ICH GCP Guidelines (E6) Addendum Now Available

So after securing approval at the November ICH meeting in Osaka, the revised text of the ICH guidelines for Good Clinical Practice – otherwise known as ICH E6(R2) – has been published on the ICH website….. and also available to download HERE. My previous blog posting highlighted some of the issues that I thought needed to be addressed. Although many were not resolved by the final approved wording of the guideline (no surprise there!), I was pleased to see some changes since the initial draft was circulated for consultation. I have these highlighted below.

The revised guideline now includes a definition for a “certified copy” and provides for such copies replacing the originals. Section 8.1 states:

“When a copy is used to replace an original document (e.g., source documents, CRF), the copy should fulfill the requirements for certified copies”.

This statement suggests strongly to me that it is acceptable to generate a certified copy (e.g. a digital scan of a paper document) and for the copy (the digital file) to completely replace the original paper version i.e. the paper copy can be destroyed. If the paper original is being retained, then the copy is not actually replacing anything….. it is being filed in addition to the original! You may want to retain originals for other reasons (e.g. originals may have greater evidential weight if relied upon in court) but this is not needed to comply with the guidelines here.

The final definition of a certified copy is slightly different from that first proposed but I think the subtle change is extremely important. The original wording proposed was:

“A paper or electronic copy of the original record that has been verified (e.g. by a dated signature) or has been generated through a validated process to produce an exact copy having all of the same attributes and information as the original.”

The two highlighted words are significant and were mentioned in my feedback to ICH during the consultation period. “Exact” is a very precise term, as is “all”. It is often the case that conversion of documents from one format to another results in a copy that is not 100% identical to the original in EVERY respect. But still, it contains all of the information, content and structure that is critical from a GCP compliance perspective and to support patient safety and data integrity. So the revised definition takes account of this nuance of document conversion:

“A copy (irrespective of the type of media used) of the original record that has been verified (i.e., by a dated signature or by generation through a validated process) to have the same information, including data that describe the context, content, and structure, as the original.”

So, I would argue that a PDF rendition of an email potentially loses some metadata components related to the email header (so is not an “exact copy” based on the original definition) but retains “the same information” contained within the email, the structure of the email and the context of the email, and would therefore constitute a certified copy (if produced through a validated process). And of course the ICH definition allows for certification via use of a validated process, not requiring a dated signature to certify each and every copy! It is worth noting that the current FDA definition of a certified copy differs from the ICH addendum definition but the FDA have stated that the “draft guidance, when finalized, will represent the current thinking of the Food and Drug Administration (FDA or Agency) on this topic”.

The second small but significant change that is of interest from a records management perspective is the specific inclusion of the requirement for “systems for archiving”. The original addendum included the following statement in section 8.1:

“The sponsor and investigator/institution should maintain a record of the location(s) of their respective essential documents. The storage system (irrespective of the media used) should provide for document identification, search and retrieval.”

The final text states:

“The sponsor and investigator/institution should maintain a record of the location(s) of their respective essential documents including source documents. The storage system used during the trial and for archiving (irrespective of the type of media used) should provide for document identification, version history, search, and retrieval.”

So there are three new concepts that are emphasised here:

  • The TMF inventory or index that is maintained both by the sponsor and by the investigator / institution must include all records considered part of the TMF, including source documents.
  • The issue of long-term retention and preservation of TMF content must be addressed and those systems selected for archival purposes must meet the same requirements for document identification, version control, search and retrieval as systems used during the trial.
  • The system for good version control and maintenance of an immutable audit trail of version history throughout the retention period must be assured – including those systems used for archiving.

The GCP addendum includes many other changes, some of which are directly relevant for records management and TMF management and can easily be found by reference to the additional sections in the guideline. I’ve just highlighted here what I consider to be two of the most significant ones for TMF management as they relate to concepts that are often misunderstood and variously interpreted across industry.


About rammellel

Records management consultant to the life sciences / pharmaceutical industry
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