Convergence: Global planning is key to successful development of companion diagnostics

Regulatory NewsRegulatory News | 21 September 2020 |  By 

Planning and alignment are the keys to successfully steering companion diagnostics through regulatory processes across the globe, according to experts who spoke at RAPS Convergence 2020.
“The most critical way to develop a companion diagnostic is really a coordinated, co-development model, and this is the most effective path to regulatory approval,” said Ken Butz, associate director of regulatory technical advisors at PPD, and the leader of a session on the evolving global regulatory landscape related to companion diagnostics.
There are currently 41 companion diagnostics approved or cleared by the US Food and Drug Administration (FDA) across 21 indications, with 42 associated targeted therapies. The field has evolved rapidly since the first companion diagnostic was approved in the US in 1998, Butz said. At the start, the framework was a single diagnostic associated with a single drug in a single indication. But today a single diagnostic may apply to multiple variants and genes, be used with multiple drugs and have multiple disease indications.
The FDA defines in vitro companion diagnostics as being a device that provides information that is essential for the safe and effective use of a corresponding therapeutic product. It might identify patients most likely to benefit from the therapeutic product, identify patients at increased risk for adverse reactions from the product, be used to monitor response to treatment for dose/schedule adjustments, or identify patients in the population for whom the therapeutic product has been studied and found to be safe and effective.
The FDA regulates companion diagnostics as medical devices, usually in Class III. Most require a Premarket Approval (PMA), 510(k) clearance, or de novo classification, according to Butz. Additionally, the agency has issued several guidance documents from 2014 to the present related to co-development with therapeutics, use in clinical investigations, oversight of laboratory developed tests, and development of oncology products, among other topics.
Meanwhile, regulators in the European Union are embarking on “landmark change” as they prepare to implement the In Vitro Diagnostic Device Regulation (IVDR), set to take effect on 26 May 2022.  The regulation adopts a risk-based rules classification scheme with classes A, B, C, and D. There are also more requirements for clinical evidence and performance studies, more stringent postmarket surveillance requirements, and a more detailed description of essential requirements, Butz explained.
There will be a greater emphasis on clinical evidence, specifically scientific validity, analytical performance and clinical performance. Also, there will be a shift from self-certification to greater involvement with the notified body, according to Armin Ritzhaupt, PhD, scientific administrator at the European Medicines Agency (EMA).
Under an implementation roadmap released in 2017, EMA was specifically identified as the responsible party for companion diagnostics and will be involved with consultations. “The aim really was to provide guidance with respect to application dossiers, consultation procedures, and the level of interaction that might be necessary in order to proceed in the most meaningful way,” Ritzhaupt said.  
But there is still additional guidance to come on how the IVDR will be implemented. For instance, there is currently a task force looking at the role of in vitro diagnostics in clinical trials of a medicinal product.
Ritzhaupt encouraged developers to engage with EMA with questions and concerns. “The European network is ready to help you,” he said. “We want to build a system that is robust.”
With all these different regulatory frameworks in play, Butz said global planning is essential for co-development of diagnostics and their related therapeutic products.
He recommends having an integrated development plan that defines the activities, steps, and goals. The plan should also include a risk assessment, a full life cycle strategy, and be aligned with quality management system (QMS) design control planning.
Additionally, he suggested a performance evaluation plan that includes several elements: intended use, device characteristics, target patient population, safety and performance requirements, best practices and guidance, software information, development phases, and post-market follow up, among other elements.
“This helps that alignment of global development and validation strategies to support jurisdictional requirements for clinical performance,” Butz said.
RAPS Convergence 2020


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