83 FR 64132 - Data Integrity and Compliance With Drug CGMP: Questions and Answers; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 83, Issue 239 (December 13, 2018)

Page Range		64132-64133
FR Document		2018-26957

The Food and Drug Administration (FDA or Agency) is announcing the availability of a final guidance for industry entitled ``Data Integrity and Compliance With Drug CGMP: Questions and Answers.'' The purpose of the guidance is to clarify the role of data integrity in current good manufacturing practice (CGMP) for drugs. (Unless otherwise noted, the term CGMP refers to CGMPs for drugs, including biologics.) The guidance has been developed in response to an increase in findings of data integrity lapses in recent inspections. FDA expects that all data be reliable and accurate. CGMP regulations and guidance allow for flexible and risk-based strategies to prevent and detect data integrity issues. Firms should implement meaningful and effective strategies to manage their data integrity risks based on their process understanding and knowledge management of technologies and business models.

Federal Register, Volume 83 Issue 239 (Thursday, December 13, 2018)

[Federal Register Volume 83, Number 239 (Thursday, December 13, 2018)]
[Notices]
[Pages 64132-64133]
From the Federal Register Online [www.thefederalregister.org]
[FR Doc No: 2018-26957]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-D-3984]

Data Integrity and Compliance With Drug CGMP: Questions and
Answers; 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 final guidance for industry entitled ``Data
Integrity and Compliance With Drug CGMP: Questions and Answers.'' The
purpose of the guidance is to clarify the role of data integrity in
current good manufacturing practice (CGMP) for drugs. (Unless otherwise
noted, the term CGMP refers to CGMPs for drugs, including biologics.)
The guidance has been developed in response to an increase in findings
of data integrity lapses in recent inspections. FDA expects that all
data be reliable and accurate. CGMP regulations and guidance allow for
flexible and risk-based strategies to prevent and detect data integrity
issues. Firms should implement meaningful and effective strategies to
manage their data integrity risks based on their process understanding
and knowledge management of technologies and business models.

DATES: The announcement of the guidance is published in the Federal
Register on December 13, 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-2018-D-3984 for ``Data Integrity and Compliance With Drug CGMP:
Questions and Answers.'' 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.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; the Office of
Communication, Outreach and Development, Center for Biologics
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring, MD 20993-0002; or
the Policy and Regulations Staff (HFV-6), Center for Veterinary
Medicine, Food and Drug Administration, 7500 Standish Pl., Rockville,
MD 20855. 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.

[[Page 64133]]

FOR FURTHER INFORMATION CONTACT: Karen Takahashi, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave. Bldg. 75, Rm. 6686, Silver Spring, MD 20993-0002, 301-
796-3191; 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; or Jonathan Bray,
Center for Veterinary Medicine (HFV-232), Food and Drug Administration,
7519 Standish Pl., Rm. 130, Rockville, MD 20855, 240-402-5623.

SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a guidance for industry
entitled ``Data Integrity and Compliance With Drug CGMP: Questions and
Answers.'' In recent years, FDA has increasingly observed CGMP
violations involving data integrity during CGMP inspections. This is
troubling because ensuring data integrity is an important component of
industry's responsibility to ensure the safety, efficacy, and quality
of drugs, and of FDA's ability to protect the public health. These data
integrity-related CGMP violations have led to numerous regulatory
actions, including warning letters, import alerts, and consent decrees.
The underlying premise in 21 CFR 210.1 and 212.2 is that CGMP sets
forth minimum requirements to assure that drugs meet the standards of
the Federal Food, Drug, and Cosmetic Act regarding safety, identity,
strength, quality, and purity.
The guidance addresses specific questions about how data integrity
relates to compliance with CGMP for drugs, as well as more general data
integrity concepts, in question and answer format. This guidance was
published as a draft guidance in April 2016--``Data Integrity and
Compliance With CGMP''--and has been revised in response to comments
from the docket for clarity. Other comments to the docket requested
additional details on FDA's thinking on current best practices and
additional examples. The Agency has used clarifying language and
additional examples that also address best practices for ensuring data
integrity. A paragraph regarding independent security role assignments
for small operations or facilities was removed because the guidance for
industry ``PET Drugs--Current Good Manufacturing Practice (CGMP)''
covering this topic is sufficiently clear.
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 data integrity and compliance with drug
CGMP. 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 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 parts 210 and 211
(CGMPs), 212 (positron emission tomography CGMPs), and 11 (electronic
records and signatures) have been approved under OMB control numbers
0910-0139, 0910-0667, and 0910-0303, respectively.

III. Electronic Access

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

Dated: December 7, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-26957 Filed 12-12-18; 8:45 am]
BILLING CODE 4164-01-P

Federal Register / Vol. 83, No. 239 / Thursday, December 13, 2018 / Notices 64133

FOR FURTHER INFORMATION CONTACT: The guidance represents the current approved rare pediatric disease product
Karen Takahashi, Center for Drug thinking of FDA on data integrity and applications that meet certain criteria.
Evaluation and Research, Food and compliance with drug CGMP. It does FDA is required to publish notice of the
Drug Administration, 10903 New not establish any rights for any person award of the priority review voucher.
Hampshire Ave. Bldg. 75, Rm. 6686, and is not binding on FDA or the public. FDA has determined that GAMIFANT
Silver Spring, MD 20993–0002, 301– You can use an alternative approach if (emapalumab-lzsg) Injection,
796–3191; Stephen Ripley, Center for it satisfies the requirements of the manufactured by Novimmune S.A.,
Biologics Evaluation and Research, applicable statutes and regulations. This meets the criteria for a priority review
Food and Drug Administration, 10903 guidance is not subject to Executive voucher.
New Hampshire Ave. Bldg. 71, Rm. Order 12866.
7301, Silver Spring, MD 20993–0002, FOR FURTHER INFORMATION CONTACT:
II. Paperwork Reduction Act of 1995
240–402–7911; or Jonathan Bray, Center Althea Cuff, Center for Drug Evaluation
for Veterinary Medicine (HFV–232), This guidance refers to previously and Research, Food and Drug
Food and Drug Administration, 7519 approved collections of information that Administration, 10903 New Hampshire
Standish Pl., Rm. 130, Rockville, MD are subject to review by the Office of Ave., Silver Spring, MD 20993–0002,
20855, 240–402–5623. Management and Budget (OMB) under 301–796–4061, Fax: 301–796–9856,
SUPPLEMENTARY INFORMATION: the Paperwork Reduction Act of 1995 email: althea.cuff@fda.hhs.gov.
(44 U.S.C. 3501–3520). The collections
I. Background of information in 21 CFR parts 210 and SUPPLEMENTARY INFORMATION: FDA is
FDA is announcing the availability of 211 (CGMPs), 212 (positron emission announcing the issuance of a priority
a guidance for industry entitled ‘‘Data tomography CGMPs), and 11 (electronic review voucher to the sponsor of an
Integrity and Compliance With Drug records and signatures) have been approved rare pediatric disease product
CGMP: Questions and Answers.’’ In approved under OMB control numbers application. Under section 529 of the
recent years, FDA has increasingly 0910–0139, 0910–0667, and 0910–0303, FD&C Act (21 U.S.C. 360ff), which was
observed CGMP violations involving respectively. added by FDASIA, FDA will award
data integrity during CGMP inspections. priority review vouchers to sponsors of
III. Electronic Access
This is troubling because ensuring data approved rare pediatric disease product
integrity is an important component of Persons with access to the internet
applications that meet certain criteria.
industry’s responsibility to ensure the may obtain the guidance at either
FDA has determined that GAMIFANT
safety, efficacy, and quality of drugs, https://www.fda.gov/Drugs/Guidance
(emapalumab-lzsg) Injection,
and of FDA’s ability to protect the ComplianceRegulatoryInformation/
Guidances/default.htm, https:// manufactured by Novimmune S.A.,
public health. These data integrity-
www.fda.gov/BiologicsBloodVaccines/ meets the criteria for a priority review
related CGMP violations have led to
GuidanceComplianceRegulatory voucher. GAMIFANT (emapalumab-
numerous regulatory actions, including
warning letters, import alerts, and Information/default.htm, https:// lzsg) Injection is indicated for the
consent decrees. The underlying www.fda.gov/AnimalVeterinary/ treatment of adult and pediatric
premise in 21 CFR 210.1 and 212.2 is GuidanceComplianceEnforcement/ (newborn and older) patients with
that CGMP sets forth minimum GuidanceforIndustry/default.htm, or primary hemophagocytic
requirements to assure that drugs meet https://www.regulations.gov. lymphohistiocytosis (HLH) with
the standards of the Federal Food, Drug, Dated: December 7, 2018. refractory, recurrent or progressive
and Cosmetic Act regarding safety, Leslie Kux,
disease or intolerance with conventional
identity, strength, quality, and purity. HLH therapy.
Associate Commissioner for Policy.
The guidance addresses specific For further information about the Rare
[FR Doc. 2018–26957 Filed 12–12–18; 8:45 am]
questions about how data integrity Pediatric Disease Priority Review
BILLING CODE 4164–01–P
relates to compliance with CGMP for Voucher Program and for a link to the
drugs, as well as more general data
full text of section 529 of the FD&C Act,
integrity concepts, in question and
DEPARTMENT OF HEALTH AND go to https://www.fda.gov/ForIndustry/
answer format. This guidance was
HUMAN SERVICES DevelopingProductsforRareDiseases
published as a draft guidance in April
2016—‘‘Data Integrity and Compliance Conditions/RarePediatricDiseasePriority
Food and Drug Administration VoucherProgram/default.htm. For
With CGMP’’—and has been revised in
response to comments from the docket [Docket No. FDA–2018–N–4609] further information about GAMIFANT
for clarity. Other comments to the (emapalumab-lzsg) Injection, go to the
docket requested additional details on Issuance of Priority Review Voucher; ‘‘Drugs@FDA’’ website at https://
FDA’s thinking on current best practices Rare Pediatric Disease Product www.accessdata.fda.gov/scripts/cder/
and additional examples. The Agency AGENCY: Food and Drug Administration, daf/.
has used clarifying language and HHS. Dated: December 10, 2018.
additional examples that also address ACTION: Notice. Leslie Kux,
best practices for ensuring data
integrity. A paragraph regarding SUMMARY: The Food and Drug Associate Commissioner for Policy.
independent security role assignments Administration (FDA) is announcing the [FR Doc. 2018–27043 Filed 12–12–18; 8:45 am]
for small operations or facilities was issuance of a priority review voucher to BILLING CODE 4164–01–P
amozie on DSK3GDR082PROD with NOTICES1

removed because the guidance for the sponsor of a rare pediatric disease
industry ‘‘PET Drugs—Current Good product application. The Federal Food,
Manufacturing Practice (CGMP)’’ Drug, and Cosmetic Act (FD&C Act), as
covering this topic is sufficiently clear. amended by the Food and Drug
This guidance is being issued Administration Safety and Innovation
consistent with FDA’s good guidance Act (FDASIA), authorizes FDA to award
practices regulation (21 CFR 10.115). priority review vouchers to sponsors of

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Document Created: 2018-12-13 01:15:13
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Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Notices
Action		Notice of availability.
Dates		The announcement of the guidance is published in the Federal Register on December 13, 2018.
Contact		Karen Takahashi, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave. Bldg. 75, Rm. 6686, Silver Spring, MD 20993-0002, 301- 796-3191; 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; or Jonathan Bray, Center for Veterinary Medicine (HFV-232), Food and Drug Administration, 7519 Standish Pl., Rm. 130, Rockville, MD 20855, 240-402-5623.
FR Citation		83 FR 64132

83 FR 64132 - Data Integrity and Compliance With Drug CGMP: Questions and Answers; Guidance for Industry; Availability

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 83, Issue 239 (December 13, 2018)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration