
[Federal Register Volume 76, Number 232 (Friday, December 2, 2011)]
[Notices]
[Pages 75551-75552]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-31022]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

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


Draft Guidance for Industry on Regulatory Classification of 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availability of a draft guidance for industry entitled ``Regulatory 
Classification of Pharmaceutical Co-Crystals.'' This draft guidance 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 classification 
of co-crystal solid-state forms. This draft guidance also provides 
information about the data that should be submitted to support the 
appropriate classification of a co-crystal and the regulatory 
implications of the classification.

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draft guidance before it begins work on the final version of the 
guidance, submit either electronic or written comments on the draft 
guidance by March 1, 2012.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information, Center for Drug 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, 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access to the draft guidance document.
    Submit electronic comments on the draft guidance to http://www.regulations.gov.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 draft guidance for industry 
entitled ``Regulatory Classification of Pharmaceutical Co-Crystals.'' 
This draft guidance provides applicants of NDAs and ANDAs with CDER's 
current thinking on the appropriate classification of co-crystal solid-
state forms. This draft guidance also provides information about the 
data that should be submitted to support the appropriate classification 
of a co-crystal and the regulatory implications of the classification.
    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 co-former, 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, unlike a salt form where the components in the 
crystal lattice are in an ionized state, the molecules in the co-
crystal are in a neutral state and interact via nonionic interactions. 
Thus, pharmaceutical co-crystals offer the advantage of generating a 
diverse array of solid-state forms, even for APIs that lack ionizable 
functional groups needed for salt formation.
    Traditionally, pharmaceutical solid-state forms of an API are 
grouped as either polymorphs or salts, and applicable regulatory 
schemes for these solid-state forms are well-defined. Co-crystals, 
however, are distinguishable from these traditional pharmaceutical 
solid-state forms. Unlike polymorphs, which generally speaking contain 
only the API within the crystal lattice, co-crystals are composed of an 
API with a neutral guest compound conformer 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 regulatory paradigm exists governing co-crystal 
forms. In response to this need for regulatory

[[Page 75552]]

guidance, the draft guidance provides the Agency's current thinking on 
the appropriate classification of co-crystal solid-state forms.
    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 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 to the Division of Dockets Management 
(see ADDRESSES) either electronic or written comments regarding this 
document. It is only necessary to send one set of comments. It is no 
longer necessary to send two copies of mailed 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.

III. The Paperwork Reduction Act of 1995

    This draft guidance refers to previously approved collections of 
information found in FDA regulations. This draft 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.

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: November 29, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-31022 Filed 12-1-11; 8:45 am]
BILLING CODE 4160-01-P


