[Federal Register Volume 85, Number 102 (Wednesday, May 27, 2020)]
[Notices]
[Pages 31785-31786]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-11280]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2020-D-1301]


Q3C(R8) Recommendations for the Permitted Daily Exposures for 
Three Solvents--2-Methyltetrahydrofuran, Cyclopentyl Methyl Ether, and 
Tert-Butyl Alcohol--According to the Maintenance Procedures for the 
Guidance Q3C Impurities: Residual Solvents; International Council for 
Harmonisation; Draft Guidance for Industry; Availability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 draft recommendations for new permitted daily 
exposures (PDEs) for the residual solvents 2-methyltetrahydrofuran, 
cyclopentyl methyl ether, and tert-butyl alcohol. The PDEs were 
developed according to the methods for establishing exposure limits 
included in the guidance for industry entitled ``Q3C Impurities: 
Residual Solvents.'' The recommendations were prepared under the 
auspices of the International Council for Harmonisation (ICH), formerly 
the International Conference on Harmonisation. The draft guidance is 
intended to recommend acceptable amounts for the listed residual 
solvents in pharmaceuticals for the safety of patients.

DATES: Submit either electronic or written comments on the draft 
guidance by July 26, 2024 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

ADDRESSES: You may submit comments on any guidance 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-2020-D-1301 for ``Q3C(R8) Recommendations for the Permitted Daily 
Exposures for Three Solvents--2-Methyltetrahydrofuran, Cyclopentyl 
Methyl Ether, and Tert-Butyl Alcohol--According to the Maintenance 
Procedures for the Guidance Q3C Impurities: Residual Solvents.'' 
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 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.govinfo.gov/content/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, or the Office of 
Communication, Outreach and Development, Center for Biologics 
Evaluation and Research (CBER), Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002. Send 
one self-addressed adhesive label to assist that office in processing 
your requests. The guidance may also be obtained by mail by calling 
CBER at 1-

[[Page 31786]]

800-835-4709 or 240-402-8010. See the SUPPLEMENTARY INFORMATION section 
for electronic access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Regarding the guidance: Timothy 
McGovern, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 6426, Silver 
Spring, MD 20993-0002, 240-402-0477; or Stephen Ripley, Center for 
Biologics Evaluation and Research, Food and Drug Administration, 10903 
New Hampshire Ave., Bldg. 71, Rm. 7301, Silver Spring, MD 20993-0002, 
240-402-7911.
    Regarding the ICH: Amanda Roache, Center for Drug Evaluation and 
Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 
51, Rm. 6364, Silver Spring, MD 20993-0002, 301-796-4548, 
[email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    In recent years, regulatory authorities and industry associations 
from around the world have participated in many important initiatives 
to promote international harmonization of regulatory requirements under 
the ICH. FDA has participated in several ICH meetings designed to 
enhance harmonization and is committed to seeking scientifically based 
harmonized technical procedures for pharmaceutical development. One of 
the goals of harmonization is to identify and reduce differences in 
technical requirements for drug development among regulatory agencies.
    ICH was established to provide an opportunity for harmonization 
initiatives to be developed with input from both regulatory and 
industry representatives. FDA also seeks input from consumer 
representatives and others. ICH is concerned with harmonization of 
technical requirements for the registration of pharmaceutical products 
for human use among regulators around the world. The six founding 
members of the ICH are the European Commission; the European Federation 
of Pharmaceutical Industries Associations; FDA; the Japanese Ministry 
of Health, Labour, and Welfare; the Japanese Pharmaceutical 
Manufacturers Association; and the Pharmaceutical Research and 
Manufacturers of America. The Standing Members of the ICH Association 
include Health Canada and Swissmedic. Any party eligible as a Member in 
accordance with the ICH Articles of Association can apply for 
membership in writing to the ICH Secretariat. The ICH Secretariat, 
which coordinates the preparation of documentation, operates as an 
international nonprofit organization and is funded by the Members of 
the ICH Association.
    The ICH Assembly is the overarching body of the Association and 
includes representatives from each of the ICH members and observers. 
The Assembly is responsible for the endorsement of draft guidelines and 
adoption of final guidelines. FDA publishes ICH guidelines as FDA 
guidance.
    In the Federal Register of December 24, 1997 (62 FR 67377), FDA 
published a notice announcing the availability of the ICH guidance for 
industry entitled ``Q3C Impurities: Residual Solvents.'' The guidance 
makes recommendations as to what amounts of residual solvents are 
considered toxicologically acceptable for some residual solvents, or 
permitted daily exposure. Upon issuance in 1997, the text and appendix 
1 of the guidance contained several tables and a list of solvents 
categorizing residual solvents by toxicity, classes 1 through 3, with 
class 1 being the most toxic. The ICH Quality Expert Working Group 
(EWG) agreed that the PDEs could be modified if reliable and more 
relevant toxicity data were brought to the attention of the group and 
the modified PDE could result in a revision of the tables and list.
    In 1999, ICH instituted a Q3C maintenance agreement and formed a 
maintenance EWG (the Q3C EWG). The agreement provided for the 
revisitation of solvent PDEs and allowed for minor changes to the 
tables and list that include the existing PDEs. The agreement also 
provided for new solvents and PDEs that could be added to the tables 
and list based on adequate toxicity data. In the Federal Register of 
February 12, 2002 (67 FR 6542), FDA briefly described the process for 
proposing future revisions to the PDEs. In the same notice, the Agency 
announced its decision to remove the link to the tables and list in the 
Q3C guidance and create a stand-alone document entitled ``Q3C: Tables 
and List'' to facilitate making changes recommended by ICH; the 
document is available at https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm073395.pdf. ``Q3C: 
Tables and List'' was updated in January 2017 to include the 
recommended PDE for triethylamine and methylisobutylketone.
    In March 2020, the ICH Assembly endorsed the draft PDEs for three 
solvents--2-methyltetrahydrofuran, cyclopentyl methyl ether, and tert-
butyl alcohol--and agreed that the guidance should be made available 
for public comment. The draft guidance is the product of the ICH Q3C 
EWG. Comments on this draft will be considered by FDA and the Quality 
EWG.
    This draft guidance has been left in the original ICH format. The 
final guidance will be reformatted and edited to conform with FDA's 
good guidance practices regulation (21 CFR 10.115) and style before 
publication. The draft guidance, when finalized, will represent the 
current thinking of FDA on the PDEs for 2-methyltetrahydrofuran, 
cyclopentyl methyl ether, and tert-butyl alcohol. 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. Paperwork Reduction Act of 1995

    This draft guidance refers to previously approved FDA collections 
of information. These collections of information are subject to review 
by the Office of Management and Budget (OMB) under the Paperwork 
Reduction Act of 1995 (44 U.S.C. 3501-3521). The collections of 
information in 21 CFR part 58 pertaining to good laboratory practice 
for nonclinical laboratory studies have been approved under OMB control 
number 0910-0119.

III. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at https://www.regulations.gov, https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, or https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances.

    Dated: May 19, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-11280 Filed 5-26-20; 8:45 am]
BILLING CODE 4164-01-P