Navigating Medical Device Manufacturing – 510(k), PMA, De Novo, Oh My!
Welcome back! Today, we’re navigating briefly the medical device manufacturing environment and its commercialization process. Manufacturing a medical device is a journey marked by innovation, regulation, and meticulous attention to quality. The Food and Drug Administration (FDA) governs this area through its requirements known as the Quality System Regulation (QSR), 21 CFR Part 820. What’s in this part? This regulation defines the requirements for the methods, facilities, and controls used in the design, manufacture, packaging, labeling, storage, installation, and servicing of all finished medical devices intended for human use [1] .
The QSR (aka 21 CFR Part 820) sets the framework for quality management in medical device manufacturing in the United States. It emphasizes a risk-based approach, requiring manufacturers to implement procedures that ensure their products meet safety and effectiveness standards. The QSR applies to all entities involved in design, manufacturing, packaging, labeling, storage, installation, and servicing of medical devices.
Key Elements of 21 CFR Part 820 are:
Management Responsibly
Design Controls
Document Controls
Purchasing Controls
Production and Process Controls
CAPA
Labeling and Packaging Controls
Handling, Storage, Distribution, and Installation
Records
Demonstrating compliance is essential not only for FDA submissions, but also for passing inspections and avoiding product recalls, warning letters, and other enforcement actions.
Onward to 510(k), PMA, and De Novo Paths!
Medical devices are classified into three categories based on risk – Class I (low risk), Class II (moderate risk), and Class III (high risk). Most Class I devices are exempt from premarket submissions but must still comply with general controls and the QSR. Class II and Class III devices typically require premarket submissions through one of three paths: 510(k), Premarket Approval (PMA), or De Novo.
The 510(k) Premarket Notification [2]
A 510(k) is a premarket submission to the FDA demonstrating that a device to be marketed is “substantially equivalent” to a legally marketed predicate device. It’s required for most Class II devices, and some Class I and III devices that are not-exempt from premarket notification.
Steps in Preparing a 510(k):
Manufacturers must identify a suitable predicate device with the same intended use and technological characteristics.
Compile device description, indications for use, labeling, and substantial equivalence comparison.
Prepare performance and safety data, including bench, animal, and, if applicable, clinical testing.
Address biocompatibility, sterilization, software validation, electromagnetic compatibility, and other relevant standards.
Include 21 CFR Part 820 QSR compliance statement.
Once these steps are completed, the manufacturer files the 510(k) electronically via the FDA’s eSTAR (electronic Submission Template and Resource) or CDRH (Center for Devices and Radiological Health) Portal. FDA may request additional information and prompt response should occur. The typical review time is around ninety (90) days but additional information requests can prolong this.
Premarket Approval (PMA) [3]
The most stringent type of device marketing application is the PMA, this is typically reserved for Class III devices that support or sustain human life or are of substantial importance in preventing impairment of health.
Components of a PMA Application:
Comprehensive device description and intended use statement.
Nonclinical laboratory studies (bench and animal testing) and clinical investigations demonstrating safety and effectiveness.
Manufacturing methods and quality controls, including facility inspections for compliance with the QSR.
Detailed labeling and instructions for use.
Bibliography and summary of all available information relevant to the device.
PMA Submission Process:
Pre-submission meetings with the FDA are highly recommend to clarify requirements and expectations.
Submit all required data and analysis using FDA’s electronic submission gateway.
FDA’s review includes scientific, regulatory, and manufacturing inspections and typically takes one hundred eighty (180) days or longer.
Panel review by the FDA advisory committee may be required for novel or complex devices.
De Novo Classification [4]
The De Novo process is intended for novel low-to-moderate risk devices without a legally marketed predicate. This is used when no predicate exists and the device presents reasonable assurance of safety and effectiveness.
De Novo Application Steps:
Manufacturers should prepare a comprehensive device description, intended use, and classification rationale.
They should provide nonclinical and clinical evidence, labeling, and proposed special controls.
The application is submitted via the CDRH portal and if there are any additional information requests by the FDA, the manufacturer should promptly respond.
If granted, the device is classified as Class I or II and establishes a predicate for future 510(k) submissions.
All of these can achieve FDA clearance or approval with strategic approaches to compliance, data collection, and communication with some of the approaches below:
Early and Proactive Planning
Manufacturers should start with a thorough regulatory assessment and understand the device classification and applicable submission type.
They should design the product development process to comply and align with the QSR design controls from the beginning.
Engage with the FDA
Manufacturers should obtain FDA’s feedback on their testing strategy, submission content, and regulatory expectations. Addressing FDA questions openly and promptly and clarifying ambiguities early will help avoid delays.
Robust Documentation
Maintain detailed and well-organized design history files (DHFs), device master records (DMRs), and device history records (DHRs).
Ensure that all performance, safety, and validation data are complete, accurate, and traceable to the requirements.
Leverage Standards and Guidance Documents
Reference FDA guidance documents and where applicable to international standards (e.g., ISO 13485) to ensure the submission addresses current expectations.
Anticipate and Mitigate Risks
Manufacturers should also conduct thorough risk assessments (using tools like Failure Modes and Effects Analysis – FMEA) and implement corrective and preventive action (CAPA) processes to proactively identify and resolve potential issues.
Manufacturers should also stay current on FDA regulations as they evolve.
After approval is granted, the lifecycle and continuous post-market surveillance begins to monitor its long-term performance, safety, and potential issues in real-world use. Monitoring also includes reporting adverse events and for some devices, the FDA may require post-approval studies to gather more information on long-term safety, effectiveness, and optimal use. Medical device manufacturing is a complex and highly regulated endeavor, but by following a structure approach, adopting proactive strategies, establishments can deliver safe and effective medical devices that improve and save patients’ lives!
Do you need help with your QSR or have any questions about medical device manufacturing?
Contact us here [5] !
If you haven’t seen our previous medical device blogs for the International Organization for Standardization (ISO) portion – ISO 13485:2016, check them out here [6] !
See you next time!
References
[1] https://www.ecfr.gov/current/title-21/chapter-I/subchapter-H/part-820
[5] https://www.solaris-srb.com/contact-compliance-support
[6] https://www.solaris-srb.com/blogs-fda-regulations-consulting-resources