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
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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
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