How Medical Manufacturers Can Practice Due Diligence for Change Control

We are back to discuss the regulatory and legal importance of having and using controlled processes for company activities. The processes provide both consistency and objectivity but they also prevent the regulatory repercussions that can impede the most commercially successful company from advancing to the next level of growth and success. Design and process changes are part of life when a company manufactures a product.

If Apple had waited for the iPhone design to be perfect, we would never have seen an iPhone hit the market at all. If Apple had not undertaken iPhone design changes, the company would have died on the vine (or tree). It is, however, important that changes be made throughout a process that consistently ensures the changes do not negatively impact the final product’s quality.

The focus is abundant on new product development and commercialization in all industries. An example of this in the consumer world is with new cars; we are inundated with commercials about new cars and features but not with seemingly minor design updates. If Cadillac develops a new manufacturing process or component design for window clips that reduces the frequency at which they break free from the regulator, there will be little to no glory or marketing. As someone who made this specific repair on a 2005 Cadillac DeVille six times during the vehicle’s life, I would have appreciated any design changes that could have prevented these failures.

Initial commercialization of a medical device is just one step in the product lifecycle; there will be feedback from users, innovative technologies, and new ideas that lead to design or process changes for any product. These design and process changes must be made using controlled, sacred processes that reduce the chances that low quality or dangerous products will be delivered to the market.

FDA Findings: 483 Observations

Design changes are consistently one of the top 10 causes for 483 observations from the FDA year after year. It is one of the handful of quality systems guaranteed to be included in the most cursory of inspections completed by the FDA. According to the FDA’s 2023 report for site inspections, there were 720 total observations (483s) issued to medical device companies. There were 65 observations related to design or process changes:

• 46 for “Design changes – Lack of or Inadequate Procedures”
• 10 for “Process changes – Review, evaluation and revalidation”
• 5 for “Production and Process Change Procedures, lack of or [Inadequate]”
• 4 for “Change records, content”

The details of each inspection are not automatically published into the public domain, though they can be made available through a Freedom of Information Act (FOIA) request. The summary published each year, however, gives the industry a snapshot of data from which it is possible to see where FDA inspections have focused and where common deficiencies exist in quality systems. Each of these observations will require a response from the inspected company and that response will include both correction of the immediate observation and corrective action to prevent the reoccurrence of similar events.

FDA Findings: Warning Letters

In some instances, companies don’t respond in ways that satisfy the FDA’s concerns about the effectiveness of the quality system, which can result in a public warning letter. On Sept. 22, 2023, Sonesta Medical AB received a warning letter¹ that included a finding related to the method, or lack thereof, of handling design changes:

“Failure to establish and maintain procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation, as required by 21 CFR 820.30(i). Specifically, your firm does not have procedures for defining control for changes to existing device design requirements and design results, to include a) describing the changes and the reason for the changes; b) determining the need to verify and/or validate the changes; c) determining impact on the design risk analysis; d) determine any new regulatory requirements, such as premarket clearance or approval, as needed.”

This FDA warning letter reiterates the importance of having and following a process for each design or process change. That process shall involve documenting not only the change, the verification or validation testing, and the regulatory actions required, but also the justification for those decisions. A defendable design change process doesn’t include yes or no questions like “Is verification or validation required?” The justification for the decision is as important as the decision made in any change process.

FDA Findings: Do Not Use Orders

As can be seen in the quantity and strength of the FDA’s admonitions, the importance of a change control process cannot be overstated. When adequate systems aren’t put in place—even after a warning letter has been issued—the FDA has the authority to issue “do not use” orders. On Jan. 4, 2024, the FDA issued a public “do not use” order² for the Synovo Total Hip Resurfacing System based on previous inspection results and a lack of acceptable response from the sponsor. In March 2023, the FDA issued a warning letter³ to Synovo Production Inc. because “the Femoral Resurfacing Cup has been, in multiple ways, significantly changed or modified in design, components, method of manufacture, or intended use within the meaning of 21 CFR 807.81(a)(3)” without the applicable testing and regulatory submissions for the changes. Specifically, the company “changed the biologic fixation coating for the hip replacement system from a sintered beads porous coating to a Titanium Plasma Spray (TPS) coating” and “discontinued the second machining process for the Femoral Resurfacing Component” without re-validating that the process still produces a product meeting the product specifications.

As the original sintered bead porous coating was validated, the TPS coating should have been validated to the same requirements. The device was cleared on May 23, 1991, under K904870 with the name “Modified New Jersey Femoral Hip Resurfacing Component” with the product code KXA and the device wasn’t permitted to be labeled or promoted for non-cemented use. The company made changes to the labeling to promote the device for cementless fixation, contradicting the product’s original 510(k) clearance. The change was made through the letter-to-file process instead of through the 510(k) or PMA process that would have been applicable. “The referenced changes, individually and collectively, are likely to expose patients to increased risks of loosening and subsequent revision surgery (e.g., from pain, proximal femur fracture, or component fracture).” To the inexperienced eye, swapping one coating process for another or a labeling change might not have the severe implications the more experienced eyes of the FDA have foreseen in this example.

Although I don’t know the internal workings of Sonesta Medical or Synovo Production—only what’s available in the links provided—I’ve spent enough time in the industry to understand how these things can happen when design and process change controls aren’t closely followed. Development teams often have representatives from multiple departments, including marketing, operations, process development, regulatory affairs, quality control, quality assurance, design engineering, clinical, and manufacturing engineering. All aspects of a new product are reviewed and discussed—sometimes heatedly—to confirm the design and processes meet all of each department’s requirements. Often, less scrutiny is given to changes after initial launch but changes that might seem small to someone intimately involved might have larger implications when viewed with a wide-angle lens provided through a multi-departmental review.

Although it’s unacceptable to circumnavigate or shortcut change control processes, it’s often human nature to get lazy in our assessments. Additional stresses can include pressure from upper management or lack of training. It’s hard to sit at a conference table, look the company president in the eye, and say what they want to do will require clinical trials, a PMA, three to five years, and $3 million to $5 million.

Because evaluating changes is grueling and often boring work, it’s often assigned to newer, lower-level employees. If, for example, the change control process includes junior engineers and regulatory affairs personnel, they may make poor choices simply because they don’t know better. Of course, that’s a failure that should still be owned by the company’s management team, as appropriate training is the foundation for any organization to make good choices. All of these are possible details about the failures in the organization but they all boil down to one root cause: lack of organizational commitment to the sanctity of the change control process.

We should always strive to launch a high-quality, clinically effective product from initial commercialization but we should also understand it won’t be perfect. Before the first product is put into finished goods, a change control process should be in place. Everyone, including management and any others who could exert pressure on those making important change decisions, should be adequately trained to respect and use the process, avoiding shortcuts. A broader view of design and process changes and the implications of those changes is critical to both the product’s and company’s continued success. 

References

1. bit.ly/dueprocess03241
2. bit.ly/dueprocess03242
3. bit.ly/dueprocess03243

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Meredith P. Vanderbilt is an internationally known medical device regulatory affairs consultant unafraid to communicate directly and honestly with regulatory bodies and clients about strategies and submissions to provide compliant and high-quality devices to the market. She is an industry influencer through workshops, networking, presentations, articles, textbook chapters, and (coming soon) an orthopedic industry book about additive manufacturing. She has decades of experience in performing and managing medical device development, commercialization, and marketing activities. She has a high success rate for gaining regulatory clearances in relatively short periods of time and is a participant in all aspects of quality management systems and post-marketing activities. She has the ability to manage multiple projects and clients while maintaining constant communication and productivity. She also has a high success rate for gaining regulatory clearances in relatively short periods of time.