Clinical Development of Medical Devices: Points to be considered
Development of Medical devices has its own challenges that have become more complicated due to complexity of devices themselves having have multiple different constituent parts, including hardware, software (Software as Medical Device, Digital Therapeutics, artificial intelligence) and medicinal components as well as complexity of regulatory frameworks across all major regulatory authorities like USFDA, EU MDR, MVPI etc. Devices may be therapeutic, diagnostic, monitoring, supportive, surgical, and more. According to USFDA, there are five stages of medical device development:
Step 1: Device Discovery and Concept
Step 2: Preclinical Research-Prototype
Step 3: Pathway to Approval
Step 4: FDA Device Review
Step 5: FDA Post-Market Device Safety Monitoring
Clinical experts should be involved from the conceptualization stage
Traditionally, technology experts dominate the device discovery phase. Once the device passes preclinical research stage, clinical experts are being involved. Contrary to the traditional approach, clinical expert, especially Key Opinion Leaders/User Advocates should be involved from concept stage itself to decide intended use, product viability (financially and clinically), possibility of drug-device combination products, advantages the technology offers to build in clinical trial endpoints and market position of the device.
They can also contribute in prototyping to decide whether product is working in preclinical stage, selection of animal models, evaluation of safety and biocompatibility and toxicology data review.
Do not forget to implement QBD (Quality by Design) principles from inception!
Clinical Trials for Medical Devices
Build on clinical trial program based on intended markets and regulatory requirements necessary for approval.
Prepare a comprehensive plan consisting of pilot/exploratory studies, pivotal efficacy and safety study and post marketing studies. Clinical plan varies from class of the medical device. Class I devices do not generally require premarket submission requirements and typically do not require clinical data to support their safety and effectiveness. Class III devices have to follow a more rigorous clinical development process.
Build in stop gates with competent data review committees in place.
Ensure your medical writing teams are well versed with clinical and safety endpoints and innovative in building them with optimum sample size. Usually, available literature is sparse for medical device clinical studies or some times comparator is surgical intervention (e.g. cardiac devices). In such scenarios, it is essential to do thorough literature search, construct systematic literature reviews and determine effect size for sample size calculation and hypothesis building (superiority/equivalence/non-inferiority etc.).
Prepare well documented safety management plans.
Select expert vendors to conduct the studies in suitable populations.
Do not forget to plan robust human factor/usability studies. These studies can be part of clinical studies or can be designed separately.
Ensure adherence to QMS standards and regulations throughout the device's lifespan, from design to use. Common frameworks include like ISO 13485, EN ISO 13485, and IEC 62304.
Have effective program management keeping in mind end result, i.e. regulatory dossier submission
Clinical Development does not end with regulatory approval
As long as a medical device remains in use, regulatory obligations never cease. Post-marketing surveillance can be considered a long extension of clinical research.
Ensure your PMS studies are in line with regulatory requirements. According to EU MDR, Monitoring the operation of CE-marked equipment is important for the systematic identification of all risks associated with the use of the product. Some of the safety issues are only identified during use, transport, storage, sterilization or cleaning of medical devices. Only during continuous and systematic PMS can manufacturers ensure that medical devices are effective and safe.
Ensure your spontaneous reporting systems are compliant to regulatory reporting timelines as well as other requirements FSN/FCNA and PSUR submissions.