This is the second in a series of three posts on Laboratory Developed Tests (LDT).  In this installment, I summarize developments in the past few years as the FDA eventually announced its intention to more actively regulate all LDTs.  The first first post covered the definition of LDTs and the current state of regulatory oversight.  In the next (and last) post, I discuss where to find comparative analysis reviews of LDTs and add a few thoughts on LDT policies for pathology departments, cancer centers, and healthcare systems.  

The FDA recently decided to end its policy of enforcement discretion and more actively regulate LDTs.  The agency has said it plans adopt a phased-in risk-based regulatory framework, but the details have yet to be established.  A summary of key developments over the past few years is provided below:

• The FDA issued a revised draft guidance in 2007 stating that In Vitro Diagnostic Multivariate Index Assays (IVDMIA) do not fall in the category of LDTs for which the agency had exercised enforcement discretion.  This was a revision to a draft guidance issued in 2006.
• The FDA cleared the first IVDMIA, MammaPrint® (a breast cancer gene expression profiling test), in February of 2007. 
• The FDA later dropped its proposal to regulate IVDMIA as a subset of LDTs and announced plans to more actively regulate LDTs in general.
• In April of 2008, the (Health and Human Services) Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS), recommended that "FDA should address all laboratory tests in a manner that takes advantage of its current experience in evaluating laboratory tests". 
• In an effort to get more input from laboratory professionals, treating physicians, patients, and industry, the FDA and the Center for Devices and Radiological Health (CDRH) held a public meeting on the oversight of LDTs in July 2010.  The subsequent public comment period originally scheduled to end on August 15, 2010 was extended to September 25, 2010.
• In July 2010 the FDA and CMS signed a Memorandum of Understanding (MOU) stating that the agencies would work together to build the infrastructure and processes required to evaluate LDTs safety, efficacy, coverage, payment, etc.

The FDA expects to begin providing details of the new regulatory structure a few months after the July 2010 meeting.  At the time this post was written (December 30, 2010), few, if any, new details were available.

Several key questions remain:

What type of premarket evaluation will be required?  Will companies and laboratories go through existing premarket evaluation [i.e. 510(k) clearance or premarket approval (PMA)] or a modified (or new) version of these requirements designed for LDTs?

The language in the MOU between the FDA and CMS included the words “payment” and coverage.”  But, will the agencies indeed work together to match reimbursement to the increased cost of premarket evaluation by the FDA?

What will the risk-based framework for evaluation of LDTs look like?  The College of American Pathologists (CAP) proposed it own risk-based scheme for LDTs.  It consists of three categories: low, moderate, and high risk.  The risk stratification is based on the likelihood of an incorrect result leading to serious morbidity/mortality and whether the test methodology is well understood and/or independently verifiable.  Premarket review by the FDA would only be required for high risk LDTs.  Moderate risk LDTs would undergo prior review and approval by CMS-deemed accreditors. 

If you would like to follow developments in the regulation of  LDTs, I recommend the following sources:

GenomeWeb (take a look at Kirell Lakhman’s blog, The Sample, and Turna Ray’s articles in the Pharmacogenomics Reporter)

Myraqa (timely blog posts by Mya Thomae and others)

American Clinical Laboratory Association (the ACLA and its president, Alan Mertz, have followed the evolution of LDT regulation closely, click here for more from their web site)

College of American Pathologists (information on LDTs can be found under the Advocacy tab)