After more than 35 years of industry and FDA device and diagnostic evolution, it remains difficult to measure regulatory effectiveness because we are still seeing a moving target in submission reviews and enforcement. Examples include performance testing, clinical data, and quality system regulation (QSR)-related information and claims. While the FDA-requested Institute of Medicine report published last summer called for a rewrite of the 510(k) process, in part based on perceived 510(k) process deficiencies, the effectiveness of that process can be better managed and measured without a total rewrite.
FDA management can fix the 510(k) process starting with top-level conceptual policy updates separating compliance from the content of a submission. FDA leadership, including leadership at OIVD, should do the following:
1. Rebalance staffing and duties between headquarters and field investigations. Requesting more manufacturing data in submissions is not necessarily the best path to take to resolve or evaluate QSR compliance. Product quality failure after initial demonstration of substantial equivalence (SE) on production units should be addressed via inspections and enforcement.
2. Coordinate all aspects of lab developed tests (LDTs) and companion diagnostics (CDx) as a single project rather than issuing a series of unrelated guidance documents.
3. When products have significant QSR issues, treat new regulatory submissions for these products as de novo submissions requiring clinical data and other actions to address the specifics of the recall trends.
Regarding the IVD SE process, OIVD should further clarify that comparing individual product aspects to more than one predicate is acceptable. Technology doesn’t really matter as long as the clinical data show results are correct and understood by the physician  to be substantially equivalent to information from products previously available, with no new significant questions of safety or effectiveness. This approach should be formalized for OIVD. For the rest of CDRH, where there has not been clinical data, ODE should apply the de novo 510(k) process (for low- or moderate-risk products) using the existing pre-IDE and IDE processes, allowing IDE exemptions for nonsignificant-risk studies. Alternatively, providing product-specific guidance within the current regulatory framework, such as exists for infusion pumps, would be appropriate. The draft infusion-pump guidance clearly demonstrates the flexibility of the current 510(k) system.
So, as a policy matter, what will it take to update systems as described? The answer is enhanced leadership, not new 510(k) regulation. And, as mentioned, a reallocation to the field of resources to premarket reviews is warranted as well.
CDx assays, whether LDTs or PMA tests, are usually qualitative tests that do not reveal cut-off or precision. This is a potential source of patient harm since the products may vary. A coordinated regulatory policy is needed. This policy should require all qualitative tests to have their cut-offs and precision published. For example, when a patient is declared “mutation positive,” physicians would understand the cut-off being used and whether that cut-off and precision from a CLIA lab is the same as those of a product reviewed by FDA. This approach would go a long way to address the Genentech petition to regulate laboratory LDTs and allow regulatory effectiveness to be measured.
It is not in patients’ interest for FDA to say, “Use only the FDA-approved companion diagnostic tests,” because that is not how the LDT and FDA-regulated markets operate. This is a true opportunity for regulation to actually serve and protect the public. To improve and measure regulatory effectiveness, FDA leadership should focus inspection resources on QSR compliance and on OIVD leadership’s using current regulation to improve the 510(k) process. LDTs, companion diagnostics, and other IVDs need to provide physicians a consistent interpretation. This means a requirement that all test labeling document cut-off and precision.
Finally, where quality systems fail, FDA should hold the most senior individuals in management responsible, rather than shareholders. Imagine if a consent decree disqualified top executives when not closed in three years, and policy-based civil penalties should be considered for top executives rather than shareholders. Holding executives responsible financially would surely improve quality. With these changes, we can improve medical products and processes and the measurement of regulatory effectiveness.

Glen Paul Freiberg, RAC, is president, RCQ Consulting (Rancho Santa Fe, CA). He can be reached at glenf92067@aol.com.

Part 1 of this column appeared in the March 2011 issue.