[Federal Register Volume 82, Number 242 (Tuesday, December 19, 2017)]
[Notices]
[Pages 60201-60203]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-27279]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2017-N-6716]


New Insights for Product Development and Bioequivalence 
Assessments of Generic Orally Inhaled and Nasal Drug 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 ``New Insights for 
Product Development and Bioequivalence Assessments of Generic Orally 
Inhaled and Nasal Drug Products.'' The purposes of the workshop are to 
present the outcomes from the research projects conducted under the 
Generic Drug User Fee Amendments (GDUFA) Regulatory Science Research 
Program; discuss how regulatory science initiatives have helped address 
regulatory science knowledge gaps by providing insights on factors that 
influence the performance of generic orally inhaled and nasal drug 
products (OINDPs); share the Agency's experience on the utility of 
novel analytical tools and methods developed under the regulatory 
science initiative for generic OINDP product development and 
bioequivalence assessments; and obtain input from the public on what, 
when, where, and how analytical methods and procedures should be 
applied in the development and review of abbreviated new drug 
applications (ANDAs) for complex OINDPs.

DATES: The public workshop will be held on January 9, 2018, from 8:30 
a.m. to 4:30 p.m. Individuals who wish to attend the workshop must 
register by December 30, 2017. Submit either electronic or written 
comments on this public workshop by February 14, 2018. 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 February 14, 2018. The https://www.regulations.gov electronic filing system will accept comments until 
midnight Eastern Time at the end of February 14, 2018. 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-6716 for ``New Insights for Product Development and 
Bioequivalence Assessments of Generic Orally Inhaled and Nasal Drug 
Products.'' 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 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.

[[Page 60202]]


FOR FURTHER INFORMATION CONTACT: Renishkumar Delvadia, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 75, Rm. 4704, Silver Spring, MD 20993, 240-402-
7979, email: [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    In the Regulatory Science Enhancements section of the GDUFA 
Reauthorization Performance Goals and Program Enhancement Fiscal Years 
2018-2022 (GDUFA II Commitment Letter) (available at: https://www.fda.gov/downloads/ForIndustry/UserFees/GenericDrugUserFees/UCM525234.pdf) FDA committed to ``conduct internal and external 
research to support fulfilment of submission review and pre-ANDA 
commitments.'' This continues commitments made in the GDUFA Program 
Performance Goals and Procedures for fiscal years 2013 through 2017 
(GDUFA I Commitment Letter) (available at: https://www.fda.gov/downloads/ForIndustry/UserFees/GenericDrugUserFees/UCM282505.pdf). For 
complex OINDPs, this research is intended to support the development of 
scientific guidance and Agency policy to clarify the ANDA pathway for 
OINDPs and aid our understanding about the critical product attributes 
relevant for in vivo performance of OINDPs. This work has led to the 
development of tools beneficial to both industry and FDA for developing 
and evaluating generic OINDPs. This regulatory science research 
includes, but is not limited to, the following: (1) Identification of 
critical formulation and device attributes of generic OINDPs; (2) 
development of clinically relevant in vitro tools for prediction of in 
vivo regional drug deposition and dissolution from OINDPs; (3) 
development of computational fluid dynamic (CFD) and physiologically-
based pharmacokinetic (PBPK) models for prediction of the local and 
systemic exposure of drugs delivered through OINDPs and to assess their 
applicability in generic OINDP development programs; and (4) 
identification, validation, and standardization of novel techniques 
that can be used for future bioequivalence assessments for generic 
OINDPs.
    Since its commencement in 2012, the GDUFA Regulatory Science 
Research Program has continuously aided our understanding about the 
critical product attributes that are relevant for in vivo performance 
of OINDPs, and has led to the development of tools beneficial to both 
industry and FDA for developing and assessing generic OINDPs. Several 
external and internal research projects have been initiated under the 
GDUFA Regulatory Science Research Program. The outcomes from these 
research studies have provided valuable insight about the factors 
influencing the performance of OINDPs and have helped the Agency fill 
regulatory science gaps in this area. For instance, advanced modeling 
tools developed under this initiative, such as CFD and PBPK, can 
provide insights about patient-device interactions and information 
about both local and systemic bioavailability, which can better 
characterize critical device and formulation attributes to further our 
understanding of generic drug-device combination products. Clinically 
relevant mouth-throat and nasal models are another example of this 
research which have shown good in vivo correlations in predicting 
regional drug deposition; these physical models allow us to predict the 
impact of certain performance characteristics of OINDPs on regional 
drug deposition in a realistic manner, potentially without the need for 
conducting comparative clinical endpoint studies. Similarly, 
Morphologically Directed Raman Spectroscopy (MDRS), a novel particle 
sizing method explored under the initiative, has shown promise in 
differentiating nasal suspension formulations of different drug 
particle sizes, and has opened the possibility of a new regulatory 
pathway for the approval of generic nasal suspension products without 
the need to conduct a comparative clinical endpoint study. Another 
research outcome developed under the science initiative for OINDPs has 
been work involving in-vitro dissolution methods, which are providing 
insights on the bridge between local drug deposition and its downstream 
systemic bioavailability. Our enhanced understanding about OINDPs from 
these regulatory science-based initiatives have informed us during the 
development of product-specific guidances for OINDPs, resulting in the 
publication of more than 39 product-specific guidance documents since 
the implementation of GDUFA in 2012.
    To enhance communication of recent advances, including those 
supported by GDUFA funds, FDA plans to hold a public workshop on new 
analytical methods and assessment criteria for characterization of 
OINDPs.

II. Purpose and Scope of the Workshop

    The purposes of the workshop are as follows:
    1. To present the outcomes from the research projects initiated 
under the GDUFA Regulatory Science Research Program;
    2. To discuss how regulatory science initiatives have helped 
address regulatory science gaps by providing insight on factors that 
influence the performance of OINDPs;
    3. To share the Agency's experience on the utility of novel 
analytical tools and methods developed under the regulatory science 
initiative for OINDP product development and bioequivalence 
assessments; and
    4. To obtain input from the public on what, when, where, and how 
analytical methods and procedures should be applied in the development 
and review of complex OINDP ANDAs for therapeutic equivalence.
    The scope of the workshop covers the current status of methods for 
characterization and bioequivalence evaluation of generic OINDPs.
    The focus of this public workshop is on the evaluation of these new 
methods for characterizing and demonstrating therapeutic equivalence of 
OINDPs, including discussing the areas in which these methods may 
significantly contribute to generic product development and regulatory 
understanding, how and under what conditions the methods should be 
conducted and evaluated, and inherent scientific challenges with this 
complex class of products.
    Public input will improve FDA's current understanding of present 
and future methods available for evaluating OINDP therapeutic 
equivalence. The knowledge gained through this workshop discussion will 
be summarized and disseminated to the scientific community by 
publication(s).

III. Scope of Public Input Requested

    FDA seeks input from the public on when, where, and how to utilize 
new methods for development of generic OINDPs and in the regulatory 
review of bioequivalence. Specific topics to be addressed include:
    1. Identifying the areas in which new in vitro and computational 
methods can contribute to the development of generic OINDPs;
    2. Discussing how in vitro testing for demonstrating OINDP 
therapeutic equivalence should be conducted and evaluated; and
    3. Addressing the scientific challenges in assessing critical 
quality attributes of OINDPs and in developing new

[[Page 60203]]

methods for demonstrating OINDP therapeutic equivalence.
    Registration: Persons interested in attending this public workshop 
must register online by December 30, 2017, by going to https://www.fda.gov/Drugs/NewsEvents/ucm576064.htm. Please provide complete 
contact information for each attendee, including name, title, 
affiliation, address, email, and telephone. The workshop agenda and 
other background materials will be available approximately 2 weeks 
before the workshop at https://www.fda.gov/Drugs/NewsEvents/ucm576064.htm. The agenda will include time for questions and answers 
throughout the day and for general comments and questions from the 
audience following panel discussions.
    Registration is free and based on space availability, with priority 
given to early registrants. Persons interested in attending this public 
workshop must register by December 30, 2017, midnight Eastern Time. 
Early registration is recommended because seating is limited; 
therefore, FDA may limit the number of participants from each 
organization. If time and space permit, onsite registration on the day 
of the public workshop will be provided beginning at 8:30 a.m.
    If you need special accommodations due to a disability, please 
contact Renishkumar Delvadia no later than December 30, 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/r19djs3yfsf/ on the day of the workshop. 
A video record of the workshop will be available at the same web 
address for 1 year. 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 website addresses in this 
document, as of the date this document publishes in the Federal 
Register, but websites are subject to change over time.

    Dated: December 13, 2017.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2017-27279 Filed 12-18-17; 8:45 am]
 BILLING CODE 4164-01-P


