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Guest post, ICH GCP, Regulatory

Regulatory requirements: differences between FDA and EMA

As promised, and announced at the end of last week, this week’s post is from Carl Anderson, a U.S. based regulatory affairs and quality assurance consultant. Carl specialises in the field of FDA health product approvals including drugs, biologics, and medical devices. From 1987 to 2005 he worked for the United States Food and Drug Administration, primarily conducting inspections in the Bioresearch Monitoring program, which includes clinical trials.

Here is his guest commentary concerning different approaches in the USA and Europe to the enforcement of GCP in the conduct of clinical trials.


FDA and EMA: Differences in Approach

by Carl Anderson

The United States Food & Drug Administration (FDA) has just released a new inspection guidance (Compliance Program) for GCP inspections of Sponsors and CROs (CP 7348.810: Sponsors, Contract Research Organizations, and Monitors). The guidance is for FDA staff conducting GCP inspections and is the equivalent of the EMA Annex IV: Sponsor site and/or Contract Research Organizations (CRO) inspections procedure. The biggest difference is the FDA Compliance Program makes no mention of Essential Documents found in the trial master file, the TMF. EMA has numerous documents requiring review of Essential Documents including the following in Annex IV:

Determine if all essential documents listed in the section 8 CPMP/ICH/135/95 Note for guidance on GCP, are available during the inspection.” The CPMP/ICH/135/95 Note for guidance on GCP is referred to in the United States as “ICH E6: Good Clinical Practice: Consolidated Guidance (ICH E6). The FDA Compliance Program does not mention ICH E6 even though it is an official FDA Guidance Document that was published in the U.S. Federal Register in 1996.

Another significant difference is that FDA does not have requirements for written procedures in clinical trials. The only exceptions are for monitoring plans in medical device trials and extensive SOPs required for Institutional Review Boards (IRBs/IECs). Note: There are no SOP requirements for clinical sites (none). SOPs or written procedures are sometimes referenced in the Sponsor/CRO Compliance Program but never as a requirement. Here is one passage:

Obtain a copy of the sponsor’s/CRO’s/monitor’s written procedures (SOPs and guidelines) for monitoring and determine if the procedures were followed for the selected study. In the absence of written procedures, conduct interviews of the monitors as feasible and/or otherwise determine how monitoring was conducted.”

There are several other requirements that are unique to FDA inspections. One is a new requirement that clinical trials be registered on the website ClinicalTrials.gov. It is a requirement of the United States Congress. The Compliance Program states: ClinicalTrials.gov is a website maintained by the National Library of Medicine (NLM). Its establishment was mandated by the 1997 FDA Modernization Act (FDAMA) to provide a public resource for information on studies of drugs, including biological drug products.” This is a requirement of all clinical trials conducted under FDA regulations that include an Investigational New Drug application (IND) for drugs and biologics and an Investigational Device Exemption (IDE) for medical devices. There are also regulatory requirements for financial disclosure and emergency research that are specific to FDA.

One way I have heard the difference between EMA and MHRA inspections from FDA inspections is that the European inspections are process driven, while FDA inspections are more detail oriented and focus on specific regulatory requirements. The roots of the differences in clinical trial regulations are that they were written at different times in the evolution of clinical research. FDA’s regulations are a result of the Thalidomide tragedy of the early 1960s that culminated in passage of the Kefauver-Harris amendments of 1962. Senator Estes Kefauver of Tennessee was a colorful character in United States politics, who was known for wearing a coonskin hat and dueling with President John F. Kennedy.

The European regulations are the result of the Clinical Trials Directive of 2001, almost 40 years later when clinical research looked very different. The ICH GCP Guidelines are far more specific than anything from FDA. The differences have made harmonisation and FDA/EMA collaboration very difficult.

Web Links: ClinicalTrials.gov: http://clinicaltrials.gov/

FDA Compliance Programs for Sponsor/CRO, Clinical Investigators, IRBs (Bioresearch Monitoring Program) Read Section III, Inspectional:



About Dr M | The SOP Doc

I'm a pharmaceutical industry specialist, with more than 25 years experience, and a background in medical and social sciences. Developing my niche one step st a time.



  1. Pingback: SOPs in Europe: Required for GCPs? « GxP Perspectives - April 5, 2011

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