In the November/December 2010 issue of IVD Technology, I discussed moves made by FDA to regulate laboratory-developed tests (LDTs, formerly known as “home brews”). Examples of inadequate LDTs were formally submitted to FDA in Genentech’s December 2008 Citizens’ Petition, but the agency’s discomfort with LDTs has a long history. New guidance documents and presentations in recent months have sought to clarify FDA’s intentions and produced many responses from those who might be adversely affected by these positions.
The document that initiated the current debate was issued on June 1, 2011, and titled “Draft Guidance for Industry and FDA Staff - Commercially Distributed In Vitro Diagnostic Products Labeled for Research Use Only or Investigational Use Only: Frequently Asked Questions”—mercifully abbreviated “RUO/IUO.” This is not a new pronouncement but an updated draft guidance. It is clear that FDA learned something from the In Vitro Diagnostic Multivariate Index Assay (IVDMIA) adventure, because the new document identifies manufacturers as the party the FDA wishes to regulate, rather than hospitals. As Alberto Gutierrez explained during an AACC webinar in October of last year, RUO products may be marketed only for research use by general-discovery laboratories and are appropriate “for products used in legitimate research to develop fundamental scientific knowledge.”
The scope of FDA’s proposed definition of RUO products potentially covers a wide range of instrumentation and reagents. Many groups are struggling to understand how this guidance would affect everyday business in the clinical laboratory. AACC, in its August 23, 2011, response to the draft, mentioned “spectrophotometers, balances, and tandem mass spectrometers” as RUO/IOU instruments that may be affected. A document drawn up by the College of American Pathologists and dated August 29, 2011, states that “patient care especially in areas of hematology, tumor immunology and chemotherapy, prenatal diagnosis, women’s reproductive health, prenatal screening, genetic testing, and histocompatibility testing” would be “negatively impacted” by the guidance. And at a December 15 teleconference organized by ARUP Laboratories, their lab directors asked, “Will manufacturers discontinue reagents that clinical labs have validated as LDTs?” They also asked about how to encourage kit/system manufacturers to submit to FDA.
The June 1, 2011, draft guidance is not the only recent agency pronouncement addressing components of a final product. On July 1, 2011, FDA announced its intention to regulate the food-supplement industry with a draft guidance document. Note that it is not products themselves that will be regulated but “dietary ingredients.”  Dr. Gutierrez, during his AACC webinar, clearly stated why FDA is concerned about raw materials-these materials “lack FDA review, are generally not manufactured under GMP,” and “lack all other general controls.” Furthermore, their “safety and effectiveness [are] unknown, putting patients at risk.”
I don’t believe that anyone in our highly regulated diagnostic industry would add melamine or over-sulfated chondroitin to our products to save a dollar. Yet the food and drug industries have experienced these contamination problems in recent years, with serious consequences. But what about a biological material, from a small supplier, that fails to perform as expected? This is an everyday experience in research. Would you use an antigen from a new supplier in your FDA-cleared kit without running QC tests? Would you substitute a new lot of antibody into a marketed product without an extensive evaluation? Do you have confidence that laboratories offering LDTs routinely perform these steps?
Ultimately I could express the debate about RUO/IUO by asking one simple question: “This is 2012: How much science do we need to do before we modify healthcare?” In fact, many entrepreneurs lack faith in science, have no time for it, or can’t afford it; it is a secondary consideration within the general category of “running a business.” At the JP Morgan conference in January 2012, the CEO of a small molecular diagnostics reference laboratory proudly announced that his lab will not launch an LDT until a study has been published to demonstrate clinical utility. But anyone who has followed biomarker development for the past decade knows that peer review of a single manuscript may not be a significant indicator of quality. Given the current rate of market introduction of new tests, I would like to know that there are some common definitions of quality for diagnostic methods, regardless of their source.