[Federal Register Volume 82, Number 189 (Monday, October 2, 2017)]
[Notices]
[Pages 45856-45858]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-21018]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2017-N-5776]


Equivalence of Complex Products; Public Workshop; Request for 
Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public workshop; request for comments.

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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is 
announcing the following public workshop entitled ``Demonstrating 
Equivalence of Generic Complex Drug Substances and Formulations: 
Advances in Characterization and In Vitro Testing.'' The purpose of the 
workshop is to share FDA's current experiences on the evaluation and 
characterization of critical quality attributes for complex drug 
substances (e.g. polymeric and naturally derived substances and 
peptides) and formulations (e.g. liposomes, emulsions, suspensions, and 
polymeric inserts); discuss current and future innovative approaches 
for the development and regulatory review of equivalent complex drug 
products; obtain input from various stakeholders on how to conduct and 
assess critical quality attribute measurements to demonstrate 
equivalence of complex drug products; and request comments on these 
topics.

DATES: The public workshop will be held on October 6, 2017, from 8:30 
a.m. to 4:30 p.m. Submit either electronic or written comments on this 
public workshop by November 10, 2017. See the SUPPLEMENTARY INFORMATION 
section for registration date and information.

ADDRESSES: The public workshop will be held at FDA White Oak Campus, 
10903 New Hampshire Ave., Bldg. 31 Conference Center, the Great Room 
(Rm. 1503 B+C), Silver Spring, MD 20993-0002. Entrance for the public 
workshop participants (non-FDA employees) is through Building 1 where 
routine security check procedures will be performed. For parking and 
security information, please refer to https://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.
    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 November 10, 2017. The https://www.regulations.gov electronic filing system will accept comments until 
midnight Eastern Time at the end of November 10, 2017. 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-2017-N-5776 for ``Demonstrating Equivalence of Generic Complex Drug 
Substances and Formulations: Advances in Characterization and In Vitro 
Testing.'' 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.
     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

[[Page 45857]]

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.gpo.gov/fdsys/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.

FOR FURTHER INFORMATION CONTACT: Xiaohui Jiang, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 75, Rm. 4716, Silver Spring, MD 20993, 240-402-
4468, [email protected]; or Darby Kozak, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 75, Rm. 4710, Silver Spring, MD 20993, 240-402-
2647, [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    In July 2012, Congress passed the Generic Drug User Fee Amendments 
(GDUFA) (Title III of the Food and Drug Administration Safety and 
Innovation Act (Pub. L. 112-144)). GDUFA is designed to enhance public 
access to safe, high-quality generic drugs and reduce costs to 
industry. To support this goal, FDA agreed in the GDUFA commitment 
letter to work with industry and interested stakeholders on identifying 
regulatory science research priorities specific to generic drugs for 
each fiscal year covered by GDUFA. The commitment letter outlines FDA's 
performance goals and procedures under the GDUFA program for the years 
2012 to 2017. The commitment letter can be found at https://www.fda.gov/downloads/ForIndustry/UserFees/GenericDrugUserFees/UCM282505.pdf.
    In the Regulatory Science section of the GDUFA Commitment Letter, 
FDA outlined its plans to advance regulatory science, including 
research to support the development of guidance and policy that 
clarifies the ANDA pathway for complex drug products. This regulatory 
science research includes but is not limited to: (1) Assessing 
innovative analytical methods and procedures for characterizing the 
active ingredient sameness and pharmaceutical equivalence of complex 
drug substances, such as peptides and naturally derived substances, and 
(2) developing and evaluating new techniques to measure the critical 
quality attributes of complex formulations, such as liposomes, 
emulsions, suspensions, and polymeric inserts, with the goal of 
providing robust in vitro alternatives to in vivo bioequivalence 
studies, and (3) developing and evaluating critical quality attributes 
for complex drug-device combination products. To facilitate 
communication of recent advances in this regulatory science, including 
those supported by GDUFA funds, FDA plans to hold a public workshop on 
new analytical methods and assessment criteria for demonstrating the 
equivalence of complex drug substances and formulations.

II. Topics for Discussion at the Public Workshop

    The purposes of the workshop are to:
    1. Share FDA's current experiences on the evaluation and 
characterization of critical quality attributes for complex drug 
substances (e.g. polymeric and naturally derived substances and 
peptides) and formulations (e.g. liposomes, emulsions, suspensions, and 
polymeric inserts);
    2. Discuss current and future innovative approaches for the 
development and regulatory review of equivalent complex drug products;
    3. Obtain input from various stakeholders on how to conduct and 
assess critical quality attribute measurements to demonstrate 
equivalence of complex drug products; and
    4. Request comments on these topics.
    The scope of the workshop covers the current status, from an 
academic, industry, and regulatory perspective, of methods for 
assessing the pharmaceutical equivalence of complex drug substances and 
the bioequivalence of complex generic drug product formulations.
    Complex drug substances and formulations present unique development 
and regulatory challenges for generic drugs as establishing equivalence 
may not be straightforward by conventional practices. New and 
innovative analytical and statistical approaches may overcome these 
hurdles and thereby reduce product development time and cost, and 
inform regulatory decisions. For example, new high resolution 
analytical methods and advanced statistical models can provide better 
understanding of the complex structure, and greater confidence of 
structural sameness, needed for demonstrating the pharmaceutical 
equivalence of a generic peptide, carbohydrate, or other naturally-
sourced complex drug substance. In the same fashion, new and innovative 
in vitro characterization methods can provide an accurate measure of 
the critical quality attributes of generic liposomal, emulsion, 
suspension, or polymeric matrix drug products. These in vitro tests can 
often be used to support a demonstration of bioequivalence, in lieu of 
in vivo studies, depending, among other factors, on the sensitivity, 
robustness and/or correlation of these in vitro tests to the product 
performance. The focus of this public workshop is on the evaluation of 
new analytical and statistical methods for demonstrating equivalence of 
complex products, including discussing the areas in which these methods 
can contribute significantly, how and when the methods should be 
conducted and evaluated, and inherent scientific challenges.
    Public input will improve FDA's current understanding of present 
and future methods available for evaluating complex product 
equivalence. The knowledge gained from, and consensus reached, through 
this workshop will be summarized and disseminated to the scientific 
community by publication(s).
    FDA seeks input from the public on when, where, and how to utilize 
new methods for development of equivalent complex drug products and in 
the regulatory review of pharmaceutical equivalence and bioequivalence. 
Specific topics to be addressed include:
    1. Identifying the areas in which new in vitro analytical and 
statistical methods can contribute to the development of equivalent 
complex products and regulatory evaluation of pharmaceutical 
equivalence and bioequivalence;
    2. Discussing how in vitro testing for demonstrating complex 
product equivalence should be conducted and evaluated; and
    3. Addressing the scientific challenges in assessing critical 
quality attributes of complex products and in developing new analytical 
methods for demonstrating complex product equivalence.

[[Page 45858]]

III. Participating in the Public Workshop

    Registration: Persons interested in attending this public workshop 
must register online at https://survey.co1.qualtrics.com/jfe/form/SV_6X23XS8WXHtfWAJ. Please provide complete contact information for 
each attendee, including name, title, affiliation, address, email, and 
telephone.
    Registration is free and based on space availability, with priority 
given to early registrants. Persons interested in attending this public 
workshop must register by October 2, 2017, midnight, Eastern Time. 
Early registration is recommended because seating is limited; 
therefore, FDA may limit the number of participants from each 
organization.
    If you need special accommodations due to a disability, please 
contact Xiaohui Jiang (see FOR FURTHER INFORMATION CONTACT) no later 
than October 2, 2017.
    Streaming Webcast of the public workshop: This public workshop will 
also be webcast. A live webcast of this workshop will be viewable at 
https://collaboration.fda.gov/complexgenericdrugs/ on the day of the 
workshop.
    If you have never attended a Connect Pro event before, test your 
connection at https://collaboration.fda.gov/common/help/en/support/meeting_test.htm. To get a quick overview of the Connect Pro program, 
visit https://www.adobe.com/go/connectpro_overview. FDA has verified 
the Web site addresses in this document, as of the date this document 
publishes in the Federal Register, but Web sites are subject to change 
over time.
    Transcripts: Please be advised that as soon as a transcript of the 
public workshop 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://www.fda.gov/drugs/newsevents/ucm552461.htm.

    Dated: September 26, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-21018 Filed 9-29-17; 8:45 am]
 BILLING CODE 4164-01-P