PRECLINICAL/NONCLINICAL STUDY DESIGN &
MANAGEMENT
We are able to tailor resources in a
vendor-agnostic manner and
provide our clients 1) the best
value financially, 2) the highest
quality technically, and 3) the
lowest risk programmatically.
Also, as a wholly-owned subsidiary
of CSC, DVC is able to leverage a
deep network of expertise in
information technology,
biostatistics, program management
and contracting/subcontracting
best practices.
For more than 15 years, DynPort Vaccine
Company LLC (DVC) has been a leader in
advanced development of medical
countermeasures against high-threat
biological and chemical agents for a
number of US Government clients,
including the Department of Defense and
Health and Human Services. This
advanced development is accomplished by
managing the life cycle of medical products
and services through systems integration,
using in-house scientific expertise, a
network of highly qualified subcontractors,
consultants and industry partners.
Every stage in the process is designed to
support the overall regulatory strategy, and
studies are designed to provide only
essential information required for product
licensure. Additionally, the overall study
design is developed to achieve efficiencies
in schedule and budget without sacrificing
quality of the data. This approach has
been informed by extensive interaction
with regulatory agencies and is designed
to meet the specific needs of our clients.
NONCLINICAL STUDIES: KEY TO
PROGRAM SUCCESS
Development of medical products requires
the use of in vivo and in vitro studies,
collectively referred to as “nonclinical”
studies. These studies include assessment
of both safety and efficacy, and are
required before any medical product can
be tested in humans. With our experience
in advanced development and licensure of
biopharmaceutical products, DVC has
established a system of robust and
reproducible nonclinical study design
modules based on best practices and
successful regulatory interactions.
EXPERIENCE WITH THE FDA ANIMAL
RULE
The FDA Animal Rule was established to
facilitate the licensure of products when
standard clinical trials are inappropriate,
particularly high-hazard threats such as
Chemical, Biological and Radiological
threats. Strategies for addressing the
Animal Rule include a close interaction
PRECLINICAL/NONCLINICAL STUDY DESIGN & MANAGEMENT
SUCCESS STORY:
Ensuring Safety
Well-designed and carefully
conducted nonclinical safety studies
are crucial in the drug development
lifecycle, since they are necessary
before any product can be tested in
humans. For small molecule drugs,
the specific types of safety testing are
highly defined and conducted in a
specific sequence.
However, nonclinical safety
assessment for vaccines is quite
different. In general, vaccines have
historically been seen as intrinsically
safer than other medical products
and, as a result, have required far less
stringent testing. Consequently,
designing safety studies for vaccines
should be tailored to the nature of the
product itself.
As part of our development program
for the rBV A/B botulinum neurotoxin
vaccine for the DoD, DVC conducted
a series of standard toxicology tests in
animals. This vaccine uses a region of
the botulinum neurotoxin that is
theoretically incapable of producing
the toxicity associated with the whole
neurotoxin. However, to ensure the
greatest confidence of safety, DVC
designed studies to evaluate any
potential neurovirulence of the
vaccine as well. The challenge: all of
our safety studies used the mouse,
which is not routinely used for
neurovirulence studies.
Working closely with our
subcontractor, we were able to adapt
the existing neurovirulence study
design to accommodate mice. As a
result, we were able to complete the
safety assessment in one animal
model, preventing the need to perform
costly and time-consuming development
of additional animal models.
between nonclinical and clinical studies,
since the results of each of these types of
studies must be combined to demonstrate
the efficacy of products that can’t be tested
directly in humans. To date, few products
have met the stringent requirements of the
Animal Rule.
Working with expert subcontractors, the
FDA and our clients, DVC has developed
significant practical expertise in designing
and managing nonclinical studies that
meet the specific requirements of
individual products. It’s important to note
that there are no “standard” design
templates or protocols for addressing the
Animal Rule – each product has its own
specific needs. More importantly, because
only a limited number of products have to
date been licensed this way, few
companies have experience with such
designs.
DVC has designed Animal Rule strategies
for a number of products, and is currently
successfully managing advanced
development of three products that require
use of the Animal Rule.
The graphic on the previous page
illustrates DVC’s Animal Rule approach to
incorporating nonclinical study design,
management, and data interpretation into
successful medical product development.
nonhuman primates (cynomolgus and
rhesus macaques), rabbits, rodents and
guinea pigs. DVC works with a network of
proven subcontractors to perform these
studies, carefully selecting laboratories
with specific expertise and capabilities. By
choosing laboratories this way, we are able
to match capabilities with requirements,
ensuring the most effective and efficient
testing program possible.
A LEGACY OF SUCCESS
We have designed and managed
nonclinical study programs for medical
products associated with the following
agents:

Francisella tularensis (tularemia vaccine)

Bacillus anthracis (anthrax vaccine)

Yersinia pestis (plague vaccine)

Venezuelan Equine Encephalitis Virus
(vaccine)

Variola major (smallpox vaccine)

Botulinum neurotoxin (vaccine)

Vaccinia immune globulin intravenous
(plasma-derived therapeutic antibody)
While DVC’s experience has historically
been in developing medical
countermeasures, our approach and
methodology are highly adaptable to any
type of medical product or service.
SAFETY STUDIES
The paramount concern in development of
any medical product is safety in humans.
Accordingly, extensive studies are required
for testing safety of such products prior to
conducting clinical trials, as well as during
the entire clinical trial period. Working with
our network of expert subcontractors, as
well as our in-house toxicology expertise,
DVC can design and manage all studies
necessary for licensing medical products.
EFFICACY STUDIES
While the only true predictor of a product’s
effectiveness can only be assessed using
human (clinical) trials, it is necessary to
test efficacy initially in animals. DVC has
more than 11 years of experience with a
variety of animal models species including
EXAMPLES OF RECENT NONCLINICAL
STUDIES MANAGED BY DVC
Shearer, J.D., Manetz, T.S. and House,
R.V. (2012). Preclinical safety assessment
of recombinant botulinum vaccine A/B (rBV
A/B). Vaccine. 30(11):1917-1926.
Inhalational botulism in rhesus macaques
exposed to botulinum neurotoxin complex
serotypes A1 and B1.
http://1.usa.gov/1chWO55
Establishment of a Swiss Webster mouse
model of pneumonic plague to meet
essential data elements under the Animal
Rule. http://1.usa.gov/1d3T0pc