DRW Monthly
January 2007
Issue No. 2

Regulatory Issues Surrounding Genetic Testing in the US

The US is currently lacking a coherent system of regulations to evaluate the accuracy and reliability of genetic testing. The federal agencies involved in genetic testing oversight are all within the Department of Health and Human Services (HHS) and include the Centers for Medicare and Medicaid Services (CMS), the Centers for Disease Control (CDC), the Food and Drug Administration (FDA) and the Office for Human Research Protections (OHRP). Despite their shared public health goals, these agencies have largely worked independently to regulate the laboratory, clinical and product development aspects of genetic testing. The three regulations governing genetic testing that are administered by these agencies include the Clinical Laboratory Improvement Amendments of 1988 (CLIA), the Federal Food, Drug and Cosmetic Act and the Federal Policy for the Protection of Human Subjects.

CMS has regulatory authority over all laboratory testing and is also responsible for the implementation of CLIA and CLIA standards. CDC is responsible for categorizing laboratory tests. FDA regulates as in vitro diagnostic devices those genetic tests which are sold as "test kits" if the components of the test are bundled together, labeled for a particular use, and sold to a laboratory as a unit. However, since most genetic tests are developed in-house at laboratories (referred to as "home brew"), they are treated as clinical laboratory services and are not subject to FDA approval. There are about 1000 genetic tests clinically available today and only five have been approved by the FDA as test kits.(1) FDA also regulates as medical devices the active ingredients or "analyte-specific reagents" (ASRs) used to perform home brew tests. ASRs may be sold only to laboratories certified to perform high complexity tests and must be labeled in accordance with FDA requirements.(2) "A September 2006 draft guidance also extended FDA enforcement to a subset of laboratory-developed-and-provided genetic tests, which FDA terms in vitro diagnostic multivariate index assays (IVDMIAs). These tests use laboratory data and an algorithm (analytical tool) to generate a result for the purpose of diagnosing, treating, or preventing disease."(3)

Although genetic testing laboratories must be certified by CMS under CLIA, the amendments contain no laboratory standards that specifically address molecular or biochemical genetic testing. Nor does the regulation provide uniform proficiency testing procedures for genetic tests even though they are classified as "high complexity" tests under CLIA. Since CMS has not created a genetic testing "specialty area," there is no mandate for laboratories to enroll in formal proficiency testing programs which has resulted in widely divergent quality control practices among these laboratories. In 2000, CDC published a "Notice of Intent" in the Federal Register, announcing the HHS would release a notice of proposed rulemaking (NPRM) recommending the creation of a new genetic testing specialty under CLIA. However, to date, no NPRM has been issued.(4)

In addition to the federal oversight provided by the HHS agencies, a number of advisory bodies were convened as early as 1995 to review the regulatory status of genetic testing in the US. The first government task force was jointly assembled by the National Institutes of Health (NIH) and the Department of Energy (DOE) to ensure the development of safe and effective genetic tests. The NIH/DOE Task Force was succeeded by the Secretary's Advisory Committee on Genetic Testing (SACGT) in 1998 and charged with advising HHS on all aspects of genetic test development and use. Both the NIH/DOE Task Force and the SACGT recommended that CLIA regulations be expanded to encompass specific provisions for genetic testing laboratories and recommended that CMS, CDC and FDA work together to develop and implement additional genetic testing oversight.(5) The Clinical Laboratory Improvement Advisory Committee (CLIAC), an advisory group within the CDC, was formed in 1992 to provide scientific and technical advice regarding revisions to clinical laboratory standards. CLIAC also became involved in providing advice on the regulation of genetic testing in 1998. Although CLIAC and SACGT share some areas of overlap, CLIAC's expertise is in laboratory testing while SACGT's focus is on the medical/social areas of genetic testing.(6) The SACGT has since been replaced by the Secretary's Advisory Committee on Genetics, Health, and Society (SACGHS) which is charged with making recommendations concerning the broader implications of developing and using genetic technologies.

More recently, several groups in the US, including the Genetics and Public Policy Center, the Public Citizen's Health Research Group and the Genetic Alliance, submitted a petition to CMS requesting that the agency implement CLIA by creating a genetic testing specialty and establishing standards for proficiency testing. CMS placed the issuance of a proposed rule on its Semiannual Regulatory Agenda and testified before the SACGHS that it was in clearance in June 2006. However, in August, CMS officials indicated they were dismissing their original intent to create a specialty because the current regulations are adequate to ensure the accuracy and reliability of genetic testing laboratories.(7) The latest action taken on this issue was a notice appearing in the January 19th Federal Register to announce a CLIAC meeting to be held on February 14th. The meeting agenda will include updates from the CDC, CMS and FDA as well as a discussion of the status of the ``Notice of Proposed Rulemaking'' for genetic testing.(8) It will be interesting to see what conclusions emerge from this meeting and whether CMS will resume its intent to create a specialty area for genetic testing.

Related Resources

If you desire further information about this topic or any other regulatory issue, please feel free to contact me:

Diane Whitworth
DRW Research & information services, LLC
(tel.) 301.916.9669
drwresearch@comcast.net

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