Your Medtech Regulatory Strategy Is Your Market Strategy

In previous columns, we described concepts for Phase Zero of new product development. In this column, we dive deeper into regulatory issues. Gaining regulatory approval is a necessary milestone for most medical devices. Regulatory considerations affect the product roadmap and having a clear list of regulatory milestones is critical in planning development activities.

Key Considerations for FDA Approval

The degree of FDA oversight of a medical device depends on the risk presented by the device. This is correlated in large part with the potential clinical impact of the device, which in turn, depends on the intended clinical use of the device. Thus, one of the first regulatory decisions is to establish the “intended use” of the device (i.e., how the device will be used and by whom—a clinician or a patient). It is also important to specify for which patient populations the device can be used, including those for whom it may be contraindicated (e.g., pediatric patients), as well as the device use environment (e.g., a clinic, operating room, or in the home). These details comprise the formal “Indications for Use,” which determine the scope of FDA approval or clearance. Upon receiving the FDA’s OK, the company is restricted to marketing the device only for its indications for use or risk regulatory action. Thus, your regulatory strategy is your market strategy.

The FDA classifies device risk primarily into three classes—Class I (low), Class II (medium), or Class III (high). In rare cases, devices may be “unclassified” or have special classification status, such as a wellness device subject only to “enforcement discretion.” The approval process, also known as the “regulatory pathway” depends on the risk classification.

Most Class I devices are exempt from pre-market review requirements and, in some cases, are also exempt from specific quality management requirements. This is described as the 510(k) Exempt pathway. These devices are typically subject only to “general controls,” which include company registration and a listing of the product with the FDA.

Class II devices and some “reserved” Class I devices are subject to additional “special controls.” These typically consist of specific performance and safety tests, such as those demonstrating electrical safety or biocompatibility, required for a particular type of device. The two most common regulatory pathways for Class II devices are the easier 510(k) pathway (named after the regulation number) and the De Novo pathway. In the more typically used 510(k) pathway, the device needs to be shown to be “substantially equivalent” in terms of safety and effectiveness to a previously approved device (called a “predicate” device). In cases where no suitable predicate is available (such as for novel devices), the De Novo pathway must be used. This consists of demonstrating that the clinical benefits of the device outweigh its risks and typically requires some degree of clinical testing.

Class III devices are subject to general and special controls similar to Class II devices, but also require more rigorous clinical validation. The regulatory pathway used is known as the PMA (pre-market approval) pathway. 

The graphic illustrates how clinical uses with greater clinical impact are subject to a greater regulatory burden.

While 510(k) and De Novo pathways may typically be completed within a year or two of development effort, the PMA pathway can take five to seven years. Thus, very serious consideration needs to be given to the implications for the product development timelines and costs involved.

Engaging with the FDA

Gaining an FDA OK for a complex device typically requires compiling and submitting a significant amount of information about the product design, testing, and clinical use—an expensive and time-consuming endeavor. As such, it is important to de-risk the FDA review process to the extent possible. The FDA offers the opportunity to have pre-submission meetings with them. This is a formal process where the company sends the FDA a “Q-Sub” documentation package with preliminary information about the product along with specific questions. The FDA will review the Q-Sub and provide written feedback, typically within eight to 10 weeks. The company can accept the feedback as provided or request a video conference to get further clarification. Records are kept of all feedback and enable both the company and FDA to refer to them in the future. This is very helpful in maintaining a consistent understanding of the regulatory requirements as the product development proceeds. Good questions to ask the FDA using the pre-submission process include:

• Suitability of proposed indications for use and appropriateness of associated labeling, including marketing language 

• Appropriate regulatory pathway; if attempting a 510(k) pathway, the suitability of a proposed predicate device

• Adequacy of a proposed clinical testing plan, including the trial size, randomization scheme, number of sites, etc.

• Specific concerns about demonstrating product performance or safety

A special type of Q-Sub is a request for a “Breakthrough Device Designation” (BDD)—granted to a novel product with potentially high clinical impact. Gaining a BDD allows for expedited review by the FDA, which can shorten the approval timeline by years. Additionally, a BDD device is currently eligible for six months of transitional reimbursement under Medicare, which can be valuable when fundraising for novel product development.

A key requirement for all medical products is they must be designed, developed, and manufactured under a quality management system with records that are subject to audit at a later time.

Once the required information is compiled, a pre-market submission is made for FDA review. Upon successful completion of the review, the FDA will grant marketing authorization for the product. Any modifications made to the product following this must be carefully evaluated to ensure they do not require a new submission. Records of modifications and evaluations must be kept and are subject to audit. Key considerations in determining device modifications originate from feedback or complaints received about the product. Specifically, any information that implies an actual or potential safety concern requires timely follow-up, including potentially reporting adverse events to the FDA.

Considerations for Complex Medical Devices

For complex devices, there are additional special considerations for ensuring safety and effectiveness. Complex devices are often built on a technology platform that supports multiple allied products. For example, technology for cardiac function monitoring may be commercialized in a product line addressing atrial fibrillation, heart failure, and coronary artery disease. Separately, the products may be used at different points in the care workflow, such as for screening, diagnosing, or monitoring. From a regulatory perspective, each of these use cases represents a different indication for use and will need its own regulatory approval. Depending on the market opportunity in addressing each of these conditions, the business strategy and the regulatory roadmap will need to be aligned. One approach is to first introduce the product with the lowest regulatory bar (i.e., the minimal viable regulated product) and then introduce products with higher clinical claims. A different approach may be to develop the product with the easiest market entry first and sequence the required regulatory activities accordingly.

In addition, since variants are built on a common technology platform, they share functionality. As product development proceeds, the functional modules can vary widely in their maturity. For example, standard “utilities” such as user authentication and patient demographic information recording may be shared. These modules may already be well developed when a new product development project is initiated, while other more variant-specific modules may need to be developed from scratch. However, as each new module is added to the platform, there is an increased risk of adverse emergent conditions, where there are unsafe interactions or those producing errors. These are additional risk considerations for regulatory authorities and updates required for products already on the market.

A good regulatory strategy is also useful in optimizing a product roadmap and establishing realistic and efficient product development timelines. It is critical to identify key regulatory milestones early in the product lifecycle and develop a regulatory strategy that is consistent with the business goals of the product line.

Dr. Geetha Rao is CEO of Springborne Life Sciences, a company providing compliance as a service to medical device and digital health companies. She specializes in compliance strategy and rapid commercialization of complex medical technology platforms.

Russ Singleton, principal consultant with Russ Singleton Consulting LLC, is based in California. He has extensive experience in VP R&D, general management, and C-suite roles in the semiconductor equipment and medtech sectors. He holds a Ph.D. and M.S. in electrical engineering from the University of Illinois and a Bachelor of Engineering from the Pratt Institute.