Download February 2, 2015 The Honorable Margaret

March of Dimes Foundation
Office of Government Affairs
1401 K Street, NW Suite 900A
Washington, DC 20005
Telephone (202) 659-1800
Fax (202) 296-2964
February 2, 2015
marchofdimes.com
nacersano.org
The Honorable Margaret Hamburg, MD
Commissioner
Food and Drug Administration
U.S. Department of Health and Human Services
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852
Re: Docket No. FDA-2011-D-0360
Dear Dr. Hamburg,
The March of Dimes, a unique partnership of scientists, clinicians, parents, members of the
business community and other volunteers affiliated with chapters in every state, the District of
Columbia and Puerto Rico, appreciates this opportunity to submit comments regarding the Food
and Drug Administration’s (FDA) Draft Guidance, Framework for Regulatory Oversight of
Laboratory Developed Tests (LDTs), as published in the Federal Register on October 3, 2014.
As an organization committed to the health and wellbeing of women, infants, children, and
families, the March of Dimes commends the FDA for its effort to ensure that the diagnostic tests
offered to patients are safe, effective and accurate. The March of Dimes would like to urge the
agency to direct special attention to the appropriate balance among safety, efficacy, innovation,
and timeliness, as well as to the particular implications of this proposal for newborn screening
tests.
A Balance Must Be Established
Throughout its 77 year history, the March of Dimes has repeatedly played a central role in the
development of lifesaving tests and products. Founded by President Franklin Delano Roosevelt
to develop a vaccine for polio, the March of Dimes went on from achieving that goal to funding
research that has contributed to numerous additional tests and drugs, ranging from screenings
for devastating newborn metabolic disorders to surfactant for premature infants’ lungs. We
therefore have a strong interest in developing innovative products to improve patients’ health
and bringing them to patients expeditiously as well as ensuring the safety, reliability and
effectiveness of those products.
The FDA faces a significant challenge in striking the appropriate balance among these goals. The
March of Dimes expects that the coming years will witness the development of an array of new
screening and diagnostic tests that could transform the field of maternal and child health. The
March of Dimes is currently completing the establishment of a $75 million dollar network of
Prematurity Research Centers to pursue a comprehensive research agenda on the causes,
detection and prevention of preterm birth. It is our full
expectation that this investment will result in groundbreaking tests and therapies that will
revolutionize our understanding of both normal pregnancy, labor and delivery and also the
conditions of pregnancy that can result in poor birth outcomes. As these new tests and
products are developed, we will have a keen interest in seeing they are commercialized and
adopted as quickly as possible to save lives and improve patient health. We are also, however,
committed to demonstrating their safety and validity to the FDA’s satisfaction. It is therefore
incumbent upon all parties to work together in designing a system that allows us to achieve all
of these goals in an expeditious manner.
Beyond the March of Dimes’ own research, the coming years are expected to see the
development of new tests and products on a range of other maternal and child health issues,
many of which have a profound impact on patients’ health and lives. The field of fertility and
reproductive health research will likely see advances in tests that predict a couple’s ability to
conceive, and in the health and viability of the embryo and fetus at various stages of
development. We look forward to the development of new tests for neonates suffering from
prematurity, low birthweight, birth defects and other conditions that result in long stays in
Neonatal Intensive Care Units. The advance of “precision medicine” may allow us to predict
which newborns will experience adverse reactions to certain medications, thereby averting
devastating health consequences. Each of these has the potential to transform the lives and
health of individuals and families.
The March of Dimes would therefore like to express our commitment to working closely with
the FDA to ensure that any regulatory framework for LDTs promotes patient health through a
rigorous but timely process. Our patients need and deserve tests and therapies that are safe
and effective, but also made available to them with all deliberate speed.
Newborn Screening Tests Require Special Consideration
The March of Dimes would like to draw the FDA’s attention to the particular implications the
new LDT framework could have for newborn screening programs. As the agency is aware, every
infant born in the U.S. is tested for over two dozen genetic, metabolic, hormonal and
functional conditions that, if left untreated, can cause disabilities, developmental delays,
illnesses or even death. If diagnosed early, many of these disorders can be managed
successfully. In general, the bloodspots collected from newborns are sent to public health
laboratories, which perform the required screening. Many newborn screening tests started out
as LDTs, and some remained LDTs for many years before a commercial version was developed.
The proposed framework leaves unanswered a number of key questions about how LDTs for
newborn screening might be classified or regulated.
Classification of newborn screening tests should be stated explicitly. It is unclear how FDA
would classify newborn screening tests, and whether they might qualify as either rare tests or
LDTs for unmet needs. While newborn screening identifies rare disorders, they are hardly rare
tests under the FDA’s proposed threshold of 4,000 individuals since they are performed on
millions of newborns each year.
It is possible that certain newborn screening tests might qualify as LDTs for unmet needs. For
example, while the HHS Secretary accepted the recommendation of her Advisory Committee on
Heritable Diseases in Newborns and Children for universal newborn screening for Severe
Combined Immunodeficiency (SCID) in 2011, the FDA only approved a commercial test for SCID
in December 2014. Prior to that, SCID testing was performed utilizing only LDTs.
Requiring each public health laboratory to submit its newborn screening tests individually may
represent a significant burden and interfere with testing. Public health laboratories, which
often operate in an environment of constrained staff and resources, may face unique challenges
in submitting to FDA a list of every LDT in use, much less validating data for them. In the case of
newborn screening, it is common for labs to share information and utilize the same LDT
formulation. Under the FDA’s proposed framework, however, each public health laboratory
would be required to report its LDTs individually, and potentially to submit data for approval. If
a laboratory were unable to complete the FDA’s reporting requirements, it is further unclear if
they would be in violation of the FDA’s rules to continue the state-mandated newborn
screening. The March of Dimes urges the agency to explore solutions that would address the
special challenges faced by public health laboratories with regard to newborn screening in ways
that will not interrupt these critical tests.
FDA should designate a grace period for LDTs after a commercial test becomes available. As
noted above, many newborn screening programs use LDTs for an extended period of time
before a commercial version of the test is approved by FDA. The agency notes in the guidance
that, “…once FDA clears or approved an IVD for the same intended use, FDA will no longer
consider the LDT to be an “LDT for Unmet Needs.”” The agency should state clearly a time
period within which laboratories will be expected to shift to the commercial product. Because
commercial tests may be more expensive than LDTs, such changes may have implications for
newborn screening program budgets that must be addressed through the state’s legislative
process. Again, there is the potential for the FDA’s approach to interrupt these critical statebased testing systems if the downstream implications are not fully considered by the FDA.
The March of Dimes appreciates the opportunity to share our views on this important draft
guidance. If we may provide further information or otherwise be of assistance, please contact
James Gelfand, Director of Federal Affairs, at 202-659-1800 or [email protected].
Sincerely,
Dr. Jennifer L. Howse
President