application (IND) and
research PET drugs produced with approval of a Radioactive Drug
Research Committee (RDRC), the requirement (FD&C Act) to follow CGMP is
met by complying with the regulations under part 212 or complying with
United States Pharmacopeia (USP) 32 Chapter 823. We believe that PET
production facilities producing drugs under INDs and RDRCs are already
substantially complying with the recordkeeping requirements of USP 32
Chapter 823 (see section 121(b) of FDAMA). Some IND and RDRC PET
facilities also produce approved NDA (new drug application) and
abbreviated new drug application (ANDA) PET drugs. While we do not have
sufficient information to estimate burdens for all IND and RDRC PET
facilities, our estimates have included those facilities that also
produce NDA and ANDA PET drugs. Those facilities are included under
academic and small firms.
II. Recordkeeping Burden
A. One-Time Burden for Corporate Firms
We estimate corporate firms will have to employ one-time and
ongoing annual recordkeeping. There are three major PET manufacturing
corporations and most of the quality, manufacturing, and testing
procedures are developed at the corporate level and then issued to the
individual sites located in various States across the country. There
are an estimated 115 such sites under three major corporations. Thus,
the burden has been calculated for 3 recordkeepers instead of 115
individual sites.
It would take approximately 8 hours for each corporate firm to
create one master batch record per drug, and an average of three PET
drugs have been taken into consideration. We also estimate that
approximately 3 firms will create and maintain approximately 27 records
associated with production and quality testing for an average of 3
drugs, with a total recordkeeping burden of approximately 216 hours.
Sections 212.20(c), 212.30(b), 212.50(d), and 212.60(f) (21 CFR
212.20(c), 212.30(b), 212.50(d), and 212.60(f)) contain standard
operating procedures (SOPs) dealing with equipment operation,
maintenance, and cleaning, including maintenance of physical
facilities.
It would take approximately 5 hours for each corporate firm to
establish and maintain procedures for equipment and facility
maintenance. We estimate that the 3 corporate firms will establish and
maintain 39 procedures, with a total recordkeeping burden of
approximately 195 hours.
Sections 212.20(c) and 212.40(a) and (b) contain requirements on
SOPs regarding receiving, testing, and accepting components. We
estimate that the burden for corporate firms to create procedures for
acceptance of raw materials and components would be approximately 8
hours and that there will be approximately three corporate firms
performing these activities, with a total recordkeeping burden of
approximately 48 hours. The burden for corporate firms to create
component specification data sheets would be approximately 2 hours with
approximately 3 corporate firms performing these activities, with a
total recordkeeping burden of approximately 150 hours for approximately
25 component specification sheets for each firm.
Sections 212.20(c) and 212.71(a) and (b) require that PET drug
firms establish procedures for investigating ``deviations'' and ``out
of specifications failures'' of products during manufacturing and
testing that do not conform to specifications and to conduct these
investigations and record them as needed. We estimate that it will take
approximately 8 hours for three corporate firms to establish one
procedure, with a total recordkeeping burden of approximately 24 hours.
Sections 212.20(c) and 212.90(a) require that written procedures
regarding distribution of PET drug products be established and
maintained. We estimate that it will take approximately 8 hours for
each corporate firm to establish written procedures regarding
distribution of PET drugs with a total of approximately three records,
with a total recordkeeping burden of approximately 24 hours.
Sections 212.20(c) and 212.100(a), (b), and (c) require that PET
drug firms establish and maintain written procedures for handling
complaints and procedures for field alert reports (FARs). We estimate
that each corporate firm will create three written procedures to
establish complaints and FARs process and it will take approximately 24
hours for each corporate firm. A total of 72 hours will be required to
create 27 procedures by 3 corporate firms.
B. One-Time Burden for Academia, Small Firms, and Precursors
There is a total of 52 sites combined for academic and small
commercial firms, including some IND and RDRC sites. There are nine
starting material/precursors/sterile raw material manufacturing
entities who are required to follow selected regulations from part 212,
according to the PET drug definition under section 121(a) of FDAMA and
codified in section 201(ii)(1)(A) of the FD&C Act (21 U.S.C.
321(ii)(1)(A)). We will refer to them as high-risk component
manufacturing firms in the tables and other sections of this document.
[[Page 46539]]
It would take approximately 8 hours for each firm to perform the
same activities as corporate firms regarding creating master batch
records and manufacturing and quality procedures. We estimate that
there will be a total of approximately 488 records, with a total
recordkeeping burden of approximately 3,904 hours.
It would take approximately 8 hours for each firm to create
equipment and facility related procedures as corporate firms. We also
estimate that there will be a total of approximately 793 records, with
a total recordkeeping burden of approximately 6,344 hours.
We also estimate that the burden for each firm to create and
maintain specification sheets would be approximately 2 hours and that
there will be a total of approximately 61 firms performing these
activities, with a total recordkeeping burden of approximately 3,050
hours. Furthermore, the burden for these firms to create and maintain
procedures for acceptance of raw materials and components would be
approximately 8 hours and that there will be a total of approximately
61 firms performing these activities, with a total recordkeeping burden
of approximately 976 hours.
It would take approximately 8 hours for each firm to perform the
same activities as corporate firms. We estimate that there will be a
total of approximately 61 records, with a total recordkeeping burden of
approximately 488 hours.
We estimate that 61 academia, small firms, and high-risk component
manufacturers will create about one procedure related to deviations and
out of specifications and that each firm will expend approximately 8
hours, for a total of 488 hours. Similarly, 488 hours will be spent for
procedures on distribution of PET drugs. There will be 3 procedures
created by each firm related to customer complaints, recalls, and FARs,
with a total of 156 records from 52 sites and a total of 1,248 hours.
C. Annual Burden for Corporate Firms
In this section, we considered 115 individual corporate sites under
the 3 major corporations in our estimates. These activities will be
related to individual PET drugs manufactured at each of the sites
located across the country. We estimate that it would take 30 minutes
each to fill 144 batches (approximately 4 batches/month), for a total
of 8,280 hours. In the second row of table 3, we have also estimated
that on an annual basis, some new batch records or quality records may
have to be created for newly introduced or existing drugs. It would
take each firm approximately 24 hours for three new quality procedure/
master batch records, with a total recordkeeping burden of
approximately 216 hours for nine records from three corporate
organizations.
We estimate that 115 individual corporate sites belonging to 3
major corporate entities will create 164 records for equipment
maintenance, cleaning, calibration, and facilities maintenance records,
with a total recordkeeping burden of 9,430 hours.
Sections 212.20(c) and 212.40(a) and (b) also set out requirements
for raw material and component shipments received at the manufacturing
facility on an ongoing basis. We estimate that the burden for each firm
to create incoming raw material acceptance records for 2 shipments per
month and 30 minutes per shipment will be 1,380 hours for 2,760 records
from 115 sites.
Sections 212.60(g), 212.61(b), and 212.70(d)(2) and (3) set out
requirements for documenting laboratory testing results from each PET
drug manufactured referred to in laboratory testing, including final
release testing. Each firm must keep records of different tests for
each of their products. We estimate that approximately 115 corporate
sites will document 144 records of cumulative quality control (QC) test
results (one record with 5 to 6 tests included), with a total
recordkeeping burden of approximately 8,280 hours.
We estimate that each firm will take approximately 1 hour to record
out-of-specification (OOS) events and perform investigations for each
incident. We also estimate an average of 2 ``Out of Specification''
investigations per firm, with a total of 230 records for ``OOS''
investigations from 115 sites, which results in a burden of 460 hours.
This estimate includes any reprocessing or special release events,
which are very rare.
Section 212.100(b) and (c) requires that PET drug firms document
how each complaint is handled. We estimate that this will take
approximately 2 hours for each site to document and investigate one
complaint. We estimated 2 complaints per year per site, with a total
expended hour of 460 hours for 115 individual sites. We believe the
estimate is appropriate since not all sites receive complaints.
We also estimate annual recordkeeping for PET drug firms to perform
quality assurance (QA) and release of manufactured PET drugs from the
115 corporate sites to be 4,140 hours, for a total of 144 released
batches estimating 15 minutes per batch.
Section 212.90(b) requires that corporate firms maintain
distribution records. We estimate that it will take each firm
approximately 15 minutes to create a distribution record for each batch
of PET drug products, with a total burden of approximately 4,140 hours
for 144 released batches from 115 sites.
D. Annual Burden for Academia and Small Firms
It is estimated that each firm will expend the same amount of time
to perform the same activities as corporate firms. Approximately 52
academia and small firms will fill 1,248 batch and production records,
totaling 624 hours. For any new master batch record or quality
procedures we have estimated 156 total records (3 per site), with a
total of 1,248 hours.
For calibration and cleaning records like filling information in
log books for each piece of equipment and documenting calibration
records in each PET production firm, we estimate approximately 30
minutes on average for each piece of equipment for all firms. The
calibration efforts are once per year per equipment, with estimated 10
pieces of equipment per site. We estimate that 52 academic and small
firms will record a total of 884 hours for 34 records per site and a
total of 1,768 records.
For Sec. Sec. 212.20(c) and 212.40(a) and (b), approximately 1,768
raw material and component acceptance records will be filled on an
ongoing annual basis. We estimate that the burden for each firm to
create incoming raw material acceptance records for 12 shipments per
year and 30 minutes per shipment will be 312 hours for 624 records from
52 sites.
We also estimate that approximately 52 academia and small firms
will document 1,248 laboratory QC tests for 24 batches of drugs, with a
total recordkeeping burden of approximately 624 hours.
We estimate that each firm will take approximately 1 hour each to
record OOS and customer complaint events and perform investigations. We
also estimate that an average of two ``Out of Specification'' and
customer complaints and investigations per firm, with a total of 208
hours for each category. This estimate has included any reprocessing or
special batch release events, which have been rarely observed.
We also estimate annual recordkeeping for PET drug firms to perform
QA and release of manufactured PET drugs from 52 sites to be 312 hours,
for a total of 24 batches per site released if estimating 15 minutes
per batch.
[[Page 46540]]
Section 212.90(b) requires that corporate firms maintain
distribution records. We estimate that it will take approximately 15
minutes to create a distribution record for each batch of PET drug
products, with a total burden of approximately 312 hours for 24 batches
per site.
E. Annual Burden for High-Risk Component Manufacturers
According to section 121(a) of FDAMA, the PET drug definition
includes any non-radioactive or radioactive reagents, kits, nuclidic
generators, target materials, synthesizers, and so forth. FDA performs
risk assessments of each manufacturer and inspects such manufacturers.
Sterile manufacturers and complex labels fall under this category,
including sterile raw material or reagent manufactures. We have
estimated nine such facilities based on inspections so far and have
included them in this section. These manufacturers must comply with
selected sections of part 212 since they are not final PET drug
manufacturers. We will refer to them as high-risk component
manufacturers in general in this document.
We estimate that it would take 9 high-risk component manufacturers
about 30 minutes to fill each manufacturing batch records (12 per year)
and that there will be a total of approximately 108 records, with a
total recordkeeping burden of approximately 54 hours.
We also estimate that it will take nine component manufacturers 30
minutes to fill and create equipment and facilities related records,
with a total recordkeeping burden of 72 hours.
We estimate that 9 high-risk component manufacturers will document
54 components, containers, and closures for incoming acceptance tests,
with a total recordkeeping burden of approximately 27 hours.
We estimate that 9 high-risk component manufacturers will document
12 QC records related to 12 batches, with a total recordkeeping burden
of approximately 54 hours.
We also estimate annual recordkeeping for PET drug firms to perform
QA and release manufactured PET drugs from 9 sites to be 27 hours, for
a total of 108 batches released, estimating 15 minutes per batch.
We further estimate that it would take each precursor 15 minutes to
create and maintain distribution records and that there will be
approximately 108 records, with a total recordkeeping burden of
approximately 27 hours.
III. Process Verification
Section 212.50(f)(2) requires that any process verification
activities and results be recorded. Process verification is usually
performed as a one-time activity before a product is approved or if any
major manufacturing process or equipment changes are made. This effort
to conduct process verification has been estimated under annual new
creation of master batch records and manufacturing and quality
procedures in section II of this document.
IV. Conditional Final Releases
Section 212.70(f) requires PET drug producers to document any
conditional final releases of a product. We believe that conditional
final releases will be uncommon, and we have them estimated under
annual ``OOS'' investigations and final QA release efforts for each
manufactured batch.
V. Reprocessing Procedures
Sections 212.20(c) and 212.71(d) require PET drug producers to
establish and document procedures for reprocessing PET drugs. We rarely
see any reprocessing option being submitted for application of such
drugs and, if reprocessing occurs, we have estimated such rare events
under annual QA release efforts.
VI. Third-Party Disclosure Burden
Section 212.70(e) requires that PET drug producers notify all
receiving facilities if a batch fails sterility tests. FDA receives
FARs reports based on confirmed sterility failures of released PET
drugs. Based on our experience of such reporting, we estimated a total
of 12 failures from all 167 sites (corporate, small firms, and
academia). Therefore, we have estimated that 12 PET drug producers will
file 2 reports to FDA and send a notification to the affected clinical/
receiving site per year. PET drug producers would transmit the notice
by email or Fax and submit the FARs notice to FDA electronically, with
2.5 hours per incident in total.
In the Federal Register of November 30, 2018 (83 FR 61653), FDA
published a 60-day notice requesting public comment on the proposed
collection of information. Three comments were received and are
summarized here.
One comment questioned the necessity of this proposed collection.
One comment suggested that FDA allow both paper recordkeeping and
simplified electronic report submission. Two comments questioned some
of FDA's burden collection estimates. Two comments questioned whether
Annual Product Review (APR) is being required by the regulations. Two
comments pertained to an inadvertent oversight in section VI. Third-
Party Disclosure.
FDA believes that this proposed collection is necessary in keeping
with the Agency's mission of ensuring the safety and efficacy of human
drugs. Regarding the estimates included, FDA has taken a generalized
approach for these estimates, assuming that corporate firms will take
on certain burdens for all facilities under their purview, rather than
calculating all burdens per facility, and understanding that due to
variation among facilities the number of batches and products being
produced will vary. We have also only included estimates for tasks that
are included within part 212 and note that some of the comments
referenced tasks, such as APR, that are outside that scope. Electronic
recordkeeping is also outside the scope of this regulation. Regarding
the typographical error in section VI. Third Party Disclosure, on page
9350, we estimate that it will take PET drug producers 2 hours to
submit to FDA notices of sterility test failures. We intended to
estimate 2.5 hours as accurately shown in Table 6, page 9352. In
section VI of this document, we have included this change. We
appreciate these comments and will continue to consider the burden
estimate. If commenters believe certain estimates are insufficient, we
request comments on specific estimates for these requirements and why
alternative estimates would be more accurate.
The estimated burden of the information collection, therefore, is
as follows:
Table 1--Estimated One-Time Recordkeeping Burden for Corporate Firms \1\
----------------------------------------------------------------------------------------------------------------
Number of Average
Activity/type of respondent/21 Number of records per One-time burden per Total hours
CFR section recordkeepers recordkeeper records recordkeeper \2\
----------------------------------------------------------------------------------------------------------------
Batch Production and Control 3 9 27 8 216
Records (Sec. Sec. 212.20(c)
and (e) and 212.50(a) and (b)).
[[Page 46541]]
Equipment and Facilities Records 3 13 39 5 195
(SOP) (Sec. Sec. 212.20(c),
212.30(b) 212.50(d), and
212.60(f)).....................
Records of Components, 3 2 6 8 48
Containers, and Closures (SOP)
(Sec. Sec. 212.20(c) and
212.40(a) and (b)).............
Records of Components, 3 25 75 2 150
Containers, and Closures
(specifications data sheets)
(Sec. Sec. 212.20(c) and
212.40(a) and (b)).............
Out-of-Specification 3 1 3 8 24
Investigations (SOP) (Sec.
Sec. 212.20(c) and 212.71(a))
Distribution Records (SOP) (Sec. 3 1 3 8 24
Sec. 212.20(c) and
212.90(a)).....................
Complaints, Recalls (Sec. Sec. 3 3 9 8 72
212.20(c) and 212.100(a)).....
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 729
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ Number rounded to the nearest whole number.
Table 2--Estimated One-Time Recordkeeping Burden for Academia, Small Firms, and High-Risk Component
Manufacturers \1\
----------------------------------------------------------------------------------------------------------------
Number of Average
Activity/type of respondent/21 Number of records per One-time burden per Total hours
CFR section recordkeepers recordkeeper records recordkeeper \2\
----------------------------------------------------------------------------------------------------------------
Batch Production and Control 61 8 488 8 3,904
Records (Sec. Sec. 212.20(c)
and (e) and 212.50(a) and (b)).
Equipment and Facilities Records 61 13 793 8 6,344
(SOP) (Sec. Sec. 212.20(c),
212.30(b) 212.50(d), and
212.60(f)).....................
Records of Components, 61 25 1,525 2 3,050
Containers, and Closures
(specification only) (Sec.
Sec. 212.20(c) and 212.40(a)
and (b)).......................
Records of Components, 61 2 122 8 976
Containers, and Closures (SOP)
(Sec. Sec. 212.20(c) and
212.40(a) and (b)).............
Out-of-Specification 61 1 61 8 488
Investigations (SOP) (Sec.
Sec. 212.20(c) and 212.71(a))
Distribution Records (SOP) (Sec. 61 1 61 8 488
Sec. 212.20(c) and
212.90(a)).....................
Complaints, Recalls (Sec. Sec. 52 3 156 8 1,248
212.20(c) and 212.100(a)).....
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 16,498
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ Number rounded to the nearest whole number.
Table 3--Estimated Annual Recordkeeping Burden for Corporate Firms \1\
----------------------------------------------------------------------------------------------------------------
Number of Average
Activity/21 CFR section Number of records per Total annual burden per Total hours
recordkeepers recordkeeper records recordkeeper \2\
----------------------------------------------------------------------------------------------------------------
Batch Production (Creating 115 144 16,560 * 0.50 8,280
Manufacturing Records (creating
batch-related records per year)
(Sec. Sec. 212.20(c) and (e)
and 212.50(a) and (b)).........
Creating Any New Batch Records/ 3 9 27 8 216
Quality Records for New or
Existing Drugs (Sec. Sec.
212.20(c) and (e) and 212.50(a)
and (b)).......................
Equipment and Facilities Records 115 164 18,860 * 0.50 9,430
(calibration and cleaning
records systems) (Sec. Sec.
212.30(b), 212.50(d), and
212.60(f)).....................
Records of Components, 115 24 2,760 * 0.50 1,380
Containers, and Closures (Sec.
Sec. 212.20(c) and 212.40(a)
and (b)).......................
Laboratory Testing Records 115 144 16,560 * 0.50 8,280
(record laboratory test
results) (Sec. Sec.
212.60(g), 212.61(b), and
212.70(d)(2) and (3))..........
Out-of-Specification 115 2 230 2 460
Investigations (record events
and investigations) (Sec.
212.71(b)).....................
Complaints (Sec. Sec. 115 2 230 2 460
212.100(b) and (c))............
QA and Release of Batches....... 115 144 16,560 + 0.25 4,140
Distribution Records (Sec. 115 144 16,560 + 0.25 4,140
212.90(b)).....................
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 36,786
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ Number rounded to the nearest whole number.
[[Page 46542]]
* (30 minutes).
+ (15 minutes).
Table 4--Estimated Annual Recordkeeping Burden for Academia and Small Firms \1\
----------------------------------------------------------------------------------------------------------------
Number of Average
Activity/21 CFR section Number of records per Total annual burden per Total hours
recordkeepers recordkeeper records recordkeeper \2\
----------------------------------------------------------------------------------------------------------------
Batch Production (creating 52 24 1,248 * 0.50 624
manufacturing records) (filling
batch related records per year)
(Sec. Sec. 212.20(c) and (e)
and 212.50(a) and (b)).........
Creating Any New Batch Records/ 52 3 156 8 1,248
Procedures for New Drugs (Sec.
Sec. 212.20(c) and (e) and
212.50(a) and (b)).............
Equipment and Facilities Records 52 34 1,768 * 0.50 884
(calibration and cleaning
records) (Sec. Sec.
212.30(b), 212.50(d), and
212.60(f)).....................
Records of Components, 52 12 624 * 0.50 312
Containers, and Closures
(incoming acceptance tests)
(Sec. Sec. 212.20(c) and
212.40(a) and (b)).............
Laboratory Testing Records (QC 52 24 1,248 * 0.50 624
test results) (Sec. Sec.
212.60(g), 212.61(b) and
212.70(d)(2) and (3))..........
Out-of-Specification 52 2 104 2 208
Investigations (record events
and investigations) (Sec.
212.71(b)).....................
Complaints (Record events and 52 2 104 2 208
investigations) (Sec. Sec.
212.100(b) and (c))............
QA and Release of Batches....... 52 24 1,248 + 0.25 312
Distribution Records (Sec. 52 24 1,248 + 0.25 312
212.90(b)).....................
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 4,732
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ Number rounded to the nearest whole number.
* (30 minutes).
+ (15 minutes).
Table 5--Estimated Annual Recordkeeping Burden for High Risk Component Manufacturers \1\
----------------------------------------------------------------------------------------------------------------
Number of Average
Activity/21 CFR section Number of records per Total annual burden per Total hours
recordkeepers recordkeeper records recordkeeper \2\
----------------------------------------------------------------------------------------------------------------
Batch Production (creating 9 12 108 * 0.50 54
manufacturing records and batch
related records per year) (Sec.
Sec. 212.20(c) and (e) and
212.50(a) and (b)).............
Equipment and Facilities Records 9 16 144 * 0.50 72
(calibration and cleaning
records systems) (Sec. Sec.
212.30(b), 212.50(d), and
212.60(f)).....................
Records of Components, 9 6 54 * 0.50 27
Containers, and Closures
(incoming acceptance test)
(Sec. Sec. 212.20(c) and
212.40(a) and (b)).............
Laboratory Testing Records 9 12 108 * 0.50 54
(record QC test results) (Sec.
Sec. 212.60(g), 212.61(b) and
212.70(d)(2) and (3))..........
Out-of-Specification 9 1 9 1 9
Investigations (Record events
and investigations) (Sec.
212.71(b)).....................
QA and Release of Batches....... 9 12 108 + 0.25 27
Distribution Records (Sec. 9 12 108 + 0.25 27
212.90(b)).....................
-------------------------------------------------------------------------------
Total....................... .............. .............. .............. .............. 270
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ Number rounded to the nearest whole number.
* (30 minutes).
+ (15 minutes).
Table 6--Estimated Annual Third-Party Disclosure Burden \1\
----------------------------------------------------------------------------------------------------------------
Number of Number of
sterility disclosures Total annual Average
Activity/21 CFR section failure per disclosures burden per Total hours
incidents respondent disclosure
----------------------------------------------------------------------------------------------------------------
Sterility Test Failure Notices 12 \2\ 3 36 2.5 90
(Sec. 212.70(e)).............
----------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
\2\ There are two reports sent to FDA per incident and notification to receiving site.
[[Page 46543]]
These burden estimates reflect adjustments since last OMB approval.
Previously we had based the estimated number of respondents on the
number of individual production sites, however we believe using the
number of registered organizations better reflects the burden
attributable to information collection. This results in an overall
decrease to the collection.
Dated: August 26, 2019.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2019-19030 Filed 9-3-19; 8:45 am]
BILLING CODE 4164-01-P
