This column is directed at the small medical device company hoping to obtain its first U.S. Food and Drug Administration (FDA) 510(k) Premarket Notification. While such an undertaking can be nerve-racking, it also can be quite rewarding, provided the applicant avoids some key pitfalls common to many organizations seeking the authorization.

One of the mistakes frequently made by first-time 510(k) aspirants—even those led by brilliant leaders—is failing to make preparations for the development, assembly, and submission of the application until a prototype is in hand. This is too late in the process to begin the planning, as the FDA’s design control requirements are very comprehensive.

A brief depiction of each element within 21 CFR Part 820.30 (Design Controls) follows. Bear in mind, however, that I have simplified the individual requisites due to space constraints; for the official design controls requirements, go to https://bit.ly/2P5HtS1.

• Design and Development Planning. This includes, but is not limited to, a plan or plans that describe or reference the design and development activities and define responsibility for implementation; identify and describe the interfaces with different groups or activities that give input to the design and development process. Plans must be reviewed, updated, and approved as design and development evolves.
• Design Input. Must-have procedures to ensure the design requirements relating to a device are appropriate and address its intended use, including all user and patient needs. The procedures must address incomplete, ambiguous, or conflicting requirements. Input mandates must be documented, reviewed, and approved by designated individuals, and the approval must be documented.
• Design Output. Procedures must define and document design output in terms that allow an adequate evaluation of conformance to design input requirements. These procedures must address acceptance criteria and ensure the design outputs that are essential for proper device functioning are identified. Design output must be documented, reviewed, and approved before release. The approval must be documented.
• Design Review. Formal, documented reviews of the design results must be planned and conducted at appropriate stages of a product’s design development. In addition, each design review should be conducted by representatives of all functions involved with the specific design stage under assessment—including specialists and those with indirect responsibility for that phase. All design review results, including identification of the design, the date, and the individual(s) performing the review, must be documented in the design history file (DHF).
• Design History File. Manufacturers must establish and maintain a DHF for each type of device. The DHF shall contain or reference records that demonstrate the design was developed in accordance with an approved design plan and the requirements of 21 CFR Part 820.30 Design controls.
• Design Verification. Procedures must establish design verification. Design verification confirms the design output meets the design input requirements. The results—including design identification, method(s), date, and individual(s) performing the verification, must be documented in the DHF.
• Design Validation. Procedures must establish design validation. Design validation must be performed under defined operating conditions on initial production units, lots, or batches, or their equivalents. Design validation must ensure 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. Design validation results, including design identification, method(s), date, and individual(s) performing the validation, must be documented in the DHF.
• Design Transfer. Procedures must ensure the device design is correctly translated into production specifications.
• Design Changes. Procedures must be established to identify, document, validate or where appropriate, verify, review, and approve design changes before they are implemented.

There are various supporting procedures involved in a 510(k) Premarket Notification beyond those used for design controls. Companies should follow part of the quality management system when design and development activities begin, and certainly well before developing, assembling, and submitting its application to the FDA. Other procedures that must be established, developed, and implemented (including appropriate training) consist of:

• Document Management. All procedures and records entail a formal document management process.
• Change Control. Change control goes beyond documentation and must be applied to device, software (if applicable), and manufacturing processes. Configuration management methodology is often addressed in change control procedure(s).
• Supplier Qualification. Startups typically have little, if any, leverage with suppliers because they don’t usually place big orders, and they’re considered a significant risk. Nevertheless, companies must still establish a procedure to properly qualify suppliers of key components, services, and contract manufacturers.
• Purchasing. This is not a typo. A purchasing procedure must be established, even in the design and development phase. Why? To document and validate any materials and services purchase.
• Receiving and Inspection. As the design develops and prototypes are being used for key design and development activities, a formal method to receive key materials and perform inspections becomes necessary. 
• Equipment and Tools Calibration and Preventive Maintenance. Reliability and accuracy of the tools and equipment used to make and measure key components and finished prototypes is required in the design and development process.
• Risk Management for Design and Development. Ultimately, risk management must be established throughout the product lifecycle and quality management system. A risk management procedure will help drive the risk management application during product design and development.

There are various other key considerations for the 510(k) Premarket Notification. One is identification of the predicate device(s)—i.e., the legally marketed U.S. product that is substantially equivalent to the innovation under development. A direct performance comparison between the new device and predicate(s) is required to establish substantial equivalence. Picking the right predicate is an essential part of the 510(k) Premarket Notification development process.

Another consideration is device complexity and its impact on the time and cost of developing a 510(k) Premarket Notification. Devices containing software, for example, are more complex than those without software, so additional processes are required and additional standards apply. Materials also can affect device complexity. If the product uses common materials and has its choice of predicate devices, the 510(k) will be simpler than that of a device made from less established substances and with few predicate devices for comparison. Implants—especially active implants (those containing an energy source)—warrant more complex 510(k) applications as well. New age manufacturing processes can complicate a 510(k) too, because more evidence is required to show the manufacturing process is effective. Here’s a good rule of thumb to help determine 510(k) complexity: The higher risk the device, the more complex the 510(k) Premarket Notification. This “rule” also applies to design and development processes. These processes increase in complexity as the product design becomes more intricate.

Part of the design and development process is identifying the verification and validation activities required to support the 510(k) Premarket Notification. Factors such as cleaning and sterilization validation, biocompatibility testing, electromagnetic compatibility testing, transportation testing, and stability testing (accelerated and real-time) are some of the activities that may need to be considered, depending on intended use/indications for the device under development. Much of this testing is usually performed by an outside laboratory or test center, thus creating one more reason for the purchasing and supplier qualification procedures.

There are a few high risk devices that would require a clinical study to be performed, but this is very rare. These devices usually do not qualify to be submitted under 510(k) Premarket Notification; they require the much more complex Premarket Application (PMA).

In summary, the 510(k) process is not a “fill out a form” kind of procedure—it must be supported by the appropriate design and development processes. Considerable planning is required and many product design and development activities must be completed before the application can be submitted. Therefore, it should not be an afterthought, but rather  fostered as part of the design and development process.  

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James A. “Jim” Dunning’s consulting career began in 2001. He has provided quality and regulatory consulting services for various companies ranging from Fortune 500 medical device firms to startups. Dunning’s passion, however, lies with startups and small companies, especially those in regulatory distress. He has amassed significant experience in preparing 510(k) applications, developing complete Quality Management Systems, providing Quality System Training, and advising on quality, business, and leadership issues. Dunning is a senior member of the American Society for Quality (ASQ) and a member of the Regulatory Affairs Professional Society (RAPS). He can be reached at jdunning@qpcservices.com.