
[Federal Register Volume 78, Number 81 (Friday, April 26, 2013)]
[Notices]
[Pages 24754-24755]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-09872]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


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

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a guidance for industry entitled ``Regulatory 
Classification of Pharmaceutical Co-Crystals.'' This guidance provides 
applicants of new drug applications (NDAs) and abbreviated new drug 
applications (ANDAs) with the Center for Drug Evaluation and Research's 
(CDER's) current thinking on the appropriate regulatory classification 
of pharmaceutical co-crystal solid-state forms. This guidance also 
provides information about the data the applicant should submit to 
support the appropriate classification of a co-crystal, as well as the 
regulatory implications of the classification.
    The recommendations in this guidance apply to materials that the 
Agency has not previously evaluated and determined to be pharmaceutical 
co-crystals. The recommendations do not apply to materials that the 
Agency has previously designated as salts, complexes, or other non-co-
crystalline forms.

DATES: Submit either electronic or written comments on Agency guidances 
at any time.

ADDRESSES: Submit written requests for single copies of this guidance 
to the Division of Drug Information, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
51, rm. 2201, 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 
guidance document.
    Submit electronic comments on the guidance to http://www.regulations.gov. Submit written comments to the Division of Dockets 
Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT:

Andre Raw, Center for Drug Evaluation and Research, Food and Drug 
Administration, Metro Park North II, 7500 Standish Pl., Rockville, MD 
20855, 240-276-8500; or
Richard Lostritto, Center for Drug Evaluation and Research, Food and 
Drug Administration, Bldg. 21, rm. 1626, 10903 New Hampshire Ave., 
Silver Spring, MD 20993, 301-796-1900.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Regulatory Classification of Pharmaceutical Co-Crystals.'' 
This guidance provides applicants of NDAs and ANDAs with CDER's current 
thinking on the appropriate regulatory classification of pharmaceutical 
co-crystal solid-state forms. This guidance also provides information 
about the data the applicant should submit to support the appropriate 
classification of a co-crystal, as well as the regulatory implications 
of the classification.
    On December 2, 2011 (76 FR 75551), FDA announced the availability 
of the draft version of this guidance. The public comment period closed 
on March 1, 2012. A number of comments were received from the public, 
all of which the Agency considered carefully as it finalized the 
guidance and made appropriate changes. Any changes to the guidance were 
minor and made to clarify statements in the draft guidance.
    Co-crystals are solids that are crystalline materials composed of 
two or more molecules in the same crystal lattice. These solid-state 
forms, composed of an active pharmaceutical ingredient (API) with a 
neutral guest compound (also referred to as a conformer), have been the 
focus of significant interest in drug product development. 
Pharmaceutical co-crystals have opened the opportunity for engineering 
solid-state forms designed to have tailored properties to enhance drug 
product bioavailability and stability, as well as enhance 
processability of the solid material inputs in drug product 
manufacture. Pharmaceutical co-crystals are of interest because they 
offer the advantage of generating a diverse array of solid-state forms 
from APIs that lack ionizable functional groups needed for salt 
formation.
    Traditionally, solid-state polymorphic forms of an API are 
classified as either crystalline, amorphous, or solvate and hydrate 
forms, and applicable regulatory schemes for these solid-state 
polymorphic forms are well-defined. Co-crystals, however, are 
distinguishable from these traditional pharmaceutical solid-state 
forms. Unlike

[[Page 24755]]

polymorphs, which generally speaking contain only the API within the 
crystal lattice, co-crystals are composed of an API with a neutral 
guest compound in the crystal lattice. Similarly, unlike salts, where 
the components in the crystal lattice are in an ionized state, a co-
crystal's components are in a neutral state and interact via nonionic 
interactions.
    At present, no formal regulatory policy exists governing the 
classification of pharmaceutical co-crystals. In response to this need 
for regulatory guidance, the guidance provides the Agency's current 
thinking on the appropriate classification of co-crystal solid-state 
forms.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents the 
Agency's current thinking on regulatory classification of 
pharmaceutical co-crystals. 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. Comments

    Interested persons may submit either written comments regarding 
this document to the Division of Dockets Management (see ADDRESSES) or 
electronic comments to http://www.regulations.gov. It is only necessary 
to send one set of comments. Identify comments with the docket number 
found in brackets in the heading of this document. Received comments 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov.

III. 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 314.94(a)(9) have been approved under 
OMB control number 0910-0001. The collections of information in the 
current good manufacturing practice (CGMP) regulations (21 CFR part 
211) have been approved under OMB control number 0910-0139.

IV. Electronic Access

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

    Dated: April 22, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-09872 Filed 4-25-13; 8:45 am]
BILLING CODE 4160-01-P


