The FDA process for medical device clearance is a frequently heard story … but not from the engineer’s perspective. When it comes to commercializing a medical device, the engineering team plays a key role in facilitating successful market entry.
When it comes to regulatory compliance and public safety, most medical device companies rely upon the skills of a professional engineer to ensure their product effectively fulfills its intended use. The contributions the technical team can make to facilitate the commercialization process are both critical and substantial. In fact, thinking of commercialization strategies that include engineering expertise from product concept through completion may help your product get to market faster, more easily and more affordably.
Preparing for and Anticipating the FDA Commercialization Process
One of the most common questions we hear from emerging medical device companies is, “When should we begin preparing for the FDA?” The answer is, “As soon as possible.” Emerging companies often devote their time, talent and treasure to product development. During the R&D phase, companies are typically driving toward the completion of their pre-clinical program or a final prototype. Because the focus is so intent on product development, and commercialization seems to be in the distant future, it can be easy for activities like documentation related to meeting FDA expectations to be pushed aside.
Documentation, however, is critical for an FDA submission. There are a number of activities the engineering team will be involved in supporting, such as the development of technical documentation that is part of a submission. At minimum, these activities include preparing documentation like completing risk assessments and performing validation activities. Engineers are vital for these activities because they intimately know and understand the technical functionality of the product to an extent that other team members typically do not. Prior to jumping into documentation, however, it is important to have a general understanding of the FDA’s approach for product clearance, as well as the requirements US medical device manufacturers must comply with.
Understanding the Process for FDA Clearance
The FDA uses a risk-based approach when clearing medical devices for the US market. The FDA segments devices into three risk classifications (see Figure 1). The higher the risk, the greater the requirements for evidence that demonstrates product safety and efficacy. The cost of commercialization and time to market is often influenced by the product’s risk classification. That is, a Class II product has a significantly easier path to market than a Class III product, and a Class I product has the easiest path to market.
Figure 1: US Medical Device Classification Table: The FDA segments devices into three risk classifications. The higher the risk, the greater the requirements for evidence that demonstrates product safety and efficacy.
As part of your regulatory strategy, you will identify your device classification, the product code your device is regulated under and potential predicate devices. Comparison to a predicate device is required for FDA Pre-market Notification, also known as a 510(k) submission. This is the most common regulatory pathway, and the one we field the most questions about.
The 510(k) process is designed to demonstrate the substantial equivalence of a new device to an FDA cleared, or predicate device. This means that rather than proving safety and efficacy via clinical trials, medical device companies can prove their device is as safe and effective as a device that has already been cleared by the FDA. Demonstrating substantial equivalence includes establishing that your device has the same intended use as the predicate and that any technical differences between your product and the predicate device do not raise the risk profile of your product above a Class II classification. Because of their technical expertise, the engineering team can be instrumental in reviewing the technological characteristics of potential predicate devices and help establish technical equivalence for the purpose of assessing the product’s risk profile.
Product classification determines the extent of documentation a medical device manufacturer is required to submit to the FDA for product clearance and to maintain on-going compliance. Regulations that are most likely to be required include FDA 21 CFR Part 820 Quality System Regulation, ISO 14971 Application of Risk Management for Medical Devices and, if your device includes electrical components, IEC 60601-1 General Requirements for Basic Safety and Essential Performance. To demonstrate compliance to these requirements, the engineering team may apply their product technical expertise to build technical documentation that accurately describes the product, such as design specifications, product requirements and supporting drawings.
Satisfying the Quality System Regulation
FDA product clearance is dependent on the expectation that you will, at a minimum, comply with 21 CFR Part 820 Quality System Regulation, also known as Good Manufacturing Practices (GMPs). According to this regulation, medical device manufacturers must establish a Quality Management System. Manufacturers of Class II products must also implement design controls to ensure their products meet requirements and do not pose unacceptable risk to the consumer or public.
GMPs ensure the manufacturer is producing the product based on the parameters the FDA cleared for the marketplace. To demonstrate that you follow good manufacturing practices, you will need to establish:
- A Quality Management System that addresses
- Risks presented by the device
- Procedures, processes and resources for implementing quality management
- The requirements of the Quality System Regulation
- Controls for your organization, such as
- Design controls
- Equipment and facility controls
- Production and process controls
- Document, records and change controls
Satisfying 21 CFR Part 820 is a necessary expense and typically involves all functional aspects of a company. Engineering supports compliance to Part 820 by assisting in the development of the QMS and the technical development and implementation of design controls. For example, the engineering team may have design or technical input ranging from security controls in the clean rooms to software controls for the operation of the device. Engineers are subject to the expectations of the QMS, making it important that they understand the processes they must conform to.
Establishing a Quality Management System
It makes sense for a medical device company to get an early, practical handle on 21 CFR Part 820. During the pre-clinical or prototyping design stage, it is not overly difficult or resource-intensive to implement a few formal Quality Management System processes around the management and control of documents and records. With a Design Control procedure and a Document Control and Records Management procedure (and perhaps one or two other procedures), you will have the processes in place to properly prepare and maintain documents during the early stage engineering of your product. Quality and regulatory personnel may collaborate with the engineering team to use their expertise to create processes that best reflect business practices. For example:
- Design Control: describes your company’s process for the design and development of your device. This procedure provides a structure for each stage of product development.
By implementing it at the beginning of your design process, you ensure your device is meeting design control requirements.
- Document Control: explains how your organization manages the approval and distribution of documents, as well as how document changes are authorized and implemented. This process should be implemented early on to ensure documentation is developed in a compliant manner when they are created – which means documents will not need to be corrected retrospectively.
- Records Management: describes how records are maintained. This includes your Device Master Record (DMR) and Device History Record (DHR). The DMR includes your device specifications and drawings that are created during the product design stage.
The benefits of this approach are numerous. In addition to demonstrating competence around FDA Design Controls, these procedures position your company for a transition from an R&D firm to a Medical Device Manufacturer. It further shows your company’s competence as a potential partner who can support regulatory obligations.
Implementing Design Controls
21 CFR Part 820 prescribes specific design controls, or processes, for bringing Class II medical devices to market. Design controls allow you to implement a risk prevention approach to the quality of your medical device. Risk prevention is an efficient and cost-effective way to control manufacturing processes and maintain quality. While it may not be possible to eliminate all potential risks, we consistently observe that our clients have a very poor appetite for risk that could have been mitigated.
Design controls are established to ensure that specified design requirements are met. These controls frequently overlap with what the engineers know, and more often than not, depend upon the engineer’s input. If implemented well, design controls create a number of surprising benefits, including a better-documented product that is more attractive to buyers or acquirers. They result in a more efficient development cycle due to a reduction of mistakes thanks to early analysis of key questions and a clear distribution of a team’s responsibilities.
- Design and Development Planning: during this phase, the engineering team plans the activities they will perform during design and development of the product. These activities might include defining stages, assigning responsibilities, evaluating suppliers and documenting product design and processes.
- Design Input: this is the starting point for product design. The engineering team creates input documents that explain marketing and user expectations for the device, such as concept documents and product requirements. These documents become part of the DHF.
- Design Output: the engineering team identifies and documents the design outputs. These outputs describe the design specifications that address the requirements, such as risk assessments, drawings and component specifications. The design and development outputs become part of the DHF.
- Design Verification: are the activities performed by engineering to confirm that the design outputs meet the requirements identified in the design inputs, such as safety testing and the inputs/outputs matrix.
- Design Validation: are the activities often performed to confirm the intended use of the device from the user’s standpoint.
- Design Review: these are formal meetings where the engineering team and subject matter experts meet to confirm that inputs/outputs and V&V activities are appropriate for the intended use of the device.
- Design Changes: this is documented evidence of changes performed on the device once design controls are established. Once the design input is approved, the need for design changes becomes effective.
- Design History File: this is a compilation of records, or an index that references the location of all design-related records that describe the product design life cycle.
Using the processes identified above, a credible Design History File (DHF) can be created by formally authoring and approving Design and Development Plans, Product Requirements, Design Reviews and other necessary content at the appropriate product development stages (see Figure 2). During the early stages of the design, it is crucial that the engineering team captures specifications and requirements. This is not a task that is easy or efficient to complete retrospectively and recreation from memory is subject to error; therefore, creating these documents should not be delayed.
Figure 2: Elements of Design Control: 21 CFR Part 820 prescribes specific design controls, or processes, for bringing Class II medical devices to market.
While establishing design controls, the focus often shifts to include managing risk and safety. Using their intimate knowledge of the device and its technological characteristics, engineers are often able to contribute to potential risk identification and corresponding mitigations that need to be explained to the FDA as part of risk management.
Managing Risk and Safety
Risk management and meeting safety requirements often go hand-in-hand. ISO 14971 Application of Risk Management provides the methodology medical device companies follow for managing risk. This standard requires a medical device company to identify the harms and hazardous situations, evaluate their associated risks, control the risks and monitor the effectiveness of the controls throughout the product’s lifecycle.
Not only is the risk management process part of your Quality Management System, but it is a central part of your medical device’s development, as well. Engineers play a critical role in the risk management team because they can explain the risks from the design, development and manufacturing standpoint of the device and can contribute to the assessment of risk. During the risk assessment process, it is possible that the engineering team may be asked to implement design controls that will mitigate potential risks.
In addition to risk management, and depending on the technology incorporated into your medical device, applicable safety standards may be identified during the design stages of the product. For example, the most widely accepted benchmark for establishing safety for electrical medical devices is IEC 60601-1 3rd Edition and its collateral standards.
Failing to conform to a safety testing standard is a sure way to halt a device’s commercialization progress. As a consequence, we see more and more engineers from medical device and medical device contract manufacturing companies work through what it means to satisfy safety testing requirements early in the design phase. Taking this kind of proactive approach can identify not only documentation needs, but also design requirements that must be met in order to satisfy Test Laboratory product evaluations. By building conformance to a safety standard into a medical device as early as possible, the medical device engineer saves their company the pain and expense of redesign work due to testing failures after the company thought the design was locked down. Demonstrating that the requirements of IEC 60601-1 have been met can be integrated into the device’s risk assessment for the FDA to review.
Effectively Participating in the Commercialization Process
In our experience, medical device manufacturers whose engineers extend their role beyond design and development activities to support the commercialization processes make for more successful companies. As an engineer, you can be more effective in this role by:
- Familiarizing yourself with relevant compliance requirements for your device, including 21 CFR Part 820 and ISO 14971
- Developing an understanding of FDA expectations, such as demonstration of risk mitigation and safety
- Communicating with the Quality Assurance and Regulatory Affairs personnel to ensure products can get to market and your company’s legal compliance obligations are met.
Thinking of the commercialization strategy from concept through completion will enable you to develop processes that bring your product to market faster, easier and, quite possibly, more affordably… allowing you to move on to your next brilliant idea!
Russ King is the president and managing partner of MethodSense, a leading global life science consulting firm, providing services and solutions in regulatory strategy, quality assurance, technology and operations. Combining experience and skills across the medical device sector, MethodSense works at the intersection of engineering and quality to help clients meet compliance requirements, improve their performance and create sustainable value for their stakeholders.