A03-FAR-Part6-Sanaria_Multi-Strain_Revised_20171221_FINAL_Redacted_FINAL.pdf

Control No:

Contractor: Sanaria, Inc.

Version – MAY 2016 FOR OFFICIAL USE ONLY

FAR Part 6 Justification and Approval for Other than

Full and Open Competition

1. Contracting Activity: U.S. Army Contracting Command, Aberdeen Proving Ground, Natick Contracting Division (ACC-APG-NCD)

2. Description of Action: Navy Medical Research Center (NMRC) Advanced Medical Development program requests a new contract containing cost reimbursement and firm fixed priced CLINs with Sanaria, Inc., located at 9800 Medical Center Drive, Rockville, MD, 20850. The Government projects award for Dec 2017 and FY17 Research, Development, Test and Evaluation (RDT&E) funds will be used.

An acquisition plan is required in accordance with FAR 7.103(e), this is a cost reimbursement effort.

3. Description of Supplies/Services: Approval is requested to award a new contract with Sanaria, Inc. to produce a candidate multi-strain malaria vaccine under a quality management system and regulatory support systems. The proposed new contract involves specific manufacturing activities (production, storage) of multiple strains of the malaria parasite sporozoites suitable for use in a candidate malaria vaccine under a quality management system and associated preparatory activities for utilization in the future Phase 2 dosage optimization and Phase 3 clinical trials. The contractor, Sanaria, Inc., is currently performing on existing contracts to develop a manufacturing process of a single strain irradiated sporozoites-based malaria vaccine candidate for use in Phase 3 clinical trials under two (2) contracts W911QY-15-0076 and W911QY-17-C-0064.

The proposed new contract described herein is for the optimization of production and quality control release of multiple strain Plasmodium falciparum (Pf) sporozoites (SPZ) vaccine, hereafter multi-strain PfSPZ, in compliance with current Good Manufacturing Practices (cGMPs) that will produce a multi-strain malaria vaccine to be utilized in the planned future Phase 2 dose optimization clinical trials. The vaccine candidate(s), PfSPZ, PfSPZ-CVac, PfSPZ of Pf7G8, PfNF135.C10 and NF166 – (the multiple strain malaria vaccine candidates) will be administered intravenously and must utilize aseptic, purified, cryopreserved, attenuated (irradiation, genetic, or chemically-attenuated) and/or fully infectious multi-strain sporozoite-based malaria parasites that are metabolically active Plasmodium falciparum (Pf) sporozoites (SPZ) extracted from mosquitos that are grown and incubated.

The work under the existing contracts W911QY-15-C-0076 and W911QY-17-C-0064 involved the performance of a gap analysis to identify aspects of the single strain PfSPZ manufacturing process requiring enhancement, modification or new processes as well as manufacturing capacity expansion to achieve the requisite quality standards and production quantities to support clinical trials and ultimately licensure. The new contract requires the manufacture of a multi-strain malaria vaccine candidate with production under an appropriate quality management system that is necessary to support future Phase 2 dose optimization and Phase 3 clinical studies required to achieve a Biologics License Application (BLA) from the U.S. Food and Drug Administration (FDA). This new contract will address specific tasks specific for the manufacturing of a multiple strain candidate malaria vaccine variant with the potential for increased immunogenicity against various geographically disparate malaria parasite strains. The multi-strain sporozoites-based malaria vaccine candidate will be based upon two (2) to potentially three (3) other Pf parasites (PfG8 from Brazil, NF135.C10 from Cambodia, and/or NF166 from Guinea) cover geographical ranges from South America, Asia and Africa. The resultant vaccine has the potential to elicit protective immunity in military populations against malaria over extended geographical ranges (e.g., Africa, Asia, and South America). The development of optimized manufacturing processes under an appropriate quality management system combined with complimentary robust regulatory support for a multi-strain Pf candidate vaccine will support scaled optimized manufacturing for use in Phase 2 dose optimization clinical trials, Phase 3 clinical trials Biological License Application to support potential FDA licensure, and ultimately enable production of a militarily relevant malaria vaccine regime that will prevent malaria infection of United States service members worldwide.

Specifically, the work under the new contract will include: (1) Optimization of multi-strain PfSPZ manufacture under current Good Manufacturing Practices (cGMP) and quality controlled release of attenuated and fully infectious multi-strain PfSPZ vaccines base on at least two (2) and potentially three (3) other Pf parasites, PfSPZ of Pf7G8, PfNF135.C10 and/or NF166; (2) Enhancement in the multi-strain PfSPZ manufacture quality management system for full compliance with U.S. Food and Drug Administration (FDA) regulations; and 3) Regulatory support for the multi-strain PfSPZ manufacture clinical development. Each of the objectives are necessary components of the clinical development of the multi-strain PfSPZ vaccine to develop, maintain, manufacture, and release a multi-strain malaria vaccine candidate for clinical evaluation in the effort to ultimately deliver a protective malaria vaccine with expanded breath of protective immunity against the Plasmodium falciparum (Pf) malaria parasites in the various geographies with military operations. The resultant manufactured multi-strain malaria vaccine (PfSPZ with PfSPZ of Pf7G8, PfNF135.C10 and/or NF166 and PfSPZ-CVac) are purified, cryopreserved, attenuated (non-replicating) or fully infectious, metabolically active Plasmodium falciparum sporozoites extracted from mosquitos. The multi-strain candidate malaria vaccine is a eukaryotic vaccine comprised of at least two (2) and potentially three (3) Pf parasites. Vaccines need to follow cGMP practices as well as employ optimized production of the mosquitos which requires clean mosquitos that are needed to estimate the viral load and the appropriate dose.

The contemplated new work will fill critically important gaps for a multi-strain malaria vaccine thereby significantly augmenting the end stage goals of a successful BLA from FDA, marketing authorization, and product launch of a vaccine with ability to elicit immunity against a range of geographically diverse malaria strains. The effort requested herein will support the overall goal to successfully submit a BLA and launch multi-strain malaria vaccine to protect both DoD Service Members and citizens deployed or traveling abroad in malaria endemic areas worldwide.

Estimated value for this contract is for an eighteen (18) month period of performance.

Control No: NCD-18-08

Sanaria, Inc. is the only organization in the world that can manufacture the aseptic, purified, cryopreserved PfSPZ required for a multi-strain PfSPZ vaccine with suitability for use in clinical trials. Furthermore, it is the only organization in the world that has a manufacturing facility that is designed and suited for manufacturing the aseptic, purified, cryopreserved malaria parasite sporozoites suitable for use in clinical trials. Thus, Sanaria, Inc. is the only organization in the world capable of performing the optimized manufacture of multi-strain PfSPZ malaria vaccine candidate to Phase 2 & 3 compliant manufacturing of a PfSPZ vaccine and the only organization conducting FDA reviewed clinical trials of a PfSPZ malaria vaccine under and IND

As the only source of PfSPZ-based malaria vaccine candidates and the sole holder of the Investigation New Drug for PfSPZ malaria vaccine, Sanaria, Inc. is the sole responsible party for the appropriate clinical development (e.g., clinical studies to demonstrate both safety and efficacy) as well as the Chemistry, Manufacturing, and Control (CMC) of the investigational PfSPZ malaria vaccine. Specifically, CMC responsibilities as detailed in 21 CFR 312 state responsibility of the IND holder to ensure the “identification, quality, purity, and strength of the investigational drug, the amount of information needed to make that assurance will vary with the phase of the investigation.”

Restated, as the PfSPZ IND holder, the activities for compliance to FDA regulations for a manufacturer of any investigational drug (or biologic) require the product to be prepared under appropriate quality. The two tasks – manufacture of PfSPZ-base malaria vaccines and a QMS -- are intrinsically linked and cannot be feasibly separated. Further as the holder of the IND, Sanaria, Inc. is solely responsible for the regulatory approach.

The potential benefits to the Government if this effort is successful are substantial.

Specifically, the effort will result in enabling optimized, high quality production of the multi-strain PfSPZ vaccine suitable for clinical evaluation that will potential prevent malaria infection of US Service Members as well as civilians world-wide. This technology will enhance efficiency and synergy within the US Government's vision of assisting in the reduction of pandemic infectious disease and biological threats, global surveillance efforts and bio-defense. No other organization besides Sanaria, Inc. has the extensive breadth and depth of technical expertise with the multi-strain PfSPZ sporozoites required to perform the work.

6. Efforts to Obtain Competition:

Market research was conducted to identify sources of malaria vaccine developers. A number of malaria vaccines are under development, including those based on the Plasmodium falciparum reticulocyte-binding protein homologue 5 (PfRH5) antigen as well as recombinant vaccines consisting of the Plasmodium falciparum circumsporozoite protein from the pre-erythrocytic stage. However, market research could only identify one (1) source utilizing PfSPZ sporozoites in clinical evalatuon under an IND with the ability to optimize the sporozoite manufacture of multiple Pf strains to meet the Government requirement including compliance with FDA regulations including, 21 CFR Part 820, Sanaria, Inc. A notice of intent to award this sole source contract to Sanaria, Inc. was issued on 18 Aug 2017 on FedBizOpps. No responses were received from other sources in reference to the synopsis posting.

7. Actions to Increase Competition:

The considerations for further competition have largely centered on the ability to leverage the manufacture abilities at another organization. The program office is actively considering using of biologics manufacture capabilities from other services to specifically meet Government demand. As the demand from DoD may be limited, supporting large scale biological production facility may be unsustainable. Buttressing this, commercial viability of a large biological vaccine production may not be viable. The program office is considering leveraging agile and flexible advanced development and manufacturing capabilities to support the manufacturing of medical countermeasures, but only after FDA licensure is approved.

The separate competitions of quality management and regulatory support are not feasible for technical reasons describe above. Any consideration of distinct performers for this effort (PfSPZ manufacture, Quality management support, and Regulatory support) would require the USG to assume the IND as well as obtain the proprietary IP for PfSPZ manufacture. While a possibility, the assumption of IND and procurement of the IP would not be in the best interest of the USG as it would be cost and resource prohibitive and may further limit the wider malaria vaccine development investments through commanding significant financial resources. The estimate of the IP is rough $100M-$300M and the current enterprise does not have the personnel resources to be the IND sponsor of this effort.

Current contract requirements support NMRC AMD's efforts to finalize establishment of capability requirement specifications by FY18-FY19. It is expected that a capability review will take place at the onset of FY19-FY20 in an effort to then generate a request for commercial procurement, via a Request for Proposals, to field procurement-ready technology for a malaria vaccine satisfying the performance specification and capability gap by FY20-21.

8. Market Research:

Market research was conducted to identify sources of malaria vaccine developers by the AMD Program. The market research report was completed by CDR Cassady on 15 Sep 2017. There are number of malaria vaccines are under development, including those based on the Plasmodium falciparum reticulocyte-binding protein homologue 5 (PfRH5) antigen as well as recombinant vaccines consisting of the Plasmodium falciparum circumsporozoite protein from the pre-erythrocytic stage, however the market research could only identify one (1) source utilizing malaria sporozoites capable of meeting the NMRC AMD program requirements.

Market research determined that Sanaria, Inc. (Rockville, MD) is the only company that has produced the PfSPZ vaccine based upon irradiated sporozoites and there are no other such companies that have shown any part of a capability to manufacture the malaria parasites sporozoites (single Pf strain or multiple stain Pf) in sufficient quantity and quality suitable for use in clinical trials. Sanaria, Inc. is the only company conducting FDA reviewed clinical evaluation of candidate malaria vaccines using PfSPZ-based vaccines under an IND. Other malaria vaccines are in development but none utilize sporozoites as required by the NMRC AMD program.

The NRMC AMD Program has a requirement for the development of a multi-strain Plasmodium falciparum sporozoite malaria vaccine to expand the breadth of the protective immunity against Pf malaria parasites worldwide, and a finalized suitable quality systems and regulatory program to support the development, final manufacturing, and eventually licensure of this vaccine from the U.S. Food and Drug Administration (FDA). This multi-strain vaccine will be an irradiated, attenuated, or live sporozoites-based malaria vaccine that meets the following requirements:

• Large scale automated production and manufacturing process(es) in compliance with current Good Manufacturing Practices (cGMPs) capable of producing large amounts of multi-strain candidate malaria vaccine using sporozoites for utilization in late Phase 2 clinical trial dosage optimization, Phase 3 pivotal clinical trials, and product launch.

• Established manufacturing process for Plasmodium falciparum sporozoite malaria vaccine, using malaria sporozoites, under cGMPs demonstrated to be successful in Phase 1 and Phase 2 Clinical Trials.

• Capability to develop semi-automated process for the dissection and collection of infected mosquito salivary glands containing multiple strains of Plasmodium falciparum sporozoites.

• Multi-strain PfSPZ vaccine candidate must be suitable for intravenous (IV) administration.

• Multi-strain PfSPZ malaria vaccine candidate must utilize irradiated, attenuated, or live aseptic, purified, cryopreserved, metabolically active Plasmodium falciparum (Pf) sporozoites (SPZ) extracted from infected mosquitoes that are grown and incubated.

The AMD office requires an expansion of the work currently being performed on other AMD contracts (W911QY-15-C-0076 and W911QY-17-C-0064) that involves additional manufacturing, quality systems, and regulatory activities to produce a multi-strain PfSPZ vaccine candidate suitable for late Phase 2 dose optimization and Phase 3 clinical trials and product launch. This includes manufacturing the components of multi-strain PfSPZ vaccine candidate regime, institution of an electronic quality management system that unites compliance, quality, validation, training records, and document management that will enable meeting of International Organization for Standardization (ISO) standards, and FDA regulations including, 21 CFR Part 820, and further implementation of a compliant regulatory electronic document management system and continued support for submissions to FDA in an electronic format.

The goals of this contract can only be accomplished by Sanaria, Inc. and will support the long-term goal and objective of successfully submitting and/or amending new/existing Investigational Drug applications (INDs) to the FDA for each component of multi-strain PfSPZ vaccines, and eventually a Biological License Application (BLA) and launch The objectives include: Optimization of production; GMP manufacture and quality control release of radiation attenuated (for PfSPZ Vaccine) and fully infectious (for PfSPZ-CVac) PfSPZ of Pf7G8, PfNF135.C10, and/or NF166 or another suitable strain; Conversion of

Control No: NCD-18-08 quality management system to an electronic quality management system that is fully compliant with all FDA regulations; and Support for Regulatory programs efforts in the ongoing process of providing FDA submissions in electronic Common Technical Document (CTD) format in accordance with FDA mandate for submissions of regulatory documents in electronic format, and implementation of a compliant regulatory electronic document management system.

Based on updated market research conducted on 15 September 2017 via internet searches using keywords, Pf, PfSPZ vaccine, multi-strain malaria vaccine, and malaria vaccine: Sanaria, Inc. (Rockville, MD) is the only vendor that comes up in the search results:

1. https://en.wikipedia.org/wiki/PfSPZ vaccine

2. http://www.sanaria.com/

3. http://science.sciencemag.org/content/341/6152/1359

4. https://www.ncbi.nlm.nih.gov/pubmed/?term=26469720

5. http://www.makingmalariahistory.org/initial-trials-of-sanaria-vaccine-provide-complete-protection-against-malaria/

6. http://outbreaknewstoday.com/malaria-vaccine-pfspz-vaccine-offers-protection-in-us-adults-in-phase-i-trials-73339/

7. http://www.nature.com/nm/journal/v22/n6/full/nm.4110.html

8. http://www.pnas.org/content/early/2017/02/14/1615324114.abstract

A SBA “Dynamic Small Business Search” was conducted on 15 September 2017 under NAICS code 325413, using the relevant key words “PfSPZ vaccine”, yielding no results.

A SAM search was also conducted on 15 September 2017 using relevant key words “PfSPZ vaccine”, yielding no results. Results indicate that Sanaria is the sole company that has the capability to produce the PfSPZ vaccine using attenuated (irradiated or genetically attenuated) and live Pf sporozoites. There is no other company in the world that demonstrates this unique and innovative concept and capability to provide this particular research services. According to Sanaria’s SAM registration, it is a veteran-owned small business concern. The Sanaria PfSPZ malaria vaccine won the 2014 Vaccine Industry Excellence Award for “Best Prophylactic Vaccine.”

In addition, knowledgeable subject matter experts were also contacted regarding market capabilities to meet requirements. The following SME input is noted and identified below:

identified Sanaria, Inc. as the only company in the world that currently produces PfSPZ vaccines that is in compliance with cGMPs. She indicated that there are other companies working on developing malaria vaccines but none that uses malaria parasite sporozoites. She also noted that Sanaria has collaborated with the Naval Medical Research Center (NMRC) and the Center for Disease Control (Malaria Epidemiology Branch) under Cooperative Research and Development Agreements.

identified Sanaria, Inc. (Rockville, MD) as the only company in the world that currently produces sporozoite-based malaria vaccine candidates that is in near compliance with cGMPs. The results further indicated that there are other companies working on developing malaria vaccines but none that uses malaria parasite sporozoites.

It is also noted that Sanaria, Inc. (Rockville, MD) has collaborated with the Naval Medical Research Center (NMRC) and the Center for Disease Control (Malaria Epidemiology Branch) under Cooperative Research and Development Agreements and well as a prior contracts with AMD.

Based on the market research findings, only one vendor, Sanaria, Inc. meets all of the basic requirements to meet the objectives of this acquisition. It has been ascertained then that there is a reasonable expectation of obtaining from Sanaria, Inc. the best scientific and technological source consistent with the demands of the proposed acquisition for the best mix of cost, performance, and schedule.

The potential benefits to the Government if this effort is successful are substantial.

Specifically, the effort will result in enabling production of a vaccine candidate that will prevent malaria infection of U.S. service members as well as civilians world-wide with a range of protective immunity against multiple strains of the malaria parasite. This technology will enhance efficiency and synergy within the U.S. Government's vision of assisting in the reduction of pandemic infectious disease and biological threats, global surveillance efforts, and bio-defense. No other organization besides Sanaria, Inc. has the extensive breadth and depth of technical expertise with the malaria sporozoite manufacture under quality management systems in compliance with cGMP required to perform the work.

In accordance with Defense Federal Acquisition Regulation Supplement (DFARS) 205.205-71, DFARS 206.302-1(d), and DFARS Procedures, Guidance and Information (PGI) 206.302-1(d), a request for information was posted to Federal Business Opportunities) on 18 Aug 2017 for 15 days and the results were as follows: No responses were received from other sources in reference to the synopsis posting.

9. Interested Sources:

To date, no other sources have written to express interest in the acquisition.

10. Other Facts:

a. Procurement History:

(1) Contract numbers and dates of the last several contracts for these same requirements.

a. W911QY-15-C-0076, awarded 9 Sep 2015

b. W911QY-17-C-0064, awarded 30 Jun 2017

(2) Both contracts noted above were awarded Sole Source to Sanaria, Inc.

(3) Authority(ies) previously cited if less than full and open competition was used:

10 U.S.C. 2304(c)(1), as implemented by FAR 6.302-1, Only one responsible source and no other supplies or services will satisfy agency requirements.

(4) If a justification was prepared to support the procurement(s) made before this one, provide a summary of the contents of paragraph 7 of the justification for that procurement and an explanation of the results:

Para 7 from Justification-Upon conclusion of this effort, should the Government determine that procurement of an irradiated sporozoites-based malaria vaccine is necessary to support Phase 3 clinical trials, a market survey will be conducted at that time to identify capable vendors that can supply such a vaccine meeting those specifications.

(5) If a justification was prepared to support the procurement made before this one, briefly describe the circumstances justifying the procurement and whether there have been any significant changes.

Please see Sections 3 and 5 of this Justification.

11. Technical Certification: I certify that the supporting data under my cognizance which are included in the justification are accurate and complete to the best of my knowledge and belief.

Typed Name:

Title: Program Manager

12. Requirements Certification: I certify that the supporting data under my cognizance which are included in the justification are accurate and complete to the best of my knowledge and belief.

Typed Name:

Title: Program Manager

13. Fair and Reasonable Cost Determination: I hereby determine that the anticipated cost or price to the Government for this contract action will be fair and reasonable.

This determination will be made using the following:

1. Cost Analysis

2. Comparison to IGCE

As a part of this basis, certified cost or pricing data will be required.

Typed Name: Date:

Title: Contracting Officer Signature:

14. Contracting Officer Certification: I certify that this justification is accurate and complete to the best of my knowledge and belief.

Typed Name: Date:

Title: Contracting Officer Signature:

Approval

Based on the foregoing justification, I hereby approve the procurement of Research and Development of Multi-strain Vaccine and Improved Quality and Regulatory Systems for Military Relevant Malaria Vaccine on an other than full and open competition basis pursuant to the authority of 10 U.S.C.2304(c)(1), as implemented by FAR 6.302-1, Only one responsible source and no other supplies or services will satisfy agency requirements, subject to availability of funds, and provided that the services or property herein described have otherwise been authorized for acquisition.

If the proposed contract action is not completed within 180 days from the below date or if there is a change to the substance of this J&A that does not meet the conditions of AFARS 5106.303-1-90, the Contracting Officer shall document these changes in a memorandum for file and obtain concurrence from the approval authority below.

Date:

Special Advocate for Competition Signature:

2 Jan 2018