5 Common Mistakes That Can Derail a Clinical Trial Inspection (Part 1)

In a business niche as highly critical, closely scrutinised and heavily regulated as pharmacovigilance it remains a puzzle why clinical development organisations struggle so often with the “end of process task” of distributing Safety Reports*. These are commonly known as Suspected Unexpected Serious Adverse Reaction or SUSARs. Timely safety report distribution is important because of its part in improving patient safety but also due to the compelling regulatory obligation to distribute this material promptly.

A Pharmacovigilance Process Summary

  1. Site reports Serious Adverse Reaction (SAR) within 48 hours.
  2. Sponsor determines if SAR is unexpected or not.
  3. Sponsor reports SUSAR to relevant regulators within days (for EMA within 7 days and typically 15 days for the FDA).
  4. In parallel to step 3 the sponsor has a responsibility to promptly inform other sites once the matter is identified as a safety issue. While there is some scope for interpretation here, “promptly” is normally interpreted as meaning a number of days and not some longer period of time. Typically sponsors will aim to distribute safety reports within 15 days.

For reference here is how the FDA explain things – p16 of FDA Guidance Safety Reporting Requirements for INDs and BA/BE Studies.

The reality is that this end of process task sounds simple to define but it is in fact pretty complex and time critical. In addition – organisations are often so blindly addicted to using email that alternative, more dynamic and reliable means of information distribution are strangely alien and fantastical. But why not use distribution means that allow for active information distribution, with real-time dynamic readership information? In an age where audience behaviour is closely tracked, isn’t it time you knew who has read your latest Safety Report, and more crucially who has not?

Mistake #1: Storing your documents in multiple locations — resulting in not knowing where necessary documents are when they are needed.

This is a very common occurrence originating with the source of the documents themselves. The fact is, key documents for clinical trials are generated at different times, by different functions in an organization, and they are subject to different regulatory controls. Take the protocol or the investigator’s brochure as examples. They start their lives as Word documents on the desktop of a clinical scientist. There are a number of inputs over weeks and months coming from inside and outside the organization, with the final versions being subject to (hopefully) an SOP controlling the final publication and submission to regulatory authorities. Since our global regulatory authorities have entered the modern era, they require a special process to receive these documents electronically. There it starts. The first of the final essential documents in a clinical trial reside in a regulatory publishing system not readily accessible to the clinical study team.

How does the study team receive the final versions of the protocol and IB? Email. Intra-organizational email. That’s okay. It is within the firewall. What does each person in turn do with it? They save it on their desktop of course, or sometimes to a shared drive on the network server with the prior draft, near final draft, final final draft and final versions that preceded publishing. When someone asks them for a copy of the protocol, they forward it. From their desktop. Via email. Does anyone forget to check to be sure that the version they are emailing is an exact match with the one controlled version in the regulatory publishing system?

Yes, often.

Pharmacy and laboratory manuals are examples of documents requiring a precise degree of care to ensure patient safety and data integrity. They may originate with the sponsor company or be created by a third party service provider for sponsor collaboration and approval. After a tortuous path to finalization, the final version may be printed and bound for distribution to investigator sites, its electronic rendition on the desktop, in the shared drive, in an email folder, somewhere in SharePoint, or stored in the cloud for easy access by everyone. Ideally there is one true source in a specified repository. When inspection time comes, the clinical trial leader more often than not, is faced with teasing out which of the multiple versions across multiple systems was distributed to the sites.

Regulatory publishing system. Desktop. Shared drive. Email. SharePoint. Paper. Cloud.

The reality is there are multiple stakeholders and systems involved in complex clinical trials. Here is the bottom line — the clinical trial leader responsible for defending the study to an inspector needs to be backed by evidence that investigator sites, monitors, and study team members had the right version of the right document at the right time.

Two preemptive solutions:

  1. Know and control the path of each document from its origin to site distribution
  2. Establish a central distribution channel as a single source of truth for all study information needed by sites to conduct the study.

With the correct approach and due diligence, the study team can avoid this first mistake — ensuring all documents are controlled and are kept in one central and secure location. Taking preventative action is the first step towards a hassle-free inspection.

This is the first installment of our series on 5 Common Mistakes That Can Derail a Clinical Trial Inspection series. Check back again when we tackle Mistake #2: Untagged, Mislabeled, or Misfiled Documents.

By Eileen Daniel, SVP, Development Operations at Caelum Biosciences

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