BARDA_BAA_Special_Instructions_for_CM_040116.pdf

SPECIAL INSTRUCTIONS FOR CONTINUOUS MANUFACTURING TO

BROAD AGENCY ANNOUNCEMENT (BAA) FOR THE ADVANCED RESEARCH and

CBRN MEDICAL COUNTERMEASURES FOR BARDA

Special Instructions

A. PURPOSE

The purpose of this amendment is to extend Part I: Research/Development Areas of Interest to include continuous manufacturing technologies and associated innovations specifically for the advanced development of BARDA priority medical countermeasures.

The following considerations for continuous manufacturing is hereby added to Part I of BARDA’s Broad Agency Announcements # BAA-16-100-SOL-0001 – Area of Interests 1 (Vaccines), 2 (Antitoxins and Therapeutic Proteins), 3 (Antimicrobial Therapeutics), 4 (Radiological/Nuclear Threat Medical Countermeasures), 5 (Chemical Threat Medical Countermeasures); and BAA-16-100-SOL-0002 – Area of Interests 4 (Influenza Therapeutics), and 5 (Influenza Vaccines).

B. BACKGROUND

BARDA funds the advanced research and development of medical countermeasures (MCMs) against chemical, biological, radiological/nuclear (CBRN) and emerging infectious disease threats, including pandemic influenza, for which there is a critical unmet medical need. BARDA has identified continuous manufacturing (CM) as an emerging technology within the pharmaceutical industry that has significant potential to improve agility, flexibility, cost, and robustness in the development of MCM manufacturing processes. BARDA’s Innovations in CM initiative was launched in 2015 and is aligned with the vision as articulated in the President’s Council of Advisors on Science and Technology (PCAST) reports on Ensuring American Leadership in Advanced Manufacturing (2011), Capturing Domestic Competitive Advantage in Advanced Manufacturing (2012), and Accelerating U.S. Advanced Manufacturing (2014) which focused on the need for a national innovation policy regarding advanced manufacturing and recommendations to develop and sustain advanced manufacturing capability and capacity domestically. BARDA’s role to champion CM as a facet of advanced manufacturing has been described in the recently released Advancing Manufacturing: A Snapshot of Priority Technology Areas Across the Federal Government (2016) by the National Science and Technology Council’s Subcommittee for Advanced Manufacturing.

Although the continuous input of active pharmaceutical ingredient in the manufacturing of small-molecule drug products has been met with some success, as has the production of biological products (e.g. monoclonal antibodies) by means of continuous perfusion bioreactors, “true” end-to-end continuous manufacturing from raw materials and reagents to drug product at a commercial scale has not been realized. Consequently, continuous manufacturing technology is currently in need of further interest and resources from industry, government, and regulatory authorities to translate proof-of-concept technology to widespread commercial adoption. BARDA goals are currently designed to advance continuous manufacturing beyond what is feasible today and facilitate the industry-wide https://www.whitehouse.gov/sites/default/files/microsites/ostp/pcast-advanced-manufacturing-june2011.pdf https://www.whitehouse.gov/sites/default/files/microsites/ostp/pcast-advanced-manufacturing-june2011.pdf https://www.whitehouse.gov/sites/default/files/microsites/ostp/pcast_amp_steering_committee_report_final_july_27_2012.pdf https://www.whitehouse.gov/sites/default/files/microsites/ostp/pcast_amp_steering_committee_report_final_july_27_2012.pdf http://www.whitehouse.gov/sites/default/files/microsites/ostp/PCAST/amp20_report_final.pdf https://www.whitehouse.gov/sites/whitehouse.gov/files/images/Blog/NSTC%20SAM%20technology%20areas%20snapshot.pdf adoption of this emerging technology. Future BARDA investments will focus on the application of innovative CM technologies directly into advanced product development processes for BARDA-priority MCMs, demonstrating their return-on-investment required for mainstream adoption. Additionally, consistent with the President’s vision stated above, Offerors shall conduct CM activities domestically at U.S. manufacturing sites, or provide evidence/plans for technology transfer to a domestic manufacturing site.

C. SCOPE

BARDA is interested in the submission of proposals addressing translational science; specifically: the transition of novel technology from academia and Industry to pharmaceutical companies, integration of innovative CM technologies into current process development activities, or demonstration of a phase 3 /commercial process proof-of-concept utilizing CM technologies. Offerors should address how these technologies can impact the predicted return-on-investment for MCM advanced development.

Development of products should align to BARDA’s mission space. If awarded, BARDA can work with offeror to ensure technology is applied to relevant MCMs. Such CM activities should clearly quantify the improvement metric for implementation of CM at commercial scale as compared to batch or pilot production if relevant and to ultimately have potential to translate into new processes or process improvements that may have an impact in 3-5 years. These activities may include:

1. Synthetic processes that would benefit from flow processing; syntheses that could be affected through a reduced number of steps or that would not be feasible by batch production; highly selective chemistries that allow use of simple and effective continuous workup technologies, etc.

2. Improvements in CM technology for traditionally batch processes using quality by design.

3. Development of predictive models for CM early development that can later be translated to commercial scale.

4. Equipment development and implementation that address scale and process control issues that exist with CM broad implementation.

5. Non-column based chromatography and alternative purification techniques (e.g. continuous precipitation)

6. Alternatives to inherently batch unit operations (e.g. viral and sterile filtration)

7. Modular or plug and play type equipment with re-usable or flexible, interchangeable parts that allows the development of platform technologies for drug substance, drug product or end-to-end continuous manufacturing processes.

D. SUBMISSION INFORMATION

Offerors are required to follow the proposal submission guidelines in the BARDA BAA-16-100-SOL-0001 or BAA-16-100-SOL-0002. Quarterly deadlines for Quad Chart and White Paper submissions apply to these special instructions.

No individual pre-proposal conference will be held for these special instructions under BARDA BAA-16- 100-SOL-0001 or BAA-16-100-SOL-0002. Information provided at the pre-proposal conference remains applicable for these special instructions.

The Government reserves the right to award the instrument best suited to the nature of the research proposed and may award any appropriate contract type under the Federal Acquisition Regulation. If the government contemplates the award of a cost type contract, the offeror must demonstrate prior to award that its accounting system is adequate for administering a cost-reimbursement contract. The Government may also elect to make Other Transactions (OT) agreements.