Washington, DC (June 25, 2010): Yesterday, the Association for
Molecular Pathology (AMP) gave public comments at the FDA's Center
for Devices and Radiological Health (CDRH) Council meeting on
Medical Device Innovation: Barriers to Market for Molecular
Diagnostic Tests.
AMP commends the Federal departments and agencies that compose
the Council on Medical Device Innovation for making efforts to
identify and remove barriers to innovation and progress in
transitioning basic and transitional research findings into routine
clinical practice. In its remarks, AMP identified three barriers
that impede the path to FDA clearance or approval for diagnostic
tests and reduce the motivation to submit some medically useful
tests for review.
Barrier 1. The paucity of standard reference materials for all
areas of molecular diagnostics, i.e., genetic, oncology, and
infectious disease testing, inhibits the production of appropriate
control materials and methods. "AMP is eager to see more progress
and investments in this area," said Dr. Mark Sobel, AMP's Executive
Officer. "FDA can assist by providing a list of needed standard
reference materials to relevant organizations such as the National
Institute of Standards and Technology (NIST) and World Health
Organization (WHO)."
Barrier 2. The difficulty of obtaining rare specimens for
studies presents a barrier to submission of applications for the
approval of new indications for currently approved tests. Herpes
Simplex Virus (HSV) testing has been the standard of care for the
diagnosis of central nervous system (CNS) disease (HSV encephalitis
and meningitis) for over a decade, yet an FDA approved test does
not yet exist. HSV CNS infections are relatively rare and any
individual laboratory may receive only 1-2 HSV encephalitis
positive specimens a year. Manufacturers who developed assays for
the novel 2009 influenza H1N1 strain encountered similar
difficulties in validating their assays using prospective clinical
specimens after the peak of the pandemic had passed.
Dr. Sobel identified a potential solution to the shortage of
specimens, "The FDA should work to establish a biorepository of
clinically relevant infectious agents, including strain variants
and subtypes, to facilitate the rapid development and validation of
assays for infectious agents, particularly those with pandemic
potential." Alternatively, AMP also asked the FDA to consider
establishing alternative validation strategies that are independent
of primary clinical specimens, but are, nonetheless, rigorously
grounded in sound science and infectious disease medicine.
Barrier 3. Test manufacturers perceive that there is an
inconsistent and unclear regulatory pathway for their submissions.
Manufacturers have faced uncertainty and/or inconsistency in the
review of device submissions, in enforcement discretion, in device
classification [510(k), 510(k) de novo, PMA, ASR, etc.], in
requirements for acceptable analytical and clinical validations,
and in requirements changing from the time of pre-IDE meetings
through mid-trial. "IVD test manufacturers must then function
within this uncertain regulatory environment, which makes it
difficult to anticipate regulatory requirements and appropriately
amend their business models," said Dr. Sobel.
To address the barriers identified above, AMP believes that the
FDA can take several steps that would improve the regulatory
process for molecular diagnostic tests without impinging upon an
appropriate review to ensure that the public is protected.
- FDA should ensure that policies and requirements are
consistently applied, and that the scientific evidence and
rationale for decisions are communicated effectively to diagnostic
test manufacturers.
- Communication from FDA to diagnostic test manufacturers should
be as clear and as comprehensive as possible at the outset of the
submission process. This will help manufacturers better plan their
resources and time. It will also assuage undue angst that the
regulatory bar will change during the process.
- FDA should improve communication between government branches
and agencies so that consistent requirements are developed and
applied and demonstrations of clinical utility in one branch are
recognized by the other branches.
- FDA should involve the expert opinion of medical professional
associations regarding clinical utility.
The Association for Molecular Pathology recognizes the
difficulties that regulatory agencies face in the context of the
rapidly changing landscape of diagnostic devices and technology and
appreciates the transparent process FDA is undertaking to improve
the review process for medical devices. AMP believes that a
consistent, clear, and flexible regulatory process will result in
improved public access to additional higher quality innovative
tests; and could conceivably lower healthcare costs.
"AMP stands ready to assist the FDA through our expertise,
creative problem solving, and unique perspective," added Dr. Sobel.
"We would like to offer our input and interaction with the member
departments and agencies to assist in developing a more consistent,
evidence-based, and transparent process for regulating diagnostic
devices."
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