tember 14, 2010 Division of Dockets Management (HEA-305) Food and Drug Administration 5630 Fishers Lane. Ri, 1061, Rockville MD 20852 Statement for the Record Submitted to the Food and Drug Administration Department of Health and Haman Services Docket No. FDA-2010-N-0274 Oversight of Laboratory Developed Tests (LDTs) Secretary Sebelius and Commissioner Hamburg, We appreciate the opportunity to submit comments in response tothe recent open ‘meeting on oversight of laboratory developed tests (L.DTs) and are writing to you on behalf of patients who suffer from rare hereditary disor. A “rare” disorder is one affecting fewer than 200,000 individuals, and so there are approximately 30 million individuals inthe United States affected by a rare gencte disease Genetic esting for rare disorders is accomplished. in virally all eases, through LDTs. ‘These tests have been developed and are performed in boutique laboratories throughout the United Staes by American Board of Medical Gensties-cetified doctoral level ‘geneticists wien requested by health care providers. most frequently clinical geneticists fc counselors. Neary all the tests were developed in collaboration with hers who identified the gene responsible forthe disorder. and who worked with a CLIA-cenifed laboratory to establish the laboratory protocol so that the tess can be made availabe ta the affected families once the molecular basis ofthe disorder was re 1866 diseases cutrenly being tested in a CLIA-cenified laboratory here are 353 CLIA-certfied laboratories doing these tess (ass genetests one) Some do only ane ora ewe yonee and over B00 af these gene ests are available only from a single CL1A-cenified laboratory (for example, KRTI and KRT10 testing for Epidemolytic Hyperkeratosis. TGMI testing Lamellar Tehthyosis. ABCC6 testing in Pseudoxanthoma Elasticum, ANK2 testing in LongQT Syndrome Type 4. ete). An additional 450 tests are availible in only 2or 3 laboratories (PTEN sequencing for Cowden Syndrome/Bannayan-Ruvaleabe-Riley Syndrome/Autism. RET gene testing for Multiple Endocrine Neoplasia Type 2428 ‘MMirsehsprung Disease. ete.)As each of these disorders is very rare. there may be as Few as 10 oF up to a few hundred {ests for any particular disorder performed annually. In many eases. the mutation in a particular family willbe “pivate™. meaning that the entre gene oF interest must be sequenced rather than testing fora few common SNPS or mutations. a is possible for Cystic Fibrosis testing ora sereen for Ashkenaki Jewish mutations) ta identify the basis of the disease in that Family. perience withthe mutation spectrum associated with a particular disorder, and knowledge of genotype/phenotype correlation is essential to provide an appropriate interpretation of the genetic test result. Because of the expense to set-up an LD tora rare distase the limited market for any given test and the level of expertise required to perform and interpreta gene-sequencing test, larger full-service ‘commercial laboratories have not stepped forward to provide rare disorders testing. ‘The CLIA regulatory landscape has allowed the rapid development and validation of each new rare disease test and its consequent availability to patients and Families. White the rae disease community wan's to be assured that the available tests for their disorders are ‘analytically valid, and perfomed by capable genetics professionals. we are confident that ‘oversight provided by CMS *hrough the CLIA regulations strikes the appropriate balance ‘between patient access and test accuracy and reliability. We would like any new ‘oversight to actually encourage development of new tests for rare disesse, and not to ‘cause a chill that would eause current tests to be removed from the market. The east 10a small laboratory in time. pessonnel, and dollars. to bring a rare disease test through an FDA approval or clearance mechanism is prohibitive. These costs are likely to exceed ‘any revenue that would everbe realized for the most rare ofthe diseases (which are often the most severe and debilitating disorders. with very high eost to society). The alternative ‘mechanism, through the Hunnanitarian Device Exemption provisions ofthe Orphan Drug ‘Act is also impractical and unworkable forthe testing laboratories, and inappropriate since the Act was designed for devices. and is not well suited for diagnostics. The limitation on charges exceeding costs also is a disincentive for laboratories to develop such tests. Some ofthe smaller lahs provide tests for many rare diseases (for example, GeneDs in Gaithersburg, MD provides sequencing-based gene testing in>250 rare disorders) and the sheer volume of work involved in taking the tess through an approval ‘mechanism would require tht only a subset of tests those with the largest market, would be taken to the FDA while the remainder would simply become unavailable. ‘We would like fo offer an aliemative mechanism to assure that genetic testing for rare disorders remains of extremely high quality and available to the patients and families who ned these teste 1. We recommend an exemption from FDA oversight for genetic tests for rare isorders 2, Currently. vitualy all such tests provided by Cl.IA-cenified laboratories are listed in GeneTests (9 9 genetests.org). With the development ofthe Genetic ‘Test Regisiry (GTR) (hiup:/»sw.nehi,alm.ni.govgte) which is likely to expand ‘upon GeneTests. we recommend that all tess designated under a “Rare Disorders Exemption” have mandatory egistation in the GTR,3. We recommend that item 2 above) is phased-in over a 3-5 year period after the establishment ofthe GTR. tallow labs witha large number of rare disorders tests to accomplish the task of submitting data to the GTR. 4. Werecommend thatthe ordering of genetic tests. and result reporting. for rare disorders be restricted to health care professionals. inluding, bat not limited to, oneticists and genetic counselors ‘5. Werecommend that laboratories providing testing for rare genetic disorders be limited to those under the direction of appropriately certified Medicel/Ciinical or Laboratory Specially Geneticist 6. Werecommend that all laboratories performing rare yenotic testing continue tobe regulated through the CLA mechanism, and that a “Genetic Testing” specialty be ‘We thank you very much for this opportunity to provide comment, and for your consideration of our suggestions, We are available to discuss any issues pertaining 10 ing availability of rare and ulta-rare disorders genetic testing for patents, Sincere Bee SSK Sher ate, P.D..FACMG sharon. en) MA, Clineal Discor cto Geneds enc Alans 1 for 7 Century Medicine