Data Integrity and
Compliance With
CGMP
Guidance for Industry
DRAFT GUIDANCE
This guidance document is being distributed for comment purposes only.
Comments and suggestions regarding this draft document should be submitted within 60 days of
publication in the Federal Register of the notice announcing the availability of the draft
guidance. Submit electronic comments to http://www.regulations.gov. Submit written comments
to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630
Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the
docket number listed in the notice of availability that publishes in the Federal Register.
For questions regarding this draft document, contact (CDER) Karen Takahashi 301-796-3191;
(CBER) Office of Communication, Outreach and Development, 800-835-4709 or 240-402-8010;
or (CVM) Jonathan Bray 240-402-5623.
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
Center for Veterinary Medicine (CVM)
April 2016
Pharmaceutical Quality/Manufacturing Standards (CGMP)
Data Integrity and
Compliance With
CGMP
Guidance for Industry
Additional copies are available from:
Office of Communications, Division of Drug Information
Center for Drug Evaluation and Research
Food and Drug Administration
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor
Silver Spring, MD 20993-0002
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353
Email: druginfo@fda.hhs.gov
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
and/or
Office of Communication, Outreach and Development
Center for Biologics Evaluation and Research
Food and Drug Administration
10903 New Hampshire Ave., Bldg. 71, Room 3128
Silver Spring, MD 20993-0002
Phone: 800-835-4709 or 240-402-8010
Email: ocod@fda.hhs.gov
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm
and/or
Policy and Regulations Staff, HFV-6
Center for Veterinary Medicine
Food and Drug Administration
7519 Standish Place, Rockville, MD 20855
http://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/default.htm
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
Center for Veterinary Medicine (CVM)
April 2016
Pharmaceutical Quality/Manufacturing Standards (CGMP)
Contains Nonbinding Recommendations
Draft — Not for Implementation
TABLE OF CONTENTS
I. INTRODUCTION............................................................................................................. 1
II. BACKGROUND ............................................................................................................... 1
III. QUESTIONS AND ANSWERS ....................................................................................... 2
1. Please clarify the following terms as they relate to CGMP records: ......................................... 2
a. What is “data integrity”? ................................................................................................................ 2
b. What is “metadata”? ....................................................................................................................... 3
c. What is an “audit trail”? ................................................................................................................. 3
d. How does FDA use the terms “static” and “dynamic” as they relate to record formats? ............. 3
e. How does FDA use the term “backup” in § 211.68(b)? .................................................................. 4
f. What are the “systems” in “computer or related systems” in § 211.68?........................................ 4
2. When is it permissible to exclude CGMP data from decision making? .................................... 4
3. Does each workflow on our computer system need to be validated? ........................................ 4
4. How should access to CGMP computer systems be restricted? ................................................ 5
5. Why is FDA concerned with the use of shared login accounts for computer systems? ........... 6
6. How should blank forms be controlled? ...................................................................................... 6
7. How often should audit trails be reviewed?................................................................................. 6
8. Who should review audit trails? ................................................................................................... 6
9. Can electronic copies be used as accurate reproductions of paper or electronic records? ..... 7
10. Is it acceptable to retain paper printouts or static records instead of original electronic
records from stand-alone computerized laboratory instruments, such as an FT-IR instrument? . 7
11. Can electronic signatures be used instead of handwritten signatures for master production
and control records?............................................................................................................................... 8
12. When does electronic data become a CGMP record? ................................................................ 8
13. Why has the FDA cited use of actual samples during “system suitability” or test, prep, or
equilibration runs in warning letters? .................................................................................................. 9
14. Is it acceptable to only save the final results from reprocessed laboratory
chromatography? ................................................................................................................................... 9
15. Can an internal tip regarding a quality issue, such as potential data falsification, be handled
informally outside of the documented CGMP quality system? .......................................................... 9
16. Should personnel be trained in detecting data integrity issues as part of a routine CGMP
training program? ................................................................................................................................ 10
17. Is the FDA investigator allowed to look at my electronic records? ......................................... 10
18. How does FDA recommend data integrity problems identified during inspections, in
warning letters, or in other regulatory actions be addressed? ......................................................... 10
Contains Nonbinding Recommendations
Draft — Not for Implementation
1 Data Integrity and Compliance With CGMP
2 Guidance for Industry 1
3
4
5 This draft guidance, when finalized, will represent the current thinking of the Food and Drug
6 Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not
7 binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the
8 applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible
9 for this guidance as listed on the title page.
10
11
12
13
14 I. INTRODUCTION
15
16 The purpose of this guidance is to clarify the role of data integrity in current good manufacturing
17 practice (CGMP) for drugs, as required in 21 CFR parts 210, 211, and 212. Part 210 covers
18 Current Good Manufacturing Practice in Manufacturing, Processing, Packing, or Holding of
19 Drugs; General; part 211 covers Current Good Manufacturing Practice for Finished
20 Pharmaceuticals; and part 212 covers Current Good Manufacturing Practice for Positron
21 Emission Tomography Drugs. This guidance provides the Agency’s current thinking on the
22 creation and handling of data in accordance with CGMP requirements.
23
24 FDA expects that data be reliable and accurate (see the “Background” section). CGMP
25 regulations and guidance allow for flexible and risk-based strategies to prevent and detect data
26 integrity issues. Firms should implement meaningful and effective strategies to manage their data
27 integrity risks based upon their process understanding and knowledge management of
28 technologies and business models.
29
30 In general, FDA’s guidance documents do not establish legally enforceable responsibilities.
31 Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only
32 as recommendations, unless specific regulatory or statutory requirements are cited. The use of
33 the word should in Agency guidances means that something is suggested or recommended, but
34 not required.
35
36 II. BACKGROUND
37
38 In recent years, FDA has increasingly observed CGMP violations involving data integrity during
39 CGMP inspections. This is troubling because ensuring data integrity is an important component
40 of industry’s responsibility to ensure the safety, efficacy, and quality of drugs, and of FDA’s
41 ability to protect the public health. These data integrity-related CGMP violations have led to
1
This guidance has been prepared by the Office of Pharmaceutical Quality and the Office of Compliance in the
Center for Drug Evaluation and Research in cooperation with the Center for Biologics Evaluation and Research, the
Center for Veterinary Medicine, and the Office of Regulatory Affairs at the Food and Drug Administration.
