Comparison of Good Clinical Practice Inspection Processes for Marketing Applications Between the United States Food and Drug Administration and the European Medicines Agency.

Clinical investigator EMA FDA Good clinical practice inspection Inspection process Sponsor

Journal

Therapeutic innovation & regulatory science
ISSN: 2168-4804
Titre abrégé: Ther Innov Regul Sci
Pays: Switzerland
ID NLM: 101597411

Informations de publication

Date de publication:
01 2023
Historique:
received: 17 05 2022
accepted: 20 07 2022
pubmed: 17 8 2022
medline: 20 12 2022
entrez: 16 8 2022
Statut: ppublish

Résumé

The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) began collaboration on Good Clinical Practice (GCP) inspections for marketing applications since 2009. The main characteristics of the GCP inspection processes between FDA and EMA were never evaluated. This is the first analysis comparing the GCP inspection processes between the two agencies. We examined and analyzed the key characteristics of the GCP inspection processes, including the geographical distribution, inspection types and timelines from application submission to final inspection reporting for marketing applications from September 2009 through December 2015. Fifty-five shared applications were included for analysis. For these applications, a total of 433 GCP inspections were conducted in 47 countries. Most clinical investigator (CI) inspections were conducted in regions outside of each agency's own regulatory jurisdiction, while most sponsor/contract research organization (CRO) inspections were conducted in the U.S. by both agencies. Twenty-eight shared applications included common sites inspected by both agencies. There were 15 joint inspections conducted for seven of these applications and the remaining applications had common sites inspected by both agencies at separate times. Of the joint inspections, 73% were conducted in the U.S and 20% in the E.U. The median time from submission of an application to generation of final inspection reports was 232 days for FDA and 204 days for EMA, with no significant differences noted among applications with and without common sites. The inspection processes and timelines between the two agencies were similar, providing support for continued FDA-EMA GCP collaboration.

Sections du résumé

BACKGROUND
The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) began collaboration on Good Clinical Practice (GCP) inspections for marketing applications since 2009. The main characteristics of the GCP inspection processes between FDA and EMA were never evaluated. This is the first analysis comparing the GCP inspection processes between the two agencies.
METHODS
We examined and analyzed the key characteristics of the GCP inspection processes, including the geographical distribution, inspection types and timelines from application submission to final inspection reporting for marketing applications from September 2009 through December 2015.
RESULTS
Fifty-five shared applications were included for analysis. For these applications, a total of 433 GCP inspections were conducted in 47 countries. Most clinical investigator (CI) inspections were conducted in regions outside of each agency's own regulatory jurisdiction, while most sponsor/contract research organization (CRO) inspections were conducted in the U.S. by both agencies. Twenty-eight shared applications included common sites inspected by both agencies. There were 15 joint inspections conducted for seven of these applications and the remaining applications had common sites inspected by both agencies at separate times. Of the joint inspections, 73% were conducted in the U.S and 20% in the E.U. The median time from submission of an application to generation of final inspection reports was 232 days for FDA and 204 days for EMA, with no significant differences noted among applications with and without common sites.
CONCLUSION
The inspection processes and timelines between the two agencies were similar, providing support for continued FDA-EMA GCP collaboration.

Identifiants

pubmed: 35972722
doi: 10.1007/s43441-022-00441-w
pii: 10.1007/s43441-022-00441-w
pmc: PMC9755076
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

79-85

Informations de copyright

© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

Références

EMEA-FDA GCP initiative. https://www.ema.europa.eu/en/human-regulatory/research-development/compliance/good-clinical-practice . Accessed 17 May 2022.
EMA partners-networks. https://www.ema.europa.eu/en/partners-networks/international-activities/bilateral-interactions-non-eu-regulators/united-states . Accessed 17 May 2022.
Sellers JW, Mihaescu CM, Ayalew K, et al. Descriptive analysis of good clinical practice inspection findings from U.S. Food and Drug Administration and European Medicines Agency. Ther Innov Regul Sci. 2022. https://doi.org/10.1007/s43441-022-00417-w .
doi: 10.1007/s43441-022-00417-w
US Title 21 Code of Federal Regulations (CFR). https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm . Accessed 17 May 2022.
Bioresearch Monitoring Program (BIMO) Compliance Programs. FDA’s Compliance Program Guidance Manual (CPGM). https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/compliance-program-guidance-manual-cpgm/bioresearch-monitoring-program-bimo-compliance-programs . Accessed 17 May 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. https://ec.europa.eu/health/sites/default/files/files/eudralex/vol-1/dir_2001_20/dir_2001_20_en.pdf . Accessed 17 May 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. https://eurlex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2005:091:0013:0019:en:PDF . Accessed 17 May 2022.
Regulation (EU) 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. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32014R0536&rid=2 . Accessed 17 May 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. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32017R0556&rid=1 . Accessed 17 May 2022.
ICH Topic E6 (R1). Guideline for Good Clinical Practice. https://www.ema.europa.eu/en/documents/scientific-guideline/ich-e6-r1-guideline-good-clinical-practice_en.pdf . Accessed 17 May 2022.

Auteurs

Kassa Ayalew (K)

Division of Clinical Compliance Evaluation, Office of Scientific Investigations, Office of Compliance, Center for Drug Evaluation and Research, United States (US) Food and Drug Administration (FDA), Silver Spring, MD, USA. Kassa.Ayalew@fda.hhs.gov.
U.S. Food and Drug Administration, 10903 New Hampshire Ave, White Oak Building 51, Room 5370, Silver Spring, MD, 20993, USA. Kassa.Ayalew@fda.hhs.gov.

Yang-Min Ning (YM)

Division of Clinical Compliance Evaluation, Office of Scientific Investigations, Office of Compliance, Center for Drug Evaluation and Research, United States (US) Food and Drug Administration (FDA), Silver Spring, MD, USA.

Michelle J Foringer (MJ)

Division of Clinical Compliance Evaluation, Office of Scientific Investigations, Office of Compliance, Center for Drug Evaluation and Research, United States (US) Food and Drug Administration (FDA), Silver Spring, MD, USA.

Susan Leibenhaut (S)

Division of Clinical Compliance Evaluation, Office of Scientific Investigations, Office of Compliance, Center for Drug Evaluation and Research, United States (US) Food and Drug Administration (FDA), Silver Spring, MD, USA.

Jenn W Sellers (JW)

Division of Clinical Compliance Evaluation, Office of Scientific Investigations, Office of Compliance, Center for Drug Evaluation and Research, United States (US) Food and Drug Administration (FDA), Silver Spring, MD, USA.

Bei Yu (B)

Division of Clinical Compliance Evaluation, Office of Scientific Investigations, Office of Compliance, Center for Drug Evaluation and Research, United States (US) Food and Drug Administration (FDA), Silver Spring, MD, USA.

Phillip D Kronstein (PD)

Division of Clinical Compliance Evaluation, Office of Scientific Investigations, Office of Compliance, Center for Drug Evaluation and Research, United States (US) Food and Drug Administration (FDA), Silver Spring, MD, USA.

Agata Higgerson (A)

Inspections Office, Quality and Safety of Medicines Department, European Medicines Agency (EMA), Domenico Scarlattilaan 6, 1083 HS, Amsterdam, The Netherlands.

Camelia Mihaescu (C)

Inspections Office, Quality and Safety of Medicines Department, European Medicines Agency (EMA), Domenico Scarlattilaan 6, 1083 HS, Amsterdam, The Netherlands.

Miguel Rodriguez (M)

Inspections Office, Quality and Safety of Medicines Department, European Medicines Agency (EMA), Domenico Scarlattilaan 6, 1083 HS, Amsterdam, The Netherlands.

LaKisha Williams (L)

Division of Clinical Compliance Evaluation, Office of Scientific Investigations, Office of Compliance, Center for Drug Evaluation and Research, United States (US) Food and Drug Administration (FDA), Silver Spring, MD, USA.

Ni A Khin (NA)

Division of Clinical Compliance Evaluation, Office of Scientific Investigations, Office of Compliance, Center for Drug Evaluation and Research, United States (US) Food and Drug Administration (FDA), Silver Spring, MD, USA.

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