New technologies in healthcare including medical device development can improve the ability to diagnose and address the root causes of patient’s underlying conditions. The medical device industry produces a wide range of products — from cotton swabs to heart valve implants — which present a varying degree of risk to the patient. Considering the potential risk to patient safety, medical device regulation is complex and often requires guidance from regulatory bodies like the FDA for the US and EMA for the European Union.
Karthik’s proficiency in medical device development and his remarkable grip on the industry’s regulatory standards set an example in the field when he successfully worked on the design-change of a catheter in order to bring down the cost without having any impact on the performance and safety of the device. This feat addressed a major compliance aspect related to procedural delay and coherently translated into multi-million-dollar savings per annum, since the financial aspect of nailing down regulatory standards is just that apparent in the sector.
In this article, the much acclaimed and accomplished expert from the medical device industry, Karthik Bujuru provides an overview of the current state of regulations in the medical device industry. Drawing from his own experience of developing medical devices and working with regulatory bodies during the device approval process, Karthik walks us through the various regulatory standards in the US and the recent changes to the European regulations post-implementation of MDR.
Karthik explained how medical device manufacturers are subjected to a variety of regulatory controls to assure their safety and effectiveness. The regulatory standards cover various aspects including establishment registration, medical device listing, a regulatory pathway to market, investigation devices approval for clinical studies, Quality system regulation, labeling requirements, and medical device reporting. FDA requires that all medical device manufacturers, importers, and distributors are registered with the agency and annually verify their information. The various types of medical device handlers, not limited to OEMs including contract manufacturers, sterilizers, packagers, and labelers, testing agencies — all must list their devices with the FDA.
Karthik spoke at length about how the regulatory bodies also provide detailed guidance documents for the pathways to bring new medical devices to the market. He also broke down the premarket submission type depending on the product classification, which is done based on its risk profile and the potential threat it may pose to the patient’s safety and well-being. Describing the classifications, Karthik explained that class I devices, like an electric toothbrush and oxygen mask, do not come into direct contact with the patient’s internal organs, central nervous, or cardiovascular system and hence have the lowest risk profile and thus have the least number of regulations for their pathway to the commercial market. These devices have the least number of regulations and mostly are exempt from FDA requirements for premarket notification (501K) and premarket approval (PMA). However, these devices are not exempted from FDA’s general controls which include controls to prevent adulteration, misbranding, registration records, and good manufacturing practices.
Class II devices like contact lenses, surgical gloves, syringes, catheters, etc. may come into sustained contact with a patient’s internal organs. For these devices, the regulatory bodies have requirements beyond the general controls to assure patient safety and effectiveness of the device. Additional controls include the ones related to special labeling, performance standards, and patient registries. These devices also require proving their safety and effectiveness by showing equivalence to another device on the market known as a predicate device in terms of design, materials, safety, and performance characteristics. The premarket notification 501 (k) process allows the manufacturer to bring class II devices to the market by showing equivalence to the predicate device in the aspects discussed above. The likes of medical devices including breast implants, prosthetic heart implants, pacemakers, etc. are classified as Class III by the FDA as they require additional evidence beyond general and special controls to confirm their safety and effectiveness. The PMA process is the regulatory pathway for the class III devices to the market, and the manufacturers need to provide evidence of safety and effectiveness through the development of a data-driven benefit/risk profile using clinical trials. The regulatory bodies also conduct a thorough review of the OEMs and their lower-tier supplier’s quality management systems to confirm that the medical device was manufactured and tested in safe, consistent, and effective ways before being brought to the market.
As the regulatory pathways get more sophisticated with the increase in the risk factor attached to medical device classes, designing and implementing solutions that not only comply with but also complement device regulation, emerges as a much-needed skill from an ‘innovation’ point of view. For reference, Karthik Bujuru worked on the design and development of JenaValve’s next-generation catheter where, we not only witnessed significant enhancements in functionality, but also unlocked a much wider enrolment criteria for heart patients, with more complicated anatomies, that allowed for a greater volume of them to be effectively treated. This may be called a reverse-case phenomenon where device development widened and somewhat governed the scope of regulation, and not the other way around.
Karthik also created a clear differentiation between the FDA and EMA’s regulations in their risk management approaches to ensure device/drug safety, efficacy, and quality, both organizations continuously cooperate in scientific and regulatory fields to align their efforts. Because of his long-standing experience in the industry and constant involvement with the latest trends, Karthik finally talked about the recent implementation of mandatory EU MDR, which brought key changes to medical device regulations in the European Union. These changes include reclassification of a certain class of devices into a higher risk category, additional guidance on the clinical evaluation process including clinical investigations, post-market follow-up and maintenance of public records of clinical evidence, maintenance of post-market surveillance system allowing for continuous review of risk management and clinical evaluation procedures, procedures for continuous improvement of Quality management system, improvement of device traceability using unique device identifier (UDI), etc. Implementation of these new MDR changes establishes a more transparent, robust, sustainable regulatory framework for improving the overall quality of medical devices without stifling innovation in the industry.
There does exist an overlap in device development under the FDA and the EMA, and the question of being able to succeed in a project like that is one that Karthik keenly addressed. The development of Highlife Medical’s Mitral Valve delivery system reinforced the contention that experience plays a crucial role in being able to successfully navigate through the collective complexity of designing a novel solution while complying with regulatory standards. This system is used to deliver prosthetic valve to replace diseased mitral valve to treat heart disease condition called Mitral regurgitation. This disease condition is characterized by the backflow of oxygenated blood from left ventricle which results in heart working harder to pump blood. If left untreated this disease condition could lead to mortality. Bujuru illuminated that it was his experience that enabled him to support the design verification of the Mitral Valve delivery system as the Principal Engineer, that is currently used to treat patients as part of the organization’s ongoing clinical study. Similarly, his experience also allowed his work to be used used to support regulatory submissions for approval of the concerned system by both the European regulatory bodies and the FDA.
