September’s Regulatory Focus: Countdown to EU MDR and IVDR

Feature articles during September focused on aspects of the EU Medical Device Regulation (MDR) and In Vitro Diagnostic Regulation (IVDR), with articles on compliance and manufacturer obligations, and perspectives examining the current status of the regulations. The issue also included the second part of the cell and gene therapy series, and an article on regulatory tools for generic drug companies.
 
MDR and IVDR, close up
Full implementation of MDR is slated for next year and IVDR for 2022, but concerns remain about manufacturers’ ability to meet the deadlines. In Implementing the MDR: Slowing down on the homestretch?, Gert Bos, an expert in European regulations, writes that many manufacturers are far from ready to comply with the requirements, despite available guidance and clarity on the expectations. There are concerns about the limited number of notified bodies and also about the no-grandfathering rule, which does not permit remote initial MDR audits, even in the midst of the COVID-19 pandemic. Without a verified quality management system (QMS) in place, it is not possible to continue certification of medical devices under the MDR, Bos warns, and he urges the EU to address these shortcomings.
 
In IVDR, notified bodies, and technical documentation: The devil is in the detail, Sue Spencer, a medical device, IVD, and notified body expert, discusses notified bodies’ expectations for the technical file and provides some practical tips on preparing submissions. Spencer says manufacturers that have already engaged with a notified body have found the process easier than expected but warns the submission process requires meticulous, time-consuming attention to detail and applicants should set aside enough time and resources for meeting the deadline.

Distributors are also preparing for the new requirements under the regulations. In MDR, IVDR, and compliance: A guide for distributors, regulatory and compliance experts Justyna Kupis-Rozmyslowicz,
Angelina Hakim, and Andrew Gibson outline the importance of distributors having an effective QMS  in place, drafting contractual agreements, and working with notified bodies. They emphasize distributors should act early to meet the requirements and ensure device supply chains are not disrupted during the process. They also should aim to have sufficient in-house resources and consult with subject matter experts, as needed, for training staff, setting up MDR- and IVDR-compliant processes, and conducting readiness audits.
 
In Manufacturer obligations applying to importers, distributors, or others under MDR and IVDR, Erik Vollebregt, an expert regulatory and legal matters relating to medical devices, diagnostics, and medicines, discusses issues and requirements spelled out in Article 16 of Chapter 2 of both the MDR and IVDR. Vollebregt says the article has far-reaching consequences for the market in that it introduces new requirements, among them, agreement requirements for branded distribution and QMS requirements for translation of documentation and repackaging. He urges all parties in the supply chain, manufacturers, notified bodies, and end users, to conduct a gap assessment to ascertain what changes they need to make to their procedures.
 
Cell and gene therapies, part 2
Part 2 of the cell and gene therapy series includes articles on the regulatory structures for these therapies in the US and China and the upstream manufacturing process for a biologic drug substance. In Gene therapies – The regulatory road to individualized medicine, regulatory policy expert Lauren Oliva,  discusses the US regulatory landscape for gene therapies and the profession’s responsibility to establish an infrastructure that will facilitate approvals of the therapies. To achieve that, Oliva says regulators and developers need to engage early on to offset any risks during development. She suggests regulatory convergence – coregulation, self-regulation, international coordination – will play an essential role in sustainable gene therapy regulation.
 
Chinese regulators have provided guidance on clinical research for cell and gene therapy (CGT) since 1993. In Regulation of cell and gene therapy products in China, regulatory affairs expert Yingying Liu, writes that recent changes to the structure and responsibilities of the country’s regulatory bodies have resulted in closer alignment with scientific and international regulatory developments relating to CGTs. Liu provides an overview of China’s CGT regulations and guidance documents, as well as its regulatory approval process for the therapies.
 
Regulatory requirements for manufacturing process and control for a biologic drug substance are detailed and extensive to ensure consistent product quality. In An overview of upstream manufacturing process and process controls for biologic drug substance: A cytokine case, marketing authorization and life-cycle maintenance specialists Vivek Mamidwar and Yuessef Elsheikh provide an overview for writing up the biological drug substance manufacturing process and process controls. They cover several complex steps in the manufacturing process expected to be included in the Food and Drug Administration’s Common Technical Document (CTD) for the Registration of Pharmaceuticals for Human Use. The authors warn the guidances are regularly revised and updated and that manufacturers should be sure they are familiar with the latest updates when working on the CTD.  
 
Facilitating generic drug approval
Generic drug companies must comply with numerous regulations and submit enough data to receive product approval from the FDA. In Regulatory tools for generic drug companies: Formal FDA meetings and controlled correspondence, Sonal Jagani, an expert in complex product submissions, discusses formal meetings and controlled correspondence for the generic drug industry and the use of these regulatory tools in the abbreviated new drug application process. She notes the tools are useful in avoiding unexpected delays for product approval and therefore expediting faster generic drug approvals.
 
What’s coming in October?
Articles during October will focus on the regulatory toolbox – the tools regulatory professionals need and where to find them. Articles will focus on websites, guidances, meeting minutes, and Food and Drug Administration correspondence. Look for these topics and more throughout October at www.raps.org.
 
December Call for Articles
For December, Regulatory Focus will look at Advertising, promotion, and labeling, and the role of social media. The submission deadline for articles is 2 November 2020. To contribute to the December issue or suggest a topic, contact Renée Matthews at rmatthews@raps.org.
 
Citation Matthews R. September’s Regulatory Focus: Countdown to EU MDR and IVDR. Regulatory Focus. September 2020. Regulatory Affairs Professionals Society.