The MHRA today released on their website their annual report of GCP inspection findings. It is interesting to note two critical findings for data integrity issues…. something that industry has been talking much about over recent months. It would be wise to do a comprehensive review of the MHRA draft guidance on this topic!
In addition, the MHRA cited a critical finding for management and maintenance of the trial master file (TMF). This includes the following:
- The TMF was not defined (i.e., no quality system record to confirm all the systems that held TMF records, e.g. regulatory document system)
- TMFs provided for inspection were incomplete (missing records)
- There was a lack of Quality Control (QC) process of the TMFs
- The DIA TMF Reference model had been implemented (although with modifications) via a table of contents for each trial to identify the location of TMF essential documents in defined sections, however the structure of the actual TMF electronic folders had not been changed to reflect the model.
- The TMF table of contents was found to be unreliable as the location of documents was not accurate.
- The document date was in the file name and the date in the system was either the upload date or finalisation date. For this reason it was not possible to order documents in document date order.
- There was a lack of integration with other TMF systems i.e. there were no links or placeholders directing the inspectors to the relevant repository or system for the relevant documents and data.
- It was not possible to set the TMF to archive status to prevent further changes.
- Documents were not consistently held in the TMF.
- Previous versions of documents were not present.
- There was extensive duplication of scanned documents.
- There was evidence that the uploading of documents was not being undertaken in a timely manner.
- If a document was not “finalised”, the inspectors could not view it.
Many of these observation reflect what is now becoming our common industry understanding of the MHRA expectations for a TMF…. so shouldn’t be a surprise anymore. However, it may be worth passing comment on a couple of these topics:
- I found it interesting to note the comment regarding not being able to view a “finalised” document. My assumption – and this is only conjecture – is that this does not imply a requirement to view draft documents but is simply the fact that a final document had not had its status changed in the eTMF to “finalised” and was therefore not accessible. If this however relates to an expectation to view non-final (i.e. draft, unapproved) documents in the eTMF, that would represent a major shift.
- As I predicted, the MHRA seem to be providing greater focus on archive processes and how systems comply with the regulatory requirements for an archive. This means under the control of an archivist and having the necessary security and access controls (amongst many other requirements!).
- The lack of integration comment is also an interesting one…. I would like to know more about this one. For sure, the location of all TMF content must be very clear and it must be readily and directly accessible wherever it may be stored. But this is the first time I’ve come across any kind of expectation that an eTMF should be integrated with sources of document content held elsewhere. Placeholders or a TMF Index…. yes.
- And great to see that the TMF Reference Model was in use…. though disappointing that there seems to have been some inconsistency in the way it was adopted.
Go to the MHRA website to view the full report.