Know Your Regs: A TMF Regulatory Overview

Part 1: ICH GCP

As part of a recent webinar series, LMK Clinical Research Consulting was lucky enough to host Marie-Christine Poisson-Carvajal, Head of TMF & Registry Operations at Pfizer, to discuss the main regulations that predicate the trial master file.

During the webinar, Marie-Christine outlined the four most common relevant regulatory authorities and their associated TMF regulations: ICH GCP, EMA Clinical Trial Regulation and Guidance, the MHRA Gray Guide, and FDA 21 CFR Part 11. Marie-Christine established that these regulations are the foundation of every TMF and that the TMF is the foundation of every clinical trial. Marie-Christine also mentioned that regulatory expectations are growing and so are the resources required to conduct the average clinical trial compliantly. Because of this increasing complexity and the growing importance of the TMF, everyone who creates, handles, or reviews regulatory documents as a TMF stakeholder should have a basic understanding of these regulations and how they apply to the TMF.

To learn more about these essential TMF regulations and best practices for applying them to your TMF business processes, watch the recording of Marie-Christine’s webinar, or read on, as we cover the most well-known set of TMF regulations, ICH GCP. Check back regularly to catch the next post in this multi-part series and gain the regulatory knowledgebase necessary to achieve TMF health!

What is ICH?

ICH stands for The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH is a nongovernmental initiative. Since 1990, the mission of ICH is to “promote public health by achieving greater harmonisation through the development of technical guidelines and requirements for pharmaceutical product registration.” ICH is not a government agency, but rather acts as a forum bringing together authorities from the US, EU, Japan, and other member regions to reduce redundancy and regulatory administrative burden.

What is GCP?

ICH’s main work product is guideline documents. These documents are not laws and are not regulation unless implemented in accordance with the applicable national/local/regional rules. ICH GCP, or good clinical practice, is one set of guidelines produced by ICH that define “international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects.” These standards are published with the intent to insure “that the rights, safety, and well-being of trial subjects are protected…”  The current GCP guidelines are the sixth of ICH’s efficacy guidelines and the current document is on its second revision since its first publication in 1996—therefore the guidelines are known as ICH GCP E6(R2).

Why do I need to follow GCP?

GCP’s principles are codified in several sections of The Code of Federal Regulations (CFR). Additionally, the FDA has published ICH GCP E6(R2) as an official guidance document. Failure to adopt the many principles of GCP according to FDA’s interpretation of the guidance will result in noncompliance with one or several GCP-harmonized regulations in the CFR. Noncompliance, of course, can result in a variety of FDA enforcement actions. See the link to FDA’s website in the last item below for a list of the most relevant GCP/human subject protection related regulations.


What parts of the guidelines apply specifically to my TMF?

Although many GCP principles intersect with aspects of essential document collection and storage, section 8 specifically addresses the TMF. Section 8 contains a list of essential documents that should be considered the bare minimum necessary to achieve compliance. In reality, in order to document compliance with other GCP principles, to comply with other regional regulations, and in order to reduce regulatory risk, many more document types will be required to reside within your TMF than what is listed in section 8.

Section 8 also outlines some of the following basic principles of the TMF and good document practices:

  • The sponsor and investigator should maintain a record of the location(s) of their respective essential documents. The storage system should provide for document identification, version history, search, and retrieval.
  • The essential documents for a specific trial should be supplemented or may be reduced as appropriate.
  • Sponsors should ensure that the investigator has control of and continuous access to the case report form data.
  • When a copy is used to replace an original document it should fulfill the requirements for certified copies outlined in the guidelines.
  • Investigators should have control of all essential documents and records generated by the investigator before, during, and after the trial.

The specific circumstances of your clinical trial will impact the documents your team should collect as well as the business processes that must be conducted and documented in order to achieve GCP compliant documentation.

What are some good resources to learn more about ICH GCP?

Contact LMK Clinical Research Consulting today for a complementary GCP essential document gap analysis and ensure your TMF reflects the recent changes outlined in ICH GCP E6(R2).