
[Federal Register Volume 81, Number 76 (Wednesday, April 20, 2016)]
[Notices]
[Pages 23303-23304]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-09137]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-D-0973]


Comparability Protocols for Human Drugs and Biologics: Chemistry, 
Manufacturing, and Controls Information; Draft Guidance for Industry; 
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance for industry entitled ``Comparability 
Protocols for Human Drugs and Biologics: Chemistry, Manufacturing, and 
Controls Information.'' This document is a revised version of a draft 
guidance that published in February 2003 entitled ``Comparability 
Protocols: Chemistry, Manufacturing, and Controls Information.'' A 
related draft guidance entitled ``Comparability Protocols--Protein Drug 
Products and Biological Products--Chemistry, Manufacturing, and 
Controls Information,'' that published in September 2003, was withdrawn 
on May 6, 2015.
    The revised draft guidance provides recommendations to human drug 
and biologics manufacturers on implementing a chemistry, manufacturing, 
and controls (CMC) postapproval change(s) through the use of a 
comparability protocol (CP). By using a CP, manufacturers who fall 
within the scope of this guidance will not have to submit commercial-
scale CMC information on postchange products to FDA before making the 
proposed change. This draft guidance is intended to establish a 
framework to promote manufacturing of quality drug products.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115 (g)(5)), to ensure that the Agency considers your comment on 
this draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by June 20, 2016.

ADDRESSES: You may submit comments as follows:

Electronic Comments

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://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 http://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): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, 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-2016-D-0973 for ``Comparability Protocols for Human Drugs and 
Biologics: Chemistry, Manufacturing, and Controls Information.'' 
Received comments will be placed in the docket and, except for those 
submitted as ``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management 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 http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. 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: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://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 Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.
    Submit written requests for single copies of the draft guidance to 
the Division of Drug Information, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10001 New Hampshire Ave., 
Hillandale Building, 4th Floor, Silver Spring, MD 20993-0002. Send one 
self-addressed adhesive label to assist that office in processing your 
requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the draft guidance document.

FOR FURTHER INFORMATION CONTACT: Stephen Moore, Center for Drug 
Evaluation and Research, Food and Drug Administration, Bldg. 21, Rm. 
2012, 10903 New Hampshire Ave.,

[[Page 23304]]

Silver Spring, MD 20993-0002, 301-796-7579 or Stephen Ripley, Center 
for Biologics Evaluation and Research, Food and Drug Administration, 
Bldg. 71, Rm. 7268, 10903 New Hampshire Ave., Silver Spring, MD 20993-
0002, 240-402-7911.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Comparability Protocols for Human Drugs and Biologics: 
Chemistry, Manufacturing, and Controls Information.'' This draft 
guidance is a revised version of a draft guidance that published in 
February 2003 entitled ``Comparability Protocols: Chemistry, 
Manufacturing, and Controls Information.'' A related draft guidance 
entitled ``Comparability Protocols--Protein Drug Products and 
Biological Products--Chemistry, Manufacturing, and Controls 
Information,'' which published in September 2003, was withdrawn on May 
6, 2015 (80 FR 26059).
    The revised draft guidance provides recommendations to holders of 
applications for human drugs and biologics on implementing a chemistry, 
manufacturing, controls (CMC) postapproval change(s) through the use of 
a comparability protocol (CP). The revised draft guidance applies to 
new drug applications (NDAs), abbreviated new drug applications 
(ANDAs), or biologics license applications (BLAs) regulated by the 
Center for Drug Evaluation and Research (CDER) or the Center for 
Biologics Evaluation and Research (CBER) or supplements following 21 
CFR 314.70 or 21 CFR 601.12.
    On February 25, 2003 (68 FR 8772), FDA announced the availability 
of the first draft version of this guidance. The public comment period 
closed on June 25, 2003. A number of comments were received, which the 
Agency considered carefully as it prepared this revised draft guidance.
    We revised the guidance for the following reasons:
     To provide more flexibility regarding filing procedures 
for a notification of change in a condition established in an approved 
application.
     To include current pharmaceutical quality concepts.
     To add an appendix to address commonly asked questions.
    This revised draft guidance provides recommendations to human drug 
manufacturers on implementing CMC postapproval change(s) through the 
use of a CP. By using an approved CP, manufacturers whom fall within 
the scope of this guidance will not have to submit commercial-scale CMC 
information on postchange products to FDA before making the proposed 
changes. The draft guidance is intended to establish a framework to 
promote manufacturing of quality drug products by employing the 
following:
     Effective use of knowledge and understanding of the 
product and manufacturing process.
     A robust control strategy.
     Risk management activities over a product's life cycle.
     An effective pharmaceutical quality system.
    This draft guidance incorporates the modern regulatory concepts 
stated in the guidance for industry entitled ``PAT--A Framework for 
Innovative Pharmaceutical Development, Manufacturing, and Quality 
Assurance,'' (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070305.pdf) the 
Pharmaceutical Current Good Manufacturing Practices for the 21st 
Century Initiative (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/Manufacturing/QuestionsandAnswersonCurrentGoodManufacturingPracticescGMPforDrugs/UCM071836), the Critical Path Initiative (http://www.fda.gov/scienceresearch/specialtopics/criticalpathinitiative/default.htm), and 
the quality by design principles described in the guidance for industry 
entitled ``Q8(R2) Pharmaceutical Development'' (http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm073507.pdf). In publishing this draft guidance, FDA is communicating 
its expectations and support for the described approach.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent the Agency's current thinking on 
comparability protocols for applications regulated in CDER and CBER as 
described previously. It does not create or confer any rights for or on 
any person and does not operate to bind FDA or the public. An 
alternative approach may be used if such approach satisfies the 
requirements of the applicable statutes and regulations.

II. Paperwork Reduction Act of 1995

    This draft guidance contains information collection provisions that 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The 
collection of information requested in the draft guidance is covered 
under FDA regulations 21 CFR 314.50, 314.70, and 314.81(b)(2) for human 
drugs and 21 CFR 601.2 and 601.12 for biologics. The collection of 
information is approved under the following OMB Control Numbers: 0910-
0001 for human drugs and 0910-0338 for biologics.

III. Electronic Access

    Persons with access to the Internet may obtain the document at 
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm, http://www.regulations.gov, or http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.htm.

    Dated: April 14, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-09137 Filed 4-19-16; 8:45 am]
BILLING CODE 4164-01-P


