[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.

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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, 
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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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).
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    \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

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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


