How Will You Be Inspection Ready Next Time? (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?

Real world perspectives from a clinical site, a sponsor, and a technology vendor.

As part of our ongoing series myClin and Clinical Works recently organized the Clinical Innovators Summit (CIS) West Coast 2019 to help clinical trial professionals simplify, unify, and advance oversight and collaboration processes in clinical trials. We have created this series of articles in an effort to catch up those who were unable to attend CIS West Coast on the expert panel discussion Our panelists shared actionable insights and new perspectives on the topic of inspection readiness in the context of the ICH E6 R2 regulations.

ICH E6 (R2) has been in preparation for several years and was formally adopted by the FDA in March last year 2018. Consistent feedback from regulators is that they expect more detailed oversight evidence from the start to end of the study.

In other words:

  • Content such as the notes you make in CRO bid defenses are expected to end up in your TMF.
  • Study teams need to define in advance your oversight activity and execute on that plan on a continuous, contemporaneous basis.
  • Teams are expected to use their suite of eClinical tools: IRT, EDC, myClin etc to proactively identify and manage risk. When you have access to insights from such tools you are expected to use them.
  • The sponsor should maintain oversight of functions carried out on its behalf. [ICH E6 (R2)]

Erin Silverman, Ph.D. CCC-SLP, CRCC, Research Coordinator and Adjunct Assistant Professor, University of Florida

“Maintain a high standard of record keeping and communication.”

Erin Silverman works as a pulmonary medicine research coordinator at the University of Florida. She is also a researcher in her own right, having completed her Ph.D. in Communication Sciences and Disorders, with a focus on airway protection in adults who suffer from neurocognitive and/or neuromuscular diseases. She regularly has her worked published in peer-reviewed medical journals and has authored or coauthored well over 30 research reports as well as numerous textbook chapters on the topics of voice disorders and respiratory anatomy and physiology. Erin serves as an Adjunct Assistant Professor in the graduate speech, language, and hearing program at UF. She also regularly presents medical education seminars on the topic of respiratory muscle strength training across the US, as well as abroad.

“We are an extremely high-volume research center. Fortunately, this means we already have numerous processes in place that allow us to trace events back and see what happened during a study. But when I read the new regulations, my mind automatically assumes that there’s going be another log form that I have to figure out.”

“I understand that there’s a need for this. The lazy route to take is to pass it on to your study coordinator as just an additional log form, but I think it’s important to devote more thought to slowing down and thinking things through. It’s important to find a middle ground. We should look at all areas of the business and ensure that communication is a strong focus.”

“It’s important that everybody is on the same page and has the same study base, in a way that is achievable, retrievable, and well-documented. It can’t be something like, I called her that day and she said “x, y and z”. Everything should be communicated in writing, but at the same time it needs to cut through that kind of clutter.”

Lorne Cheeseman – Managing Director, Kestrel Biologic

“Sponsors need an Oversight Plan.”

Lorne Cheeseman has an extensive background in international clinical research. His experience includes managing and training clinical teams, monitoring clinical trial sites, and developing quality systems and SOPs. He has held leadership positions in companies such as Pfizer, Quintiles, Gilead Pharmaceuticals and Allergan, all of which have provided a solid base for his role at Kestrel Biologic. Lorne took on the role as CEO at Kestrel Biologic in 2013. He has taken the company to the next level and is determined to make the iQROS™ integrated monitoring and Oversight tool a household name in the pharmaceutical industry.

“Inspection readiness means having your documents in order as you’re going along with the study, ensuring not to lag behind. You also need to slow down in order to get compliant. I think this is key. A lot of the time we rush with start-ups and then we end up with a pile of documents that CTA is going to need to file at some point in the future. In reality, we haven’t yet hired that CTA and that’s where the problems start.”

“With ICH E6 R2, the sponsor can’t just brush it off and think that that’s the CRO’s problem: There must be Oversight. The sponsor should always be maintaining and managing necessary documentation. They can’t just delegate everything out to the CRO.”

John Silowsky – Clinical Operations Consultant & Former Sr. Director Clinical Operations, Nektar Therapeutics

“There are three core steps: Protocol, data map, and risk management. They inform the rest of your study plans and documentation.”

John Silowsky is a clinical research consultant who specializes in clinical operations. He has 20 years of experience, having filled roles ranging from site study coordination to director level leadership. John has worked for companies and clients as diverse as boutique CROs to large pharma. Prior to entry into this industry, John practiced as a nurse in infectious disease, critical care, and emergency care.

“I feel like the concept of risk management is going to be looked at a lot more closely in future inspections. This concept has been a long time coming. Many risk-based approaches to provide study Oversight have already been developed. In the future, inspectors are more likely to look at how you identified your risk at the beginning, and what that risk was based on. For instance; they won’t be interested in the fact that you just took boiler plate risks. They won’t be looking at how many AEs are reported at sites and doing a risk assessment based on anybody who deviates from that. They’re looking for something that is tailored specifically to your drug, your protocol, your study setup, and your site.

“Slowing down to speed up later involves pulling these core pieces together: What are your risks? Where is your data? What is your protocol? You would then develop the detailed documentation based on this, not the template from the monitoring plan. They want to see a Monitoring plan that works for your study specifically.”

Follow myClin and Clinical Works’ official pages and stay tuned for our next article on inspection readiness. Catch up on the Clinical Innovators Summit with this recap video and join our next event at

By Adam Wood, VP, Business Development at myClin

About myClin: Are you really ready for an inspection? Start using the myClin platform to take control of intricate and error-prone study documentation. Keep essential information at your fingertips to stay audit-ready at all times. Get started with more free resources and a demo at

About Clinical Works: Are you ready to move faster and smarter with a high impact, curated ClinOps team? We help new bio-pharm ventures and start-ups bridge the gap from investment to clinical development. Find out more at