81 FR 54808 - Regulatory Classification of Pharmaceutical Co-Crystals; Draft Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 81, Issue 159 (August 17, 2016)

Page Range		54808-54809
FR Document		2016-19596

The Food and Drug Administration (FDA or Agency) is announcing the availability of a draft guidance for industry entitled ``Regulatory Classification of Pharmaceutical Co-Crystals.'' This guidance provides applicants planning to submit new drug applications (NDAs) and abbreviated new drug applications (ANDAs) with information on the appropriate regulatory classification of pharmaceutical co-crystal solid-state forms. This guidance also provides information about the data that applicants should submit to support the appropriate classification of a co-crystal as well as the regulatory implications of the classification. This draft guidance revises the guidance for industry entitled ``Regulatory Classification of Pharmaceutical Co- Crystals'' issued in April 2013.

Federal Register, Volume 81 Issue 159 (Wednesday, August 17, 2016)

[Federal Register Volume 81, Number 159 (Wednesday, August 17, 2016)]
[Notices]
[Pages 54808-54809]
From the Federal Register Online [www.thefederalregister.org]
[FR Doc No: 2016-19596]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2011-D-0800]

Regulatory Classification of Pharmaceutical Co-Crystals; Draft
Guidance for Industry; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of a draft guidance for industry entitled ``Regulatory
Classification of Pharmaceutical Co-Crystals.'' This guidance provides
applicants planning to submit new drug applications (NDAs) and
abbreviated new drug applications (ANDAs) with information on the
appropriate regulatory classification of pharmaceutical co-crystal
solid-state forms. This guidance also provides information about the
data that applicants should submit to support the appropriate
classification of a co-crystal as well as the regulatory implications
of the classification. This draft guidance revises the guidance for
industry entitled ``Regulatory Classification of Pharmaceutical Co-
Crystals'' issued in April 2013.

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 October 17, 2016.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

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-2011-D-0800 for ``Regulatory Classification of Pharmaceutical Co-
Crystals.'' 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

[[Page 54809]]

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: Richard (Rik) Lostritto, Center for
Drug Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 4148, Silver Spring, MD 20993-0002, 301-
796-1697.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a draft guidance for industry
entitled ``Regulatory Classification of Pharmaceutical Co-Crystals.''
This guidance provides NDA and ANDA applicants with information on the
appropriate regulatory classification of pharmaceutical co-crystal
solid-state forms.
Co-crystals are crystalline materials composed of two or more
different molecules, typically drug and co-crystal formers
(``coformers''), in the same crystal lattice. Pharmaceutical co-
crystals have opened up opportunities for engineering solid-state forms
beyond conventional solid-state forms of an active pharmaceutical
ingredient (API), such as salts and polymorphs. Co-crystals can be
tailored to enhance drug product bioavailability and stability and to
enhance the processability of APIs during drug product manufacture.
Another advantage of co-crystals is that they generate a diverse array
of solid-state forms for APIs that lack ionizable functional groups,
which is a prerequisite for salt formation.
This guidance revises the guidance for industry ``Regulatory
Classification of Pharmaceutical Co-Crystals'' issued in April 2013,
which classifies co-crystals as a drug product intermediate (or as an
in-process material). This classification has contributed to
uncertainty regarding the interpretation of the guidance because in a
commercial setting, co-crystals are typically manufactured in drug
substance facilities, yet when classified as a drug product
intermediate, additional current good manufacturing practice
requirements apply. Therefore, the guidance has not been conducive to
the development of co-crystals. In response to this and other feedback
from stakeholders, FDA has reconsidered the appropriate classification
of co-crystals. This revision addresses the concern by providing
information on the appropriate classification of co-crystal solid-state
forms, the data that should be submitted to support the classification,
and the regulatory implications of such a classification.
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 current thinking of FDA on regulatory
classification of pharmaceutical co-crystals. It does not establish any
rights for any person and is not binding on FDA or the public. You can
use an alternative approach if it satisfies the requirements of the
applicable statutes and regulations.

II. The Paperwork Reduction Act of 1995

This guidance refers to previously approved collections of
information found in FDA regulations. This guidance refers to
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 collections of information in 21 CFR
314.50(d)(1) and 314.94(a)(5) and (a)(9) have been approved under OMB
control number 0910-0001.

III. Electronic Access

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

Dated: August 11, 2016.
Jeremy Sharp,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2016-19596 Filed 8-16-16; 8:45 am]
BILLING CODE 4164-01-P

Federal Register / Vol. 81, No. 159 / Wednesday, August 17, 2016 / Notices 54809

Hampshire Ave., Hillandale Building, solid-state forms, the data that should be (OMB) for review and clearance under
4th Floor, Silver Spring, MD 20993– submitted to support the classification, the Paperwork Reduction Act of 1995.
0002. Send one self-addressed adhesive and the regulatory implications of such DATES: Fax written comments on the
label to assist that office in processing a classification. collection of information by September
your requests. See the SUPPLEMENTARY This draft guidance is being issued 16, 2016.
INFORMATION section for electronic consistent with FDA’s good guidance ADDRESSES: To ensure that comments on
access to the draft guidance document. practices regulation (21 CFR 10.115). the information collection are received,
FOR FURTHER INFORMATION CONTACT: The draft guidance, when finalized, will OMB recommends that written
Richard (Rik) Lostritto, Center for Drug represent the current thinking of FDA comments be faxed to the Office of
Evaluation and Research, Food and on regulatory classification of Information and Regulatory Affairs,
Drug Administration, 10903 New pharmaceutical co-crystals. It does not OMB, Attn: FDA Desk Officer, FAX:
Hampshire Ave., Bldg. 51, Rm. 4148, establish any rights for any person and 202–395–7285, or emailed to
Silver Spring, MD 20993–0002, 301– is not binding on FDA or the public. oira_submission@omb.eop.gov. All
796–1697. You can use an alternative approach if comments should be identified with the
SUPPLEMENTARY INFORMATION:
it satisfies the requirements of the OMB control number 0910–NEW and
applicable statutes and regulations. title, ‘‘Voluntary Qualified Importer
I. Background Program Guidance for Industry.’’ Also
II. The Paperwork Reduction Act of
FDA is announcing the availability of 1995 include the FDA docket number found
a draft guidance for industry entitled in brackets in the heading of this
This guidance refers to previously document.
‘‘Regulatory Classification of
approved collections of information
Pharmaceutical Co-Crystals.’’ This FOR FURTHER INFORMATION CONTACT: FDA
found in FDA regulations. This
guidance provides NDA and ANDA PRA Staff, Office of Operations, Food
guidance refers to information
applicants with information on the and Drug Administration, Three White
collection provisions that are subject to
appropriate regulatory classification of Flint North, 11601 Landsdown St.,
review by the Office of Management and
pharmaceutical co-crystal solid-state 10A63, North Bethesda, MD 20852,
Budget (OMB) under the Paperwork
forms. PRAStaff@fda.hhs.gov.
Reduction Act of 1995 (44 U.S.C. 3501–
Co-crystals are crystalline materials SUPPLEMENTARY INFORMATION: In
3520). The collections of information in
composed of two or more different compliance with 44 U.S.C. 3507, FDA
21 CFR 314.50(d)(1) and 314.94(a)(5)
molecules, typically drug and co-crystal has submitted the following proposed
and (a)(9) have been approved under
formers (‘‘coformers’’), in the same collection of information to OMB for
OMB control number 0910–0001.
crystal lattice. Pharmaceutical co- review and clearance.
crystals have opened up opportunities III. Electronic Access
for engineering solid-state forms beyond Persons with access to the Internet FDA’s Voluntary Qualified Importer
conventional solid-state forms of an may obtain the draft guidance at either Program (VQIP); Guidance for Industry
active pharmaceutical ingredient (API), http://www.fda.gov/Drugs/Guidance OMB Control Number 0910—NEW
such as salts and polymorphs. Co- ComplianceRegulatoryInformation/ The FDA Food Safety Modernization
crystals can be tailored to enhance drug Guidances/default.htm or http:// Act (FSMA) (Pub. L. 111–353) enables
product bioavailability and stability and www.regulations.gov. FDA to better protect public health by
to enhance the processability of APIs helping to ensure the safety and security
Dated: August 11, 2016.
during drug product manufacture. of the food supply. It enables FDA to
Another advantage of co-crystals is that Jeremy Sharp,
focus more on preventing food safety
they generate a diverse array of solid- Deputy Commissioner for Policy, Planning, problems rather than relying primarily
state forms for APIs that lack ionizable Legislation, and Analysis.
on reacting to problems after they occur.
functional groups, which is a [FR Doc. 2016–19596 Filed 8–16–16; 8:45 am] FSMA recognizes the important role
prerequisite for salt formation. BILLING CODE 4164–01–P industry plays in ensuring the safety of
This guidance revises the guidance for the food supply, including the adoption
industry ‘‘Regulatory Classification of of modern systems of preventive
Pharmaceutical Co-Crystals’’ issued in DEPARTMENT OF HEALTH AND controls in food production. Under
April 2013, which classifies co-crystals HUMAN SERVICES FSMA, those that import food have a
as a drug product intermediate (or as an responsibility to ensure that their
Food and Drug Administration
in-process material). This classification suppliers produce food that meets U.S.
has contributed to uncertainty regarding [Docket No. FDA–2011–N–0144] safety standards.
the interpretation of the guidance FSMA also requires FDA to establish
because in a commercial setting, co- Agency Information Collection a voluntary, fee-based program for the
crystals are typically manufactured in Activities; Submission for Office of expedited review and importation of
drug substance facilities, yet when Management and Budget Review foods by importers who achieve and
classified as a drug product Comment Request; Voluntary Qualified maintain a high level of control over the
intermediate, additional current good Importer Program Guidance for safety and security of their supply
manufacturing practice requirements Industry chains. This control includes
apply. Therefore, the guidance has not AGENCY: Food and Drug Administration, importation of food from facilities that
been conducive to the development of have been certified under FDA’s
mstockstill on DSK3G9T082PROD with NOTICES

HHS.
co-crystals. In response to this and other ACTION: Notice. accredited third-party audit program, as
feedback from stakeholders, FDA has well as other measures that support a
reconsidered the appropriate SUMMARY: The Food and Drug high level of confidence in the safety
classification of co-crystals. This Administration (FDA) is announcing and security of the food they import.
revision addresses the concern by that a proposed collection of Expedited entry incentivizes importers
providing information on the information has been submitted to the to adopt a robust system of supply chain
appropriate classification of co-crystal Office of Management and Budget management and further benefits public

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Document Created: 2018-02-09 11:35:03
Document Modified: 2018-02-09 11:35:03

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Notices
Action		Notice of availability.
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 October 17, 2016.
Contact		Richard (Rik) Lostritto, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 4148, Silver Spring, MD 20993-0002, 301- 796-1697.
FR Citation		81 FR 54808

81 FR 54808 - Regulatory Classification of Pharmaceutical Co-Crystals; Draft Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 81, Issue 159 (August 17, 2016)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration