Clinical Evaluation Reports for EU-Marketed Medical Devices – A Summary of the Regulatory Guidance

Following the June 2016 release of the new MEDDEV 2.7/1, revision 4 guidance (Rev 4), manufacturers of CE-marked medical devices are scrambling to maintain compliance. Clinical evaluation is necessary for the initial CE-marking of new devices, as well as for devices that have been marketed for years. Manufacturers are required to provide sufficient evidence to show conformity of the medical device to the Essential Requirements, and its performance and safety when used clinically according to the instructions for use. Clinical Evaluation Reports (CERs) must be created during device development and updated periodically throughout the marketed lifetime of the device in the EU. This summary outlines the major aspects of this regulatory requirement. Rev 4 specifies the required steps to perform a robust clinical evaluation, which include; defining the scope of the evaluation, systematically identifying and analyzing the available clinical data, and reporting the results of the evaluation. The scope of the evaluation takes into consideration the disease state and progression, target user populations, current “state of the art” of the available treatment options, as well as the known benefits and risks of using the device, and any gaps in knowledge. Clinical evaluation is based on data from clinical investigations or a literature review, although a combination of both data sources is commonly used in practice. During development of new medical devices, a gap analysis defines what data is needed to demonstrate conformity, and any necessary clinical investigations should be incorporated into the overall development plan. For currently-marketed devices, any clinical data obtained during development as well as post-market surveillance data can be used. The safety and performance of a...

Quality Assurance: An Important Contributor to Value Creation

For most start-up pharma companies the drive to the next fundraising milestone and value inflection point consumes most of their planning. Sometimes, however, some of the details “behind the scenes” can be deprioritized, such as a designated person responsible for quality assurance, a preliminary quality system and quality procedures. From a regulatory perspective a quality assurance function ensures compliance with regulatory guidances and the integrity of the data generated by all parties involved so it is suitable for regulatory submission or for review by potential future partners. Quality Assurance clearly needs to ensure compliance with GLP, GMP and GCP requirements (collectively GXP). Studies conducted under these guidelines are inextricably linked, so all need to be addressed in a similar manner. However, compliance goes beyond just meeting regulatory requirements since it can also serve to prevent wasted time and money on delays or repeating GXP activities and also supports informed business decision-making. Some issues recently seen with clients include: R&D staff found a second supplier for a key active ingredient for use in a drug device but the supplier was not audited and qualified. The material received was later found to be sub-potent which delayed the start of a clinical trial. R&D staff faced a tight timeline to produce clinical material for a Phase 2 trial and agreed to batch record changes without QA review that jeopardized a link to a completed Phase 1 study. A company chose a well-known API supplier and did not conduct an audit or complete supplier qualifications. Since the API supplier has supplied many companies worldwide and has many regulatory approvals, qualification was not considered...

Entrepreneurial Pharma: Confronting the Adage, “Experience Is Something You Get Just After You Need It.”

During my 23 years working in the entrepreneurial pharma environment I have witnessed many lessons learned and I continue to see many companies focusing primarily on reaching key funding milestones while neglecting good drug development practices. This is a mindset that can cost them dearly and deliver experience after it’s needed! It is crucial for entrepreneurs to focus on creating a strong value proposition for the company, attracting the top investors and scientific advisors and moving quickly to key milestones and the additional funding they provide. It’s the nature of the environment. However, at the same time, pharma development requires early and consistent compliance with regulatory guidelines and quality assurance standards and exemplary collaboration skills to enable critical preclinical and clinical trials. The paradox is the need to move quickly AND carefully comply with regulatory requirements and solve technical challenges. This can create confusion when weighing the “must haves” and the “nice to haves”. Often, many important elements are considered “nice to have”. Many entrepreneurs have trouble discerning which is which. Usually, a lack of time or staff or cash is reason for projects moving ahead without the “must haves” like proper documentation or quality checks. In addition, the outsourcing environment is something that is both art and science, something not fully appreciated by all entrepreneurs. Staffing at outsourcing firms varies in expertise, especially in the areas of regulatory strategy and documentation. This requires experienced oversight by the sponsor company.   Here are some real-world examples of my observations of companies that failed to focus on the fundamentals and paid the price: When I was working as and independent...

Trends at the FDA in Medical Device Approvals

Dr. Carol Stephens delivered a speech at the LifeSciences BC McCarthy Spotlight Speaking Series event in Vancouver, BC on November 17, 2016. The speech was focused on the trends at the Food and Drug Administration regarding medical device approvals.   View and download the full presentation View and download the full presentation About the Author Dr. Carol Stephens has 28 years of experience in drug development and support with focus on regulatory planning, negotiation, execution, and compliance. In her spare time she likes to design new gardens, spoil her dog Moxie, and travel with her...

Trends at the FDA in Drug Approvals

Dr. Thomas Stephens delivered a speech at the LifeSciences BC McCarthy Spotlight Speaking Series event in Vancouver, BC on November 17, 2016. The speech was focused on the trends at the Food and Drug Administration regarding drug approvals.   View and download the full presentation View and download the full presentation   About the Author Thomas W. Stephens, Ph.D. has 28 years of pharmaceutical development preceded by 12 years of in vitro diagnostic experience with emphasis in research, regulatory, project management and administration. In his spare time Tom pursue various interests including astrophotography, underwater photography, swimming, gardening and...

How Do We Create the Most Value With Limited Resources?

Questions to Consider From the Beginning: Drug development is a time and resource expensive proposition and most if not all companies pursuing such a path must find ways to make the greatest progress as fast as possible within their resource limitations. This article intends to help the reader understand some of the necessary considerations to achieve this efficiency by providing answers to these questions: How do we utilize limited time, money and talent to achieve the most value the most efficiently? How do we focus these resources on the critical questions and risks or opportunities? How do we assure that expended resources are delivering the intended product? How do we prepare for our final or intermediate submissions as the work are being conducted minimizing the turnaround time? How do we organize, manage, store and maintain the integrity of our data? Keeping the End in Mind From the Beginning: What are the attributes of a therapeutic product that are needed to achieve a successful launch and commercialization? How do the current marketed products stand up? What are the products in the development pipeline and how will they differ in hurdles and potential? Keeping the end in mind from the beginning is a fundamental requirement to achieving the ultimate goal effectively. Of course at first there are goals that must be met on the way to keep the ball rolling and the funds coming. How do these intermediate goals impact the ultimate success or failure of the intended product? There are many approaches to creating a map for the final product profile. The FDA and industry have worked together to provide...