Four Tips to Protect Medical Device Regulatory Submissions

In February this year, U.S. regulators issued a stark warning to medical device manufacturers about the integrity of data submitted by third-party test laboratories. The agency highlighted reports of fabricated and unreliable data from some laboratories, particularly those based in China and India. In its letter, the regulatory body urged device manufacturers to rigorously verify performance testing data before submission to ensure medical devices marketed in the United States meet the highest safety and efficacy standards. Imagine you’re a medical device manufacturer that has a new or existing relationship with a third-party lab from one of the named countries. What do you do? Cut your losses and throw your data onto the scrap heap? Cancel your contracts? Re-run all testing with another laboratory? Those are drastic measures. Before you make any decisions, there are four key takeaways to consider.

Use ASCA-Accredited Testing to Ensure Data Integrity

U.S. regulators may be using advanced technology to sift through its database for unusual data patterns. According to its statement, the agency has discovered a troubling trend of third-party test labs contracted by device companies that are providing testing data proclaimed to be fabricated, copied from other device submissions, or otherwise untrustworthy. To combat this issue, the Center for Devices and Radiological Health’s (CDRH) agency recommends working with ASCA (Accredited Scheme for Conformity Assessment) accredited labs. ASCA accreditation ensures that a laboratory’s quality systems meet stringent requirements, adopting a process like the ISO notified body concept in which notified bodies can verify a laboratory’s quality systems. This accreditation adds additional credibility to the testing laboratory. When U.S. regulators receive data from an ASCA-accredited laboratory, they can trust the data without the need for re-verification. Currently, the ASCA scheme includes seven biocompatibility tests, and only a limited number of labs worldwide hold this accreditation.

Conduct Due Diligence When Selecting a Lab Partner

Selecting a laboratory for biocompatibility testing is a significant investment, comparable to purchasing a car or a house. It is essential to trust your instincts and verify the information provided. Engaging with potential lab partners, understanding their expertise, visiting the lab to inspect their facilities and verifying their accreditation are crucial steps to ensure data integrity and avoid regulatory setbacks. Assessing the qualifications and experience of the personnel working on a manufacturer’s project is vital, as it directly impacts the quality and accuracy of the testing and analysis performed. This process also helps determine the potential partner’s competence and familiarity with regulatory expectations, advanced technologies, and existing methodologies. A collaborative approach is beneficial, ensuring that manufacturers and regulators are aligned on the biocompatibility testing plan. This alignment can save significant time and reduce stress for manufacturers, while helping laboratories stay in sync with testing requirements. Manufacturers cannot afford not to heed U.S. regulators’ emphasis on using ASCA-accredited labs. Doing thorough homework and confirming the lab’s capability to provide accurate and acceptable data is crucial to avoid delays and additional costs. Ensuring accuracy and reliability from the outset will save time and money in the long run.

Leverage the Pre-Submission Process

Scheduling a pre-submission meeting is relatively straightforward. U.S. regulators typically will assign you a timeslot within 75 days of your request. But before that meeting happens, make sure you have a thorough knowledge of your device. That means understanding your device’s constituent materials and their testing histories. It also means articulating your entire development process and understanding your device’s risk category and classification. U.S. regulators will also review testing plans to ensure they are current and comprehensive. Your preparation for a pre-submission meeting will often determine your level of success during it. Some manufacturers are reluctant to engage in the pre-submission process because they fear they will encounter issues with regulators, but a pre-sub meeting can help companies avoid larger problems later. Proceeding with testing and submissions without the guidance of a pre-submission meeting can lead you down the wrong path and  could drastically delay your clearance or approval. Properly leveraging this process can provide valuable insights and align expectations, ultimately facilitating a smoother and more successful submission process.

Insist on Collaboration and Complete Chemical Characterization

Chemical characterization is perhaps the most variable capability among lab testing facilities. Despite overwhelming regulatory support for complete chemical identification and characterization in medical devices, not all laboratories have the technical expertise and are fully committed to doing it right. Robust extractables and leachables (E/L) studies require a dedicated commitment to complete chemical identification and characterization. Achieving this necessitates an infrastructure that includes advanced instrumentation, cross-functional skill sets, a robust LC-MS database, and staff capable of generating and interpreting data meaningfully. Collaboration between manufacturers and testing laboratories is crucial. Sharing detailed information about the device, including materials and processing aids, enables the laboratory to perform the best possible testing. This collaborative approach enhances the accuracy of chemical identifications, significantly contributing to risk assessment and expediting the regulatory submission timeline.

A Final Word

U.S. regulators’ recent warning highlights the need for medical device manufacturers to be vigilant and proactive in their approach to ensuring data accuracy and regulatory compliance. By leveraging accredited testing, conducting due diligence when selecting lab partners, taking advantage of the pre-submission process, and insisting on complete chemical characterization (with no unknowns reported), manufacturers can safeguard their submissions. Implementing these strategies helps manufacturers meet the highest safety and efficacy standards and streamlines the regulatory process, ultimately saving time and resources. Fostering collaboration and maintaining rigorous standards means manufacturers can navigate regulatory submissions more effectively and bring devices to market confidently.

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Sandi Schaible is executive director, Analytical Chemistry and Regulatory Toxicology, at WuXi AppTec, a global company with operations across Asia, Europe, and North America that provides R&D and manufacturing services for the pharmaceutical and life sciences industries. With more than 25 years of experience, Schaible joined WuXi AppTec in 2011 and supports clients through the oversight and direction of the Analytical Chemistry Department in St. Paul, Minn. The analytical staff she manages is responsible for providing custom chemistry testing services including extractables/leachables, materials characterization and target analysis testing, method development, and method validation as well as standardized testing including compendial testing. Schaible has experience working in the pharmaceutical, medical device, environmental, and R&D industries, including more than 15 years of analytical experience in GLP, GMP, FDA and ISO regulated laboratories. Schaible provides technical guidance and testing program design, and is an international and U.S. delegate for TC 194, the technical committee for ISO 10993.