Funding-Army
A--Candidate therapeutics
against the hemorrhagic fevers caused by members of the family Filoviridae: Ebola virus and Marburg virus; deadline Feb. 27, 2009
Agency
U.S. Army
Space and Missile Defense Command
Description
REQUEST FOR
INFORMATION: Candidate therapeutics against the hemorrhagic fevers caused by
members of the family Filoviridae: Ebola virus and
Marburg virus.
The Joint Product Manager for the Joint Program Executive Office for Chemical
Biological Defense, Transformational Medical Technologies Initiative, Advanced
Development (JPEO CBD/TMTI AD) is conducting a market survey to determine the
availability of candidate therapeutics against the hemorrhagic fevers caused by
members of the family Filoviridae: Ebola virus and
Marburg virus.
BACKGROUND: Filoviruses belong to a virus family
called Filoviridae and can cause severe hemorrhagic
fever in humans and nonhuman primates. Because there is no known effective
treatment for the hemorrhagic fevers caused by filoviruses,
JPEO CBD/TMTI AD is soliciting responders to submit current capabilities
related to therapeutic development for use by the government in developing
medical countermeasures against the Ebola virus and the Marburg virus. The
indication for the therapeutics candidates being sought will be post agent
exposure, post-exposure prophylaxis. TMTI is seeking anti-sense pharmacologic
agents. Submissions involving monoclonal antibodies or other passive immune
therapeutics, vaccines, or vaccine candidates will not be evaluated. JPEO
CBD/TMTI AD requests that submittals briefly, yet clearly describe the
technical approach, outline critical technical issues, and comment on the
expected robustness and affordability of the proposed approach.
INFORMATION SOUGHT: The information sought is to determine the availability of
anti-sense therapeutic candidates that have demonstrated efficacy against the
hemorrhagic fevers caused by members of the family Filoviridae:
Ebola virus and Marburg virus. The therapeutic candidate(s) must have
documented a well characterized and proven efficacy in non-human primates,
enough GMP grade bulk and formulated drug product
needed for clinical testing and a well defined ADME/Tox
profile (conducted under GLP) that would allow the therapeutic candidates to
readily proceed into Phase I clinical trials. The candidate therapeutics being
sought must meet all requirements equivalent to a Technical Readiness Level
(TRL) Six (TRL 6) level of maturity [as defined by the One Portfolio Integrated
Countermeasure TRLs]. A copy of the One Portfolio Integrated
Countermeasure TRLs have been provided below as a reference. The
candidate therapeutics being sought do not have to have started, nor completed
Phase I clinical trials, but responders must have the requisite abilities to
obtain an FDA approved/licensed product to include the management skills
necessary to accomplish all tasks for that goal. Favorable experience working
with the FDA in advance development of a therapeutic is needed.
INSTRUCTIONS TO RESPONDERS: Sources having the capability and/or concept to
meet these requirements are invited to respond to this RFI. Responses should be
limited to ten (10) pages, double spaced, for any given concept, not including
cover page, cover letter, references and table of contents. Any proprietary
concepts of information should be clearly identified as such. Responders must
use the One Portfolio Integrated Countermeasure TRLs shown below to validate
the technical maturity of their therapeutic candidate(s). Responders must
submit supporting data that documents current capabilities against each TRL
element and subordinate elements up to and including TRL6; excluding Phase I clinical trials.
Submitted capability documents must include references with descriptions of similar
services/products offered to the Government or to commercial customers. Include
contract magnitude (dollar value and length of performance) and points of
contact for each example provided (company /agency name, name of POC, address,
e-mail, telephone number, fax number). Include evidence of capability and
experience with Integrated Product Teams (IPT), favorable experience working
with the FDA with a brief summary of regulatory inspections and results,
managing clinical trials (how many sites, number of participants, significant
outcomes), and a description of the responders current necessary resources
(facilities, personnel) available for this effort. For any anticipated teaming
arrangements and or anticipated subcontractors, provide documentation regarding
their capabilities and responders demonstrated ability to carry out
identifying, awarding and management of subcontracted effort.
Submitted data and information will not be returned. Input on technical aspects
of the responses may be solicited from non-government consultants/experts who
are bound by appropriate non-disclosure requirements. For all RFI responses, an
additional, non proprietary cover page is also requested identifying your
company name, technical point of contact, and contact information. The North
American Industry Classification Systems (NAICS) for this notice is 541711
Research and Development in Biotechnology, with a size standard of 500
employees. Responders must identify their company’s business size (based on the
NAICS size standard), business status (i.e. small business, disadvantaged, HUB
zone, woman owned, service disabled veteran owned).
This is a Sources Sought Synopsis/ Request for Information (RFI). There is no
solicitation available at this time. Requests for Solicitation and inquiries
related to same will not receive a response. This RFI is published for market
research purposes only, and in no way obligates the Government to issue a
solicitation or otherwise make a contract award. Any and all information
submitted in response to this synopsis is strictly voluntary. The Government
will not pay for any information submitted in response to this RFI.
Only electronic submissions of information provided to the email address
specified will be accepted. RFI responses should be sent to Ms Sandra OConnell, Contract Specialist, USASMDC; email address: Sandra.Oconnell@us.army.mil. All emails
should include in the subject line the RFI number and the submitting
organizations name. Responses should be submitted electronically not later than
5:00 p.m. EST on Friday, February 27 2009. All questions or inquiries must be
in writing or by e-mail to the government point of contact noted herein. No
telephone inquiries will be accepted.
Program Office Address:
Joint Program Executive Office for Chemical and Biological Defense (JPEO-CBD),
Transformational Medical Technologies Initiative, Advanced Development (JPEO
CBD/TMTI AD), 8725 John J Kingman Rd, Fort Belvoir, Va. 22060
Points of Contact:
Technical: Dr. Jay Vasudevan (703) 767-3427; email: Jayanand.Vasudevan_CONTRACTOR@dtra.mil
Deputy, Joint Product Manager, Advanced Development: Mr. Stephan Fernandez,
(703) 767 2376; email: Stephan.Fernandez@dtra.mil
Contracting Office Address: USASMDC, ATTN: SMDC-RDC-EB, 64 Thomas Johnson
Drive, Frederick, MD 21702
Point of Contact: Ms Sandra OConnell, Contract
Specialist, USASMDC; email address: Sandra.Oconnell@us.army.mil.
Integrated Medical Countermeasure Technical Readiness Levels (TRLs):
TRL 1 - Review of Scientific Knowledge Base
Active monitoring of scientific knowledge base. Scientific findings are
reviewed and assessed as a foundation for characterizing new technologies.
TRL 2 - Development of Hypotheses and Experimental Designs
Scientific paper studies to generate research ideas, hypotheses, and
experimental designs for addressing the related scientific issues. Focus on
practical applications based on basic principles observed. Use
of computer simulation or other virtual platforms to test hypotheses.
TRL 3 - Target/Candidate Identification and Characterization of Preliminary Candidate(s)
Begin research, data collection, and analysis in order to test hypothesis.
Explore alternative concepts, identify and evaluate critical technologies and
components, and begin characterization of candidate(s). Preliminary efficacy
demonstrated in vivo.
3A Identify target and/or candidate.
3B Demonstrate in vitro activity of candidate(s) to counteract the effects of
the threat agent.
3C Generate preliminary in vivo proof-of-concept efficacy data (non-GLP).
TRL 4 - Candidate Optimization and Non-GLP In Vivo
Demonstration of Activity and Efficacy
Integration of critical technologies for candidate development. Initiation of animal model development. Non-GLP in vivo
toxicity and efficacy demonstration in accordance with the products intended
use. Initiation of experiments to identify markers,
correlates of protection, assays, and endpoints for further non-clinical and
clinical studies.
Animal Models: Initiate development of appropriate and relevant animal model(s)
for the desired indications.
Assays: Initiate development of appropriate and relevant assays and associated
reagents for the desired indications.
Manufacturing: Manufacture laboratory-scale (i.e. non-GMP) quantities of bulk
product and proposed formulated product.
4A Demonstrate non-GLP in vivo activity and potential for efficacy consistent
with the products intended use (i.e. dose, schedule, duration, route of
administration, and route of threat agent challenge).
4B Conduct initial non-GLP toxicity studies and determine
pharmacodynamics and pharmacokinetics and/or immune
response in appropriate animal models (as applicable).
4C Initiate experiments to determine assays, parameters, surrogate markers,
correlates of protection, and endpoints to be used during non-clinical and
clinical studies to further evaluate and characterize candidate(s).
TRL 5 - Advanced Characterization of Candidate and Initiation of GMP Process
Development
Continue non-GLP in vivo studies, and animal model and assay development.
Establish draft Target Product Profiles. Develop a scalable and reproducible
manufacturing process amenable to GMP.
Animal Models: Continue development of animal models for efficacy and
dose-ranging studies.
Assays: Initiate development of in-process assays and analytical methods for
product characterization and release, including assessments of potency, purity,
identity, strength, sterility, and quality as appropriate.
Manufacturing: Initiate process development for small-scale manufacturing
amenable to GMP.
Target Product Profile: Draft preliminary Target Product Profile. Questions of
shelf life, storage conditions, and packaging should be considered to ensure
that anticipated use of the product is consistent with the intended use for
which approval will be sought from FDA.
5A Demonstrate acceptable Absorption, Distribution,
Metabolism and Elimination characteristics and/or immune responses in non-GLP
animal studies as necessary for IND filing.
5B Continue establishing correlates of protection and/or surrogate markers for
efficacy for use in future GLP studies in animal models. Identify minimally
effective dose to facilitate determination of humanized dose once clinical data
are obtained.
TRL 6 - GMP Pilot Lot Production, IND Submission, and Phase 1 Clinical Trial(s)
Manufacture GMP pilot lots. Prepare and submit Investigational New Drug (IND)
package to FDA and conduct Phase 1 clinical trial(s) to determine the safety
and pharmacokinetics of the clinical test article.
Animal Models: Continue animal model development via toxicology, pharmacology,
and immunogenicity studies.
Assays: Qualify assays for manufacturing quality control and immunogenicity, if
applicable.
Manufacturing: Manufacture, release and conduct stability testing of GMP bulk
and formulated product in support of the IND and clinical trial(s).
Target Product Profile: Update Target Product Profile as appropriate.
6A Conduct GLP animal studies for toxicology, pharmacology, and immunogenicity
as appropriate.
6B Prepare and submit full IND package to FDA to support initial clinical
trial(s).
6C Complete Phase 1 clinical trial(s) that establish an
initial safety and pharmacokinetics assessment.
TRL 7 - Scale-up, Initiation of GMP Process Validation, and Phase 2 Clinical
Trial(s)
Scale-up and initiate validation of GMP manufacturing process. Conduct animal
efficacy studies as appropriate4. Conduct Phase 2 clinical trial(s)3.
Animal Models: Refine animal model development in preparation for pivotal GLP
animal efficacy studies.
Assays: Validate assays for manufacturing quality control and immunogenicity if
applicable.
Manufacturing: Scale-up and validate GMP manufacturing process at a scale
compatible with USG requirements. Begin stability studies of the GMP product in
a formulation, dosage form, and container consistent with Target Product
Profile. Initiate manufacturing process validation and consistency lot
production.
Target Product Profile: Update Target Product Profile as appropriate.
7A Conduct GLP animal efficacy studies as appropriate for the product at this stage .
7B Complete expanded clinical safety trials as appropriate for the product
(e.g., Phase 2)3.
TRL 8 - Completion of GMP Validation and Consistency Lot Manufacturing, Pivotal
Animal Efficacy Studies or Clinical Trials3, and FDA Approval or Licensure
Finalize GMP manufacturing process. Complete pivotal animal efficacy studies or
clinical trials (e.g., Phase 3), and/or expanded clinical safety trials as
appropriate. Prepare and submit NDA/BLA.
Manufacturing: Complete validation and manufacturing of consistency lots at a
scale compatible with USG requirements. Complete stability studies in support
of label expiry dating.
Target Product Profile: Finalize Target Product Profile in preparation for FDA
approval.
8A Complete final pivotal GLP animal efficacy studies or pivotal
clinical trials (e.g., Phase 3), and any additional expanded clinical safety
trials as appropriate for the product3.
8B Prepare and submit New Drug Application (NDA) or Biologics Licensing
Application (BLA) to the FDA.
8C Obtain FDA approval or licensure.
TRL 9 - Post-Licensure and Post-Approval Activities
9A Commence post-licensure/post-approval and Phase 4 study commitments, such as
safety surveillance, data to support use in special populations, and clinical
trials to confirm safety and efficacy as feasible and appropriate .
9B Maintain manufacturing capability as appropriate.
Announcement Number: W9113M-09-S-0001
Closing Date: February 27, 2009
Link to Full Announcement
https://www.fbo.gov/?s=opportunity&mode=form&id=f6246b5fa678b0b327ab299902ed2015&tab=core&_cview=1
Contact Information
Sandra OConnell, 301-619-2895