Potential Medication Error Risks With Investigational Drug Container Labels; Public Meeting; Request for Comments, 14457-14459 [2021-05370]
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Federal Register / Vol. 86, No. 49 / Tuesday, March 16, 2021 / Notices
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2021–N–0127]
Potential Medication Error Risks With
Investigational Drug Container Labels;
Public Meeting; Request for Comments
AGENCY:
Food and Drug Administration,
HHS.
Notice of public meeting;
request for comments.
ACTION:
The Food and Drug
Administration (FDA, the Agency, or
we) is announcing the following public
meeting entitled ‘‘Potential Medication
Error Risks with Investigational Drug
Container Labels.’’ This public meeting
is being convened and supported by a
partnership between the Reagan-Udall
Foundation and FDA. The purpose of
the public meeting is to solicit input
from stakeholders (e.g., sponsors,
clinical sites, entities that supply or
otherwise label investigational drugs) on
the risk of medication errors potentially
related to the content and format of
information on investigational drug
container labels, the prevalence and
nature of such errors, and to gather
information on practices that minimize
the potential for medication errors.
DATES: The public meeting will be held
virtually and broadcast via webcast on
May 18, 2021, from 1 p.m. to 4 p.m.
(Eastern Time), and May 19, 2021, from
10 a.m. to 1 p.m. (Eastern Time). Submit
either electronic or written comments
on this public meeting by June 18, 2021.
See the SUPPLEMENTARY INFORMATION
section for registration date and
information.
SUMMARY:
Please note that due to the
impact of the COVID–19 pandemic, all
meeting participants will be joining this
public meeting via an online
teleconferencing platform.
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 June 18, 2021. The https://
www.regulations.gov electronic filing
system will accept comments until
11:59 p.m. Eastern Time at the end of
June 18, 2021. 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.
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ADDRESSES:
Electronic Submissions
Submit electronic comments in the
following way:
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• 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–0127 for ‘‘Potential Medication
Error Risks With Investigational Drug
Container Labels.’’ 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
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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
and/or go to the Dockets Management
Staff, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852, 240–402–7500.
FOR FURTHER INFORMATION CONTACT: Jo
Wyeth, Center for Drug Evaluation and
Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 22, Rm. 4326, Silver Spring,
MD 20993, 301–796–1985, Jo.Wyeth@
fda.hhs.gov; or Stephen Ripley, Center
for Biologics Evaluation and Research,
Food and Drug Administration, 10903
New Hampshire Ave., Bldg. 71, Rm.
7301, Silver Spring, MD 20993, 240–
402–7911.
SUPPLEMENTARY INFORMATION:
I. Background
The purpose of the public meeting
announced in this notice is to solicit
input from stakeholders (e.g., sponsors,
investigators, clinical sites, contract
research organizations and other entities
that supply or otherwise label
investigational drugs, regulators,
professional organizations, and study
participants) on the risk of medication
errors potentially related to the content
and format of the information on
investigational drug container labels,
the prevalence and nature of such
errors, and to gather information on
practices that minimize the potential for
medication errors.
For the purpose of this meeting, an
investigational drug means a drug or
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Federal Register / Vol. 86, No. 49 / Tuesday, March 16, 2021 / Notices
biological product that is used in a
clinical investigation under an
investigational new drug application.
FDA definitions and requirements
related to investigational new drug
applications are provided in 21 CFR
part 312. The requirements for labeling
an investigational new drug include: (1)
The immediate package of an
investigational new drug intended for
human use shall bear a label with the
statement ‘‘Caution: New Drug—Limited
by Federal (or United States) law to
investigational use’’ and (2) the label or
labeling of an investigational new drug
shall not bear any statement that is false
or misleading in any particular and
shall not represent that the
investigational new drug is safe or
effective for the purposes for which it is
being investigated (21 CFR 312.6).
While not a regulatory requirement,
some investigational new drug container
labels may include additional
information such as the protocol/
clinical trial number, concentration
and/or strength, dosage form (e.g.,
tablets, injection), quantity per
container, storage requirements, and lot
number. Sponsors of an investigational
new drug application are required to
report to FDA any suspected adverse
reaction that is both serious and
unexpected (21 CFR 312.32(c)(1)(i)) 1.
Adverse reactions that are not serious or
unexpected or medication errors that do
not result in adverse reactions may be
reported in the annual report, or not
reported at all. FDA is aware that
globally, other regulatory agencies have
varying requirements related to
investigational drug labeling and safety
reporting (Refs. 1 to 3).
The incidence and scope (e.g., error
type; stage in the medication use system
where the error occurred; actual, or
potential for, adverse events; reporting
practices) of medication errors
associated with investigational drugs is
unknown. FDA recognizes that clinical
research is conducted globally (Ref. 4).
Published literature from outside the
United States has pointed to the
container labels as a contributing factor
for potential medication errors with
investigational drugs and recommended
global harmonization of the information
on the labels (Refs. 5 and 6). For
example, a Canadian study that
included labels from blinded protocols
provided by European and American
sponsors found almost half of the labels
affixed to investigational drug
containers were missing important
information (usually the expiration date,
1 Sponsors have additional investigational new
drug safety reporting requirements that may apply
(see 21 CFR 312.32(c)(1)(ii) through (iv)).
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sponsor address, or storage conditions)
(Ref. 5). The study also found other
factors that may contribute to
medication errors, including the use of
small font sizes (less than 8 point),
variable formats for expiration dates and
lot numbers, the presence of error-prone
abbreviations, limited use of color or
other differentiation techniques, and
highly similar product or protocol
identification numbers (Ref. 5). A
French simulation study using
investigational drug container labels
found an error rate of approximately 12
percent (most errors were related to
dosage unit, trial code, drug confusion,
or expiration date) (Ref. 6).
Best practice guidelines, such as those
released by the American Society of
Health System Pharmacists, have
recommended specific content and
format for investigational drug container
labels (Ref. 7). In 2018, the Institute for
Safe Medication Practices (ISMP)
published two reports on medication
error risks with investigational drugs
(Refs. 8 and 9). The first report
(published in April 2018) explored
reported risks with investigational drug
nomenclature, labeling, and packaging,
which included unlabeled containers
and look-alike product identifiers,
confusing or missing information (e.g.,
container labels missing, route of
administration, dosage form, or net
quantity) to support safe use, small
unreadable text, and the use of codes
and error-prone abbreviations on
container labels (Ref. 9). The second
report (published in May 2018)
recommended error mitigation strategies
for clinical sites, sponsors, and other
entities that supply investigational
drugs and included the
recommendation to standardize the
content and format of information on
investigational drug container labels
(Ref. 8).
FDA reviewed additional reports of
medication error concerns related to
unlabeled or poorly labeled
investigational drug container labels
(Refs. 10 to 13). The design of container
labels can impact the ability of
healthcare providers to readily locate
and understand critical information for
product use (Ref. 14), which in turn may
threaten the integrity of clinical
investigations and impact the safety and
protection of subjects who participate in
these investigations.
II. Topics for Discussion at the Public
Meeting
During the public meeting, speakers
and participants will cover a range of
issues related to medication errors and
investigational drugs. Discussion topics
related to the format and content of
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information on investigational drug
container labels include: (1) The
prevalence and types of medication
errors attributed to container labels; (2)
the impact of such errors on clinical
investigations; (3) information that
should always be on the container label,
and how that information should be
presented to facilitate safe use; (4)
entities responsible for labeling
containers; (5) existing processes for
reporting and analyzing medication
errors and complaints related to
container labels; and (6) global
regulatory convergence and differences
for the information on container labels.
III. Participating in the Public Meeting
Registration: To register for the public
meeting, complete the registration form
at https://reaganudall.org/news-andevents/events/investigational-druglabels. Please provide complete contact
information for each attendee, including
name, title, affiliation, address, email,
and telephone number. Registration is
free.
If you need special accommodations
due to a disability, please contact Jo
Wyeth (see FOR FURTHER INFORMATION
CONTACT) no later than May 5, 2021.
Requests for Oral Presentations:
During online registration you may
indicate if you wish to present during a
public comment session or participate
in a specific session, and which topic(s)
you wish to address. We will do our
best to accommodate requests to make
public comments and requests to
participate in the focused sessions.
Individuals and organizations with
common interests are urged to
consolidate or coordinate their
presentations, and request time for a
joint presentation, or submit requests for
designated representatives to participate
in the focused sessions. All requests to
make oral presentations must be
received by April 28, 2021. We will
determine the amount of time allotted to
each presenter and the approximate
time each oral presentation is to begin,
and will select and notify participants
by May 3, 2021. If selected for
presentation, any presentation materials
must be emailed to Jo Wyeth (see FOR
FURTHER INFORMATION CONTACT) no later
than May 10, 2021. No commercial or
promotional material will be permitted
to be presented or distributed at the
public meeting.
Streaming Webcast of the Public
Meeting: This public meeting will be
webcast. Persons interested in
participating in the webcast are
encouraged to register in advance (see
Registration). The webcast will also be
available on the day of the event
without preregistration. Detailed
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Federal Register / Vol. 86, No. 49 / Tuesday, March 16, 2021 / Notices
information for participating in the
webcast is available at the following
website: https://reaganudall.org/newsand-events/events/investigational-druglabels.
Registered participants will be sent
technical system requirements in
advance of the event. It is recommended
that you review these technical system
requirements before joining the
streaming web conference of the public
meeting.
FDA has verified the website
addresses in this document, as of the
date this document publishes in the
Federal Register, but websites are
subject to change over time.
Transcripts: Please be advised that as
soon as a transcript of the public
meeting is available, it will be accessible
at https://www.regulations.gov. It may
be viewed at the Dockets Management
Staff (see ADDRESSES). A link to the
transcript will also be available on the
internet at https://reaganudall.org/newsand-events/events/investigational-druglabels.
IV. References
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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. European Commission, ‘‘EU Guidelines
to Good Manufacturing Practice;
Medicinal Products for Human and
Veterinary Use,’’ Public release date:
February 3, 2010 (available at https://
ec.europa.eu/health/sites/health/files/
files/eudralex/vol-4/2009_06_
annex13.pdf).
2. Smith-Gick, J., N. Barnes, R. Barone, et al.,
‘‘The Near-Term Viability and Benefits of
eLabels for Patients, Clinical Sites, and
Sponsors,’’ Therapeutic Innovation and
Regulatory Science, vol. 52(5), pp. 537–
545, 2018.
* 3. Health Canada, Good Clinical Practices
Guidance Document, ‘‘Annex 13 to the
Current Edition of the Good
Manufacturing Practices Guidelines
Drugs Used in Clinical Trials,’’ August 7,
2009 (available at https://
www.canada.ca/en/health-canada/
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services/drugs-health-products/
compliance-enforcement/good-clinicalpractices/guidance-documents/annex13-good-manufacturing-practicesguidelines-drugs-clinical-trials0036.html#a8_7).
* 4. FDA, Guidance for Industry and FDA
staff, ‘‘FDA Acceptance of Foreign
Clinical Studies Not Conducted Under
an IND; Frequently Asked Questions,’’
March 2012 (available at https://
www.fda.gov/media/83209/download).
For the most recent version of a
guidance, check the FDA guidance web
page at https://www.fda.gov/regulatoryinformation/search-fda-guidancedocuments.
5. Duhamel, A., M. Thibault, D. Lebel, et al.,
‘‘Investigational Drug Labeling
Variability,’’ Clinical Trials, vol. 16(2),
pp. 204–213, 2019.
6. Dollinger, C., V. Schwiertz, L. Sarfati, et
al., ‘‘SIMulation of Medication Error
Induced by Clinical Trial Drug Labeling:
The SIMME–CT Study,’’ International
Journal for Quality in Health Care, vol.
28(3), pp. 311–315, 2016.
7. Kay, S.C., D.G. Luke, and H.R. Tamer,
‘‘ASHP Guidelines for the Management
of Investigational Drug Products,’’
American Journal of Health-System
Pharmacy, vol. 75(8), pp. 561–573, 2018.
* 8. ISMP, ‘‘Investigational Drugs: Strategies
for Sponsors, FDA, and Clinical Sites to
Prevent Product-Related Errors (Part II),’’
Public release date: May 3, 2018 (available
at https://www.ismp.org/resources/
investigational-drugs-strategies-sponsorsfda-and-clinical-sites-prevent-productrelated).
* 9. ISMP, ‘‘Investigational Drugs: ProductRelated Issues Pose Significant
Challenges (Part I),’’ Public release date:
April 19, 2018 (available at https://
www.ismp.org/resources/investigationaldrugs-product-related-issues-posesignificant-challenges-part-i).
10. Cruz, J.L. and J.N. Brown, ‘‘Safety Risks
With Investigational Drugs: Pharmacy
Practices and Perceptions in the Veterans
Affairs Health System,’’ Therapeutic
Advances in Drug Safety, vol. 6(3), pp.
103–109, 2015.
11. Grissinger, M., ‘‘Reducing the Potential
for Mistakes With Investigational Drugs,’’
Pharmacy and Therapeutics, vol. 36(3),
pp. 120–138, 2011.
12. Brown, J.N., S.R. Britnell, A.P. Stivers, et
al., ‘‘Medication Safety in Clinical Trials:
Role of the Pharmacist in Optimizing
Practice, Collaboration, and Education
To Reduce Errors,’’ Yale Journal of
Biology and Medicine, vol. 90(1), pp.
125–133, 2017.
* 13. ISMP, ‘‘Remdesivir Investigational Drug
Labeling Confusion,’’ Acute Care, vol.
25(9), 2020.
* 14. FDA, Draft Guidance for Industry,
‘‘Safety Considerations for Container
Labels and Carton Labeling Design to
Minimize Medication Errors,’’ April
2013 (available at https://www.fda.gov/
regulatory-information/search-fdaguidance-documents/safetyconsiderations-container-labels-andcarton-labeling-design-minimize-
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14459
medication-errors). When final, this
guidance will represent the FDA’s
current thinking on this topic. For the
most recent version of a guidance, check
the FDA guidance web page at https://
www.fda.gov/regulatory-information/
search-fda-guidance-documents.
Dated: March 11, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for
Policy.
[FR Doc. 2021–05370 Filed 3–15–21; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Health Resources and Services
Administration
National Vaccine Injury Compensation
Program; List of Petitions Received
Health Resources and Services
Administration (HRSA), Department of
Health and Human Services (HHS).
ACTION: Notice.
AGENCY:
HRSA is publishing this
notice of petitions received under the
National Vaccine Injury Compensation
Program (the Program), as required by
the Public Health Service (PHS) Act, as
amended. While the Secretary of HHS is
named as the respondent in all
proceedings brought by the filing of
petitions for compensation under the
Program, the United States Court of
Federal Claims is charged by statute
with responsibility for considering and
acting upon the petitions.
FOR FURTHER INFORMATION CONTACT: For
information about requirements for
filing petitions, and the Program in
general, contact Lisa L. Reyes, Clerk of
Court, United States Court of Federal
Claims, 717 Madison Place NW,
Washington, DC 20005, (202) 357–6400.
For information on HRSA’s role in the
Program, contact the Director, National
Vaccine Injury Compensation Program,
5600 Fishers Lane, Room 08N146B,
Rockville, Maryland 20857; (301) 443–
6593, or visit our website at: https://
www.hrsa.gov/vaccinecompensation/
index.html.
SUMMARY:
The
Program provides a system of no-fault
compensation for certain individuals
who have been injured by specified
childhood vaccines. Subtitle 2 of Title
XXI of the PHS Act, 42 U.S.C. 300aa–
10 et seq., provides that those seeking
compensation are to file a petition with
the United States Court of Federal
Claims and to serve a copy of the
petition to the Secretary of HHS, who is
named as the respondent in each
SUPPLEMENTARY INFORMATION:
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Agencies
[Federal Register Volume 86, Number 49 (Tuesday, March 16, 2021)]
[Notices]
[Pages 14457-14459]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-05370]
[[Page 14457]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2021-N-0127]
Potential Medication Error Risks With Investigational Drug
Container Labels; Public Meeting; Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of public meeting; request for comments.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
announcing the following public meeting entitled ``Potential Medication
Error Risks with Investigational Drug Container Labels.'' This public
meeting is being convened and supported by a partnership between the
Reagan-Udall Foundation and FDA. The purpose of the public meeting is
to solicit input from stakeholders (e.g., sponsors, clinical sites,
entities that supply or otherwise label investigational drugs) on the
risk of medication errors potentially related to the content and format
of information on investigational drug container labels, the prevalence
and nature of such errors, and to gather information on practices that
minimize the potential for medication errors.
DATES: The public meeting will be held virtually and broadcast via
webcast on May 18, 2021, from 1 p.m. to 4 p.m. (Eastern Time), and May
19, 2021, from 10 a.m. to 1 p.m. (Eastern Time). Submit either
electronic or written comments on this public meeting by June 18, 2021.
See the SUPPLEMENTARY INFORMATION section for registration date and
information.
ADDRESSES: Please note that due to the impact of the COVID-19 pandemic,
all meeting participants will be joining this public meeting via an
online teleconferencing platform.
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 June 18, 2021. The https://www.regulations.gov
electronic filing system will accept comments until 11:59 p.m. Eastern
Time at the end of June 18, 2021. 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-0127 for ``Potential Medication Error Risks With
Investigational Drug Container Labels.'' 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 and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240-402-7500.
FOR FURTHER INFORMATION CONTACT: Jo Wyeth, Center for Drug Evaluation
and Research, Food and Drug Administration, 10903 New Hampshire Ave.,
Bldg. 22, Rm. 4326, Silver Spring, MD 20993, 301-796-1985,
[email protected]; or Stephen Ripley, Center for Biologics
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993, 240-402-
7911.
SUPPLEMENTARY INFORMATION:
I. Background
The purpose of the public meeting announced in this notice is to
solicit input from stakeholders (e.g., sponsors, investigators,
clinical sites, contract research organizations and other entities that
supply or otherwise label investigational drugs, regulators,
professional organizations, and study participants) on the risk of
medication errors potentially related to the content and format of the
information on investigational drug container labels, the prevalence
and nature of such errors, and to gather information on practices that
minimize the potential for medication errors.
For the purpose of this meeting, an investigational drug means a
drug or
[[Page 14458]]
biological product that is used in a clinical investigation under an
investigational new drug application. FDA definitions and requirements
related to investigational new drug applications are provided in 21 CFR
part 312. The requirements for labeling an investigational new drug
include: (1) The immediate package of an investigational new drug
intended for human use shall bear a label with the statement ``Caution:
New Drug--Limited by Federal (or United States) law to investigational
use'' and (2) the label or labeling of an investigational new drug
shall not bear any statement that is false or misleading in any
particular and shall not represent that the investigational new drug is
safe or effective for the purposes for which it is being investigated
(21 CFR 312.6). While not a regulatory requirement, some
investigational new drug container labels may include additional
information such as the protocol/clinical trial number, concentration
and/or strength, dosage form (e.g., tablets, injection), quantity per
container, storage requirements, and lot number. Sponsors of an
investigational new drug application are required to report to FDA any
suspected adverse reaction that is both serious and unexpected (21 CFR
312.32(c)(1)(i)) \1\. Adverse reactions that are not serious or
unexpected or medication errors that do not result in adverse reactions
may be reported in the annual report, or not reported at all. FDA is
aware that globally, other regulatory agencies have varying
requirements related to investigational drug labeling and safety
reporting (Refs. 1 to 3).
---------------------------------------------------------------------------
\1\ Sponsors have additional investigational new drug safety
reporting requirements that may apply (see 21 CFR 312.32(c)(1)(ii)
through (iv)).
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The incidence and scope (e.g., error type; stage in the medication
use system where the error occurred; actual, or potential for, adverse
events; reporting practices) of medication errors associated with
investigational drugs is unknown. FDA recognizes that clinical research
is conducted globally (Ref. 4). Published literature from outside the
United States has pointed to the container labels as a contributing
factor for potential medication errors with investigational drugs and
recommended global harmonization of the information on the labels
(Refs. 5 and 6). For example, a Canadian study that included labels
from blinded protocols provided by European and American sponsors found
almost half of the labels affixed to investigational drug containers
were missing important information (usually the expiration date,
sponsor address, or storage conditions) (Ref. 5). The study also found
other factors that may contribute to medication errors, including the
use of small font sizes (less than 8 point), variable formats for
expiration dates and lot numbers, the presence of error-prone
abbreviations, limited use of color or other differentiation
techniques, and highly similar product or protocol identification
numbers (Ref. 5). A French simulation study using investigational drug
container labels found an error rate of approximately 12 percent (most
errors were related to dosage unit, trial code, drug confusion, or
expiration date) (Ref. 6).
Best practice guidelines, such as those released by the American
Society of Health System Pharmacists, have recommended specific content
and format for investigational drug container labels (Ref. 7). In 2018,
the Institute for Safe Medication Practices (ISMP) published two
reports on medication error risks with investigational drugs (Refs. 8
and 9). The first report (published in April 2018) explored reported
risks with investigational drug nomenclature, labeling, and packaging,
which included unlabeled containers and look-alike product identifiers,
confusing or missing information (e.g., container labels missing, route
of administration, dosage form, or net quantity) to support safe use,
small unreadable text, and the use of codes and error-prone
abbreviations on container labels (Ref. 9). The second report
(published in May 2018) recommended error mitigation strategies for
clinical sites, sponsors, and other entities that supply
investigational drugs and included the recommendation to standardize
the content and format of information on investigational drug container
labels (Ref. 8).
FDA reviewed additional reports of medication error concerns
related to unlabeled or poorly labeled investigational drug container
labels (Refs. 10 to 13). The design of container labels can impact the
ability of healthcare providers to readily locate and understand
critical information for product use (Ref. 14), which in turn may
threaten the integrity of clinical investigations and impact the safety
and protection of subjects who participate in these investigations.
II. Topics for Discussion at the Public Meeting
During the public meeting, speakers and participants will cover a
range of issues related to medication errors and investigational drugs.
Discussion topics related to the format and content of information on
investigational drug container labels include: (1) The prevalence and
types of medication errors attributed to container labels; (2) the
impact of such errors on clinical investigations; (3) information that
should always be on the container label, and how that information
should be presented to facilitate safe use; (4) entities responsible
for labeling containers; (5) existing processes for reporting and
analyzing medication errors and complaints related to container labels;
and (6) global regulatory convergence and differences for the
information on container labels.
III. Participating in the Public Meeting
Registration: To register for the public meeting, complete the
registration form at https://reaganudall.org/news-and-events/events/investigational-drug-labels. Please provide complete contact
information for each attendee, including name, title, affiliation,
address, email, and telephone number. Registration is free.
If you need special accommodations due to a disability, please
contact Jo Wyeth (see FOR FURTHER INFORMATION CONTACT) no later than
May 5, 2021.
Requests for Oral Presentations: During online registration you may
indicate if you wish to present during a public comment session or
participate in a specific session, and which topic(s) you wish to
address. We will do our best to accommodate requests to make public
comments and requests to participate in the focused sessions.
Individuals and organizations with common interests are urged to
consolidate or coordinate their presentations, and request time for a
joint presentation, or submit requests for designated representatives
to participate in the focused sessions. All requests to make oral
presentations must be received by April 28, 2021. We will determine the
amount of time allotted to each presenter and the approximate time each
oral presentation is to begin, and will select and notify participants
by May 3, 2021. If selected for presentation, any presentation
materials must be emailed to Jo Wyeth (see FOR FURTHER INFORMATION
CONTACT) no later than May 10, 2021. No commercial or promotional
material will be permitted to be presented or distributed at the public
meeting.
Streaming Webcast of the Public Meeting: This public meeting will
be webcast. Persons interested in participating in the webcast are
encouraged to register in advance (see Registration). The webcast will
also be available on the day of the event without preregistration.
Detailed
[[Page 14459]]
information for participating in the webcast is available at the
following website: https://reaganudall.org/news-and-events/events/investigational-drug-labels.
Registered participants will be sent technical system requirements
in advance of the event. It is recommended that you review these
technical system requirements before joining the streaming web
conference of the public meeting.
FDA has verified the website addresses in this document, as of the
date this document publishes in the Federal Register, but websites are
subject to change over time.
Transcripts: Please be advised that as soon as a transcript of the
public meeting is available, it will be accessible at https://www.regulations.gov. It may be viewed at the Dockets Management Staff
(see ADDRESSES). A link to the transcript will also be available on the
internet at https://reaganudall.org/news-and-events/events/investigational-drug-labels.
IV. 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. European Commission, ``EU Guidelines to Good Manufacturing
Practice; Medicinal Products for Human and Veterinary Use,'' Public
release date: February 3, 2010 (available at https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/2009_06_annex13.pdf).
2. Smith-Gick, J., N. Barnes, R. Barone, et al., ``The Near-Term
Viability and Benefits of eLabels for Patients, Clinical Sites, and
Sponsors,'' Therapeutic Innovation and Regulatory Science, vol.
52(5), pp. 537-545, 2018.
* 3. Health Canada, Good Clinical Practices Guidance Document,
``Annex 13 to the Current Edition of the Good Manufacturing
Practices Guidelines Drugs Used in Clinical Trials,'' August 7, 2009
(available at https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/good-clinical-practices/guidance-documents/annex-13-good-manufacturing-practices-guidelines-drugs-clinical-trials-0036.html#a8_7).
* 4. FDA, Guidance for Industry and FDA staff, ``FDA Acceptance of
Foreign Clinical Studies Not Conducted Under an IND; Frequently
Asked Questions,'' March 2012 (available at https://www.fda.gov/media/83209/download). For the most recent version of a guidance,
check the FDA guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents.
5. Duhamel, A., M. Thibault, D. Lebel, et al., ``Investigational
Drug Labeling Variability,'' Clinical Trials, vol. 16(2), pp. 204-
213, 2019.
6. Dollinger, C., V. Schwiertz, L. Sarfati, et al., ``SIMulation of
Medication Error Induced by Clinical Trial Drug Labeling: The SIMME-
CT Study,'' International Journal for Quality in Health Care, vol.
28(3), pp. 311-315, 2016.
7. Kay, S.C., D.G. Luke, and H.R. Tamer, ``ASHP Guidelines for the
Management of Investigational Drug Products,'' American Journal of
Health-System Pharmacy, vol. 75(8), pp. 561-573, 2018.
* 8. ISMP, ``Investigational Drugs: Strategies for Sponsors, FDA,
and Clinical Sites to Prevent Product-Related Errors (Part II),''
Public release date: May 3, 2018 (available at https://www.ismp.org/resources/investigational-drugs-strategies-sponsors-fda-and-clinical-sites-prevent-product-related).
* 9. ISMP, ``Investigational Drugs: Product-Related Issues Pose
Significant Challenges (Part I),'' Public release date: April 19,
2018 (available at https://www.ismp.org/resources/investigational-drugs-product-related-issues-pose-significant-challenges-part-i).
10. Cruz, J.L. and J.N. Brown, ``Safety Risks With Investigational
Drugs: Pharmacy Practices and Perceptions in the Veterans Affairs
Health System,'' Therapeutic Advances in Drug Safety, vol. 6(3), pp.
103-109, 2015.
11. Grissinger, M., ``Reducing the Potential for Mistakes With
Investigational Drugs,'' Pharmacy and Therapeutics, vol. 36(3), pp.
120-138, 2011.
12. Brown, J.N., S.R. Britnell, A.P. Stivers, et al., ``Medication
Safety in Clinical Trials: Role of the Pharmacist in Optimizing
Practice, Collaboration, and Education To Reduce Errors,'' Yale
Journal of Biology and Medicine, vol. 90(1), pp. 125-133, 2017.
* 13. ISMP, ``Remdesivir Investigational Drug Labeling Confusion,''
Acute Care, vol. 25(9), 2020.
* 14. FDA, Draft Guidance for Industry, ``Safety Considerations for
Container Labels and Carton Labeling Design to Minimize Medication
Errors,'' April 2013 (available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/safety-considerations-container-labels-and-carton-labeling-design-minimize-medication-errors). When final, this guidance will represent the FDA's current
thinking on this topic. For the most recent version of a guidance,
check the FDA guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents.
Dated: March 11, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-05370 Filed 3-15-21; 8:45 am]
BILLING CODE 4164-01-P