By Paula Gray and Sharon Kvistad, Navigant Consulting
This two-part series discusses the ramifications of the U.S. Food and Drug Administration’s (FDA) increased interest in laboratory developed tests (LDTs) in CLIA-certified laboratories. Until recently, CLIA-certified labs and the tests that they develop/offer remained largely untouched, though not unnoticed, by the FDA. But, draft guidance issued by FDA last October reaffirms the agency’s interest in these tests and its awareness of this segment of the industry. Read part one here.
By Paula Gray and Sharon Kvistad, Navigant Consulting
In part one of this series, we discussed the differences between quality management systems (QSR) constructed based on the medical device industry’s quality system regulation (QSR) and those built based on the Clinical Laboratory Improvement Amendments (CLIA) — particularly those differences that might place a manufacturer in a regulation noncompliant position. In this second exploration of quality systems for CLIA laboratories, we’ll discuss how to make the most of your interactions with the FDA and third-party organizations.
FDA Will Not Spell Out What Your QMS Requires…
Compared to the QSR QMS, the CLIA regulations are relatively prescriptive. CLIA regulations define requirements for personnel and steps to be taken to qualify specific tests performed. They also outline a how to monitor testing and obtain certification that it is sufficient, so that when all the steps are completed, the QMS will be compliant. This works for CLIA because it is always dealing with a laboratory system. However, the QSR quality system cannot be as prescriptive, based on the extraordinarily broad spectrum of devices that it must be applied to.
For example, a medical device manufacturer that makes a tongue depressor is allowed to have a different quality system than the manufacturer of an implantable heart valve (within the confines of the QSR). The FDA expects medical device manufacturers to be able to explain what their medical device is, the risks associated with that device, and how they have established their QMS to control and address the risks associated with the device. Along those same lines, the FDA expects manufacturers to be experts in both their product and the type of QMS needed to maintain their product.
However, this does not mean that the manufacturer has final say in its interpretation of the regulations and how it has implemented them: FDA maintains final authority over what is considered “right” or “wrong” for a manufacturer’s QMS, based on similar types of devices. Therefore, it is up to a manufacturer to make sure it has clearly described its device to the FDA to support the QMS that it has established.
So, if you are a CLIA lab and you want to put a QMS in place that is compliant with the QSR under 21CFR 820, how do you make sure you are on the right track? Can you ask the FDA? The short answer is “yes,” but there is a caveat: Be specific. The FDA’s Center for Devices and Radiological Health (CDRH) has established mechanisms that allow manufacturers to request meetings with CDRH to discuss a variety of topics — the construction of a company’s QMS is one of those (refer to FDA’s guidance “Request for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with Food and Drug Administration Staff – Guidance for Industry and Food and Drug Administration Staff,” February 18, 2014).
…But FDA (Or A Third Party) Can Confirm Whether You’re On The Right Track
The value of a presubmission lies entirely in the clarity of the information provided and in the questions posed to FDA for its response. Questions like “What should I do?” or “What do you expect for a compliant QMS?” are ill-advised — You will likely receive an answer that leads to an overbuilt and burdensome-to-use quality system, or a QMS that is not in step with your particular company’s requirements.
A better tactic is to approach FDA with specific, pointed questions regarding subparts of your QMS. For example, if you are unsure whether FDA will expect you to comply with the servicing section of the QSR (21 CFR 820.200), you might tell FDA, “We currently believe our QMS is exempt from the requirements identified in 21 CFR 820.200 for servicing, and here’s why,” subsequently providing an explanation. Then, ask “Do you agree that 21 CFR 820.200 is not applicable to our QMS?” Note that FDA will not disclose how other manufacturers have built their quality systems — due to confidentiality — so don’t ask.
An alternative to seeking FDA guidance on your QMS is retaining an independent third party to audit your quality system against FDA requirements for your device classification. This gives you an impartial evaluation of your QMS by someone familiar with the QSR, allowing you to identify any gaps or areas of non-compliance before the FDA comes in to conduct an inspection. Beyond maintaining impartiality, having an independent party review your quality system provides a new opinion and interpretation of the regulation, segregated from the person, or persons, who constructed the system. In addition to a report identifying system gaps or possible areas of non-compliance, a third-party assessment could outline the risks resultant of these findings in an FDA inspection and, if requested, provide recommendations for remediation of such non-compliance or risks.
If having an audit performed after your QMS is implemented feels too late, you can bring in a third party earlier in the process, helping you to create a plan for development and implementation of a QMS, as well as conduct a gap assessment with your existing QMS or processes/systems. This method typically includes not only the identification of gaps within any existing QMS, but also includes the third party’s recommendations for mitigating/removing such gaps and creating a QSR QMS that is compliant with 21 CFR 820.
Such activities can be done at a variety of levels, based on need and company resources. For example, a high-level procedure comparison could determine if all of the required elements have been addressed, while an in-depth audit might develop a remediation plan to close gaps.
Continuous Improvement To QMS Is Key
The ultimate determining factor of a compliant QSR QMS can take several forms. It may come as part of the approval or clearance process for your in vitro diagnostic (IVD) or companion diagnostic (CDx). For Class III medical devices, a pre-approval inspection (PAI) of the manufacturer’s facility is a requirement for approval of a medical device; such an inspection would be a determining factor of QMS compliance.
However, many IVDs are considered Class II or Class I medical devices. Facilities manufacturing such Class II and Class I devices are not as high on the FDA’s priority list of inspections, and facility inspection may not occur for up to two years after device clearance. Since most Class II submissions require little to no inclusion of procedures for the manufacturer’s QMS, there is virtually no feedback from the FDA, before the device is cleared, that the QMS is in compliance.
However, manufacturers can mitigate risk by choosing to comply with a consensus standard for QMS, (i.e., ISO 13485, a consensus standard which exists for medical device QMS). While such compliance will not guarantee full compliance with the QSR, due to some nuances, it will get you pretty close.
Compliance is a bit of moving target and it’s up to the manufacturer to be aware of changes in regulations and industry practice — a manufacturer that is in compliance today may be deemed out of compliance tomorrow. At the heart of the QSR is the concept of continuous improvement of the QMS, requiring the manufacturer’s QMS to evolve over time, just as their product(s) and their business do.
About The Authors
Paula Gray is a senior consultant with Navigant with over 15 years of experience in regulatory compliance, quality systems, and auditing (internal and supplier) in the medical device and diagnostics spaces. She can be reached at 317-288-8725 or at email@example.com.
Sharon Kvistad is an associate director in Navigant's Healthcare and Life Sciences Disputes, Regulatory, Compliance, and Investigations practice, focusing on FDA regulatory matters. Kvistad has over 30 years of experience in U.S. and global regulatory affairs as they relate to medical devices, with domestic submission preparation experience including IDE, PMA, PMA/S, HUD/HDE, and 510(k). She can be reached at 317-228-8715 or at firstname.lastname@example.org.