New Normal? Takeaways from A Virtual Regulatory Inspection During COVID-19

David J. Lewis
Novartis Pharma GmbH, Germany
University of Hertfordshire, UK

magine the challenge: ahead of you is a Supervisory Authority inspection focusing on Good Pharmacovigilance Practices, with three inspectorates involved. You are the Qualified Person for Pharmacovigilance (QPPV) with oversight of the pharmacovigilance (PV) system of a multinational pharmaceutical company with a broad product portfolio comprising pharmaceutical medicines, biologicals, advanced therapy medicinal products (ATMPs), and gene therapy products. Fifty subject matter experts are planning to travel to mainland Europe in support of the inspection. The day before the inspection, a call is received requesting a remote inspection — to be conducted via video and telephone calls. The cause is the COVID-19 global pandemic. Outbreaks of COVID-19 affecting France, Switzerland, and Germany enforce a new approach as the WHO has released recommendations limiting travel.

A public holiday in the city hosting the inspection, which fell on the day that the decision was made, complicates matters even further. Such inspections are taken very seriously by all parties; in this instance, a formal, timed agenda, in accordance with the European guideline on PV inspections, was planned for 3.5 days. Five inspectors working from three locations in Germany, plus one in Switzerland, added to the complexity. Network connections were centered in Basel, Switzerland. Remote login occurred from two company sites in Germany, two in Spain as well as one each in India, Ireland, the UK, and the US. In total, over one hundred and fifty associates were prepared to support the inspection. Specialists were assigned to interviews conducted by expert inspectors on a series of topics, including changes to the company, the PV system, global safety database, case processing and medical assessment, periodic safety update reports, the risk management system, signal management, safety-related labelling variations, the quality system for the PV system, and oversight of the QPPV. Time zone differences (CET versus US Eastern) required one agenda change; nevertheless, several individuals (in India Standard Time) connected late at night.

The PV system master file (PSMF) and a macroflow diagram of the PV system were provided to the inspectors for reference. Rooms were prepared. The main room was reserved for interviewees; there was a back-office for immediate support, a preparation room for prospective interviewees, and a debriefing room for discussion after completion of each agenda item. Advanced audiovisual technology was installed, so when it was decided to connect remotely, testing began immediately. All attendees in all locations were asked to connect during a specified time window using virtual meeting room (VMR) technology. This allowed the main room to act as a central hub, controlling and monitoring participation with an on-screen view of all connections and their audiovisual capabilities. VMR was set up to permit a one-way video feed from the company side and permit observation by the inspectors. Sound-activated video cameras were directed at the individual who was responding to questions. All participants had access to presentations and documents via a web-based collaborative platform. Business instant messaging (IM) was available across all company participants and was in constant use.

At the outset, two scribes were on duty in the inspection room, both with permanent connections to IM. One recorded inspectors’ questions and comments, the other relayed the interviewees’ responses. A full record of the dialogue was transmitted to all participants, keeping everyone informed of progress in real time. In addition, the back office dialed into the VMR and viewed a large-screen display of the IM transcript. A parallel IM communication ran from the back office to ensure that the inspectors’ requests for evidence in the form of documentation were addressed promptly and efficiently. Document requests were received from individual inspectors via a designated email address, and responses were shared with the inspectors via the secure EudraLink system.

Rigor was required of all participants. Everyone connected to the hub was professional, courteous, and disciplined. Deliberate pauses were interpolated in order to allow each speaker to finish and to avoid simultaneous broadcasts. Despite initial unease (talking to cameras was unfamiliar to most interviewees), it soon became apparent that this calm, methodical approach allowed both inspectors and interviewees to operate at maximal efficiency. Questions were carefully documented, resulting in clearly articulated explanations, and all requests for information were provided in writing. End-of-day alignment between the lead inspector and back office ensured the completeness and accuracy of the request tracker. Inspectors aligned and coordinated requests for further information via telephone calls during breaks from interviews.

In conclusion, the inspection ran efficiently from the point of view of all participants. Ninety-nine document requests were recorded during the inspection. Ninety responses (91 percent) were provided before the close, and the balance was sent within four working days. Company participants included approximately 70 interviewees. Over 200 personnel in total supported the inspection.

Critical success factors were identified. Vocal and visual recognition was essential throughout: Each agenda item commenced with formal introductions, and speakers were asked to repeat their name when answering a question. Otherwise, the inspection proceeded for all intents and purposes as if all parties were in the same room.

The inspection would not have been possible without a robust IT infrastructure, which played a vital supporting role throughout. Cost savings from avoiding long-haul travel and hotel accommodations were substantial. The inspection closed at the end of day three (14 percent time saving). Many process efficiencies occurred: No time was wasted in traveling to the venue, document management was efficient, communication was transparent via sharing of screens and one-way video, verbal communications were generally clear and concise, and presentation of materials was disciplined and focused on the PV system.

It is our view that this operating model will work in multiple settings beyond the Supervisory Inspection, such as national inspections, audits, ISO-certification, and more. Last, and most importantly, both the inspectors and company associates were able to fulfill their obligations and safeguard personal health during the pandemic.

The author thanks Monika Borchert, Jaquie Mills, Marina Ribeiro de Sousa, and Manoj Kumar for their comments and suggestions for improvement of the text.