Lab Matters Summer 2019 - Page 23

INDUSTRY MATTERS FDA Clears Two Tests for Extragenital CT and NG By Nicholas J. Moss, MD, MPH, director, HIV STD Section, Division of Communicable Disease Control & Prevention, Alameda County Public Health Department and Mark Pandori, PhD, HCLD(ABB), director, Division of Communicable Disease Control & Prevention, Alameda County Public Health Laboratory In May 2019 the US Food and Drug Administration (FDA) cleared two long- awaited laboratory tests for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) in extragenital specimens. The approval reflects the clinical importance of extragenital rectal and pharyngeal CT and NG infections and the changing epidemiology of these organisms. The US Centers for Disease Control and Prevention (CDC) recently reported “steep and sustained increases” for CT and NG. This resurgence appears to be driven by changes in sexual behavior, decreasing public awareness of HIV, use of the internet to meet sexual partners and the opioid and methamphetamine epidemics. Young people, gay men and other men who have sex with men (MSM) are particularly impacted. Untreated CT and NG can cause pelvic inflammatory disease, chronic pelvic pain, ectopic pregnancy and infertility in woman. Routine screening for CT and NG is recommended for young women but typically limited to urogenital sites. Yet rectal and pharyngeal CT and NG infections are common, often asymptomatic and can occur in the absence of urogenital infection. Undiagnosed infections are a reservoir for transmission, and pharyngeal infection may facilitate the spread of NG antimicrobial resistance. The CDC recommends screening extragenital sites in MSM, and the California Department of Public Health recently made similar recommendations. Despite such guidance, extragenital testing for CT and NG is not widely performed. Among the notable barriers has been the shortage of laboratories offering tests. For years, the lack of FDA-cleared tests for extragenital CT and NG has been addressed with laboratory-developed tests (LDTs), but only some laboratories have been able to supply these. Any test that is not FDA-cleared, or any test that is FDA-cleared but used “off-label,” is categorized as an LDT, with several notable consequences. First, there are PublicHealthLabs @APHL Chlamydia trachomatis more stringent verification requirements for LDTs, including determination of analytical sensitivity and specificity. Second, classification of a test as an LDT automatically makes it “High Complexity,” limiting the types of staff that can perform it (substantially so when the original test was deemed “Moderate Complexity”). Third, regulatory bodies are redefining (and likely tightening) LDT oversight, perhaps leading to more complexity in their use. Also, for laboratories seeking to validate existing molecular tests for use with extragenital CT and NG specimens, the process has been daunting. Panels of positive and negative specimens for rectal and pharyngeal CT and NG were (and remain) hard to obtain. Very few laboratories are able to provide such specimens, and they often have waiting lists. This issue will complicate the verification of the FDA-cleared tests as well. The use of spiked specimens may need to be considered. Despite this, the recent FDA clearance will allow for extragenital CT and NG testing at many more laboratories. The clearance is also notable because two different tests were cleared, each with different strengths. The Hologic APHL.org Aptima Combo 2 ® assay provides high sensitivity and can be efficiently run in small, medium and large laboratories using the Panther system. The Cepheid Xpert CT/NG provides a moderately complex test that is easy to perform near point-of-care for possible use in STD or public health clinics. The development and wide dissemination of new technologies can have profound public health impacts. The newly cleared extragenital CT and NG tests will have such an impact. Moreover, the clearance illustrates how laboratories can wield the tools to provide leadership through capability. It is now the responsibility of laboratories to ensure that these tests are made known to clinicians and other stakeholders within their communities. n The Alameda County Public Health Laboratory participated as one of two laboratories that performed testing and data collection for the FDA clearance process. Hologic is a Diamond Level Sustaining Member of APHL. Summer 2019 LAB MATTERS 21