Manufacturing Approvals means any manufacturing approvals or quality assurance assessments that may be required for the Sublicensee to Manufacture Licensed Compound and Licensed Product at the Facility in accordance with this Sublicense Agreement and to sell Licensed Product to Customers for subsequent Commercialization in the Territory, including without limitation the WHO Prequalification for the Manufacture of Licensed Compound and Licensed Product by the Sublicensee at the Facility(ies).
4. TECHNICAL ASSISTANCE
4.1 Documentation and Assistance; Regulatory Filings in the Territory
(a) Upon the Sublicensee’s request, GARDP will provide, or will in accordance with the Shionogi License Agreement request that Shionogi provide, the Sublicensee with access to the content of the regulatory filings included within the Sublicensed Rights and described on Schedule C (collectively, the “Shionogi Regulatory Approvals”) to the extent reasonably required for the Manufacture of Licensed Product(s) by the Sublicensee and for obtaining Manufacturing Approvals, all for use in accordance with the license granted pursuant to this Sublicense Agreement.
(b) The documentation provided by GARDP and/or Shionogi (including the Shionogi Regulatory Approvals) will not be used by the Sublicensee for any purpose other than the Development (solely to the extent permitted by Section 3.1(c)) and Manufacture of the Licensed Compound and Licensed Product in accordance with this Sublicense Agreement, and constitutes Confidential Information and trade secrets of GARDP and Shionogi.
(c) The Sublicensee shall be responsible for seeking all Manufacturing Approvals required for the Manufacture of the Licensed Product as contemplated in this Sublicense Agreement, which Manufacturing Approvals shall be in the Sublicensee’s name and in respect of which the Sublicensee shall have all rights and responsibilities. The Sublicensee shall be responsible to maintain its own regulatory documentation, provided that, if Shionogi regulatory documentation has been provided to the Sublicensee, the Sublicensee shall use and maintain such documentation as it maintains its own regulatory documentation. The Sublicensee assumes full responsibility and liability to GARDP and Shionogi for any unauthorized use or disclosure of any Confidential Information received by the Sublicensee from GARDP and/or Shionogi. Any and all such documents and materials delivered to the Sublicensee pursuant to this Section 4 are and will remain the sole property of Shionogi and/or GARDP, as applicable.
(d) Shionogi will be responsible for providing one set of electronic copies only. GARDP will, or will in accordance with the Shionogi License Agreement request that Shionogi, respond to reasonable requests from the Sublicensee for clarification on the information provided under this Section 4.1, where responses to such requests are, in Shionogi’s good faith judgment reasonably necessary to clarify the Manufacture (in the manner Manufactured by or for Shionogi and registered by Shionogi on the effective date of the Shionogi License Agreement) of the Licensed Compound or the Licensed Product.
(e) Notwithstanding the foregoing, the Sublicensee acknowledges that neither GARDP nor Shionogi represents that, merely because the Sublicensee is Manufacturing the Licensed Product using the Manufacturing process transferred by Shionogi, such Licensed Product Manufactured by the Sublicensee is equivalent to any product containing cefiderocol (including but not limited to cefiderocol sulfate tosylate) which is Manufactured or sold by Shionogi, and no regulatory exclusivity waiver granted by Shionogi shall be understood to make any such representation. Orchid shall have the right and responsibility to demonstrate the equivalence of the Licensed Product Manufactured by the Sublicensee with the product Manufactured by Shionogi for all regulatory purposes in accordance with the applicable regulatory guidelines.
(f) The Sublicensee acknowledges and agrees that neither Shionogi nor GARDP shall be responsible for the performance of additional studies or submission of additional data for the grant of Manufacturing Approvals for Licensed Compound and Licensed Product Manufactured pursuant to this Sublicense Agreement. The Sublicensee agrees not to seek any further regulatory exclusivity (i.e. other than Shionogi’s, if applicable) in any country.
4.3 Regulatory Assistance to Commercial Sublicensees. The Sublicensee shall provide assistance to any Commercial Sublicensees as may be reasonably requested by them to make submissions to obtain regulatory approval to Commercialize Licensed Product in the countries for which they have a Commercial Sublicense. This assistance shall include providing access to any information included in the Sublicensee’s WHO Prequalification filings as may be required for the regulatory submissions of Commercial Sublicensees or to respond to any enquiries by the competent regulatory authorities.
6. PHARMACOVIGILANCE AND QUALITY MATTERS
6.1 Pharmacovigilance and Adverse Event Reporting
(a) The Parties agree that the primary regulatory responsibility for pharmacovigilance and adverse event reporting for Licensed Product in any given country in the Territory shall lie with the Commercial Sublicensee commercializing Licensed Product in such country. However, the Sublicensee will, in accordance with its standard protocols, maintain effective and reliable systems for receiving and tabulating any reports of adverse reactions to the Licensed Product and any quality concerns reported to the Sublicensee by any Customers or other Third Parties. The Sublicensee will promptly report to any Customers concerned any safety concerns relating to Licensed Product identified by the Sublicensee. The responsibilities of the Sublicensee for safety related or Licensed Product related inquiries will be performed in accordance with applicable local laws and regulations and with the relevant Supply Agreement(s) and if applicable any Safety Data Exchange Agreement entered into pursuant to paragraph (b) below.
(b) The Sublicensee acknowledges that Shionogi will be responsible for maintaining the global pharmacovigilance database for the Licensed Product. The Sublicensee undertakes to enter into a Safety Data Exchange Agreement (“SDEA”) with Shionogi, GARDP and Commercial Sublicensees on terms reasonably acceptable to Shionogi and based on a first draft proposed by Shionogi, governing the exchange of Licensed Product safety information among the Sublicensee, Shionogi, GARDP and Commercial Sublicensees that is consistent with applicable regulations and global pharmacovigilance standards. Such SDEA shall be entered into by the parties no later than the first sale of Licensed Product by the Sublicensee to a Customer.
6.2 Quality – Manufacturing Standards
(a) The Sublicensee will Manufacture the Licensed Compound and the Licensed Product in a manner consistent with:
(i) Good Manufacturing Practices; and
(ii) the WHO Prequalification standards and specifications set out in the Sublicensee’s WHO Prequalification submission and approval.
If applicable and if requested by GARDP in the event the Facility(ies) is/are audited and approved by a Stringent Regulatory Authority (“SRA”), and as an alternative to WHO Prequalification contemplated in (ii) above, the Sublicensee will Manufacture the Licensed Compound and the Licensed Product in a manner consistent with the standards of the SRA.
(b) Until the Facilities are audited and approved by WHO Prequalification or an SRA, the Sublicensee shall if requested by GARDP allow a Third Party regulatory expert appointed by GARDP to conduct a GMP audit of the Sublicense’s Facility and Manufacturing processes (and if applicable those of any Sublicensee Contractors involved in the production of Licensed Compound of Licensed Product) and to assess and confirm the Sublicensee’s compliance with WHO Prequalification standards or a SRA’s standards, and in such case the Sublicensee will Manufacture the Licensed Compound and the Licensed Product in a manner consistent with the relevant standards.
(c) The Sublicensee shall provide GARDP and Shionogi the ability to review and comment on the content of any preclinical and clinical data portions of all filings for any Manufacturing Approvals made by or for the Sublicensee for the Licensed Product as well as, if applicable, all proposed product labels, package inserts and Company Core Data Sheets (CCDS) (including a list prepared by GARDP and/or the Sublicensee of deviations between the proposed CCDS and the then-existing CCDS of Shionogi) proposed to be submitted to Regulatory Authorities or other competent authorities (including the WHO), if any, for Manufacturing Approvals to be obtained by the Sublicensee for the Licensed Product. Copies of all such documents shall be provided to GARDP and Shionogi in English. GARDP and Shionogi shall have the right to oppose any proposed filing in the Territory for failure to comply with the foregoing requirements, or based on reasonable concerns relating to the accuracy and quality of the data included therein, and the proposed filing may not proceed until GARDP’s or Shionogi’s opposition, as applicable, has been resolved.
6.3 Environmental, Health, Safety, Labor, Ethics and Antibiotic Manufacture Standards. The Sublicensee shall Manufacture all Licensed Compound and Licensed Product in accordance with the standards and requirements set out in Schedule K attached hereto. The Sublicensee shall allow GARDP or its agents to conduct periodic reviews (including on-site audits and/or inspections) of the Sublicensee and its Facility(ies) and practices to confirm compliance with these standards and requirements. The Sublicensee shall implement at its cost any required actions to remediate any noncompliance identified in any such audits.
The Sublicensee shall in particular Manufacture Licensed Compound and Licensed Product in accordance with any applicable industry standards for the responsible Manufacture of antibiotics.
6.4 Stability Testing and Storage. The Sublicensee shall perform stability testing for and storage of Licensed Compound and Licensed Product in accordance with applicable WHO Prequalification guidelines.