XVI. EXPERTENGESPRÄCH PROCEEDINGS – INTERDISCIPLINARY KNOWLEDGE SHARING FOR SUCCESSFUL MEDICINES DEVELOPMENT

30th April 2021

On 30 April 2021, the traditional annual drug development expert meeting was invited to by SanaClis. It was held as online conference for the second time and moderated as before by Dr. med. Johanna Schenk, FFPM GFMD, Executive Consultant and Company Officer, SanaClis DE GmbH.

The aim of that workshop attended by 60+ participants of multidisciplinary background and substantial experience and expertise in the drug development arena is to share and interactively discuss the latest thinking about current demands and opportunities to develop new medicines and vaccines most efficiently.

SanaClis announces the rescheduling of the XV Interdisciplinary Drug Development Expert Workshop

PD Dr. Michael Hennig, Head of Biostatistics & Epidemiology, GlaxoSmithKline, Munich, made the start with his talk about “Modern Study Designs - Statistical Considerations and Pitfalls to Avoid”.

He expanded on modern adaptive study designs and described basket, umbrella, and platform studies and their respective challenges. Which study design should be used for which study – exploratory or confirmatory?

Dr. Hennig stressed that particular issues might occur in long-duration (platform) studies, when the standard of care (SoC) changes. A second control arm would have to be introduced if the first control arm no longer corresponds to the SoC.

Most importantly, all the rules for adaptation have to be defined in the master protocol in advance and an early dialogue with regulatory authorities and with statisticians is strongly recommended.

The complete presentation is available here...


Dr. Gesine Bejeuhr, Pediatric Regulatory Leader, Bayer AG, Research & Development, Pharmaceuticals, Berlin, addressed a topic that is not only of relevance to every pharmaceutical development scientist but to the society at large: “Pathways to Better National Availability of Pediatric Medicines through EU Legislation”.

Dr. Bejeuhr analyzed the status quo in the development of pediatric medicines and how the pharmaceutical system in Europe is being further developed. Will the foreseen change in the regulatory framework create incentives for the pharmaceutical industry to develop new medicines for children?

The current Pediatric Regulation fostered the availability of more than 400 new therapeutic options for children since 2007, including 159 from 2017. It has to a great extent fulfilled its purpose. Yet, there is still a high need for treatments of e.g., rare pediatric diseases.

The EU Commission’s proposal to revise the Pediatric Regulation strives to improve the national availability of pediatric medicines by facilitating regulatory cooperation with HTA bodies, improving the therapeutic landscape, and addressing unmet needs (e.g., pediatric cancer) through tailored incentives. By 2022, new regulations should be finalized which also better integrate EMA's Priority Medicines (PRIME) scheme into the regulatory framework to accelerate product development and approval in areas of unmet pediatric need.

Dr. Bejeuhr finally looked into the UK where the MHRA introduced a scheme for innovations (including pediatric medicines) to facilitate a faster approval and earlier time to market as compared to the EU.

The full presentation is available here...


 

Dr. med. Jürgen Hans Schmidt, Stufenplanbeauftragter Medizin (Commissioner for the graduated plan, Medicines) and Dr. med. Christian Dalldorf, Stufenplanbeauftragter Vaccines, both Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, expanded on “Pharmacovigilance in COVID Times: New Prescribing Behavior and Adverse Events for Known Substances and PV Vaccine News”.

Pharmacovigilance (PV) is facing new challenges since the development of the COVID-19 vaccines due to

1. a very high exposure of very many subjects/patients in a very short time, processing of a huge amount of daily new data (e.g., approx. 10,000 PV cases/day for COVID-19 vaccines) which are generated in a multitude of digital reporting systems also for patients, e.g., the Paul-Ehrlich-Institute (PEI) app,

2. through new and innovative regulatory procedures, e.g., rolling reviews,

3. high political and public pressure to evaluate the vaccines in a very short time to ensure their safety and grant approvals.

Digital casework using artificial intelligence methods supports achievement of such demanding goals but needs to be set up and implemented first.

The major public concern is whether the speed of vaccine development has been at the expense of safety. Few individual cases (e.g., thrombosis/bleeding events) led to major international discussion and need for rapid action “within hours”. General procedure in case of serious vaccine risks: temporary vaccination halt - analysis of data and if necessary, clarification of pathomechanisms followed by indication restriction/warning.

The PV system has responded very quickly to the demands and has been able to generate valid hypotheses/reasons for these adverse reactions in collaboration with the scientific community in a phenomenally short time.

The entire presentation is available here...

 

Dr. med. Peter Wieloch, CEO​, Ingenium Labs GmbH, Frankfurt am Main, addressed highly topical questions relating to COVID-19 diagnostics in his presentation titled: “Corona Paves the Way for Self-testing - Paradigm Shift also for Clinical Development?”

If we will not overcome COVID-19 soon, hygiene, testing and vaccination will remain with us for years. The question is whether rapid tests by self-testing will be a viable solution.

The BfArM (German regulatory authorities for medicines and medical devices) grants special approvals according to §11 Abs.1 MPG (medical device law) for self-testing by laypersons. The MPAV (medical device dispensing regulation) was supplemented by lay tests for the direct detection of SARS-CoV-2.

Reasonable doubts remain, however, about the reliability of the antigen rapid tests.

Back to the roots, i.e., PCR, but with expanded logistics, seems to be the solution if the pandemic persists.

Test centers, laboratories and pharmacies could perform PCR testing which might serve as role model for other clinical development projects.

The full presentation is available here...

 

For the final presentation, the XVI. Expertengespräch welcomed back Prof. Burkhard Sträter, Sträter Lawyers, Bonn, as an expert in pharma law. His presentation expanded on “COVID-19 Vaccines - Medical and Legal Framework for the Evaluation of Safety”.

The regulatory status of currently available COVID-19 vaccines is a Conditional Marketing Authorization according to Art. 14a VO (EU) 726/2004, conditions ensure data completion post-submission or after marketing authorization. This is to be distinguished from authorization "under exceptional circumstances" with a regulatory evaluation based on extrapolation.

Professor Sträter expanded on the temporary vaccination halt of Vaxzevria and its legal grounds. The federal health ministry (BMG) as owner procures vaccine storage according to MedBVSV in pharmacies of the German Armed Forces. As such the BMG brings Vaxzevria into the market.

Distribution of precarious medicines is forbidden according to § 5 AMG, even punishable according to § 96 para 1 AMG.

Since the medical evaluation of benefit and risk (cerebral venous thrombosis) is not finalized, the decision on measures is of legal nature.

The Aachen Regional Court (Contergan discontinuation decision) said that there is a duty to act if the knowledge is unclear, i.e., if there are strong indications of causality, the latter must be assumed, otherwise the behavior is negligent.

The risks must be weighed up against benefits. In case of thalidomide as sleeping pill among others for pregnant women such weighing very clearly mandated an immediate recall. The COVID-19 vaccines discussed with the example of Vaxzevria have, however, an enormous benefit that clearly outweighs the worldwide threat to mankind by the pandemic, which is averted by vaccines.

The Vaxzevria vaccination halt was perfectly in line with the medicines law but the relaunch demanded an adequate warning labelling.

The full presentation is available here..., the “Streiflichter” on the same topic published by Professor Sträter in Pharm. Ind. 83, Nr. 4, 431–434 (2021) here...

 

As one of the most important features of the annual Expertengespräch, the five presentations were followed by a highly interactive discussion between the participants and speakers. The questions were addressed by the audience in person - and not by reading questions posted in the chat function - letting the participants feel as if they attended an on-site meeting. Nonetheless, the XVII. Expertengespräch intends going back to the FIZ Frankfurter Biotechnology Innovation Center on 29 April 2022 should the pandemic allow so doing.