Provision Language
Definitions
“Materials” shall mean the materials described in Annex 2.
“Programme Agreement” shall mean any other agreement entered into between MPP and a Third Party as part of the Project under which MPP is granted rights to data, Know-How or IP for further sublicensing.
“Relevant Regulatory Authority” shall mean (i) in relation to a particular country in the Territory, any applicable federal, national, regional, state, provincial, or local regulatory agencies, departments, bureaus, commissions, councils or other government entities regulating or otherwise exercising authority with respect to the Products in that country, or (ii) WHO pre-qualification programme where such approval has been deemed adequate by the authority referred to in (i).
“Technical Assistance” shall mean the assistance detailed in Section 2.4 of this Agreement.
“Technical Information” shall mean the documentation listed in Annex 3 and Annex 4 detailing technical specifications and instructions for manufacturing and testing the selected mRNA vaccine candidate. Such Technical Information shall be transferred to Biovac (Annex 3) or provided by Biovac (Annex 4) written in the English language and in a single copy.
“Technology” shall mean Materials, Technical Information and Technical Assistance.
“Technology Transfer” shall mean a logical procedure that controls the transfer of any process together with its documentation and professional expertise from development to manufacture or between manufacturing sites. It is a systematic procedure that is followed in order to pass the documented knowledge and experience gained during development and or commercialization to an appropriate, responsible and authorized party. Technology transfer embodies both the transfer of documentation and the demonstrated ability of Biovac, to effectively perform the critical elements of the transferred technology, to the satisfaction of all parties and any applicable regulatory bodies. The specific contents of the Technology Transfer to Biovac are detailed in Annex 3 (Technical Information, Technical Assistance, Materials), and the specific contents of the Technology Transfer Technical Information that Biovac will generate is detailed in Annex 4.
“Technology Transfer Package 1” shall have the meaning described in Annex 3.
“Technology Transfer Technical Information Package 2” shall have the meaning described in Annex 4.
2. TECHNOLOGY TRANSFER
2.1 MPP will cause the Technology Transfer to be conducted in accordance with the roadmap as described in Annex 1. The Technology Transfer to Biovac will comprise of Technology Transfer Package 1, as described in Annex 3, called “mRNA technology for R&D” (hands-on and mandatory), which will be finalized once Phase 1 Clinical trial material is manufactured and released. Content of Technology Transfer Package 1 will be made accessible to Biovac as soon as information is available. The Parties will meet and confer following the Effective Date to agree on a Technology Transfer Plan setting out the timeline for the delivery of Technical Transfer Package 1, as well as detailing actions, reporting, deliverables, and success criteria linked to the Technology Transfer (the “Technology Transfer Plan”).
Before Technical Transfer activities take place, Biovac will access an introduction to the mRNA technology training provided by Afrigen (timelines to be agreed upon between the Parties) and associated training material (Introduction to the mRNA Technology Package).
2.2 The Parties acknowledge that the timelines agreed in a Technology Transfer Plan are of paramount importance for planning purposes. In the event that the agreed timelines of any section of a Technology Transfer Plan changes after being agreed between the Parties, for any reason whatsoever including an Event of Force Majeure, the Parties agree to meet and discuss the potential changes and how it can be accommodated within any commercial obligations or other commitments which a Party may have towards a Third Party. While every reasonable effort will be made to accommodate changes to agreed timelines, the Parties agree and acknowledge that this cannot be guaranteed. If any amended timelines cannot be met by either Party, the Parties undertake to apply commercially reasonable efforts to continue the Project on amended timelines as soon as feasible.
2.3 The Technology Transfer Package 1 shall be considered complete by the Parties when Biovac has received the Technology and the Parties are satisfied that the production of the selected mRNA vaccine candidate meets the requirements outlined in the Technology Transfer Plan.
2.4 As part of Technology Transfer Package 1, MPP will, on dates to be agreed to by the Parties, cause Afrigen to provide Technical Assistance to Biovac, as follows:
(a) Training at Afrigen’s site by sending qualified Biovac personnel to the Afrigen Facility for training on documentation and Phase I manufacturing process and analytics.
(b) Respond in a reasonable timeframe to any query concerning the Technology Transfer Package 1 that might arise during and after the on-site training.
(c) Should any additional on-site Technical Assistance (e.g. on-site assistance of Afrigen personnel at the Biovac Facility, additional on-site training at Afrigen) be requested by Biovac beyond Sections 2.4(a)-(b), Biovac shall bear all allowance, travel and accommodation expenses incurred.
2.5 Any additional services associated therewith and the means of delivery thereof not provided for in this Agreement shall, as the need for same arises i.e. assist in data analysis, non-routine investigations, be negotiated for and agreed to by the Parties in writing, prior to implementation thereof.
3. OBLIGATIONS OF MPP
MPP undertakes to:
3.1 Work with WHO to assess Biovac capabilities and identify actions and deliverables for the Technology Transfer to Biovac to proceed, as well as to convene appropriate expertise to support Technology Transfer to Biovac, as feasible and may be necessary.
3.2 Ensure Biovac is provided with the Technology reasonably necessary to fulfil the transfer of Technology Transfer Package 1, as contemplated in Annexes 1 and 3 herein.
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3.4 Provide IP analysis on the Technology, as practicable and appropriate and endeavour to provide better visibility on freedom to operate analyses in the Territory.
3.5 Monitor the activities of Biovac and the parties to other Programme Agreements to ensure good coordination and facilitate the sharing of data, Know-How and IP as provided for in this Agreement and other Programme Agreements.
3.6 In consultation with WHO, design and draft any further governance or technology transfer documents and provide on-going technical support as necessary and as feasible to fulfil the objectives of the Agreement within the agreed timeframes.
4. OBLIGATIONS OF BIOVAC
Biovac undertakes to:
4.1 Exercise due diligence in performing the actions and deliverables presented in the Roadmap (Annex 1) and detailed in the Scope of Work (Annex 5) and the Technical Transfer Plan.
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4.3 Conduct any facility upgrades, equipment procurement and qualification, receive applicable approvals from the Relevant Regulatory Authority and perform any other activity necessary to ensure that the Facility is fit for the purposes for applying the Technology at the time of Technology Transfer.
4.4 Ensure that all Biovac personnel involved with the Technology Transfer be sufficiently qualified to as to ensure an efficient and effective transfer of the Technology.
4.5 Following the completion of Technology Transfer Package 1 from Afrigen as per the criteria outlined in Annex 3, perform all activities detailed in the Scope of Work (Annex 5) and the Technical Transfer Plan in order to provide MPP with the Technology Transfer Technical Information Packages 2a and 2 (Annex 4).
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4.8 Allow the presence of Afrigen personnel at Biovac, as nominated and mutually agreed between the Parties and for a period as described in the Technology Transfer Plan, to ensure the technology is successfully transferred to Afrigen and subsequent manufacturing and analytical processes knowledge transfer to subsequent receiving units happens smoothly.
4.9 Respond within a reasonable timeframe to any query concerning any component of the Technology Transfer Information Package 2 (Interim Technology Transfer Information Package 2a and/or Technology Transfer Information Package 2) that might arise during subsequent technology transfers to other receiving units in the mRNA Technology Transfer Programme.
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ANNEX 2. TERMS OF MATERIAL TRANSFER
1. MPP shall ensure Afrigen will provide Biovac Quality Control Standards (Afrigen materials or information for procurement from commercially available sources as appropriate) and comparators (materials manufactured at Afrigen to confirm the successful technology transfer of the methods). Detailed list including sources and amounts will be included in the Technical Transfer Plan.
ANNEX 3. TECHNOLOGY TRANSFER PACKAGE 1 CONTENT
PACKAGE 1
Package 1 shall include:
- Technology Transfer Technical Information Package 1 (content listed below)
- Technical assistance (as defined in section 2.3 of this agreement)
- Materials (detailed in Annex 2)
Technology Transfer Technical Information Package 1 content:
- Drug substance (mRNA), bulk drug product (encapsulated mRNA) and final drug product manufacturing instructions (thus including manufacturing process flows, in-process and final Quality Control flows, Waste flows, Hold points, process mass balances and personnel flow). NOTE: Expected scale of production at Afrigen: plasmid (20-30L); mRNA IVT (1-5L), LNP concentrated (2-15L).
- Analytical procedures to test Raw materials (including identity tests used for Phase I and justification of tests methods required for Phase III) and products (including release and in-process assays either qualified or pre-validated) and packaging specifications (including container closure test reports for -20 C final packaging and specifications of vials, caps and stoppers).
- Reference and supplier of raw materials, consumables and equipment.
- Materials as listed in Annex 2 of this agreement.
- Process development support data capturing key experience/product knowledge:
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i. Detailed equipment list with specifications covering the entire manufacturing process.
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ii. Cell History, batch record and analytical results.
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iii. Process development report that also outlines the manufacturing process rationale. It includes:
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technical reports (including analytical assessment reports, stability reports, detailed nonclinical and pre-clinical reports and, if applicable, cleaning verification data and reports);
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potential critical manufacturing process parameters/steps;
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the success (or failure) of the technology implementation in Afrigen;
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a history or evolution of the process through the Phase I clinical stage of development.
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iv. Batch record and analytical results of pivotal batches (preclinical/engineering/clinical batches) and technical interpretation of the results.
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v. Appropriate comparison between preclinical/engineering/clinical batches.
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vi. Rationale for proposed specifications for Phase I.
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vii. Available stability data.
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viii. Submitted Clinical Trial Application sections (including all Chemistry, Manufacturing and Controls documentation) and Phase 1 Clinical Study Report (CSR), when available.
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ANNEX 4. TECHNOLOGY TRANSFER PACKAGE 2 CONTENT
PACKAGE 2
Package 2 shall include:
- Technology Transfer Technical Information Package 2 (content listed below)
- Technical assistance (as defined by Partner needs)
NOTE: Documentation to be provided in a CTD-like format
Technology Transfer Technical Information Package 2 content:
Package 2a – mRNA Technology Platform Optimization for Industrialisation
- DS and bulk DP GMP facility layouts including personnel, materials and waste flows.
- Catalogue number and supplier of raw materials, consumables including primary packaging.
- Catalogue number, supplier, commissioning reports and maintenance plans of equipment.
- Process optimisation, characterisation and robustness capturing key experience/product knowledge (conducted on process up to 1L IVT/3-6L bulk DP):
- i. Process optimisation development report, batch records and analytical results for DS, bulk DP and final DP (sterilizing filtration, manual filling and freezing) manufacturing.
- ii. Process description of optimised process at 1L IVT/3-6L bulk DP.
- iii. Sterilizing filter selection rational and bacterial retention efficacy verification.
- iv. Process characterization and robustness study reports. Critical manufacturing process parameters (CPP) and Key Process Parameters (KPP) identified with associated acceptable ranges.
- v. Hold times study protocols and reports for the end-to-end process up to final DP.
- vi. Template and executed manufacturing batch records and analytical results of post-optimisation demonstration batches and consistency batches at 1L IVT/3-6L bulk DP.
- vii. Product specifications for DS, bulk DP and filled DP.
- viii. Process performance qualification (PPQ) protocol executed on consistency batches.
- Analytical procedures for Raw materials, DS, bulk DP and final DP, IPC and IPT in place and pre-validated:
- i. Analytical strategy and sampling plan with tests categorisation (release test, in process controls (IPC), in-process testing (IPT), characterization).
- ii. Pre-validation protocols and reports for each method (according to ICH Q2 R1 guidelines).
- iii. Trend summaries (where applicable).
- iv. For modified methods: amended SOPs, method development report describing method modifications implemented and their rationale.
- v. Elemental impurities rationale document.
- Results of accelerated stability studies conducted in representative conditions (i.e., temperature, humidity, container materials) for DS, bulk DP, filled DP.
- Appropriate immunogenicity evaluation in pre-clinical animal model studies of batches manufactured at Biovac with optimised process.
- Process development report (PDR) reflecting optimisation of the manufacturing process (DS, bulk DP and filled DP) and rationale thereof, characterisation and robustness and comparison with the process as received from Afrigen (including pre-clinical results).
- Updated Target Product Profile.
- Process description of automated bulk DP filling.
Package 2b – mRNA Technology Platform Scaled-Up for Industrialisation
- Manufacturing process scale-up: DS at 5-10 L, bulk DP 30-60L, final DP.
- i. Manufacturing Batch records (template and executed) and analytical results on at least 2 batches at scale.
- ii. Process descriptions for DS, bulk DP and final DP manufacturing process.
- iii. Product specifications for DS, bulk DP and filled DP.
- iv. Hold times, time out of refrigeration (TOR) and time out of freezing (TOF) study protocols and results for the end-to-end process up to final DP.
- Catalogue number and supplier of raw materials, consumables including primary packaging.
- Catalogue number and supplier, commissioning reports and maintenance plans of equipment.
- Cleaning validation strategy plan for non-single use equipment (for DS, bulk DP and final DP manufacturing).
- Reports of accelerated and real time stability studies (according to ICH Q1 R2 guidelines) conducted in representative conditions (i.e., temperature, humidity, container materials) for DS, bulk DP, final DP.
- Appropriate immunogenicity evaluation in pre-clinical animal model studies of batches manufactured at Biovac with scaled-up process.
- Process development report (PDR) on evolution and rationale of the manufacturing process (DS, bulk DP and final DP) and comparison (including pre-clinical results) along the product development across process as received from Afrigen up to scaled-up process.
- Updated Target Product Profile.