Anyone who’s ever prepared for an FDA Inspection of their clinical study has undoubtedly spent hundreds of hours sifting through all of the essential study documentation that makes up the Trial Master File (TMF) in an effort to make sure every single document needed to tell the study’s “story” is there, is accurate, and is complete. Sometimes this is handled internally and sometimes companies hire external contractors to assist. Either way, there can be a huge price tag associated with this. At two recent TMF audits, I found myself asking the following questions:
- “Does it have to be a huge price tag?”
- “Is there a more cost effective way to prepare for an FDA inspection?”
It’s obvious during this preparatory phase that study teams are under enormous pressure. The weight of product approval hinges on this specific collection of study documentation, and in some cases, the entire company’s existence is wrapped into the success or failure of this one product. This can be daunting at any level, so an investment in making sure that the documentation is adequate seems logical.
Depending on how a company approaches this preparatory phase, the following types of activities can impact the cost of the investment.
Costs Involved In a Typical Trial Master File Audit
- Cost of internal staff time. Internal staff familiar with the study would be needed to review, collect, sort, and organize the Trial Master File.
- Cost of an auditor. Auditors generally charge an hourly rate for their work. The more complex the study, the more hours will be required. In addition, if there was little to no preparatory work done by the internal team (#1 above), this could also lead to a longer audit.
- Travel expenses. With a typical audit lasting 3-5 days, expenses like airfare, hotels and meals, can really add up.
- Internal staff time during an audit. In a typical situation in which documents are part paper, part electronic and perhaps maintained in multiple places (including individual hard drives or individual email folders), much time is required for the staff to retrieve documents for the auditors. For some of the audits I’ve conducted recently, there were at least two people engaged with me during the audit, and another three or four who were busy printing, copying, contacting field monitors, and running documents to the audit room.
In one recent case, those assisting me during the audit were remote employees and had to fly to the main office for the audit. So now you have to add their travel and lodging costs to the above total as well. In summary:
- Internal staff time to prepare (which could be hundreds of hours)
- + External auditor expense
- + Travel expenses (both internal and external, if applicable)
- + Internal staff time to support audit
- = A huge investment
A Better Way To Conduct Trial Master File Audits
Fast forward to my most recent audit experience… I was set up in an empty office all by myself. I was provided with access to the electronic TMF and was notified that the person that was supposed to be working with me that day was home sick. I had access to every single study document and had no one there to explain anything to me. The documents had to “speak” for themselves. It dawned on me that this should be the goal of any TMF, for any FDA Inspection, no matter how big it is or how much staff turnover there was. It also dawned on me that I could be doing this from my own office, without the added expense of travel or the loss of productivity due to travel time. In this scenario, the cost would look more like this:
- Internal staff time to prepare
- + External Auditor expense
- + Internal staff time to support audit (minimal – call in for opening and closing meetings)
- = A small to moderate investment
What I deduced was that the TMF audit I did in an empty office by myself with no one to go to for questions was just as effective as the onsite audit in which I had multiple people available to me at all times… and that it could’ve been done for half the cost.
Without a doubt, the cost of preparing ahead of an FDA inspection certainly outweighs the cost of not preparing at all. An investment in an external auditor this close to the finish line makes sense, and if I was advising you, whether you used my company or not, I’d tell you it’s likely to be worth every penny. But the investment does not always have to be huge. If you use an electronic trial master file or have another means by which an auditor can access your TMF, consider alternative approaches that could save you time and money, while still adequately preparing you for test day.
See how much you stand to save in this Electronic Trial Master File Audit infographic.