REQUEST FOR PROPOSALS

Non-GMP pDNA  and Bacterial Research Cell Bank for the mRNA Technology Transfer Programme

BACKGROUND

The Medicines Patent Pool (MPP), a non-profit organisation headquartered in Geneva, Switzerland, is dedicated to improving global access to essential medicines through voluntary licensing and technology transfer.

Through its innovative business model, MPP partners with WHO, civil society, governments, international organisations, industry, patient groups, and other stakeholders, to prioritise and license needed medicines and pool intellectual property to encourage generic manufacture and the development of new formulations.

In addition, MPP is co-leading with WHO the mRNA Technology Transfer Programme, which is a global initiative that aims to improve health and health security by establishing sustainable, locally owned mRNA manufacturing capabilities in and for low- and middle-income countries (LMICs). The Programme is based around a multi-lateral technology transfer model where a Consortium, located in South Africa, will provide the technology development, training and technology transfer. Currently, 15 Programme Partners in LMICs across the world are receiving training and technology through the Programme and will then produce and sell products commercially. Its core concept is empowerment. Initially, the Programme is focusing on mRNA vaccines against COVID-19, used as a proof-of-concept pathogen to demonstrate safety, immunogenicity, and efficacy of the platform. As a starting material, pDNA is essential for manufacturing mRNA vaccines. MPP is seeking a pDNA supplier (CMO) who can meet perform the work scoped herein.

SCOPE OF WORK

1. Creation of a suitable bacterial cell line and cell bank

1. 1. Using pDNA supplied by MPP containing a Kanamycin resistance gene, transform a suitable bacterial host (e.g. E. coli).
   2. Demonstrate success of transformation and quality of pDNA material obtained. Key attributes include pDNA identity, pDNA size, and length of poly-A tail.
   3. Selection of, at least, one suitable bacterial clone based on productivity and quality attributes listed in part b.
   4. Create an RCB (Research Cell Bank) of, at least, one of the clones identified and consisting of no less than 150 vials. RCB creation protocol to be approved by MPP prior to execution.
   5. Genetic stability study of the selected clones covering, at least, the combined number of generations equivalent to the generation of a WCB, of one pDNA manufacturing batch (from revival to end of fermentation), according to the CMO’s platform process and an additional safety margin. Study protocol to be approved by MPP prior to execution. This is a pre-requisite to the work described in stage 2.
   6. RCB shipments (number, recipient locations and timelines) to be defined. Storage at CMO may be required for up to 50% of vials for up to 3 years. Applicants are required to quote this service and its conditions, if they offer it.

2. pDNA supply

1. 1. 1. Once a stable RCB, as defined in 1e above, is obtained, and using the CMO’s own up- and downstream platform process, produce a minimum of 2.0g of purified pDNA, ideally from one single batch, using one of the clones identified in part 1c and banked in part 1d (above). GMP-grade material is not required.
      2. The purified pDNA will be filled in vials of a suitable volume, corresponding to a target mass of pDNA to be specified by MPP.
      3. Release the pDNA material using the CMO’s platform analytical methods. The acceptance criteria for each assay will be agreed to by MPP. The release panel includes but may not be limited to those listed in annex 1.
      4. Manufacturing documentation, namely the process description(s) and the sampling plan(s) will be approved by MPP prior to manufacturing.
      5. Vial shipments (number, recipient locations and timelines) to be defined. Storage at CMO may be required for up to 50% of vials for up to 3 years. Please quote this service and its conditions, if you offer it.

3. Documentation

1. 1. 1. 1. The CMO will provide MPP with documentation as outlined in annex 2.

SUBMISSION OF PROPOSALS

Interested applicants who meet the requirements are requested to send their proposal in English including:

• Statement of interest with an overall description of the approach proposed to respond to the expectations of this RFP, including the necessary requirements.
• Proposed stages of work for the execution of the work herein detailed.
• Proposed timeline with an estimated number of days necessary to deliver the assignment.
• Financial proposal in USD or CHF

to technologytransfer@medicinespatentpool.org mentioning “Production of pDNA and Bacterial RCB supply” in the email subject by 31 of May 2024.

All applicants must adhere to the MPP Conflict of Interest Policy and the Code of Ethics.

SELECTION CRITERIA

MPP will review the proposal after the application closing date. Please kindly note that only shortlisted applicants will be contacted. MPP will select the successful applicant based on the following criteria:

1. Ability to perform all tasks listed in the Scope of Work herein.
2. Availability of a platform process for pDNA manufacturing and analytics that can be used in the current project.
3. Ability to supply pDNA by end of October 2024 or soonest thereafter.
4. Financial proposal.

Annex 1 . Release analytical panel for pDNA

Among others to be agreed to between MPP and the CMO, the release panel will include the following methods, for which acceptance criteria will have to be agreed upon by MPP prior to pDNA manufacturing start.

1. Appearance (compendial method)
2. pH (compendial method)
3. pDNA concentration (e.g. by A260, including A260/A280 ratio)
4. pDNA size (e.g. by gel electrophoresis)
5. pDNA identity (sequencing)
6. pDNA restriction digest analysis
7. Quantification of pDNA supercoiled, linear, and open-circular isoforms (e.g. by HPLC)
8. Determination of poly-A tail length (e.g. by capillary gel electrophoresis)
9. Bioburden (compendial method)
10. Endotoxin (compendial method)
11. Residual RNA (e.g. by Ribogreen)
12. Residual Kanamycin (e.g. by HPLC)
13. Residual host DNA (e.g. by qPCR)
14. Residual host cell proteins (e.g. by Elisa)

Annex 2 . Documents to be provided to MPP

The CMO will provide MPP with the following documents:

1. Cell Bank creation protocol (for approval prior to execution) and report
2. Cell Bank Manufacturing records
3. Cell Bank CoA
4. Cell Bank genetic stability study protocol and results
5. Cell bank stability protocol and report
6. BoM for pDNA manufacturing (including raw materials and consumables)
7. pDNA Process Description (for approval prior to manufacturing)
8. pDNA Process Sampling Plan (for approval prior to manufacturing)
9. pDNA Manufacturing records (including media, feeds and buffer preparation as applicable)
10. pDNA CoA and results of all IPCs/IPTs conducted during the batch (could be included in the manufacturing records)
11. pDNA batch report (format to be agreed upon between MPP and selected CMO)