Data Integrity and Compliance With CGMP Guidance for Industry DRAFT GUIDANCE This guidance document is being distributed for comment purposes only.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be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance.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: druginfofda.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: ocodfda.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 1 Guidance for Industry1 2 3 4 This draft guidance, when finalized, will represent the current thinking of the Food and Drug 5 Administration (FDA or Agency) on this topic. It does not