Descriptive Analysis of Good Clinical Practice Inspection Findings from U.S. Food and Drug Administration and European Medicines Agency
Tóm tắt
The United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) have collaborated in good clinical practice (GCP) inspections since September 2009. The two agencies operate under different regulatory frameworks for GCP oversight. No systematic assessments of GCP inspection findings have been reported. We identified common inspections of clinical investigators, sponsors, and contract research organizations conducted by both agencies in support of marketing applications that had the same trial data submitted between 2009 and 2015. We grouped inspection findings into deficiency areas. We reviewed and compared these findings and calculated concordance rate for each deficiency area. Twenty-six clinical investigator sites and 23 sponsors/contract research organizations were inspected by both agencies in support of 31 marketing applications during this period. For FDA, the most common GCP findings were deficiencies related to Protocol Compliance for clinical investigator inspections and Trial Management issues for sponsor/contract research organization inspections. For EMA, deficiencies related to Documentation (including Trial Master File) were the most common findings for both clinical investigator and sponsor/contract research organization inspections. There was high concordance, of approximately 90%, for deficiencies related to Protocol Compliance for clinical investigator inspections and Trial Management for sponsor/contract research organization inspections between the two agencies. There was a concordance rate of about 70% for Documentation deficiencies for both clinical investigator and sponsor/contract research organization GCP inspections. GCP inspection findings from 49 common clinical investigator and sponsor/contract research organization inspections were comparable, providing support for continued FDA-EMA GCP collaboration.
Tài liệu tham khảo
US Title 21 Code of Federal Regulations (CFR). Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm. Accessed 1 Apr 2022.
Directive 2001/20/EC OF the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the member states relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. Available from: https://www.eumonitor.eu/9353000/1/j9vvik7m1c3gyxp/vitgbgi8z5z8. Accessed 1 Apr 2022.
Commission Directive 2005/28/EC of 8 April 2005 laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use, as well as the requirements for authorization of the manufacturing or importation of such products. Available from: https://eurlex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2005:091:0013:0019:en:PDF. Accessed 1 Apr 2022.
Regulation No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC. Available from: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32017R0556&rid=1. Accessed 1 Apr 2022.
Commission Implementing Regulation (EU) 2017/556 of 24 March 2017 on detailed arrangements for the good clinical practice inspection procedures pursuant to Regulation (EU) No 536/2014 of the European Parliament and of the Council. Available from: https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32017R0556&rid=1. Accessed 1 Apr 2022.
ICH Topic E6 (R1). Guideline for Good Clinical Practice. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e6-r1-guideline-good-clinical-practice_en.pdf. Accessed 1 Apr 2022.
Thiers FA, Sinskey AJ, Berndt ER. Trends in the globalization of clinical trials. Nat Rev Drug Discov. 2008;7(1):13–4.
Glickman SW, McHutchison JG, Peterson ED, Cairns CB, Harrington RA, Califf RM, et al. Ethical and scientific implications of the globalization of clinical research. N Engl J Med. 2009;360(8):816–23.
George M, Selvarajan S, Suresh-Kumar S, Dkhar SA, Chandrasekaran A. Globalization of clinical trials—where are we heading? Curr Clin Pharmacol. 2013;8(2):115–23.
Richter TA. Clinical research: a globalized network. PLoS ONE. 2014;9(12):e115063.
Shenoy P. Multi-regional clinical trials and global drug development. Perspect Clin Res. 2016;7(2):62–7.
Drain PK, Parker RA, Robine M, Holmes KK, Bassett IV. Global migration of clinical research during the era of trial registration. PLoS ONE. 2018;13(2):e0192413.
EMEA-FDA GCP initiative. Available from: https://www.ema.europa.eu/en/human-regulatory/research-development/compliance/good-clinical-practice. Accessed 1 Apr 2022.
EMA partners-networks. Available from: https://www.ema.europa.eu/en/partners-networks/international-activities/bilateral-interactions-non-eu-regulators/united-states. Accessed 1 Apr 2022.
US Title 21 Code of Federal Regulations (CFR), Part 56 (Institutional Review Boards). Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=56&showFR=1. Accessed 1 Apr 2022.
Khin NA, Francis G, Mulinde J, Grandinetti C, Skeete R, Yu B, et al. Data integrity in global clinical trials: discussions from joint US food and drug administration and UK medicines and healthcare products regulatory agency good clinical practice workshop. Clin Pharmacol Ther. 2020;108(5):949–63.
EMA. Classification and analysis of the GCP inspection findings of GCP inspections conducted at the request of the CHMP (Inspection reports to EMA 2000–2012). Available from: https://www.ema.europa.eu/en/documents/other/classification-analysis-good-clinical-practice-gcp-inspection-findings-gcp-inspections-conducted_en.pdf. Accessed 1 Apr 2022.
US Title 21 Code of Federal Regulations (CFR), Part 312 (INVESTIGATIONAL NEW DRUG APPLICATION). Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=312.53. Accessed 1 Apr 2022.
US Title 21 Code of Federal Regulations (CFR), Part 54 (financial disclosure by clinical investigators). Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRsearch.cfm?CFRPart=54. Accessed 1 Apr 2022.
US Title 21 Code of Federal Regulations (CFR), Part 11 (electronic records; electronic signatures). Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=11. Accessed 1 Apr 2022.
FDA. Use of electronic records and electronic signatures in clinical investigations under 21 CFR Part 11—Questions and Answers. Guidance for Industry, JUNE 2017. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-electronic-records-and-electronic-signatures-clinical-investigations-under-21-cfr-part-11. Accessed 1 Apr 2022.
EU. The rules governing medicinal products in the European Union. Volume 4. Good Manufacturing Practice. Available from: https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/2017_11_22_guidelines_gmp_for_atmps.pdf. Accessed 1 Apr 2022.
ICH 5.13.1, Sponsor: Manufacturing, Packaging, Labelling, and Coding Investigational Product(s). Available from: https://ichgcp.net/5-sponsor. Accessed 1 Apr 2022.
FDA. Compliance Program Guidance Manual (CPGM), Clinical Investigators and Sponsor-Investigators. Available from: https://www.fda.gov/media/75927/download. Accessed 1 Apr 2022.
FDA. Compliance Program Guidance Manual (CPGM) sponsor. Available from: https://www.fda.gov/media/75916/download. Accessed 1 Apr 2022.
21CFR, Part 312.52, transfer of obligation to CRO. Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=312.52. Accessed 1 Apr 2022.
US Title 21 Code of Federal Regulations (CFR), Part 50 (requirements of informed consent). Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=50. Accessed 1 Apr 2022.
EMA-FDA-PMDA Trilateral GCP Feasibility Pilot Report. Available from: https://www.fda.gov/media/145550/download. Accessed 1 Apr 2022.
FDA. Real-time oncology review (RTOR) pilot program. Available from: https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review. Accessed 1 Apr 2022.
Pharmaceutical Inspection Convention, Pharmaceutical Inspection Co-operation Scheme (PIC/S) Inspectorates Academy (PIA). Working Group on Good Clinical and Pharmacovigilance Practices. Available from: https://picscheme.org/en/pia-pic-s-training-expert-circles-training-working-group-on. Accessed 1 Apr 2022.
ICH E6 (R2). Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e-6-r2-guideline-good-clinical-practice-step-5_en.pdf. Accessed 1 Apr 2022.
ICH Reflection Paper on GCP Renovation. Efficacy Guidelines E6(R3) EWG endorsed documents. Available from: https://www.ich.org/page/efficacy-guidelines. Accessed 1 Apr 2022.