83_FR_6895 83 FR 6863 - Regulatory Classification of Pharmaceutical Co-Crystals; Guidance for Industry; Availability

83 FR 6863 - Regulatory Classification of Pharmaceutical Co-Crystals; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 83, Issue 32 (February 15, 2018)

Page Range6863-6864
FR Document2018-03133

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 This guidance finalizes the draft guidance for industry entitled ``Regulatory Classification of Pharmaceutical Co-Crystals'' published in August 2016.

Federal Register, Volume 83 Issue 32 (Thursday, February 15, 2018) 
[Federal Register Volume 83, Number 32 (Thursday, February 15, 2018)]
[Notices]
[Pages 6863-6864]
From the Federal Register Online  [www.thefederalregister.org]
[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the draft guidance for industry entitled ``Regulatory Classification of 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.thefederalregister.org/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

Federal Register / Vol. 83, No. 32 / Thursday, February 15, 2018 / Notices 6863 Food and Drug Administration, 5630 third party may not wish to be posted, in the body of your comments and you Fishers Lane, Rm. 1061, Rockville, MD such as medical information, your or must identify this information as 20852. anyone else’s Social Security number, or ‘‘confidential.’’ Any information marked Dated: February 9, 2018. confidential business information, such as ‘‘confidential’’ will not be disclosed Leslie Kux, as a manufacturing process. Please note except in accordance with 21 CFR 10.20 that if you include your name, contact and other applicable disclosure law. For Associate Commissioner for Policy. information, or other information that more information about FDA’s posting [FR Doc. 2018–03134 Filed 2–14–18; 8:45 am] identifies you in the body of your of comments to public dockets, see 80 BILLING CODE 4164–01–P comments, that information will be FR 56469, September 18, 2015, or access posted on https://www.regulations.gov. the information at: https://www.gpo.gov/ • If you want to submit a comment fdsys/pkg/FR-2015-09-18/pdf/2015- DEPARTMENT OF HEALTH AND with confidential information that you 23389.pdf. HUMAN SERVICES do not wish to be made available to the Docket: For access to the docket to public, submit the comment as a read background documents or the Food and Drug Administration written/paper submission and in the electronic and written/paper comments [Docket No. FDA–2011–D–0800] manner detailed (see ‘‘Written/Paper received, go to https:// Submissions’’ and ‘‘Instructions’’). www.regulations.gov and insert the Regulatory Classification of docket number, found in brackets in the Pharmaceutical Co-Crystals; Guidance Written/Paper Submissions heading of this document, into the for Industry; Availability Submit written/paper submissions as ‘‘Search’’ box and follow the prompts follows: and/or go to the Dockets Management AGENCY: Food and Drug Administration, • Mail/Hand delivery/Courier (for HHS. Staff, 5630 Fishers Lane, Rm. 1061, written/paper submissions): Dockets ACTION: Notice of availability. Rockville, MD 20852. Management Staff (HFA–305), Food and You may submit comments on any Drug Administration, 5630 Fishers SUMMARY: The Food and Drug guidance at any time (see 21 CFR Lane, Rm. 1061, Rockville, MD 20852. Administration (FDA or Agency) is • For written/paper comments 10.115(g)(5)). announcing the availability of a submitted to the Dockets Management Submit written requests for single guidance for industry entitled Staff, FDA will post your comment, as copies of this guidance to the Division ‘‘Regulatory Classification of well as any attachments, except for of Drug Information, Center for Drug Pharmaceutical Co-Crystals.’’ This information submitted, marked and Evaluation and Research, Food and guidance provides applicants planning identified, as confidential, if submitted Drug Administration, 10001 New to submit new drug applications and as detailed in ‘‘Instructions.’’ Hampshire Ave., Hillandale Building, abbreviated new drug applications with Instructions: All submissions received 4th Floor, Silver Spring, MD 20993– information on the appropriate must include the Docket No. FDA– 0002. Send one self-addressed adhesive regulatory classification of 2011–D–0800 for ‘‘Regulatory label to assist that office in processing pharmaceutical co-crystal solid-state Classification of Pharmaceutical Co- your requests. See the SUPPLEMENTARY forms. It also provides information Crystals.’’ Received comments will be INFORMATION section for electronic about the data that applicants should placed in the docket and, except for access to the guidance document. submit to support the appropriate those submitted as ‘‘Confidential FOR FURTHER INFORMATION CONTACT: classification of a co-crystal as well as Submissions,’’ publicly viewable at Richard (Rik) Lostritto, Center for Drug the regulatory implications of the https://www.regulations.gov or at the Evaluation and Research, Food and classification. This guidance finalizes Dockets Management Staff office Drug Administration, 10903 New the draft guidance for industry entitled between 9 a.m. and 4 p.m., Monday Hampshire Ave., Bldg. 51, Rm. 4148, ‘‘Regulatory Classification of through Friday. Silver Spring, MD 20993–0002, 301– Pharmaceutical Co-Crystals’’ published • Confidential Submissions—To 796–1697. in August 2016. submit a comment with confidential SUPPLEMENTARY INFORMATION: DATES: The announcement of the information that you do not wish to be guidance is published in the Federal made publicly available, submit your I. Background Register on February 15, 2018. comments only as a written/paper FDA is announcing the availability of ADDRESSES: You may submit either submission. You should submit two a guidance for industry entitled electronic or written comments on copies total. One copy will include the ‘‘Regulatory Classification of Agency guidances at any time as information you claim to be confidential Pharmaceutical Co-Crystals.’’ This follows: with a heading or cover note that states guidance provides applicants planning ‘‘THIS DOCUMENT CONTAINS to submit new drug applications and Electronic Submissions CONFIDENTIAL INFORMATION.’’ The abbreviated new drug applications with Submit electronic comments in the Agency will review this copy, including information on the appropriate following way: the claimed confidential information, in regulatory classification of • Federal eRulemaking Portal: its consideration of comments. The pharmaceutical co-crystal solid-state https://www.regulations.gov. Follow the second copy, which will have the forms. This guidance also provides instructions for submitting comments. claimed confidential information information about the data that Comments submitted electronically, redacted/blacked out, will be available applicants should submit to support the sradovich on DSK3GMQ082PROD with NOTICES including attachments, to https:// for public viewing and posted on appropriate classification of a co-crystal www.regulations.gov will be posted to https://www.regulations.gov. Submit as well as the regulatory implications of the docket unchanged. Because your both copies to the Dockets Management the classification. comment will be made public, you are Staff. If you do not wish your name and The recommendations in this solely responsible for ensuring that your contact information to be made publicly guidance apply to materials that the comment does not include any available, you can provide this Agency has not previously evaluated confidential information that you or a information on the cover sheet and not and determined to be pharmaceutical VerDate Sep<11>2014 19:01 Feb 14, 2018 Jkt 244001 PO 00000 Frm 00030 Fmt 4703 Sfmt 4703 E:\FR\FM\15FEN1.SGM 15FEN1

6864 Federal Register / Vol. 83, No. 32 / Thursday, February 15, 2018 / Notices co-crystals. The recommendations do III. Electronic Access postmarked or the delivery service not apply to materials that the Agency Persons with access to the internet acceptance receipt is on or before that has previously designated as salts, may obtain the guidance at either date. complexes, or other non-co-crystalline https://www.fda.gov/Drugs/Guidance Electronic Submissions forms. ComplianceRegulatoryInformation/ Submit electronic comments in the Co-crystals are crystalline materials Guidances/default.htm or https:// following way: composed of two or more different www.regulations.gov. • Federal eRulemaking Portal: molecules, typically active Dated: February 9, 2018. https://www.regulations.gov. Follow the pharmaceutical ingredient (API) and co- Leslie Kux, instructions for submitting comments. crystal formers (‘‘coformers’’), in the Associate Commissioner for Policy. Comments submitted electronically, same crystal lattice. Pharmaceutical co- including attachments, to https:// [FR Doc. 2018–03133 Filed 2–14–18; 8:45 am] crystals have provided opportunities for www.regulations.gov will be posted to BILLING CODE 4164–01–P engineering solid-state forms beyond the docket unchanged. Because your conventional solid-state forms of an comment will be made public, you are API, such as salts and polymorphs. Co- DEPARTMENT OF HEALTH AND solely responsible for ensuring that your crystals can be tailored to enhance drug HUMAN SERVICES comment does not include any product bioavailability and stability and confidential information that you or a to enhance the processability of APIs Food and Drug Administration third party may not wish to be posted, during drug product manufacture. such as medical information, your or [Docket No. FDA–2015–E–1665] Another advantage of co-crystals is that anyone else’s Social Security number, or they generate a diverse array of solid- Determination of Regulatory Review confidential business information, such state forms for APIs that lack ionizable Period for Purposes of Patent as a manufacturing process. Please note functional groups, which is a Extension; ZONTIVITY that if you include your name, contact prerequisite for salt formation. information, or other information that This guidance addresses the public AGENCY: Food and Drug Administration, identifies you in the body of your comments received in response to the HHS. comments, that information will be draft guidance for industry ‘‘Regulatory ACTION: Notice. posted on https://www.regulations.gov. • If you want to submit a comment Classification of Pharmaceutical Co- SUMMARY: The Food and Drug with confidential information that you Crystals’’ issued in August 2016. In Administration (FDA or the Agency) has do not wish to be made available to the response to this and other feedback from determined the regulatory review period public, submit the comment as a stakeholders, FDA has clarified the for ZONTIVITY and is publishing this written/paper submission and in the appropriate classification of co-crystals notice of that determination as required manner detailed (see ‘‘Written/Paper and addresses the concern by further by law. FDA has made the Submissions’’ and ‘‘Instructions’’). clarifying that co-crystals can be viewed determination because of the as a special case of solvates and submission of an application to the Written/Paper Submissions hydrates, wherein the second Director of the U.S. Patent and Submit written/paper submissions as component, the coformer, is not a Trademark Office (USPTO), Department follows: solvent (including water), and is of Commerce, for the extension of a • Mail/Hand delivery/Courier (for typically nonvolatile. patent which claims that human drug written/paper submissions): Dockets This guidance is being issued product. Management Staff (HFA–305), Food and consistent with FDA’s good guidance Drug Administration, 5630 Fishers DATES: Anyone with knowledge that any Lane, Rm. 1061, Rockville, MD 20852. practices regulation (21 CFR 10.115). of the dates as published (in the The guidance represents the current • For written/paper comments SUPPLEMENTARY INFORMATION section) are submitted to the Dockets Management thinking of FDA on ‘‘Regulatory incorrect may submit either electronic Classification of Pharmaceutical Co- Staff, FDA will post your comment, as or written comments and ask for a well as any attachments, except for Crystals.’’ It does not establish any redetermination by April 16, 2018. rights for any person and is not binding information submitted, marked and Furthermore, any interested person may identified, as confidential, if submitted on FDA or the public. You can use an petition FDA for a determination alternative approach if it satisfies the as detailed in ‘‘Instructions.’’ regarding whether the applicant for Instructions: All submissions received requirements of the applicable statutes extension acted with due diligence must include the Docket No. FDA– and regulations. This guidance is not during the regulatory review period by 2015–E–1665 for ’’Determination of subject to Executive Order 12866. August 14, 2018. See ‘‘Petitions’’ in the Regulatory Review Period for Purposes II. Paperwork Reduction Act of 1995 SUPPLEMENTARY INFORMATION section for of Patent Extension; ZONTIVITY.’’ more information. Received comments, those filed in a This guidance refers to previously ADDRESSES: You may submit comments timely manner (see ADDRESSES), will be approved collections of information as follows. Please note that late, placed in the docket and, except for found in FDA regulations. This untimely filed comments will not be those submitted as ‘‘Confidential guidance refers to information considered. Electronic comments must Submissions,’’ publicly viewable at collection provisions that are subject to be submitted on or before April 16, sradovich on DSK3GMQ082PROD with NOTICES https://www.regulations.gov or at the review by the Office of Management and 2018. The https://www.regulations.gov Dockets Management Staff between 9 Budget (OMB) under the Paperwork electronic filing system will accept a.m. and 4 p.m., Monday through Reduction Act of 1995 (44 U.S.C. 3501– comments until midnight Eastern Time Friday. 3520). The collections of information in at the end of April 16, 2018. Comments • Confidential Submissions—To 21 CFR 314.50(d)(1) and 314.94(a)(5) received by mail/hand delivery/courier submit a comment with confidential and (a)(9) have been approved under (for written/paper submissions) will be information that you do not wish to be OMB control number 0910–0001. considered timely if they are made publicly available, submit your VerDate Sep<11>2014 19:01 Feb 14, 2018 Jkt 244001 PO 00000 Frm 00031 Fmt 4703 Sfmt 4703 E:\FR\FM\15FEN1.SGM 15FEN1


Document Created: 2018-02-15 00:21:17
Document Modified: 2018-02-15 00:21:17
CategoryRegulatory Information
CollectionFederal Register
sudoc ClassAE 2.7:
GS 4.107:
AE 2.106:
PublisherOffice of the Federal Register, National Archives and Records Administration
SectionNotices
ActionNotice of availability.
DatesThe announcement of the guidance is published in the Federal Register on February 15, 2018.
ContactRichard (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 Citation83 FR 6863 
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