[Federal Register Volume 84, Number 39 (Wednesday, February 27, 2019)]
[Notices]
[Pages 6403-6405]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2019-03413]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2019-D-0298]


Quality Considerations for Continuous Manufacturing; Draft 
Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``Quality 
Considerations for Continuous Manufacturing.'' This draft guidance 
provides information regarding FDA's current thinking on the quality 
considerations for continuous manufacturing of small molecule, solid 
oral drug products that are regulated by the Center for Drug Evaluation 
and Research (CDER). The draft guidance describes several key quality 
considerations and provides recommendations for how applicants should 
address these considerations in new drug applications (NDAs), 
abbreviated new drug applications (ANDAs), and supplemental NDAs and 
ANDAs, for small molecule, solid oral drug products that are produced 
via a continuous manufacturing process. FDA supports the development 
and implementation of continuous manufacturing for drug substances and 
all finished dosage forms where appropriate, including those submitted 
in NDAs, ANDAs, drug master files, biologics license applications 
(BLAs), and nonapplication over the counter products. Scientific 
principles described in this draft guidance may also be applicable to 
continuous manufacturing technologies used for these drugs. However, 
this draft guidance is not intended to provide recommendations specific 
to continuous manufacturing technologies used for biological products 
under a BLA.

DATES: Submit either electronic or written comments on the draft 
guidance by May 28, 2019 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 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

[[Page 6404]]

identified, as confidential, if submitted as detailed in 
``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2019-D-0298 for ``Quality Considerations for Continuous 
Manufacturing.'' 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.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 the draft 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 draft guidance document.

FOR FURTHER INFORMATION CONTACT: Sau L. Lee, Center for Drug Evaluation 
and Research, Food and Drug Administration (HFD-600), 10903 New 
Hampshire Ave., Bldg. 22, Rm. 2130, Silver Spring, MD 20993-0002, 301-
796-2905.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Quality Considerations for Continuous Manufacturing.'' The 
draft guidance was prepared by CDER's Office of Pharmaceutical Quality, 
which is committed to supporting and enabling pharmaceutical innovation 
and modernization as part of the Agency's mission to protect and 
promote public health. While the implementation of emerging technology, 
such as continuous manufacturing, is critical to modernizing 
pharmaceutical manufacturing and improving quality, FDA also recognizes 
that innovative approaches to manufacturing may represent challenges to 
industry and regulators. By the very nature of an approach being 
innovative, a limited knowledge and experiential base about the 
technology may exist. Pharmaceutical companies may have concerns that 
using continuous manufacturing could result in delays while FDA 
reviewers and investigators familiarize themselves with the new 
technologies and determine how they fit within existing regulatory 
approaches.
    This draft guidance provides information regarding FDA's current 
thinking on the quality considerations for continuous manufacturing of 
small molecule, solid oral drug products that are regulated by CDER. 
The draft guidance describes several key quality considerations and 
provides recommendations for how applicants should address these 
considerations in NDAs, ANDAs, and supplemental NDAs and ANDAs, for 
small molecule, solid oral drug products that are produced via a 
continuous manufacturing process.
    The draft guidance takes into account the comments that were 
submitted to Docket No. FDA-2017-N-2697 (``Submission of Proposed 
Recommendations for Industry on Developing Continuous Manufacturing of 
Solid Dosage Drug Products in Pharmaceutical Manufacturing; 
Establishment of Public Docket''). FDA invites general comments on the 
quality considerations described in the draft guidance, including 
comments on control strategy, facility, and process validation 
considerations for continuous manufacturing of small molecule, solid 
oral drug products.
    In addition to this draft guidance, pharmaceutical manufacturers 
with product-specific continuous manufacturing questions may submit a 
proposal to the Emerging Technology program. Refer to FDA guidance for 
industry, ``Advancement of Emerging Technology Applications for 
Pharmaceutical Innovation and Modernization'' (September 2017) at 
https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm478821.pdf.
    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 current thinking of FDA on ``Quality 
Considerations for Continuous Manufacturing.'' 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. Additional Issues for Consideration

    In addition to comments on the draft guidance generally, FDA is 
requesting comments and related supporting information on the following 
topics: (1) Data storage and handling from process analytical 
technology systems, (2) potential approaches for situations where 
direct attribute measurement is not possible (e.g., low-dose 
compounds), (3) contract manufacturers employing continuous 
manufacturing, (4) risk-based reporting of routine model maintenance 
and updates, and (5) statistical approaches using large samples (e.g., 
Large N). FDA is seeking public comment on topics for potential 
inclusion in the final guidance or additional guidance and any other 
alternative approaches.

III. Paperwork Reduction Act of 1995

    This draft guidance contains information collection provisions that 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3520). 
The collections of information in 21 CFR parts 210-211 have been 
approved under OMB control number 0910-0139. The submission of INDs 
under 21 CFR 312.23 is approved by OMB control

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number 0910-0014. The submission of BLAs under 21 CFR 601.2 and 601.12 
is approved by OMB control number 0910-0338. The submission of NDAs and 
ANDAs under 21 CFR 314.50, 314.70, 314.71, 314.94, and 314.97 is 
approved by OMB control number 0910-0001. The information to be 
included in a meeting request for a product submitted in an IND, BLA, 
or NDA is approved by OMB control number 0910-0429 (``Guidance for 
Industry on Formal Meetings Between the FDA and Sponsors or 
Applicants'' (December 2017)). Information to be included in a meeting 
request for a product submitted in an ANDA is approved by OMB control 
number 0910-0797 (``Guidance on Controlled Correspondence Related to 
Generic Drug Development'' (December 2015)).

IV. Electronic Access

    Persons with access to the internet may obtain the draft guidance 
at either https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or 
https://www.regulations.gov.

    Dated: February 22, 2019.
Lowell J. Schiller,
Acting Associate Commissioner for Policy.
[FR Doc. 2019-03413 Filed 2-26-19; 8:45 am]
 BILLING CODE 4164-01-P