Flu BAA Amend 5.pdf

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT

11 CONTRACT ID CODE rA~E OF PAGES

I 27

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

Amendment #5 See Block 16C N/A N/A

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

HHS/OS/ASPR/AMCG HHS/OS/ASPR/AMCG

330 Independence Avenue, SW Room G640 330 Independence Avenue, SW Room G640 Washington, DC 20201 Washington, DC 20201

8 NAME AND ADDRESS OF CONTRACTOR (No .. street, county State and ZIP Code) r-02- 9A AMENDMENT OF SOLICITATION

NO.

11-1 00-SOL-00021

9B. DATED (SEE ITEM 11)

10A MODIFICATION OF CONTRACT/ORDER NO.

D 10B. DATED (SEE ITEM 13)

CODE !FACILITY CODE

11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS

0 The above numbered solicitation is amended as set forth in Item 14 The hour and date specified for receipt of Offers 0 is extended. ~ is not extended.

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 items 8 and 15, and returning 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 ACKNOWLEDGMENT 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 your 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.

12. ACCOUNTING AND APPROPRIATION DATA (If required)

N/A

13. THIS ITEM ONLY APPLIES TO MODIFICATION OF CONTRACTS/ORDERS.

IT MODIFIES THE CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14.

CHECK ONE 1 A THIS CHANGE ORDER IS ISSUED PURSUANT TO {Spectfy authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT ORDER NO

IN ITEM 10A

D

D B THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying office. appropriation date. etc.) SET FORTH IN ITEM 14. PURSUANT TO THE AUTHORITY OF FAR 43.103(b)

D

C. THIS SUPPLEMENTAL AGREEMENT IS FNTFRED INTO PURSUANT TO AUTHORITY OF

D D. OTHER (Specify type of modification and authority)

E. IMPORTANT: Contractor ~ is not, D is required to sign this document and return ____ _ copies to the issuing office.

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

PURPOSE: The above referenced solicitation is hereby amended to include the following:

1. Presentation material for Pre-Proposal Conference No. 2 held 10/14/11.

2. Pre-Proposal Conference No. 2 Questions and Responses.

3. Add NAICS Code 325414 and Classification Code A.

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.

15A NAME AND TITLE OF SIGNER (Type or print) I16A NAME AND TITLE OF CONTRACTING OFFICER (Type or print)

Dorothy M. McMillan

15B. CONTRACTOR/OFFEROR 15C DATE SIGNED 16C. DATE SIGNED

(Signature of person authorized to sign)

NSN 7540-01-152-8070

Previous edition unusable

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STANDARD FORM 30 (REV 10-83)

Prescribed by GSA FAR (48 CFR) 53.243

United States Department of

Healtl1 & Hnn1an Services Office of the Assistant Secretary for Preparedness and Response (ASPR)

Broad Agency Announcements (BAA)

Dorothy McMillan, Sr. Contracting Officer

BARDA/AMCG

Tasha McMillian, Contract Specialist

BARDA/AMCG

October 14, 2011

Healtl1 & Hw11an Services Office of the Assistant Secretary for Preparedness and Response (ASPR}

Background and Regulatory Basis- FAR

6.1 02( d)(2) and 35.016

• This is Amendment #4 to Broad Agency Announcement BARDA BAA-11-

1 00-SOL-00021, which is a competitive announcement to obtain proposals for the following two additional areas of Interest:

Antiviral Therapeutics for Treatment and/or Prophylaxis of Influenza A & B Infections

Multi-Purpose, Broad-Spectrum Antiviral Therapeutics for Treatment and/or Prophylaxis of Influenza Virus Infections

• The BAA is described in FAR 6.102(d)(2}," Use of Competitive Procedures," and FAR 35.016, " Broad Agency Announcements."

• The BAA technique shall only be used when meaningful proposals with varying technical/scientific approaches can be reasonably anticipated.

Health & Human Services Office of the Assistant Secretary for Preparedness and Response (ASPR)

Benefits

• Streamlines the procurement process.

• Provides greater transparency and open communication.

• Promotes the advancement of Medical Counter Measure (MCM) technology.

• Allows for competition of ideas/concepts throughout the established response period.

• Provides flexibility in amending the BAA to add or subtract information or requirements.

• Can remain open for up to a one year period of time.

• White paper stage serves as market research.

United States Deportment of

Healtl1 & Hwnan Services Office of the Assistant Secretary for Preparedness and Response (ASPR)

BARD A BAA - Process The two stage process

Stage 1:

• Offerors shall submit a Quad Chart, White Paper and Addendum summarizing the proposed project. All Quad Charts shall not exceed one ( 1) page, White Papers shall not exceed ten ( 1 0) pages and Addendum shall not exceed two (2) pages.

• Electronic acknowledgement of receipt of white papers will be made within one week.

• Decision letters will be sent to Offerors within 90 days of submission or within 90 days after the submission deadline.

Health & Hw11an Services Office of the Assistant Secretary for Preparedness and Response (ASPR)

Eligibility

• This BAA is open to ALL responsible sources.

• Offerors may include single entities or teams from private sector organization, Government laboratories, Federally Funded Research and Development Centers (FFRDCs) and academic institutions.

• A prospective recipients must meet certain minimum standards pertaining to financial resources, an ability to comply with the performance schedule, prior record of performance, integrity, organization, experience, operational controls, technical controls, technical skills, facilities, and equipment.

Health & Hwnan Services ' Office of the Assistant Secretary for Preparedness and Response (ASPR)

BARDA BAA- Process (cont.)

Stage II:

• Offerors receiving a favorable evaluation will be asked to prepare a Full Proposal and submit to BARDA within 45 days depending on time and funding constraints.

• Instructions for completing the Full Proposal are found in Part IV of the Solicitation. A request to submit a Full Proposal does not assure an award.

• The Government intends to make an award decision within 120 days after submission of Full Proposals.

Healtll & Hwnan Services Office of the Assistant Secretary for Preparedness and Response (ASPR)

Differences between an RFP and a BAA

RFP BAA

• General Interest •Proposal • General Interest • Proposal

• preparation and • preparation ·Sources Sought evaluation • Pre-proposal • •RFI ~ Conference ·Proposal

• Draft-RFP ·Post-evaluation, • evaluation

+ pre-award ·Before White •

• Defined Q&A Paper • Post decision &

Sessions ~

I· RFP close I + BAA close

• White Paper evaluation

I

I Open with BARDA I I Facilitated by CO II·· Closed Communication I

Health & Hwnan Services Office of the Assistant Secretary for Preparedness and Response (ASPR}

Summary

• BAAs allow for greater flexibility in both the proposal submission and selection phases.

• BAAs have the potential to be highly effective in BARDA's ability to respond quickly to emerging threats.

Questions should be emailed to FLU-BAA@hhs.gov.

Health & Hnn1an Services Office of the Assistant Secretary for Preparedness and Response (ASPR)

BAA 11-1 00-SOL-00021

Areas of Interest 3 & 4

Antiviral Therapeutics for the Treatment and/or Prophylaxis of Influenza Infections

Technical Overview

Influenza BAA Pre-Proposal Conference

BARDA Mission

BARDA leads the Advanced Research and Development of medical countermeasures to protect the United States from public health emergency threats, including CBRN agents and pandemic influenza.

•BARDA 2011 Strategic Plan Goals -An advanced development pipeline replete with medical countermeasures and platforms

-A capability base to provide enabling core services

-Agile, robust and sustainable U.S. manufacturing infrastructure

-Responsive and nimble programs and capabilities to address novel and emerging threats

-A ready capability to develop, manufacture and facilitate distribution of medical countermeasures during public health emergencies

/ ,p; BARDA Strategies for Advanced Development of Influenza Antivirals (i~~.

• Maintain and where appropriate expand the portfolio of medical countermeasures against pandemic influenza

- Novel mechanisms of action to reduce risk of resistance

• Support the advanced development of medical countermeasures suitable for use in special populations such as children, pregnant women, the elderly and hospitalized patients

• Emphasize the advanced development of multi-purpose and/or broad-spectrum products

• Support the advanced development of host-directed therapeutics, such as small molecule immune modulators, anti inflammatory agents, and regulators of innate immunity

Area of Interest #3 Influenza Antiviral Therapeutics

• Advanced development of influenza antivirals with a novel mechanism of action

Small molecule or biological therapeutics will be considered

Mechanisms of action that reduce the risk of resistance development are preferred

Proven activity against a broad range of pandemic and seasonal strains of influenza preferred

• Development of combination therapies for treatment of influenza

- Utilize drugs with different mechanisms of action

- Combination must be superior to the individual components

• Development of alternative formulations for influenza antivirals

- Pediatric population

- Hospitalized patients

• Identification and validation of surrogate endpoints

- Reliably predict clinical outcomes in influenza trials

- Should facilitate accelerated approval of novel anti-influenza therapies

• Therapeutics being proposed for advanced development should have completed all TRL 6 activities

Area of Interest #4 Multi-Purpose, Broad-Spectrum Antivirals

• Target viral function essential for influenza virus replication with a MOA offering the potential for broad-spectrum antiviral activity

- Spectrum of antiviral activity should be clarified in preclinical data package

• Target host factors that result in reduced influenza virus replication and amelioration of symptoms

- lmmunomodulatory therapeutics

- Host factors critical for viral replication

• Combination therapy using an influenza antiviral and a host modulating therapeutic

- Combination must be superior to the individual components

• Proposed activities should focus on development of an influenza treatment indication with strategies to expand into broad-spectrum antiviral indications

• Therapeutics being proposed for advanced development should have completed all TRL 6 activities

TECHNOLOGY READINESS LEVELS (TRLS) FOR MEDICAL

COUNTERMEASURE PRODUCTS

TRL9-Post-Licensure and Post-Approval Activities

TRLB-Completion of GMP Validation and Consistency Lot Manufacturing, Pivotal Animal Efficacy Studies or Clinical

Trials3, and FDA Approval or Licensure

TRL7-Scale-up, Initiation of GMP Process Validation, and Phase 2 Clinical Trial(s)

TRL6-GMP Pilot Lot Production, IND Submission, and Phase 1 Clinical Trial(s)

TRL5-Advanced Characterization of Candidate and Initiation of GMP Process Development

TRL4-Candidate Optimization and Non-GLP In Vivo Demonstration of Activity and Efficacy

TRL3-Target Identification and Characterization of Preliminary Candidate(s)

TRL2-Development of Hypotheses and Exp Designs

TRL 1-Review of Scientific Knowledge Base

Completed Requirements for Advanced j Development of Influenza Antiviral Candidates

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

•Animal Models: Conduct GLP non-clinical studies for toxicology, pharmacology, and immunogenicity, as appropriate.

•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).

•Regulatory: Prepare and submit Investigational New Drug (IND) package to FDA.

•Clinical Development: Conduct Phase 1 clinical trial(s) to determine the safety and pharmacokinetics of the clinical test article.

Areas of Interest 3&4 Product Development and Technical Objectives

• Representative Process, Formulation and Manufacturing Development Activities Supported by BAA

Development of master and working cell banks

Process development activities to increase efficiency, yield and quality

Formulation development to evaluate combinations of excipients

Identification of Critical Quality Attributes and Critical Process Parameters

Manufacture of cGMP lots of candidate product for clinical trials

Manufacturing scale-up plan

Proposed packaging design and execution of fill-finish

Stability testing for bulk and final product

Development of Risk Evaluation and Mitigation strategies

Product Development and Technical Objectives

• Representative Clinical Development Activities Supported by

BAA

- Design and conduct phase 2 and/or phase 3 clinical studies

- Design and conduct clinical trials to evaluate safety and/or efficacy of candidate product in special populations

Development of a clinical development plan to mature the candidate product through FDA approval/licensure

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Question #1

Areas of Interest 3&4 Questions from Potential Offerors

Please clarify whether the funding intention is to support activities up to NDA. In the case of antiviral development as discussed in Amendment #4, if costs exceed that of the proposed funding limit (15- 75 million on page 7 of the solicitation), will additional funding be considered given the expense of activities related to Amendment #4? What is the revised anticipated funding range in relation to Amendment #4?

Answer The purpose of Areas of Interest 3 and 4 is to support advanced development of antiviral products; offerors are not required to propose all activities through NDA/BLA submission. The quantity of awards will be dependent on available funding.

Question #2

Questions from Potential Offerors

What is the earliest submission date for a white paper on antiviral development (areas of interest #3 and #4 described in Amendment #4 )? Does submission of the white paper start the 90 day review period, or will the 90 day review period initiate following the described deadlines for submission? Is it possible that review of the white paper will be completed prior to the allowed 90 days?

Answer White papers can be submitted at any time during the period of the BAA, and may be reviewed any time following their submission.

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Question #3

Areas of Interest 3&4 Questions from Potential Offerors

Does section 1.3 of Amendment #4 include Phase 1 clinical trials for alternative formulations if the drug in its current formulation is currently at> TRL-6?

Answer Each proposal will be fully evaluated based on its technical merits. Alternative formulations proposed must be at an appropriate stage for advanced development and must have completed all TRL 6 activities.

Question #4

Questions from Potential Offerors

In order to meet the TRL requirement for the immunomodulatory therapeutic candidate described in area #4, part 2.2, does the existing IND have to be in influenza? Must the primary indication for which the therapeutic has achieved TRL6 be influenza, or is a non-flu indication that is directly relevant to severe influenza-like illness also acceptable?

Answer Satisfactory preclinical and clinical data packages showing activity against influenza must be available to support advanced development for an influenza indication, and all activities at TRL 6 must have been completed.

Areas of Interest 3&4: Antiviral Therapeutics Points of Contact

• Contracting Point of Contact Dorothy McMillan and Tasha McMillian

Email address: FLU-BAA@HHS.GOV

For all contractual and process questions

For all white paper, quad chart and full proposal submissions

• Technical Point of Contact Email address: FLU-BAA-ANTIVIRAL@HHS.GOV

For all technical questions

Pre Proposal Conference #2

Questions and Answers

1. Question: A U.S. Department of Health and Human Services guidance document entitled "Guidance on Antiviral Drug Use during an Influenza Pandemic" is currently available for download as a PDF at the http://www.flu.gov/vaccine/antiviral use.html Web site. We did not find a publication date printed in this document, though the properties of the PDF file indicate that it was last modified on January 16, 2009. We would like to know if this document represents the most recent and current HHS guidance on influenza antiviral drug use or if more recent guidance is also available.

Answer: (not relevant)

2. Question: Presently, the BAA NAICS codes are only for equipment manufacturers (the original two areas of interest). Since Amendment 3 added two new development areas of interest regarding antiviral therapeutics, will BARDA consider allowing businesses in the antiviral therapeutics development industry to be considered as offerors?

Please consider adding some or all of these NAICS codes, appropriate to topics of interest #3 and #4:

325411 - Medicinal and Botanical Manufacturing

325412 - Pharmaceutical Preparation Manufacturing

325413- In-Vitro Diagnostic Substance Manufacturing

325414- Biological Product (except Diagnostic) Manufacturing

541711 - Research and Development in Biotechnology

541712- Research and Development in the Physical, Engineering, and Life

Sciences (except Biotechnology)

Answer: The Solicitation will be amended to add NAICS Code: 325414- Biological

Product (except Diagnostic) Manufacturing

3. Question: Please clarify whether the funding intention is to support activities up to NDA. In the case of antiviral development as discussed in Amendment #4, if costs exceed that of the proposed funding limit (15- 75 million on page 7 of the solicitation), will additional funding be considered given the expense of activities related to Amendment #4? What is the revised anticipated funding range in relation to Amendment #4?

Answer: The purpose of Areas of Interest 3 and 4 is to support advanced development of antiviral products; offerors are not required to propose all activities through NDA/BLA submission.

4. Question: What is the earliest submission date for a white paper on antiviral development (areas of interest #3 and #4 described in Amendment #4)? Does submission of the white paper start the 90 day review period, or will the 90 day review period initiate following the described deadlines for submission? Is it possible that review of the white paper will be completed prior to the allowed 90 days?

Answer: White Papers can be submitted at any time during the period of the BAA. However, in accordance with Amendment No. 1 to the solicitation, they must be received by the remaining deadlines for White Paper submissions, which are December 16, 2011, and March 30, 2012 at 3:00PM EST. After submission, decision letters will be sent to Offerors within 90 days of submission or within 90 days after the submission deadline. Please continue to monitor the solicitation posted at FedBizOpps for all future amendments and updates.

5. Question: Does section 1.3 of Amendment #4 include Phase 1 clinical trials for alternative formulations if the drug in its current formulation is currently at ~TRL-6?

Answer: Each proposal will be fully evaluated based on its technical merits. Alternative formulations proposed must be at an appropriate stage for advanced development activities.

6. Question: Does the "Buy American" requirement in the original solicitation apply for development of antiviral therapies described in Amendment #4? Can manufafturing of an active pharmaceutical ingredient (API) be performed outside of USA if the final drug product is manufactured within USA? Are clinical trials performed outside of the US required to be included in "Buy American" calcula!ions?

Answer: "Buy America" is included in all of our contracts. However, one of the restrictions of a

BAA is that it cannot be used for production.

7. How many contracts are expected to receive awards under the amended solicitation, and what is the expected contract duration?

Answer: At this time, it cannot be determined how may contract awards will be made.

8. Question: In order to meet the TRL requirement for the immunomodulatory therapeutic candidate described in area #4, part 2.2, does the existing IND have to be in influenza?

Must the primary indication for which the therapeutic has achieved TRL6 be influenza, or is a non-flu indication that is directly relevant to severe influenza-like illness also acceptable?

Answer: Satisfactory preclinical and clinical data packages showing activity against influenza must be available to support advanced development for an influenza indication.

9. Question: Please clarify the product description for the influenza antiviral described in area #3, part 1.3. Is the description of therapeutic products intentionally limited to antiviral agents or are immunomodulatory therapeutic candidates that fit the other criterion also acceptable? Must the primary indication for which the therapeutic has achieved TRL6 be influenza, or is a respiratory indication that is relevant to treatment of symptoms of severe influenza-like illness in vulnerable populations also acceptable? In order to meet the TRL requirement, does the existing IND for the therapeutic candidate have to be influenza?

Answer: See answer to question 8.

10. The different types of therapeutics described in areas 3 and 4 overlap somewhat, and actual products submitted for development may have significant overlap. In cases where therapeutic candidates are relevant to both areas but not described exactly by either one, is it recommended to submit two white papers, one under each area, or can both areas be designated on the same white paper?

Answer: The Government cannot decide how you should submit your White Paper.

The number of papers submitted is up to the offeror.

11. Question: Is an IND in a related or relevant clinical indication targeting host responses AND demonstrated anti-viral activity against influenza and other viruses acceptable to meet the TRL6 requirement for novel antiviral or immunomodulatory therapeutics?

Answer: See answer to question 8.

12. Question: Is development of a new formulation and route of administration for a therapeutic candidate that is~ TRL6 for a primary non-flu respiratory indication that is relevant to influenza, in order to use it to treat severe influenza infection in special populations of hospitalized patients with underlying respiratory and medical conditions, an acceptable activity under this BAA?

Answer: See answer to question 8.

13. Question: Development of a new route of administration for novel therapeutics that are TRL6 for non-flu indications requires that pre-clinical activities and Phase 1 trials be repeated and that dosing be optimized for flu. Will candidates requiring such activities meet the TRL6 requirement and acceptable SOW activities of this BAA?

Answer: All activities supported by this solicitation must be at TRL6 or above for an influenza indication.

14. Question: For area #3, part 1.4; identification and validation of surrogate endpoints may be either incorporated into proposed clinical trials testing antivirals and immunomodulatory agents or in non-interventional studies or archived samples. Are all of these acceptable? Are novel methods of sample collection and analysis of interest?

Will preference be given to proposals that incorporate evaluation of novel surrogate endpoints into product and clinical development plans be given any preference over those that do not?

Answer: Virological and non-virological parameters that reliably predict clinical outcomes in influenza trials that are being conducted to evaluate influenza antivirals at TRL 6 or greater are of high interest. Surrogate endpoints should facilitate accelerated approval of novel anti-influenza treatments, emergency use authorization mechanisms and risk-benefit evaluation.

15. Question: What is the maximum duration for a therapeutic product development plan that can be supported under this BAA? Must proposals be limited in scope so as not to exceed 5 years? (Development of drugs to treat influenza is dependent, among other things upon the rate at which patients can be enrolled in clinical trials, which cannot be predicted accurately. More realistic development times may be in the 6-8 year range.)

Is there a preference for completing clinical product development through NDA/BLA under a single BAA contract or limitation of SOW to what can be accomplished in a five year time period?

Answer:

Contracts may last as long as five years. However, prior to review of full proposals, there is no predetermined length of time established.

16. Question: What is the total anticipated funding level for this BAA now that two new areas of interest have been added? (Previous funding level was up to $75M).

Answer: That is to be determined.

17. Please clarify that can BARD A can fund a proposal that includes support for other federal research organizations (NIH, CDC, DoD, etc) involved in the research.

Answer: As stated in the solicitation, this BAA is open to all responsible sources. Offerors may include single entities or teams from private sector organization, Government laboratories, Federally Funded Research and Development Centers (FFRDCs) and academic institutions.

18. AVI BioPharma has an antiviral agent based on an oliognucleotide analog targeting an essential influenza virus function. This appears to be within the scope of BARDA BAA- 11-100-SOL-00021 Amendment#4 in Area oflnterest#3 part 1.1 "Advanced development of antiviral therapeutics at TRL 6 or greater with a novel mechanism of action relative to currently approved anti-influenza therapeutics" Specifically, our therapeutic agent, AVI-71 00, would appear to satisfy the TRL 6 requirement in that: 1) we have an open IND, 2) we have a pilot manufacturing capability to produce material for human clinical trials, and 3) we have human experience in a phase I trial which includes pharmacokinetic data. Our phase I human experience is limited to a single ascending dose study but we have not completed a multiple ascending dose study. We interpret the project to be equal to TRL 6, do you agree?

Answer: Agreed.