Inspection Readiness

An Alternate Path

Post by
Denise Lacey
An Alternate Path

(Word count: 437)

While gatherers spend their time compiling collections of documents, trackers build systems to ensure they can find any document at any time.

The primary system is the Trial Master File (TMF) map, a comprehensive guide to all the TMF documents in the TMF Reference Model, regardless of where they are stored. Some companies have SOPs that require this map to be produced as part of the TMF plan, but other organizations find themselves scrambling to map locations of documents even as FDA is knocking on the door. Typically, essential documents are easily accounted for, but documents controlled by functions other than Clinical may be harder to visualize. Regulatory submission documents, source documents for safety reporting, contracts, Clinical Supply records, statistical programs and outputs, and computer system validation documents may all live in different repositories.

Once this map is assembled, the next step is to track key events, such as milestones, document versions, and significant changes. Some examples:

  • Protocol versions, dates, and significant changes
  • List of study-specific plans, versions, and dates
  • Start and stop dates of all study team personnel
  • Informed consent types and versions
  • Electronic data capture releases, with versions and dates of specifications associated with each component
  • Site activation, first drug shipment, and initiation dates for each site
  • 1572 dates for each site, with sub-investigators included on each
  • Versions of site initiation training, with documents/versions covered in each
  • List of SOPs effective through the life of the study

These trackers help the study team identify the documents that should be in the TMF, so they can QC it for completeness. For example, in order to know which training records should be expected for sub-investigator X, the reviewer needs to know when the site was activated relative to the protocol; when the sub-investigator started and left the study; and which SOP governing site-specific training documentation was in effect at the time the sub-investigator was trained. Trackers are a permanent record of that research process a good QC reviewer undertakes, one that can be referenced the next time the question is asked, either by a team member or an inspector.

Sponsors rarely require their study teams to maintain trackers as official documents; usually, a Clinical Trial Assistant independently comes to the conclusion that one would make their life easier and takes the initiative to compile it, maintaining it on a hard drive. The creators of the TMF Reference Model recognized their utility, though; every zone has a subsection titled "Tracking Information." Trackers are great tools, enhancing the study team's confidence in the completeness of the TMF as well as their ability to find documents in it.

Denise DeRenzo Lacey, RQAP-GCP, has over twenty years’ experience in clinical Quality Assurance and clinical development operations.  Her practice focuses on application of quality risk management techniques for clinical studies, including risk-based approaches to auditing, data quality and integrity, and SOP development.  She has provided consulting services to a wide range of pharmaceutical, medical device, biotech and CRO clients in the US and Europe and has held senior positions at Vertex Pharmaceuticals and Radius Health.