Biotech Values

[drbio45]

DARPA and Accelerating Critical Therapeutics

http://www.darpa.mil/news/2009/AMPFactSheet17Feb.pdf

DARPA has a long-standing research program to protect warfighters from infectious diseases

encountered during deployments. Current research activities include development of new, rapid

mechanisms to discover, test and manufacture large quantities of critical therapeutics.

In response to emerging and novel biologic threats, DARPA’s Accelerated Manufacture of

Pharmaceuticals (AMP) program started in 2005. AMP focuses on identifying, developing and

demonstrating new ways to produce large amounts of pharmaceuticals, such as high-quality

vaccine-grade protein within three months of sequencing the pathogen DNA. Inspiration for this

scalable approach is a preparedness strategy that provides capability to respond quickly to

emerging biothreats.

In response to the 2009 H1N1 swine flu pandemic, AMP's plant-based platform redirected its

rapid scale-up processes that were initially developed for avian influenza. After receiving the

H1N1 DNA sequence April 29, a candidate recombinant H1 protein, an essential component of a

vaccine, was produced within four weeks.

AMP’s plant-based system combines three major components to rapidly express vaccine

candidate proteins: non-genetically modified plant seedlings, viral-based protein expression

vectors and vacuum infiltration/viral infection methodologies. Upon receipt of the gene

sequence for a target protein, that sequence is cloned into a viral-based protein expression vector.

This virus vector provides the mechanism for transferring millions of copies of the target gene

Fact Sheet

Defense Advanced Research Projects Agency

3701 North Fairfax Drive

Arlington, VA 22203-1714

sequence into the plant cells. Upon transfer to the plant, the virus replicates the target gene and

stimulates protein expression in those plants.

Essentially, this platform uses the plant's protein synthesis capabilities to produce the specific

recombinant protein material that will be the active component of a vaccine. Scale-up could be

as simple as infiltrating additional non-genetically modified seedlings. Compared to other

vaccine technologies, this platform's production time allows for protein expression, the first step

in vaccine production, in less than five weeks.

DARPA is pursuing this technology development along two, parallel paths:

1) A pilot facility to produce a vaccine-grade recombinant protein under current good

manufacturing practices (cGMP) for formulation, immunogenicity and toxicology

studies. Data along with results from those studies will lead to filing of an

investigational new drug package with the FDA allowing the start of a phase 1

clinical trial. The data generated would be needed to approve this approach for rapid,

flexible vaccine manufacturing under an emergency use authorization scenario.

2) Demonstrate a proof-of-concept capability for cGMP scale up of the plant-based

platform to 10 million doses per month.

Because of the time required to address key FDA regulatory requirements, this program is not

anticipated to deliver H1N1 vaccine for widespread human use during the 2010 flu season.

Protein produced in a facility that meets FDA requirements, is formulated into a vaccine and has

completed phase 1 clinical studies has a higher chance of being authorized by the FDA for use in

a public health emergency under an emergency use authorization.