Document ID: FDA-2011-D-0800-0045
Agency: fda
Document Type: Notice
Title: Regulatory Classification of Pharmaceutical Co-Crystals; Guidance for Industry; Availability
Posted Date: 2018-02-15T05:00Z

[Federal Register Volume 83, Number 32 (Thursday, February 15, 2018)]
[Notices]
[Pages 6863-6864]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-03133]

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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; 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 guidance for industry entitled ``Regulatory 
Classification of Pharmaceutical Co-Crystals.'' This guidance provides 
applicants planning to submit new drug applications and abbreviated new 
drug applications with information on the appropriate regulatory 
classification of pharmaceutical co-crystal solid-state forms. It 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 guidance finalizes 
the draft guidance for industry entitled ``Regulatory Classification of 
Pharmaceutical Co-Crystals'' published in August 2016.

DATES: The announcement of the guidance is published in the Federal 
Register on February 15, 2018.

ADDRESSES: You may submit either electronic or written comments on 
Agency guidances at any time as follows:

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-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 https://www.regulations.gov or at the Dockets Management Staff 
office 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.
    You may submit comments on any guidance at any time (see 21 CFR 
10.115(g)(5)).
    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, 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 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 guidance for industry 
entitled ``Regulatory Classification of Pharmaceutical Co-Crystals.'' 
This guidance provides applicants planning to submit new drug 
applications and abbreviated new drug applications 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.
    The recommendations in this guidance apply to materials that the 
Agency has not previously evaluated and determined to be pharmaceutical

[[Page 6864]]

co-crystals. The recommendations do not apply to materials that the 
Agency has previously designated as salts, complexes, or other non-co-
crystalline forms.
    Co-crystals are crystalline materials composed of two or more 
different molecules, typically active pharmaceutical ingredient (API) 
and co-crystal formers (``coformers''), in the same crystal lattice. 
Pharmaceutical co-crystals have provided opportunities for engineering 
solid-state forms beyond conventional solid-state forms of an 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 addresses the public comments received in response to 
the draft guidance for industry ``Regulatory Classification of 
Pharmaceutical Co-Crystals'' issued in August 2016. In response to this 
and other feedback from stakeholders, FDA has clarified the appropriate 
classification of co-crystals and addresses the concern by further 
clarifying that co-crystals can be viewed as a special case of solvates 
and hydrates, wherein the second component, the coformer, is not a 
solvent (including water), and is typically nonvolatile.
    This guidance is being issued consistent with FDA's good guidance 
practices regulation (21 CFR 10.115). The guidance represents 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. This guidance is not subject to Executive 
Order 12866.

II. 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 guidance at 
either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or 
https://www.regulations.gov.

    Dated: February 9, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-03133 Filed 2-14-18; 8:45 am]
 BILLING CODE 4164-01-P