RFP 09-100-SOL-00005 Amd 02.pdf

OMB No. 0990-0115

(x)

09-100-SOL-00005

x x

1 copies of the amendment; (b) By acknowledging receipt of this amendment on each copy of the offer submitted; or (c) By separate letter or telegram which includes a reference to the solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEDGEMENT TO BE RECEIVED AT

THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR OFFER. If by virtue of this amendment you desire to change an offer already submitted, such change may be made by telegram or letter, provided each telegram or letter makes reference to the solicitation and this amendment, and is received prior to the opening hour and date specified.

x

ASPR-BARDA02

Washington DC 20201 330 Independence Ave, SW, Rm G640

ASPR-BARDA

HHS/OS/ASPR/BARDA

Washington DC 20201 330 Independence Ave, SW

HHS/OS/ASPR/BARDA

04/01/2009000002

13. THIS ITEM ONLY APPLIES TO MODIFICATION OF CONTRACTS/ORDERS. IT MODIFIES THE CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14.

12. ACCOUNTING AND APPROPRIATION DATA (If required) is not extended.is extended, Items 8 and 15, and returning

Offers must acknowledge receipt of this amendment prior to the hour and date specified in the solicitation or as amended, by one of the following methods: (a) By completing

The above numbered solicitation is amended as set forth in Item 14. The hour and date specified for receipt of Offers

11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS

FACILITY CODE CODE

10B. DATED (SEE ITEM 13)

10A. MODIFICATION OF CONTRACT/ORDER NO.

9B. DATED (SEE ITEM 11)

9A. AMENDMENT OF SOLICITATION NO.

CODE

8. NAME AND ADDRESS OF CONTRACTOR (No., street, county, State and ZIP Code)

7. ADMINISTERED BY (If other than Item 6)CODE 6. ISSUED BY

PAGE OF PAGES

4. REQUISITION/PURCHASE REQ. NO.3. EFFECTIVE DATE2. AMENDMENT/MODIFICATION NO. 5. PROJECT NO. (If applicable)

1. CONTRACT ID CODE

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT

03/13/2009

CHECK ONE A. THIS CHANGE ORDER IS ISSUED PURSUANT TO: (Specify authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT

B. THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying office, C. THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF:

D. OTHER (Specify type of modification and authority) appropriation date, etc.) SET FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY OF FAR 43.103(b).

E. IMPORTANT: Contractor is not, is required to sign this document and return __________________ copies to the issuing office.

ORDER NO. IN ITEM 10A.

14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized by UCF section headings, including solicitation/contract subject matter where feasible.)

This amendment provides the following administrative information and changes:

1) A dial in number has been established for interested parties who want to join the pre-proposal conference on 8 April 2009 at 0830 EDT by phone. The dial in number is

888-603-6973. Passcode 6684949.

2) Add the following text to paragraph M.2 (3)a "Factor 1 Technical:"

EVALUATION POINT 0: MANDATORY CONTRACT REQUIREMENTS (GO/ NO-GO)

a. Offeror has met with the appropriate review division at the FDA to consult on the

Continued ...

16A. NAME AND TITLE OF CONTRACTING OFFICER (Type or print)15A. NAME AND TITLE OF SIGNER (Type or print)

15C. DATE SIGNED 16B. UNITED STATES OF AMERICA 15B. CONTRACTOR/OFFEROR 16C. DATE SIGNED

(Signature of person authorized to sign) (Signature of Contracting Officer)

LINDA D. LUCZAK

STANDARD FORM 30 (REV. 10-83)

Prescribed by GSA

FAR (48 CFR) 53.243

NSN 7540-01-152-8070

Previous edition unusable

Except as provided herein, all terms and conditions of the document referenced in Item 9A or 10A, as heretofore changed, remains unchanged and in full force and effect.

ITEM NO. SUPPLIES/SERVICES QUANTITY UNIT UNIT PRICE AMOUNT

NAME OF OFFEROR OR CONTRACTOR

2 7

CONTINUATION SHEET

REFERENCE NO. OF DOCUMENT BEING CONTINUED PAGE OF

(A) (B) (C) (D) (E) (F)

09-100-SOL-00005/000002

appropriate path for approval of their proposed therapeutic for use in treating neutropenia caused by Acute Radiation Syndrome (ARS).

b. The product offered is licensed or in clinical trials for an indication or have an Investigative New Drug (Application) for ARS (IND; as per 21 CFR 312) filed with the Food and Drug Administration (FDA) and the proposed product is not on clinical hold.

3) Change paragraph title (only) M.2 (3)a Factor 1 Technical; EVALUATION POINT 1 from "Regulatory Plan (25 Points)" to "Clinical Development and Regulatory Plan (25

Points)."

4) Change paragraph title (only) M.2 (3)a Factor 1 Technical; EVALUATION POINT 4 from "Manufacturing, Facilities and Security Plan (25 Points)" to "Manufacturing

Plan (25 Points)."

5) Change paragraph title (only) M.2 (3)d Factor 4 Compliance (1) from "Small

Business Participation Proposal" to "Small Business Participation Plan."

6) Change paragraph title (only) L.6 8(d) Volume IV-Compliance (2) from "Security

Plan" to "Draft Security Plan."

7) Attach the Draft Technical Readiness Level (TRL) descriptions.

/////////END OF CHANGES//////////

NSN 7540-01-152-8067 OPTIONAL FORM 336 (4-86)

Sponsored by GSA

FAR (48 CFR) 53.110

DRAFT FOR CLEARANCE

Page 3 2009-02-23

Technology Readiness Levels for Medical Countermeasure Products (Drugs and Biologics)1,2

Note: When using this schematic, a medical countermeasure product should be rated at a particular level only after the sponsor has completed all activities listed in that level (i.e., a product is rated at TRL 4 until it completes all activities listed in TRL 5).

T R L

Integrated Medical Countermeasure TRLs (based on October 2004 DoD Medical TRLs and May 2008 HHS PHEMCE TRLs)

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.

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.

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 (Good Laboratory Practice)).

1 This document is designed for evaluating the maturity of medical countermeasure development programs. For a detailed description of development processes for assays and animal models, please consult the Technology Readiness Levels for Product Development Tools (PDTs), developed by the PDT Working Group of the HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) and available at http://www.medicalcountermeasures.gov.

2 This document does not serve as official FDA Guidance nor does it represent FDA’s current thinking on this topic. For the purposes of a regulatory application seeking licensure or approval for a specific medical product, additional data may be required by FDA.

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Integrated Medical Countermeasure TRLs (based on Oct 2004 DoD Medical TRLs and May 2008 HHS PHEMCE TRLs)

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 product’s 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 (Good Manufacturing Practice)) quantities of bulk product and proposed formulated product.

4A Demonstrate non-GLP in vivo activity and potential for efficacy consistent with the product’s 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).

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T R L

Integrated Medical Countermeasure TRLs (based on Oct 2004 DOD Medical TRLs and May 2008 HHS PHEMCE TRLs)

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, endpoints, 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.

6 GMP Pilot Lot Production, IND Submission, and Phase 1 Clinical Trial(s)

Manufacture GMP-compliant 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-compliant 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 non-clinical and 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, pharmacokinetics and immunogenicity assessment as appropriate.

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Integrated Medical Countermeasure TRLs (based on Oct 2004 DOD Medical TRLs and May 2008 HHS PHEMCE TRLs)

7 Scale-up, Initiation of GMP Process Validation, and Phase 2 Clinical Trial(s)3

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 stage4.

7B Complete expanded clinical safety trials as appropriate for the product (e.g., Phase 2)3.

3 Identification of later regulatory stages of clinical development in this document (e.g., Phase 2, Phase 3) may not apply to some products being developed under the ‘Animal Rule’. Other than human safety studies, no additional clinical data may be feasible or ethical to obtain.

For additional information on the ‘Animal Rule’, please see http://www.fda.gov/OHRMS/DOCKETS/98fr/053102a.htm

4 These could include GLP animal efficacy studies required by FDA at this stage in support of an Emergency Use Authorization (EUA). The scientific evidence required for for issuance of an EUA will be handled on a case-by-case basis and will depend on the nature and extent of the threat at any point during the product development timeline, from the initiation of Phase 1 studies through licensure or approval. GLP animal efficacy study requirements may also vary by product type (e.g., vaccine, therapeutic, prophylactic) and U.S. government agency program office.

http://www.fda.gov/OHRMS/DOCKETS/98fr/053102a.htm

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Integrated Medical Countermeasure TRLs (based on Oct 2004 DOD Medical TRLs and May 2008 PHEMCE TRLs)

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 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.

9 Post-Licensure and Post-Approval Activities

9A Commence post-licensure/post-approval and Phase 4 studies (post-marketing commitments), such as safety surveillance, studies to support use in special populations, and clinical trials to confirm safety and efficacy as feasible and appropriate5.

9B Maintain manufacturing capability as appropriate.

5 For products approved under the ‘Animal Rule’, confirmatory efficacy data are required, if such studies are feasible and ethical, and may be obtained from use during an event.

TRL's Draft 02-23-2009.doc