How to Approach Process Validation Changes for Implantable Devices

By Jessica Sanders, Mei Lok
April 16, 2020


• Categories: 03-Manufacturing Execution, 04-Product Design & Development, 05-Quality/Regulatory, Market Access

The American National Standards Institute (ANSI) and the Association for the Advancement of Medical Instrumentation (AAMI) recently released the updated standard ST72:2019. The new standard aids many affected manufacturers in understanding bacterial endotoxin testing (BET) and the process for reducing batch testing. A thorough understanding of the 501(k) submission requirement with the BET standards and how ANSI/AAMI ST72:2019 can improve bacterial endotoxin monitoring can help ensure that your submissions pass with flying colors.

Bacterial Endotoxin Testing Overview
Devices that the ST72:2019 standard (also known as limulus amebocyte lysate (LAL) testing) applies to must be tested for bacterial endotoxins before entering the market, including each anticipated lot or batch for release. It’s essential to be aware of the acceptable endotoxin level to ensure your submissions will meet the requirements. Testing will reveal whether the endotoxin levels fall within the standard or are above the specification limit.

If the levels exceed the specified endotoxin range, you may need to document it and conduct a gap analysis to identify where the endotoxins are stemming from. A gap analysis can consist of reviewing processes, supplies, water quality and other components to determine the source. Once you have identified the source, mitigate unnecessary risk and set your submission up for success by developing a game plan on how to reduce or remove endotoxins.

When it comes to 510(k) submissions, and really all medical device submissions, taking risks is almost never worth it. Going above and beyond to ensure your medical device submissions are as close to flawless as possible will not only increase the likelihood of approval but also save time and money associated with retesting.

The History of ST72

Updates to the BET FDA regulations in 2016 included an added requirement for 510(k) submissions for implantable devices. The update was a significant change, and it left many manufacturers with questions and uncertainty. These changes pressed regulators to establish clear guidelines explaining which products do, in fact, require testing and provide best practices and instructions to conduct the testing correctly.

With the release of ANSI/AAMI ST72:2019, consolidated guidance was finally available for the first time since the original publication date (2011) and the 2016 FDA regulation update. This release expands existing guidelines on how to justify the use of batch release testing alternatives within the parameters of the regulation. ANSI/AAMI ST72:2019 applies to sterile implantable devices that make contact with non-intact tissue—now including many previously exempt orthopedic implants. It pertains to both new products for 510(k) submission and new batches of existing products.

Understanding the Updates

There are two major changes to be aware of to support your 510(k) submissions. The first change of ST72:2019 is the expanded scope of products that fall under this FDA regulation—meaning products that previously did not qualify must meet the new requirements. Unfortunately, it affects many manufacturers with little to no experience with this process, which leads to the other significant changes.

Additional guidelines around batch testing alternatives also came with this FDA regulation update. Examples of these alternatives include reducing the frequency of testing, decreasing the number of samples tested, testing representatives from product families or using substitutes to a finished product (i.e., a surrogate product). These new batch testing guidelines may save time, resources and more, but they also require a scientifically sound rationale based on a thorough risk assessment and focused on the overall risk to the patient. Risk assessment provides a method to determine whether or not an alternative to batch testing would be appropriate on a case-by-case basis.

For circumstances that require an alternative to batch testing, manufacturers can work with testing partners to develop a course of action. Following the specific guidance in ST72:2019, you can create testing instructions and perform testing against the alternative process to ensure accuracy. This transition needs to be well documented to provide proof and strategy should an FDA audit occur.

Meeting the Requirements

The harsh reality is there will be devices that do not meet the requirements. Not only would this threaten the possibility of your product not making it to the market, but it could also result in repercussions with the FDA and even consumers. This could include FDA warning letters, audits, recalls, fines or even consumer or FDA legal action. It’s important to keep in mind that not only is your product at stake but so is your reputation.

The best way to set yourself up for success and compliance is to find a testing partner with extensive BET experience. The guidance and counsel of a lab with in-depth knowledge of BET can be a tremendous asset. The right testing partner can offer the expertise you need to confidently assess your product’s compliance—whether you are new to BET or simply need additional support.

Finding the Right Testing Partner

The right testing partner can help you feel more confident in your submission and will support your success. With all that is at stake throughout this process, deciding who you will partner with for your testing needs is one of the most critical decisions affecting your submission. It must be taken seriously.

Vetting a testing partner is critical to ensure you are getting the right skill set and commitment to quality necessary for your success. The skills and expertise of the scientists carrying out the tests are going to be responsible for the quality of your results, so it is vital you feel confident in their ability.

Some factors to consider when selecting a testing partner include:

• Overall client service and follow-up support
• Up-to-date knowledge of evolving regulatory expectations
• Proven BET experience
• Clear demonstration of quality assurance
• A track record for on-time delivery

Having a good understanding of a lab’s testing experience can provide insight into their exposure and ability to adjust for different testing scenarios. A partner who not only can prove their testing is executed correctly, but that they’ll also work well with your team and provide excellent client service will make the process easier and less stressful.

Thorough and extensive testing supports a streamlined and successful product submission, and most importantly, protects the end-user. While regulations and standards continue to change and evolve, the ultimate goal is one we all support—safety. ST72:2019 can help ease this process for those who are new or unfamiliar by consolidating requirements and guidance.