If you are in the medical device industry in the U.S is likely that you heard of the 510(k) process. Those working on high-risk devices may be familiar with the PMA and De Novo pathways. These are the three options that are most commonly used by device companies.
However, there are seven major pathways that can be used to bring a medical device to market
So many people assume the 510(k) route is right for them because it is what everyone else does. Not always the case, and one of the other pathways might actually be better for your company.
Don’t look at the regulatory process as a series of hoops to jump through. Instead, focus on creating a regulatory strategy for your specific device that sets you apart from your competition.
The 7 major pathways to market in the U.S. include:
The product should be specifically designed to treat a unique pathology or physiological condition that no other device is domestically available to treat. It must be assembled from components or manufactured and finished on a case-by-case basis to accommodate the unique needs of the patient.
The device must be created or modified in order to comply with the order of an individual physician or dentist, typically in the form of a prescription. Not only must the clinician order the device, but it must also be used in the normal course of the professional practice of that physician or dentist.
The FDA even states that companies are limited to no more than 5 units per year of a particular device type.
CDE devices are exempt from PMA or 510(k) submission process but the company still needs to comply with the following regulations:
Design Controls (21 CFR Part 820).
Medical Device Reporting (21 CFR Part 803).
Labeling (21 CFR Part 801).
Corrections and Removals (21 CFR Part 806).
Registration and Listing (21 CFR Part 807).
Expanded Access Program (EAP)
The Expanded Access program, often referred to as the compassionate use or emergency use provision. It allows an investigational device to be used, outside of a clinical trial, in situations where a seriously ill patient has few if any alternatives.
Although there are often ethical considerations, it may be appropriate to evaluate this option as a way to get early feasibility data for high-risk devices, especially when suitable animal models are unavailable. Like the HDE, this data could then be used to expand the label in the future.
Expanded access may be an appropriate pathway for you to choose when all the following apply:
Providing the investigational medical product will not interfere with investigational trials that could support a medical product’s development or marketing approval for the treatment indication.
The patient has a serious disease or condition, or whose life is immediately threatened by their disease or condition.
There is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition.
Patient enrollment in a clinical trial is not possible.
Potential patient benefit justifies the potential risks of treatment.
Product Development Protocol
The Product Development Protocol (PDP) is a subset of the PMA process that allows for another pathway for companies with devices in which the technology is well established in the industry.
This pathway allows the company to come to an early agreement with the FDA about how the safety and effectiveness of the device will be shown. The two parties are essentially creating a contract that describes design and development activities, including the outputs of these activities, and acceptance criteria for these outputs.
The company can follow the plan on their own time and report back to the FDA on the agreed-upon milestones. At the end of the process, the company is considered to have “completed” a PDP, which gives them an “approved” PMA.
Premarket Notification 510(K)
The Premarket Notification 510(k) pathway is the most common route taken when launching a medical device. Almost all Class II devices and certain Class I devices will require a 510(k).
The purpose of a 510(k) submission is to provide the FDA with documented evidence showing that your medical device is substantially equivalent in terms of safety and effectiveness to a predicate device.
A predicate device is one that is already legally marketed and shares the same intended use and technological characteristics as your device. You are required to compare and contrast your device with the predicate by summarizing information from your design controls process, such as design features and verification testing.
The FDA typically processes 510(k) applications in 30–90 days. Depending on the robustness of your initial application, there may be a period of back and forth discussions, which can delay the process. It is important to plan ahead and provide all appropriate documentation at the time of initial submission.
Premarket Approval (PMA)
Class III devices, and any device that cannot provide substantial equivalence to a Class I or Class II device through the 510(k) process, must use the Premarket Approval (PMA) pathway.
The PMA process is the most involved as scientific evidence, typically in the form of a clinical trial, is needed to prove the safety and effectiveness of your device.
The FDA will either approve or reject the application within 180 days. The different steps of the review process include:
FDA staff will determine completeness through an administrative and limited scientific review.
FDA staff will conduct an in-depth scientific, regulatory, and Quality System review.
An advisory committee will review and offer any recommendations.
Any final deliberations will occur and the FDA will document and notify you of their final decision.
If you are developing a lower risk, “novel” device, and struggling to find a predicate, the De Novo pathway might be the best option for you.
The De Novo pathway has actually been around since 1997 but many people do not know about it since it is not very commonly used. Companies that do not qualify for 510(k) clearance, due to the fact that they cannot provide substantial equivalence to a device on the market, should learn more about the De Novo pathway.
Since comparison to a predicate is not needed, companies have a “blank canvas” when it comes to labeling and can set a standard that may give them a competitive advantage over others. One of the key things to remember about the De Novo pathway is you must show your device presents low to moderate risk through a robust risk mitigation strategy.
This pathway involves a two-step process. The FDA must grant a Humanitarian Use Device (HUD) exemption and the device company must then submit an HDE application to the appropriate review center.
Another important requirement is that there cannot be another comparable device on the market that shares the same intended use. The FDA will consider the following when determining if there are comparable devices on the market:
The device’s indications for use and technological characteristics.
The patient population to be treated or diagnosed with the device.
Whether the device meets the needs of the identified patient population.
Part of the rationale for providing this pathway is there may not be a large enough patient population with clinical data to satisfy regular FDA requirements of safety and efficacy. Since these devices may be very crucial to patients with rare conditions, the FDA put it in place to do a proper review to determine if the device can be sold.
The food and drug administration(FDA) quality system requirements for all medical device companies are documented in the federal code of regulations, under 21 CFR part 820.
In 1990, the FDA mandated the design history file(DHF) as part of the safe medical devices act. It contains all of the product development documentation pertaining to a finished medical device. The DHF was the last step in the design controls process mandated by the FDA in 21 CFR Part 820.
Overview of 21 CFR part 820
The FDA’s mandate for quality systems states that each medical device company must establish and maintain a quality system that meets the requirements of its regulations and is appropriate for the medical device they manufacture. Differently classified medical devices may have different requirements under the quality system guidelines. For example, Class I medical devices (with some exceptions) are exempt from the design controls portion of the regulations, but in general, the guidelines must be satisfied to permit the sale of a medical device within the United States.
Medical device companies should consider the quality system regulations as their “key to admission” into the medical devices marketplace.
Subsection j) of 21 CFR part 820 says:
Design history file. Each manufacturer shall establish and maintain a DHF for each type of device. The DHF shall contain or reference the records necessary to demonstrate that the design was developed in accordance with the approved design plan and the requirements of this part.”
DHF is primarily an organizational tool meant to show that the design controls process was properly followed and documented throughout product development while the majority of the medical device compliance regulations enforce the establishment of policies and procedures for enforcing quality standards. Design controls are one of the core processes of the overall quality management system (QMS) mandate, and the presence, completeness, and accuracy of your DHF go a long way towards helping you pass your next FDA audit.
Here are some key interpretations of the DHF guidance that medical device companies should take note of:
A DHF must be maintained for each type of device that you manufacture. For similar versions of the same device, you can include all of the data in a single DHF.
The DHF demonstrates that the device was developed in accordance with both the design plan andthe requirements of this part. Your design plan must reflect compliance with the design controls process and should be included as part of the DHF.
The DHF must either contain or reference the necessary documents, which means that you could either create a folder that contains the required documents or create a document that acts as a reference sheet for the required materials.
What belongs in your DHF?
Below, we’ve listed the steps of the design controls process and what documents should be included with each step:
Design input: include your design plan document, developed according to this part.
Design output: Design outputs are the results of the design and engineering efforts. These are normally the final specifications for the device. The outputs are normally documented in models, drawings, engineering analyses, and other documents.
Design review: is a formal review of the medical device design by representatives of each design function participating in the design efforts as well as other interested parties. The design review must be documented in the DHF and include review date, participants, design version/revision reviewed, and review results.
Design verification: is the process that confirms that the design output conforms to the design input. Design verification should demonstrate that the specifications are the correct specifications for the design. Design verification must be documented in the DHF and include the verification date, participants, design version/revision verified verification method and verification results.
Process validation: is the process in which the device design is validated using initial/low volume production processes. The purpose of the process validation is to confirm that the design functions according to design inputs when produced using normal production processes rather than prototype processes.
Design validation: Design validation shall be performed under defined operating conditions on initial production units, lots, or batches, or their equivalents. Design validation shall ensure that devices conform to defined user needs and intended uses and shall include testing of production units under actual or simulated use conditions. Design validation shall include software validation and risk analysis, where appropriate. The results of the design validation, including identification of the design, method(s), the date, and the individual(s) performing the validation, shall be documented in the DHF.
Design transfer: Design transfer is the process in which the device design is translated into production, distribution, and installation specifications.
Design changes: Design changes is the process in which the design changes are identified and documented. Also known as engineering change or enterprise change.
FDA Staff (October 7, 1966). “Part 820 ”. Federal Register. 61 (195): 52657. ISBN9781932074109. Retrieved January 13, 2017. Also available in hardcopy, as FDAnews (2003). Device Inspections Guide. Washington, DC: Washington Business Information. p. 52657. ISBN1932074104.