John Mastroianni, Principal Electrical Engineer


Toward the end of last year, a former co-worker approached me about defining the FDA quality requirements for a Class 3 medical device that he was developing for a client. The client, a well-informed cardiologist and start-up entrepreneur, invented a new medical device he was looking to bring to market. He was able to perform a proof of concept of the product by hiring a design services company. As a medical device professional and Food and Drug Administration (FDA) subject matter expert, I started preparing for the task of helping him define the FDA quality requirements he would face.

One of the first things that occurred to me is that startups developing medical devices for the US market can be unprepared for the amount of work, schedule and costs associated with dealing with FDA regulations and preparing for an FDA product submission. For example, under ISO 13485, companies need to maintain a Quality Management System (QMS). This involves maintenance of Design Controls, which can be an overwhelming task. IS0 14971 also requires risk assessment and risk management of the product. This includes a thorough hazard and risk analysis, identification of possible safety concerns and risk mitigation. All these steps are required prior to medical device premarket submission.

My presentation started with use of the Application of Design Controls to Waterfall Design Process1, depicted below. Describing this process enabled the client to understand the importance of having a quality management system under the direction of ISO 13485 and FDA 21 CFR Part 820. More importantly, it helped illustrate the importance of documenting product requirements and demonstrating objective proof that the product met those requirements.

Application of Design Controls to Waterfall Design Process

Application of Design Controls to Waterfall Design Process

The starting point of capturing Design Controls is preparation of the User Needs document. This document effectively describes the user requirements and the intended use of the product. It accurately captures how the product will be used, the operating environment, the users of the product, and user interface with the product. The next component, Design Inputs, includes the set of requirements essential to the product. It serves as the basis of the product design. It includes functional, performance and physical characteristics. As shown in the diagram, the Design Input needs to be formulated from the User Needs. The intended use of the product must be defined in terms that are measurable. Once the Design Input is established, development and implementation of the product is initiated. This phase is called the Design Process. The next step is the Design Output, the deterministic result of the Design Process for the product. This requires conformance to the Design Input.

Verification and testing is performed on the product (Design Process Block) as if it were a black box. Verification provides objective evidence that the Design Output meets the Design Input requirements. At the end of the Waterfall, the Medical Device is created and ready to undergo Product Validation.

Design Validation is performed on the product from the initial lots of production units or their equivalents. The product is built in a production environment using production equipment and production personnel. The Medical Device must conform to the defined User Needs, intended uses and applicable compliance and regulatory standards.

The final part of my presentation emphasized the ramifications of not following the FDA regulations and steps such as the Waterfall process. The FDA manages compliance via systematic audits for manufacturers of medical devices. Therefore, the FDA conducts careful inspections to determine compliance to their regulations. The FDA investigator, accompanied by a representative of the company (Production Manager or Quality Manager), examines records and studies the design process for the product. These records are usually any part of the Waterfall process that are maintained in the companies’ Quality Management System. These company records become the Design History File (DHF).

If the FDA investigator discovers a problem during the review, they provide a written report listing their inspection observations. This report is called FDA Form 483. The manufacturer has 15 days to respond to Form 483 by addressing the concerns and delivering timeframes when issues will be resolved. Typically, there is a follow up audit when the FDA investigator returns and performs another inspection. This inspection covers problems discovered in the initial FDA Form 483, but can also include any other area. If FDA violations persist, the FDA may issue a Warning Letter.

Warning Letters may lead to serious repercussions. “Why is this?” you may ask. When the FDA is dealing with Class II and III medical devices, it must maintain strict standards. Medical devices are highly regulated, especially Class III since they potentially sustain or support human life, are implanted, or present potential unreasonable risk of illness or injury. Thus, when medical device manufacturers do not handle FDA Warning Letters seriously or remedy problems listed in the Warning Letter, legal action through the US judicial system may be initiated.

I prepared my slides and presented them to my former co-worker and members of the start-up team. The meeting went well. However, it became obvious that the start-up organization was not ready to develop a Quality Management System. It did not budget for the costs associated with the two-year process of creating documentation and Design Controls. Questions also arose because the start-up did not document steps in the proof of concept for the product. In fact, the electrical schematics for the product no longer existed. However, the intended use of the product was clearly understood, as they were able to describe the purpose and use in detail. Cogmedix can provide additional value by supporting our customers through our released Design Control process. As experts in Design Controls, our customers can rely on us to maintain Design Controls while they focus on moving the business forward.

The start-up was unable to move forward although it was clear they needed quality system regulatory advice. Cogmedix understands the importance of quality and compliance, and proudly works with our customers to ensure they are meeting all required standards at all stages of product development and manufacturing.

1- Application of Design Controls to Waterfall Process – [ONLINE] Available at: Medical Devices Bureau, Health Canada