1.1 RFP Purpose and Objective
As outlined in Attachment A – Scope of Work (SOW), PQM+ seeks a manufacturer to perform services to evaluate a method to identify, propose, and demonstrate at laboratory scale a less expensive manufacturing process for rifamycin S. With PQM+ technical direction and oversight, the organization will develop the process and demonstrate its efficiency versus current commercial fermentation processes. This is a research-based SOW. PQM+ will approve and authorize each deliverable and define direction to be taken for any subsequent deliverable. If a deliverable fails to meet the desired result, the SOW will not be authorized to progress.
SECTION 2.0 – RFP PROCEDURES AND INSTRUCTIONS
This section of the RFP provides the general procedures and instructions the offeror is expected to follow in completing its response.
2.1 Proposal Contents
Offeror shall include the following with its proposal:
2.1.1 Offer Letter – prepared on the Offeror’s letterhead, signed and dated by an authorized official who has the authority to sign and legally bind the Offeror. Include offeror name, date of offer, price, quote validity period, name and title of the signing official. The Offer Letter must include acceptance of “Other RFP Requirements” detailed in the SOW.
2.1.2 Technical Proposal – using Attachment A, provide a narrative description of services required to meet the deliverables, detailed task list and description of task components, timeline, proposed personnel (including CVs and qualifications, noting if any personnel will be denoted key to implementation)
2.1.3 Cost Proposal – using Attachment A, provide a cost reimbursement budget and budget narrative outlining proposed costs and the basis for each cost category (Labor, Fringe, Materials & Supplies, Other Direct Costs, Overhead). The cost reimbursement budget shall be submitted in a MS Excel workbook (formulas unlocked) where each Deliverable is separately priced on a unique tab and totaled in a Summary Tab. If an indirect rate or fee are included, provide the most current Negotiated Indirect Cost Rate Agreement (NICRA) if applicable or detailed explanation. If an organization does not hold a NICRA, the prior three (3) years audited financial statements and a detailed calculation of indirect will be required. Any proposed fee must include a detailed description and may not duplicate any costs contained in the NICRA or indirect. Include a cost share budget tab, if applicable. The budget narrative must provide details in written form submitted in MS Word for each line-item category.
2.1.4 Past Performance – provide information of services or projects of similar size and scope as related to Attachment A of this RFP, including experience working with non-profit organizations.
2.1.5 Small business concern – if the Offeror has a small business concern designation, please provide the U.S. Small Business Administration designation and/or NAICS, the SAM.gov assigned universal entity identification (UEI) No., or name of certifying agency and date of expiration.
2.2 Period of Performance
For pricing purposes, assume a period of performance with an anticipated start date of June 20, 2023, through September 29, 2023.
2.3 Proposal Validity Period
Offeror’s proposal shall be considered valid for sixty (60) days after submission.
2.4 Third Party Services/Products
Offeror must clearly identify any third-party product(s) or service(s) that is a part of its RFP response.
2.5 Anticipated Agreement Type
It is anticipated that a work-for-hire cost reimbursement contract will be issued. Applicable flow-downs from USP and USP’s Client will be included as cited in the SOW. USP reserves the right to terminate the resultant contract if deliverable targets are not met. The selected supplier will be required to execute a Confidentiality/NDA with USP/PQM+ upon completion of the competitive bidding process.
2.6 Budget Ceiling
Based on the scope of work and proposed timeline, and previous company experience with similar projects, please include a proposed budget for the completion of this project. Additional funds may be allocated for other creative ideas, as warranted, and we welcome suggestions for these in your proposal.
2.7 Prevailing Language
All documents submitted in response to this RFP, as well as all correspondence in connection with the RFP, shall be in the English language.
SECTION 3.0 RFP EVALUATION PROCESS AND SCHEDULE
3.1 Schedule
The proposed RFP schedule is below. If necessary, USP may modify in writing.
Activity
Deadline
RFP Re/Issued
May 24, 2023,
Questions submitted by interested Offerors
June 01, 2023
Distribution of responses to questions to Offerors
June 08, 2023
RFP Responses Due
June 22, 2023, by 5:00PM EST
Notice of selected Offeror
June 29, 2023
Contract Start-up/Implementation
July 10, 2023
3.2 Evaluation Criteria
Offeror responses may be evaluated on criteria such as but not limited to the factors below. USP reserves the right to make a selection based on the proposal offering best value based on multiple evaluation factors.
Past Performance (provision of similar services)
Demonstrated ability to work in a global operating environment
Facilities capable of analyzing, testing, and producing synthesis route prototype
Proven understanding of generally accepted manufacturing best practices and methods
Completeness of Proposal
Technical Proposal approach
Cost Proposal factors of pricing/cost
SECTION 4.0 RFP CORRESPONDENCE
4.1 RFP Submission/Questions
All submissions must be delivered electronically with the subject line “RFP-RIFAMYCIN RAW MATERIAL PRICE REDUCTION” by on the date in 3.1 at GPH_Procurement@USP.org;
4.2 Proposal Response
Offerors will be notified via email if their proposal is within competitive range.
4.3 Notification of Selection
Offerors in competitive range will be notified via email of the results of the selection process.
SECTION 5.0 - RFP TERMS AND CONDITIONS
5.1 Proposal-Related Incurred Costs
The offeror shall be responsible for all costs incurred in preparing or responding to this RFP. All materials and documents submitted in response to this RFP become the property of USP and will not be returned. This RFP will in no way obligate USP to compensate any offeror for costs associated with the preparation of its proposal.
5.2 Reservation of Rights
This RFP does not commit USP to award a contract, to pay any costs incurred in the preparation of a proposal to this request, or to procure services or supplies. USP reserves the right to cancel this procurement at any time without prior notice. USP may require the offeror to participate in discussions, and to submit such monetary, technical, or other revisions of their proposals that may result from such discussions.
All information contained in this RFP is proprietary. It is for the sole use of the Offeror in connection with bid response preparation and is not to be used by Offeror for any other purpose or revealed or disclosed in any manner to any other individuals and/or company without specific written permission from USP.
5.3 Rejection of Solicitation Response
USP reserves the right to reject any or all responses received or any part thereof, to accept any response or any part thereof, or to waive any informalities when it is deemed to be in USP’s best interest.
5.4 Confidential Information
Materials submitted by Offeror in response to the RFP that are considered confidential/proprietary
must be clearly marked as such at the time of submission.
5.5 Responsibility for Compliance with Legal Requirements
The offeror’s products, services, and facilities shall be in full compliance with all applicable federal, state, and local laws, regulation, codes, standards, and ordinances, regardless of whether or not they are referred to by USP.
5.6 No Publicity
No publicity or new release pertaining to this RFP, responses to this RFP, USP’s decision regarding Offeror selection, or the award of any resultant contract as a result of RFP submission may be released without USP’s express prior written consent.
ATTACHMENT A – SCOPE OF WORK (SOW)
RIFAMYCIN RAW MATERIAL COST ANALYSIS
Background and Rationale
TB remains an important global public health problem: it is one of the top 10 causes of death and the leading cause of mortality from a single infectious agent. According to WHO, in 2019 an estimated 10 million people became ill with TB and 1.4 million people died from TB globally.[1] WHO characterizes multidrug-resistant TB (MDR-TB) as a public health crisis and a health security threat; a global total of 206,030 people with MDR-TB or rifampicin-resistant TB were detected and notified in 2019[2]. This is a 10 percent increase from 186,883 in 2018.
An important milestone in the TB effort was the UN’s first-ever high-level meeting on TB held in September 2018, elevating the discussion on the TB epidemic and how to end it to the top levels of the governments. The outcome of the UN high-level meeting was a political declaration confirming UN Member States’ commitment to the SDGs and WHO’s End TB Strategy goals and targets. The UN meeting also added new targets, including treating 40 million people for TB and 30 million people for latent TB infection (LTBI) in a five-year period (2018–2022). To achieve these targets, it is critically important that quality-assured medicines for treatment of TB, including LTBI, are available globally and accessible to the people in need.
Purpose
Rifapentine is an important medicine, not only for treatment of LTBI, but also because WHO recently recommended a shortened regimen containing rifapentine for treatment of drug- susceptible TB. As it is a shortened regimen, it has the potential to improve a patient’s adherence to treatment and produce better treatment results, but the price of rifapentine could pose problem for the new regimen’s roll out. To address this issue, PQM+ is embarking on a process to identify methods that ultimately work towards price reduction of the most costly ingredient of rifapentine—rifamycin–which is the Active Pharmaceutical Industry (API).
The key starting material in rifapentine API is rifamycin. Recently, rifamycin comprised nearly 30% of rifapentine API raw material costs. There are multiple medicines that use rifamycin as an ingredient including rifaximin, rifampin, rifapentine, and rifabutin. Rifapentine is a minor consumer in the rifamycin market thus does not control the raw material’s pricing. For example, rifaximin alone consumes the largest share of rifamycin i.e. 30,000 Kg in the US market compared to nearly 4,000 Kg from the entire worldwide rifapentine market in 2021. PQM+ seeks to lower the cost of rifamycin by seeking alternate lower cost synthesis methods. Currently rifamycin is produced in and dominated by Chinese manufacturers who use a fermentation process.
Scope of Work
With technical direction and oversight from PQM+, the manufacturer will perform services to evaluate a method to identify, propose, and demonstrate at laboratory scale a less expensive manufacturing process for rifamycin S. With PQM+ direction, the organization will develop the process and demonstrate its efficiency versus current commercial fermentation processes. This is a research-based SOW. PQM+ will approve and authorize each deliverable and define direction to be taken for any subsequent deliverable. If a deliverable fails to meet the desired result, the SOW will not be authorized to progress.
● Conduct a desk review to determine the cost drivers and true cost for the manufacture of rifamycin S by conventional routes and feasibility of leveraging cost drivers to significantly reduce the cost of rifamycin S
● Propose a small-scale manufacturing route of Rifamycin S leveraging cost driver(s)
● Demonstrate at laboratory scale a new low-cost manufacturing for rifamycin S that is commercially scalable and validate that projected costs will be significantly less than conventional commercial processes and perform technology transfer to a selected manufacturer.
Deliverables
The scope contains five major deliverables as outlined below -
Deliverable 1 – Conduct a full desk review of rifamycin S components and cost drivers as currently manufactured in the market. Identify multiple areas which could be changed and/or substituted to impact the cost of the drug during manufacturing (whereby the overall cost would be reduced). Run calculations and estimates for each hypothesis and detail the impact a change in these areas might make on the cost drivers of the drug – detailing cost, environmental, formulary, manufacturing, production, and shipping cost impacts at a minimum. Produce a report from the paper study comparing and contrasting the cost driver areas. Hold a telcon with the PQM+ team (or additional calls if necessary) to review the material and hold discussions on findings. PQM+ will evaluate the desk review for viability in accordance with PQM+ objectives. If the desk review demonstrates viable results, PQM+ will authorize the SOW to proceed. If the desk review does not demonstrate viable results, PQM+ will terminate the SOW and contract. Manufacturer must obtain PQM+ written approval and authorization to move to Deliverable 2.
Deliverable 2 – Develop a small-scale manufacturing route for the most promising areas where a formulary change/substitution could result in cost savings in drug production. Test and document each area in the laboratory environment. Identify the most successful formulary candidate(s) in the lab environment and produce a report detailing the strengths/weaknesses of the method(s); where the report documents cost/benefit ratio of factors including but not limited to a) formulary requirements; b) supply chain availability; c) safety and security of each ingredient; d) environmental impact to produce; e) disposal. Hold a telcon with the PQM+ team (or additional calls if necessary) to review the proposed manufacturing process and findings. PQM+ will evaluate the viability of Deliverable 2. Manufacturer must obtain PQM+ written approval and authorization to move to Deliverable 3. The timeline of Deliverable 3 (start date and target due date) will be contingent upon PQM+/Client identification of a technology recipient.
Deliverable 3 - Produce a laboratory-scale stable sample of the PQM+ selected method(s). Demonstrate scalability of the process to facilitate reproduction of the process by a drug manufacturer in a commercial environment. Hold a telcon with the PQM+ team (or additional calls if necessary) to review the sample process and findings for each method tested. Obtain direction from PQM+ on which method to develop at scale. Conduct validations on the selected method and submit to the PQM+ team. PQM+ will evaluate the viability of Deliverable 3. Manufacturer must obtain PQM+ written approval and authorization to move to Deliverable 4.
Deliverable 4 - Produce documentation required for selected method technology transfer including but not limited to a) development report for the formulary synthesis route; b) campaign report with detailed description of the procedures; c) intermediates Certificate of Analysis report; d) Raw materials Certificate of Analysis report; e) Analytical development report; f) List of substances; g) Recommendations for stability, storage, and handling. Hold a telcon with the PQM+ team (or additional calls if necessary) to review the proposed manufacturing process and findings. Submit reports to PQM+ team for Deliverable 4. PQM+ will evaluate the viability of Deliverable 4. Manufacturer must obtain PQM+ written approval and authorization to move to Deliverable 5.
Deliverable 5 – Produce full report demonstrating and validating new low-cost manufacturing process from desk review through technology transfer and submit to PQM+ team. Obtain written PQM+ approval of report and perform any additional reporting required by PQM+. Collaborate with PQM+ and other identified stakeholders to perform technology transfer process as requested by PQM+ and our client. If method/technology is novel; work with USP/PQM+ to submit provisional patent filing to protect the method/technology during technology transfer.
Deliverable No.
Milestone Deliverable
Illustrative Due Date
1
Desk review report
July 21, 2023
2
Manufacturing process developed
August 04, 2023
3
Laboratory scale sample produced
August 18, 2023
4
Technology Transfer report and materials
September 29, 2023
5
Full report of desk review-to-technology transfer
October 13, 2023
Timelines
June 20, 2023 – September 29, 2023 (subject to adjustment based on manufacturing cycle and USP’s Client direction on technology transfer process).
Estimated Budget based on available funding
The estimated budget is contingent upon PQM+ authorization and availability of Client funds.
In performance of the SOW, USP/PQM+ welcomes cost share from the selected supplier to demonstrate public/private partnerships leveraged in support of PQM+ objectives.
Travel (if applicable)
N/A
Organizational Point(s) of Contact
TBA
Other RFP Requirements Applicable to the Successful Offeror
1) Selected entity will be required to sign a Confidentiality/NDA Agreement with USP/PQM+ upon completion of the RFP process.
2) Selected entity agrees to perform services under a work-for-hire contract and comply with any U.S. Government Cooperative Agreement requirements and regulations applicable to the services, including but not limited to 2 CFR 200, Appendix II to 2 CFR 200, and 2 CFR 700. Contract flow-downs will include 2 CFR 200.315 and 37 CFR Part 401.14 and any potential or actual patent action resulting from these services will include a statement (aka Government Use Clause) specifying that the invention was made with U.S. Government support and that the U.S. Government has certain rights in the invention. As prime award recipient, PQM+/USP will retain title to any method/invention developed by the resulting contract.
[1] WHO Global Tuberculosis Report, 2020.
[2] https://www.who.int/tb/publications/global_report/TB20_Exec_Sum_20201014.pdf
RFP OVERVIEW
1.1 The United States Pharmacopeial Convention, Inc. (USP)
The United States Pharmacopeial Convention, Inc. (USP) is a scientific nonprofit organization that sets standards for the identity, strength, quality, and purity of medicines, food ingredients, and dietary supplements manufactured, distributed, and consumed worldwide. USP’s drug standards are enforceable in the United States by the Food and Drug Administration, and these standards are used in more than 140 countries. Since 1992, the United States Agency for International Development (USAID) and USP have collaborated to help address critical issues related to the access of quality medicines.
1.2 PQM+ Project Overview
The USAID Cooperative Agreement No. 7200AA19CA00025 entitled “Promoting the Quality of Medicines Plus (PQM+) program” is a five-year (September 27, 2019 – September 26, 2024) USAID-funded cooperative agreement with a goal to sustainably strengthen medical product quality assurance (QA) systems in low-and middle-income countries. PQM+ provides technical assistance (TA) to build in-country capacity of medical products regulatory authorities’ QA systems in assisted countries. PQM+ also provides technical support to manufacturers of quality- assured priority medical products for malaria, tuberculosis (TB), neglected tropical diseases, other infectious diseases, family planning and reproductive health, and maternal, newborn, and child health.
