When it comes to introducing new medical devices into the US market, obtaining approval from the U.S. Food and Drug Administration (FDA) is critical and a necessary step. This process ensures that medical devices meet strict safety and efficacy standards before they reach patients.
As we all know, for lower-risk Class I devices, the manufacturers need to adhere to General Controls, whereas Class II, with a higher risk, face the scrutiny of Special Controls.
When a medical device ascends to the Class III level, the highest-risk device, the FDA employs its most stringent regulatory control: the Premarket approval (PMA Submission) process.
What is PMA from the FDA?
A premarket approval process is the FDA’s evaluation process for high-risk Class III medical devices. The duration of the process varies based on the device’s complexity, ranging from several months to years.
Examples of Class III devices include implantable pacemakers, artificial heart valves, and certain diagnostic tests.
The typical timeline of the FDA is 180 days from the day of submitting the application.
PMA Basics
For a successful PMA, it is important that you present strong scientific data, clinical trial results, and detailed information about the device which is the subject of the submission. This helps the FDA check and ensure that the device is safe and effective for its intended use.
The FDA performs a rigorous review of the submitted data to ensure that only devices meeting the highest standards are granted approval for commercial distribution and use.
Let’s now understand the steps of a PMA application process.
Step 1 - Preparation and Planning
Understand the requirements, develop the plans for risk analysis, data collection, and prepare the necessary documentation.
Step 2 - Risk Analysis and Mitigation
Conduct a thorough risk analysis by identifying potential hazards and implementing risk controls for patient safety.
Step 3 - Non-Clinical Testing
Conduct comprehensive non-clinical testing to evaluate the device’s design, materials, performance, and potential risks.
Step 4 - PMA Submission
Compile and submit all data supporting the device’s safety and efficacy. This should be in accordance with the FDA requirements.
Step 5 - Clinical Trials
Conduct clinical trials on human subjects to generate data on the device’s safety and effectiveness.
Step 6 - FDA Review and Decision
The FDA reviews the submission, asks questions or clarifications, and makes an approval decision.
How does PMA review actually happen?
PMA review is a four-step review process that includes:
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Acceptance Review where the FDA evaluates the completeness and accuracy of your application.
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Substantive Review where a team of FDA experts thoroughly evaluates the scientific, clinical, and technical aspects of your device.
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Consultation with Advisory Panels (if necessary) where the FDA seek external expert input for complex devices.
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Decision and Post-Review Actions where the FDA provide decisions and this may result in approval, approval with conditions, or non-approval.
When your application meets all regulatory requirements and provides robust scientific evidence of safety and effectiveness, the FDA grants approval for commercial distribution and use within the US market.
In certain cases, the FDA may approve the application while imposing specific conditions or requirements to address any concerns. These conditions may include post-market surveillance studies, additional labelling information or ongoing safety monitoring to ensure continuous device safety.
If the application fails to meet the FDA’s safety and effectiveness standards, a “Not Approvable” letter is issued outlining the specific reasons for the decision, highlighting deficiencies in the application that need to be addressed.
What is required for your PMA submission? (A Complete Checklist)
To prepare a robust PMA application, you’ll need to compile comprehensive data and evidence to convince the FDA that your device is safe and effective for patient use. Let’s look into the elements that you should include in your PMA application:
1. Device Description and Design:
Provide a detailed description of your medical device, including its intended use, components, and how it operates. Explain its unique features and how it addresses a specific medical need.
Example: For a novel implantable cardiac device, include specifics on its materials, dimensions, and mechanisms that set it apart from existing devices, and highlight how it improves patient outcomes when compared to the current alternatives.
2. Non-Clinical Testing:
Include the results of your rigorous non-clinical testing conducted to assess the device’s safety and performance. These tests should cover bio-compatibility, electrical safety, mechanical testing, and any other relevant assessments.
Example: For a novel implantable cardiac device, if the device communicates wirelessly with external devices or networks, it is important to include details on wireless communication testing which ensures that the data transmission is secure without interference.
3. Clinical Data and Clinical Trials:
Submit detailed information about any clinical trials you conducted with the device. This data should include the trial design, patient demographics, endpoints, and results.
Example: Present data regarding advancements observed during the clinical trial of a cardiac device, such as extended battery lifespan, improved detection capabilities, heightened patient comfort, and more. Additionally, outline adverse events including infections, allergic reactions, and the development of scar tissue, if any.
4. Risk Analysis and Mitigation:
Conduct a thorough risk analysis of potential hazards associated with your device and outline effective mitigation strategies to minimize those risks.
Example: For an IVD device, the risk analysis should identify risks related to user errors (such as improper handling, inadequate sample volume), device performance (such as errors leading to false positives), IFU and labelling (such as insufficient marking, grammatical errors) etc.
5. Quality Management System (QMS):
Demonstrate that your manufacturing processes adhere to Good Manufacturing Practices (GMP) and have a robust QMS in place.
Example: Include details on the quality procedures in place to ensure that the design is verified, tested, and produced according to the design plan. Also, describe how your quality procedures control the manufacturing process by including details on the processes established for packaging, sterilizing, and testing the product to make sure it meets the defined standards.
6. Labeling and Instructions for Use:
Include clear and comprehensive labeling for your device, ensuring that healthcare professionals and patients understand how to use it safely and effectively.
Example: For a cardiac device, the labeling documents should include battery replacement instructions, warnings, precautions, information on interpreting the alerts, etc.
7. Post-Market Surveillance Plan:
Outline your post-market surveillance strategy, which includes monitoring the device’s performance and collecting real-world data after commercialization.
Example: Your plan should outline your strategy for gathering complaints and feedback from end users, distributors, and other stakeholders, and explain how this input will be utilized to enhance the product over time.ullamcorper mattis, pulvinar dapibus leo.
You can always seek the FDA’s feedback via a Pre-Submission before you file your PMA application. However, it is important to note that FDA SHOULD NOT be utilized to replace the role of a consultant, and good questions must be asked to be clarified in a pre-submission which paves the path for future submissions and set things right from the first step. A well-thought-of and thorough Pre-Submission goes a long way.
If you are planning to send your application, then you should know how to submit an eCopy. Read our article on eCopy Medical Device Submission process.
PreMarket Approval (PMA) Application Methods
Within the realm of PMA, there exist multiple application methods, each with its unique intricacies and benefits.
Traditional PMA: The Time-Tested Route
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Methodology & Applicability: Traditional PMAs involve a comprehensive review process and are suitable for complex devices for which all the required data can be submitted to the FDA in a single submission.
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Data Requirements: Your submission shall include comprehensive data and evidence such as device description, marketing history, non-clinical testing data and details on clinical trials conducted, its design, outcomes, etc to demonstrate the safety and effectiveness of the device.
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Timeline: 180 FDA days (This is considering there are no deficiencies in the review process. If there are any, depending on the type of deficiency, the review clock changes).
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Cost: $441,547 (Small Business it is $110,387) for FY 2023.
Modular PMA: Crafting Piece by Piece
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Methodology: The modular PMA application method allows you to submit the PMA application in stages or modules, addressing specific aspects of the device in each module.
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Applicability: This approach may be suitable for complex devices with extensive data requirement and allowing for more flexibility in development. The FDA reviews each module independently, to manage the extensive documentation and data needed for PMA approval.
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Data Requirements: Each module must include an executive summary, device description, and a Table of Contents (ToC). The remaining contents of each module should be specific to its focus. For instance, if Module 1 centers around non-clinical testing, it must encompass a declaration of conformance to relevant standards and comprehensive testing particulars such as the list of conducted tests, test prerequisites, and results.
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Timeline: The FDA aims to finish reviewing each module and send a response within 90 days after receiving the module. So, the total timeline depends on the number of modules one presents
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Cost: $441,547 (Small Business it is $110,387) for FY 2023
Product Development Protocol (PDP): Forging a Collaborative Path
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Methodology: PDP is a collaborative approach between medical device manufacturers and the FDA involving early constructive interaction to discuss the development of devices using established technology
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Applicability: This approach is particularly beneficial when the device's technology has been thoroughly tested and refined in similar applications, reducing uncertainties and potential risks during the regulatory evaluation. As a result, the PDP process can expedite the assessment of safety and effectiveness, leading to quicker market access for these well-established technology-driven medical devices
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Data Requirements: Your submission should encompass information such as a description of the device, proposed design modifications, data from clinical and non-clinical testing, and details regarding the manufacturing process
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Cost: $441,547 (Small Business it is $110,387) for FY 2023
Humanitarian Device Exemption (HDE): Nurturing Hope for Rare Conditions
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Methodology: Before submitting an HDE application, an applicant must secure HUD Designation from the Office of Orphan Products Development. Once a device receives HUD designation, the applicant proceeds to submit the HDE application
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Applicability: The HDE pathway is similar and is used for medical devices intended to treat or diagnose rare diseases or conditions affecting fewer than 8,000 people in the United States annually
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Data Requirements: The submission must include details such as reasons for the device's unavailability without an HDE grant, an explanation of the risk-benefit analysis, and comprehensive information on both clinical and non-clinical testing
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There are no user fees for HDE Application
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Timeline: 75 FDA days
Find Out if you Need a PMA
If you are struggling to determine if you need to submit a PMA or not, try answering the following questions to conclude your pathway for the US market.
If yes, then you should check the submission type using the product code of the device in the FDA’s Product Classification Database.
If no, see question #3 below.
While looking into the product classification database, does it say that the submission type is PMA?
If yes, PMA is your pathway.
If no, proceed as per the submission type identified in the database.
If yes, then you should classify your device as Class III and go for PMA.
Based on the FDA’s regulations, Class III devices usually sustain or support life, are implanted, or present potential unreasonable risk of illness or injury.
If No, you either fall under Class I or Class II and you should be exploring the DeNovo process.
Still, figuring out whether you need a PMA submission? We are a call away to help you figure out!
Conclusion
The PMA process is an essential and rigorous evaluation conducted by the FDA for high-risk Class III medical devices. It ensures that only devices meeting the highest safety and effectiveness standards are granted approval for commercial distribution and use. The PMA application requires scientific evidence and clinical trial results, carefully evaluated by FDA experts. Successful completion of a PMA application allows manufacturers to introduce their devices into the U.S. market, benefiting patients with innovative and life-saving technologies.
How Elexes can be your guide when it comes to PMA approval?
Embarking on the PMA journey is key for medical device creators eager to unveil groundbreaking products to the world. Grasping the FDA’s watchful eye, meeting PMA prerequisites, and picking the perfect application method are vital parts of this adventure. Fear not, for with Elexes by your side, you’ll skillfully sail through the PMA complexities, paving the way for your life-changing medical marvel to touch lives with utmost safety and effectiveness. All you need to do is email us.
Get ready to make a difference!
FAQs (Frequently Asked Questions)
PMA is for high-risk Class III devices, while 510(k) clearance is for moderate-risk Class II and some Class I devices that are substantially equivalent to a legally marketed device.
You shall address the deficiencies identified by the FDA in the “Not Approvable” letter and you may resubmit with additional data, alternatively, you can appeal the decision.
The duration of the PMA process can vary depending on the complexity of the device. It may range from several months to several years. It also depends on the PMA application that is being utilized for the submission.
A robust PMA application requires comprehensive scientific evidence, including but not limited to non-clinical testing data, clinical trial results, risk analysis, and quality control procedures such as information on the manufacturing process, risk-benefit analysis, marketing history etc. The FDA rigorously reviews this evidence to ensure the device’s safety and effectiveness.
Yes, manufacturers have alternative application methods, such as the Modular PMA and the Product Development Protocol (PDP). Each method offers unique benefits and flexibility for certain types of devices. However, for Class III devices without existing predicates, the traditional PMA route is commonly used.
Elexes Team
Elexes medical consulting is one of the leading regulatory & compliance consultant for several industries: Medical device, Pharmaceuticals, Cosmetics, Food, and Biologics.
