Showing posts with label consider FDA's convoluted relationship with pharmacy compounding.. Show all posts
Showing posts with label consider FDA's convoluted relationship with pharmacy compounding.. Show all posts

Monday, July 15, 2013

How, and When, Will FDA Regulate LDTs? For a possible answer, consider FDA's convoluted relationship with pharmacy compounding. By: Jeffrey N. Gibbs July 15, 2013

Over the years, FDA’s regulation of IVDs has raised many policy issues. Some are short-lived and quickly resolved, such as the creation of the analyte-specific reagent (ASR) regulation, and the subsequent guidance that curtailed the distribution of ASRs. Other policy issues remain open for decades. The regulation of laboratory-developed tests (LDTs) falls into the latter category.
 
FDA first asserted it could regulate LDTs in 1992. That assertion was controversial then, and it is at least as controversial today. During the 21 years since, there have been prolonged lulls, where the issue remains unresolved but simply does not receive much attention. At other times, the issue flares up. This is one of those times, as highlighted by the July 7, 2013 editorial in The New York Times asserting that “regulations are long overdue.”
 
It is uncertain how this issue ultimately will be resolved. Looking at past regulatory initiatives, though, does provide some insight. So, too, does looking at a seemingly unrelated arena: FDA’s efforts to regulate pharmacy compounding.
 

Background

Laboratories, of course, were in existence well before 1976. The Medical Device Amendments of 1976 were silent on the subject of regulating laboratories. Congress explicitly conferred authority on FDA to regulate devices used by laboratories, but the statute said nothing about FDA regulating laboratories themselves.
 
In 1988, Congress did enact legislation aimed at laboratories: the Clinical Laboratory Improvement Amendments of 1988 (CLIA). This legislation, which amended a much weaker existing law, created an elaborate regulatory structure for laboratories. While the impact of CLIA on FDA’s authority to regulate laboratory tests has been debated, it is clear that the 1988 legislation did not bestow regulatory authority over laboratories to FDA.
 
The first mention of FDA’s power to regulate laboratories appeared in an unexpected source: a draft FDA compliance policy guide regarding the regulation of research-use only (RUO) products. Although the focus of the document was RUO products, FDA inserted a comment, almost as an aside, that it could regulate LDTs. (At the time, LDTs were more commonly called “home brews;” but due to that term’s negative connotation, it has been replaced by LDTs.)
 
The issuance of the draft guidance prompted this author to file a citizen petition on behalf of some laboratories challenging FDA’s claim that it could regulate LDTs. The petition challenged FDA’s assertion on a variety of grounds.
 
After this burst of activity, quiescence reigned for five years. Then, in 1997, FDA published the proposed ASR regulation. Although the ASR proposal itself only covered products sold to laboratories, FDA reasserted in the preamble its authority to regulate laboratories. At the same time, FDA said it would exercise enforcement discretion and not regulate these tests. The following year, FDA finalized the ASR regulation and denied the LDT citizen petition.
 
Although FDA reaffirmed its asserted authority to regulate LDTs in the ASR rulemaking, another lull followed. Then, in 2006, FDA issued a new draft guidance, this one directed squarely at laboratories. Creating one of the clunkier acronyms, this draft guidance proposed regulating a subset of LDTs given the name in vitro diagnostic multivariate index analyses (IVDMIAs). Under this draft policy and a similar one issued in 2007, FDA proposed regulating LDTs that utilized complex “black box” algorithms. A fundamental premise underpinning the IVDMIA proposal was that LDTs were, in fact, devices subject to FDA’s jurisdiction. The IVDMIA proposal engendered considerable opposition and eventually was quietly shelved.
 
This was not the only instance in which FDA asserted authority over specific LDTs in this time period. A number of laboratories began to offer diagnostic tests directly to consumers. Partly in response to Congressional hearings, FDA wrote letters – primarily of the “it has come to our attention” variety – to some of these laboratories. Again, FDA’s assertion of jurisdiction over laboratories as devices undergirded these actions. No formal enforcement action was initiated by FDA against these laboratories, and no court ruled on FDA’s assertion of authority over them.
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