Provision Language
6. MANUFACTURE
6.1 Manufacturing Standards. Unless otherwise agreed by the Parties in writing, each Partner shall ensure that all components of the Project Vaccine are manufactured to GMP and any other applicable standards (including ISO9001).
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6.3 Excipients. Each Partner shall ensure that the vaccine formulation excipients that it uses or procures are on the FDA’s Generally Recognised as Safe (“GRAS”) excipient list. Each Partner shall promptly inform CEPI if a novel excipient, which is not on the FDA’s GRAS excipient list, is being considered by such Partner (or a third party acting on such Partner’s behalf) for use in connection with a Project Vaccine and if so, such Partner shall (or shall cause such third party to), undertake a detailed risk assessment and seek advice from the relevant Regulatory Authorities regarding such novel excipient including the extent of data required to demonstrate the safety of such novel excipient, which may include preclinical toxicology study design and data generation during clinical development. Before use of such novel excipient in connection with a Project Vaccine, the relevant Partner shall notify CEPI and provide such information regarding such excipient to CEPI as CEPI may reasonably request.
7. CLINICAL TRIALS
7.1 Clinical Trials. Each Partner shall undertake the clinical trial(s) listed as its responsibility in any Work Package (the “Project Clinical Trials”) in compliance with all applicable laws and regulations, including applicable requirements related to the Partners’ use of clinical data outside of the country in which a given Project Clinical Trial is conducted. Each Partner shall ensure that all Project Clinical Trials undertaken by it comply with CEPI’s Clinical Trial Policy attached hereto as Annex M.
7.2 Clinical Trial Protocols: Preparation. Each Partner undertaking a Project Clinical Trial shall be responsible for the preparation of any clinical trial protocol(s) for such Project Clinical Trial. Each Partner shall provide CEPI and/or CEPI’s designee with a draft of each clinical trial protocol for each Project Clinical Trial to be undertaken by such Partner, and shall consider any reasonable suggestions made by CEPI and/or its designee regarding the clinical trial protocols reasonably in advance of finalizing the relevant clinical trial protocol and submitting it to the institutional review boards, ethics committees, and/or Regulatory Authorities. Notification of any reasonable suggestions from CEPI and/or its designee must be received by the relevant Partner within [***] after the receipt of the draft by CEPI, failing which such Partner shall be free to assume that CEPI and/or its designee has no objection to the proposed protocol.
7.3 Clinical Trial Protocols: Reporting of Submitted Versions. Each Partner shall provide to CEPI a copy of all clinical trial protocols as approved by institutional review boards, ethics committees and Regulatory Authorities in respect of each Project Clinical Trial to be undertaken by such Partner. For clarity, all such information is the Confidential Information of the Partner who has submitted such information to CEPI hereunder.
7.4 Clinical Data. Each Partner shall include in the informed consent obtained from each clinical trial subject in any Project Clinical Trial to be undertaken by such Partner, terms to allow, to the extent permitted by and consistent with applicable laws and regulations:
7.4.1 the transfer of anonymised data to CEPI and/or CEPI’s designee. CEPI shall treat such data confidentially and not disclose to third parties in accordance with all applicable data protection legislation. For the avoidance of doubt, where any personal data is to be transferred to CEPI, the Parties will enter into appropriate data protection agreements to enable compliance with applicable data protection legislation; and
7.4.2 the collection and use of Project Materials and the use of data (duly anonymised and, as the Parties may agree, blinded) derived from such Project Materials by CEPI or its designated Assessors, solely for the purpose of research under a study protocol which has received the appropriate ethical approval.
7.5 Sponsorship and Management of Project Clinical Trials
7.5.1 As between the Parties, Barinthus Bio shall be the sponsor of any Project Clinical Trial (unless the Parties otherwise agree in writing), subject to all necessary approvals being obtained (including relevant internal approvals). Where a Partner is the sponsor of a Project Clinical Trial, such Partner shall be responsible for obtaining and maintaining all regulatory and ethical committee approvals necessary for the conduct of such Project Clinical Trial.
7.5.2 In respect of each Project Clinical Trial, upon discussion with CEPI, the sponsoring Partner shall establish either an internal Trial Steering Committee (“TSC”) or a Safety Monitoring Committee or Data Safety Monitoring Board (each, a “DSMB”), as applicable. CEPI shall be entitled to appoint, and the sponsoring Partner shall permit, a CEPI representative or designee to attend all meetings of each Project Clinical Trial’s TSC and/or DSMB as an observer (either in person or by telephone, video or other electronic means), to the extent permitted by applicable laws and regulations and agreed by the TSC or DSMB, as applicable. Subject to Clause 7.5.3 below, the sponsoring Partner shall provide a copy to CEPI of all documents, correspondence and records that a member of the TSC and/or DSMB would be entitled to receive at the same time as any such documents, correspondence and records are provided to the members of the TSC and/or DSMB (as applicable), subject to compliance with applicable laws and regulations.
7.5.3 In the event that CEPI’s attendance at a meeting of the TSC and/or DSMB or receipt of documents, correspondence and records would, in the sponsoring Partner’s reasonable discretion acting in good faith, jeopardise the integrity/blinded nature of an ongoing Project Clinical Trial, the sponsoring Partner shall promptly notify CEPI of such fact and CEPI shall not be entitled to, and the sponsoring Partner shall not be required to permit CEPI to, attend such meeting or receive such documents, correspondence and records at that time. During an ongoing Project Clinical Trial, the sponsoring Partner will continue to provide CEPI with all open session DSMB documents, DSMB recommendation forms and other “open” documents identified by the Parties in the Work Package and/or protocol for such Project Clinical Trial. After the Project Clinical Trial is unblinded, and upon reasonable written request from CEPI, the Partners shall provide a copy of all documents, correspondence and records that were provided to the members of the TSC and/or DSMB and/or that a member of the TSC and/or DSMB would be entitled to receive.
7.6 Safety Notifications. Each Partner shall notify the JMAG in writing promptly following any single safety event of concern or a series of safety events which in each case is or are considered by the DSMB as relevant enough to recommend modification of study design, dosing regimen, or discontinuation of vaccination, in relation to any Project Vaccine or any Project Clinical Trial and within five (5) days from the time when the DSMB’s recommendation in relation to such event or series of events becomes known to such Partner.
7.7 Records and Reporting. Each Partner shall use all reasonable endeavours to ensure that all clinical data in relation to any Project Clinical Trials and any other clinical trials that utilise Project Clinical Trial Materials are appropriately recorded and that all such records are kept up to date and maintained in accordance with applicable laws, regulations, and study site policies. The Partners will use all reasonable endeavours to ensure that CEPI is able to review and verify all anonymised data at the end of the relevant Project Clinical Trial or other clinical trial that utilises any Project Clinical Trial Materials and will promptly following the end of such Project Clinical Trial or other clinical trial that utilises any Project Clinical Trial Materials provide a copy of such anonymised data to CEPI in such form as CEPI may reasonably require, in each case to the extent required by and consistent with applicable laws and regulations.
7.8 Priority for Clinical Trials. The Partners acknowledge that the pool of subjects available in areas of Outbreak to participate in a clinical trial to test the Project Vaccine may be limited. Accordingly, if WHO, CEPI or a Regulatory Authority in the area where the Project Clinical Trial is to be conducted determines that a product other than the Project Vaccine has substantially greater potential and should be prioritised instead for a particular clinical trial, the Partners shall consider in good faith any written request of CEPI not to proceed with the Project Clinical Trial of such Project Vaccine, it being understood and agreed that the determination of whether to proceed or not proceed with any such Project Clinical Trial shall be made by the Partner who was to act as the sponsor of such Project Clinical Trial, in its sole discretion. Each Partner shall be reimbursed for its reasonable, non-cancellable costs incurred (whether before or after the determination) resulting from any determination to not proceed as a result of CEPI’s request.
7.9 Potential WHO Clinical Trials. In the event a Partner, pursuant to a subsequent written agreement with CEPI, participates in a Phase IIb or III clinical trial as requested by WHO to compare the Project Vaccine with any other vaccine candidates indicated for use against the same pathogen, each Partner will, promptly following the end of such clinical trial, meet and confer with CEPI regarding the results of such clinical trial and shall provide access to any data and final study reports relating to such clinical trial as may be set out in such subsequent written agreement, to the extent that WHO has given their prior written consent to such access.
8. REGULATORY ACTIVITIES
8.1 Regulatory Strategy. Upon completion of the development of the Project Vaccine, Barinthus Bio shall use [***] to obtain Regulatory Approval for such product in jurisdictions that would enable Equitable Access to such Project Vaccine. Barinthus Bio shall be responsible for developing the regulatory strategy for the Project Vaccine. Barinthus Bio shall use [***] to file for, obtain and maintain the appropriate licenses for the Project Vaccine with the relevant Regulatory Authorities.
8.2 Meetings with Regulatory Authorities. Each Partner shall notify CEPI in writing of any material meetings with Regulatory Authorities with respect to the Project Vaccine, or any Project Clinical Trial or other clinical trial that utilises any Project Clinical Trial Materials at least [***] in advance of such meetings, or if a Partner itself receives less than [***] notice of such a meeting, as soon as practicable. At CEPI’s option, the Partners shall consult with CEPI or its designee regarding any material interactions between a Partner and Regulatory Authorities relating to the Project Vaccine, or any Project Clinical Trial or other clinical trial that utilises any Project Clinical Trial Materials. At CEPI’s reasonable request, a Partner shall request a meeting with Regulatory Authorities to address any significant unresolved issues with respect to any Project Clinical Trial or other clinical trial that utilises any Project Clinical Trial Materials.
8.3 Regulatory Strategy. The Partners shall consult regularly with CEPI regarding the regulatory strategy for the Project Vaccine and each Project Clinical Trial or other clinical trial that utilises any Project Clinical Trial Materials and shall provide copies of the clinical trial authorisation and all material regulatory submissions with respect to such trial(s) to CEPI no later than [***] prior to their contemplated submission to a Regulatory Authority. For the avoidance of doubt the Partners shall have final editorial control of such submissions. If a final version is not available by [***] prior to submission, then a mature draft version may be electronically delivered to CEPI for review at that time. Additionally, the Partners shall promptly make available for review by CEPI or its designated Assessors at one of the Partner’s premises copies of the following to the extent reasonably required for CEPI to evaluate the progress of the conduct and completion of each Project Clinical Trial or other clinical trial that utilises any Project Clinical Trial Materials:
8.3.1 all submissions to Regulatory Authorities and regulatory filings for the Project Clinical Trial or other clinical trial that utilises any Project Clinical Trial Materials together with all data included or referenced therein (other than ministerial submissions that do not involve safety or efficacy issues); and
8.3.2 material documents and information exchanged between any Regulatory Authority and a Partner, including relating to the Project Clinical Trial or other clinical trial that utilises any Project Clinical Trial Materials including official meeting minutes.
8.4 Referencing Market Authorisation package. At the reasonable request of CEPI, each Partner agrees to co-operate with CEPI to allow CEPI or its nominee to cross-reference the market authorization package, the drug master file and all existing data of the Project Vaccine only for the purpose of supporting regulatory filings and submissions for any vaccines that may be used in the event of a potential public health emergency utilizing the same, or a similar, platform technology, if applicable. For clarity, (i) no Partner shall be required to disclose any non-public information that is proprietary to a third party other than to the Regulatory Agency with which the applicable market authorization package is filed, and (ii) a Partner’s market authorization package or data may not be disclosed to or cross-referenced by a third party without prior approval of the applicable Partner, which shall not be unreasonably withheld or delayed.
8.5 Redactions. Notwithstanding any other provision of this Clause 8 or other terms or conditions of this Agreement, a Partner shall have the right to redact any documentation made available pursuant to this Agreement to the extent reasonably necessary to protect its trade secrets or other non-public sensitive information or financially sensitive information or data that is proprietary to a third party that Partner is prohibited from disclosing.
10. DISSEMINATION OF PROJECT RESULTS; PUBLICATION
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10.4 Clinical Trial Registration and Results
10.4.1 Project Clinical Trials and any other clinical trials that utilise any Project Clinical Trial Materials must be registered through an easily discoverable existing public route such as clinicaltrials.gov, The EU Clinical Trials Register, or the International Clinical Trials Registry Platform, in accordance with all applicable laws and regulations. The information provided shall follow the current WHO Trial Registration Data Set. The clinical trial ID or registry identifier code/number shall be included in all publications of clinical trials.
10.4.2 Publication of clinical trial results (including negative results) from Project Clinical Trials and any other clinical trials that utilise any Project Clinical Trial Materials shall be made by the Partner who has been responsible for the applicable Project Clinical Trial Materials or other clinical trial promptly through an easily discoverable existing public route (website or system). Such Partner shall submit clinical trial data from Project Clinical Trials and any other clinical trials that utilise any Project Clinical Trial Materials for publication as soon as reasonably possible but, in any event, within [***] after study completion. During the same time period, such Partner shall make the results available to the national Ministry of Health or equivalent in the countries where Project Clinical Trials are held. Such Partner shall deposit Clinical Trial data in an open sharing platform such as ClinicalStudyDataRequest.com, Vivli Center for Global Clinical Research Data, or an equivalent service.