The Present and Future of Remote Audits
One of the tasks required under GMP regulations, but also as part of business continuity for marketing authorisation holders, manufacturers and contract givers in the context of purchasing or outsourcing, is to qualify suppliers and contractors. An important part of such a qualification process is the performance of on-site audits. However, due to the Covid 19 pandemic, an on-site audit may pose a potential risk to all parties involved or may not even be possible due to travel bans. This does not only affect auditors from companies, but also inspectors from almost all global regulatory authorities. This in turn has an impact on the qualification programmes of companies, but also on ongoing and new authorisation applications. What is important here is not only how to deal with the current situation, but also to look ahead; namely, to what extent distant assessments may become part of qualification activities in the future. This important topic was therefore highlighted at the 16th QP Forum of the European Qualified Person Association (EQPA) in two contributions by three speakers. As in 2020, this forum again took place completely live online and attracted more than 300 participants over a total of three days in December 2021.
First of all: Distant assessments will not be able to replace on-site audits. But they can be a valuable addition to both the inspection programmes of the authorities and the supplier qualification programmes of the industry.
Difficult naming
Remote audit, distant assessment - which one is it? As there is no real uniform legal regulation so far, there are a number of different terms worldwide for the activities currently taking place. In addition to those mentioned above, there are also, for example, virtual inspection, remote evaluation, remote assessment, remote inspection, desktop inspection and desktop audit used by various authorities. In Europe, two are mainly used: Remote Inspection e.g. as "real-time remote GMP Inspection"(EDQM) and Distant Assessment (e.g. by the EU Commission and the EMA in their Questions and Answers on regulatory expectations for medicinal products for human use during the Covid-19 pandemic1). In the following article, we will therefore use these terms as a guide, despite the title of this article.
Real-Time Remote Inspections of the EDQM
In a first presentation titled "Conducting Remote GMP Inspections of API Manufacturers in Real Time", Dr Thomas Hecker, GMP Inspector at the EDQM, Council of Europe presented the EDQM programme. The EDQM, which monitors both compliance with Good Manufacturing Practice (GMP) and the application for Certificates of Suitability for the monographs of the European Pharmacopoeia (CEP) at API manufacturers, also had to modify its inspection programme. For this purpose, the concept of "Real-Time Remote Inspections" (RTEMIS) was conceived and implemented. The aim was to find a way of obtaining better information and results than remote assessment procedures, which are carried out solely on the basis of documents. The aim was to use live real-time video connections between the inspectors and the inspected facilities. In doing so, the following technical challenges had to be taken into account, among others:
• Data security
• Suitable platforms for sharing documents
• Secure web conferencing applications
• Bandwidth via Wi-Fi or mobile networks (data transfer rate of more than 100 kilobytes/second)
• Different time zones
In September 2020, things got underway and the EDQM contacted production sites that had already been inspected by the EDQM and had good GMP compliance for a voluntary pilot phase. It quickly became apparent that this type of remote inspection requires more thorough preparation than an on-site inspection. Preparatory conference calls and connectivity tests are also important here.
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The secure exchange of confidential documents in real time required some consideration. For this, the EDQM uses its own document sharing tool. Another important technical issue was what types of devices could be used to capture live images from potentially dangerous manufacturing areas. However, secured mobile phones are already available for this purpose and have been used for some time in other potentially explosive areas such as refineries.
The EDQM is satisfied with the results of the study. Even though the inspectors were not on site, a number of minor and major deficiencies were identified.
Where do we go from here?
Based on the principles of quality risk management, remote inspections should become part of the EDQM inspection programme. These will be used in cases of travel restrictions or when the safety of the inspectors cannot be guaranteed. Real-time GMP remote inspections should also be possible at companies with an appropriate GMP compliance history. Remote inspections will not be used, for example, to evaluate aseptic manufacturing processes or for companies that have not yet been inspected by the EDQM or have demonstrated poor GMP compliance in previous inspections.
Real-time remote inspections thus provide the EDQM with another way to assess a site's GMP compliance. At the same time, however, it is emphasised that these remote inspections cannot replace onsite inspections in terms of value and effectiveness.
The industry perspective
In a second contribution, both the industry's view and the GMP regulatory authorities' view were presented.
Tor Gråberg, Head of External Advocacy, Global Quality, Operations at AstraZeneca and member of the EQPA Board of Directors, welcomed the new opportunities that remote assessments present for industry. "Virtual inspections have the potential to save time and resources, while offering additional flexibility," said Tor Gråberg in his first slide. However, the industry is well aware of the disadvantages and challenges. For example, while remote audits and inspections can be another tool in the qualification toolbox, there are limitations, as on-site audits simply allow for better interaction between auditor and auditee.
However, experience within the industry and with legislation is constantly being expanded and developed to further optimise processes. Also, more advanced IT technologies will better support and facilitate distant assessments in the future.
The GMP authority's view
Dr. Rainer Gnibl, GMP inspector for the Bavarian government and the EMA and member of the Authority Advisory Board of the EQPA has an even more critical view. He observes that parts of the industry are striving for an equivalency of distant assessments to on-site inspections or audits. In addition to the direct intervention possibilities, sensory conditions such as feeling, smelling and the so important gut feeling are missing during a distant assessment. Just like Dr. Thomas Hecker before him, he presented possible processes within a distant assessment with the associated restrictions. He also had some very interesting examples of observations that could not have been made in a distant assessment. It is difficult to reliably assess the actual GMP compliance of a site on the basis of such remote assessments.
There was complete agreement on the duration. Not only in terms of preparation, but also in terms of implementation, distant assessments sometimes take considerably longer than classic inspections or audits - at least if one tries to do them properly and wants to delve comparably deeply into what is going on. This also puts a damper on the industry's hopes of saving resources.
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Conclusion
Because of its importance, the conclusion was already in the introductory text: Distant assessments will not be able to replace onsite audits. The authorities will not accept this. But they will be a complement, both in the inspection programmes of the authorities and in the supplier qualification programmes of the industry. This can also be done in hybrid forms, where one part is inspected at one's own desk, but other parts are then inspected directly on site.
Note: The Qualified Person Forum 2022 will take place from 01-02 December in Berlin and live online. This year, the EQPA will again address interesting and current topics at its Forum2, such as changed requirements for supply chain control due to the new Annex 21, Brexit but also due to further developed technologies and their meta data.
About the Author:
Wolfgang Schmitt
... is Vice President at CONCEPT HEIDELBERG and organises and conducts courses and conferences on behalf of the ECA Academy
in the areas QA and GMP. He is also Administration Manager of the European QP Association.
1 https://ec.europa.eu/health/sites/default/files/human-use/docs/guidance_regulatory_covid19_en.pdf
2 https://www.qp-forum.org/
