“Regulatory Dossier” means all regulatory documents and filings registered with a Drug Regulatory Authority for a Marketing Authorisation containing the administrative, safety, efficacy, quality, non-clinical and clinical data and CMC data for the Drug Product as it may change from time to time;
“Regulatory Plan” shall mean a regulatory plan outlining the regulatory strategy for obtaining Marketing Authorisations for the Drug Product and split of regulatory responsibilities of the Parties with the aim of ensuring equitable and affordable access to the Product for people in the DNDi Territory and the Entasis Territory at the earliest possible date, as further described in Schedule 4 hereto and in Clause 5, as may be amended from time to time;
5. Regulatory Strategy And Activities For Obtaining Marketing Authorization
5.1 The regulatory strategy (including timelines and milestones) and the regulatory responsibilities of the Parties are set out in detail in the Regulatory Plan. As of the Effective Date the regulatory strategy is based on the principles that:
5.1.1 clinical development is intended to facilitate the process for registration of the Drug Product in the first instance with the FDA and the EMA;
5.1.2 Entasis shall use its best efforts to file the application for the first Marketing Authorisation for the Drug Product in the Field with the FDA, provided that, in Entasis’ reasonable determination, the data generated by completion of the Phase III MC Trial will be acceptable by the FDA, and would not otherwise cause
5.1.3 Entasis is responsible for obtaining Marketing Authorisations for the Drug Product in the Entasis Territory if and as it elects, and DNDi is responsible for obtaining Marketing Authorisations for the Drug Product in such countries of the DNDi Territory as it elects.
First Marketing Authorisation with the FDA and the EMA
5.2 Entasis shall:
5.2.1 use its best efforts to file the application for the first Marketing Authorisation for the Drug Product in the Field with the FDA by no later than six (6) months from the completion of the Phase III MC Trial (which shall mean database lock for clean file for the Phase III MC Trial) provided that, in Entasis’s reasonable determination, the data generated by completion of the Phase III MC Trial will be acceptable by the FDA, and would not otherwise cause Entasis to violate applicable law;
5.2.2 use commercially reasonable endeavors to maintain the Marketing Authorisation with the FDA when granted;
5.2.3 use commercially reasonable endeavors to file the application for the first Marketing Authorisation for the Drug Product in the Field with the EMA;
5.2.4 use commercially reasonable endeavors to reasonably support DNDi in its conduct of any additional activities conducted by DNDi pursuant to Clause 5.3.2;
5.2.5 permit DNDi to review and make suggestions in relation to the Regulatory Dossier prior to submission to the FDA and EMA and reasonably consider such suggestions;
5.2.6 inform DNDi regularly through the JSC of the progress of the regulatory activities for obtaining Marketing Authorization with the FDA and the EMA; and
5.2.7 promptly provide to DNDi a copy of the Regulatory Dossier file submitted to the FDA and the EMA and any correspondence in relation thereto.
5.3 DNDi shall:
5.3.1 provide to Entasis relevant clinical and CMC data in its possession that is required for the purpose of registering the Drug Product with the FDA and the EMA, and, upon reasonable request by Entasis, DNDi shall reasonably assist Entasis in the preparation of regulatory materials for the FDA and the EMA registration, including the applicable portion of the CMC section;
5.3.2 use commercially reasonable endeavors to conduct any additional activities that may be required by the FDA or be agreed between the Parties in addition to those set forth in the Development Plan to obtain the FDA Marketing Authorization;
5.3.3 be responsible for the full costs of the additional activities mentioned under clause 5.3.2 to obtain the FDA Marketing Authorization;
5.3.4 review and make suggestions in relation to the Regulatory Dossier prior to submission by Entasis to the FDA and the EMA; and
5.3.5 reimburse Entasis for [*] of costs incurred by Entasis in filing the Marketing Authorisation for the Drug Product in the Field with the EMA if DNDi uses or references such Marketing Authorisation in any filing for Marketing Authorisation in the DNDi Territory in accordance with Clause 5.7 within [*] of DNDi submitting any such Marketing Authorisation in the DNDi Territory.
Phase IV Clinical Trials
5.4 Each Party shall be responsible for financing such additional Clinical Trials in its respective Territory as it elects to conduct in accordance with this Agreement.
Market Authorizations in countries other than the USA
5.5 Each Party will, except as otherwise specified in this Agreement, be responsible at its own cost, for using commercially reasonable endeavours to take all other necessary steps for obtaining and, during the Term of this Agreement, maintaining Marketing Authorisations in its Territory on behalf of itself or its Sublicensee if appropriate.
5.6 Each Party shall use commercially reasonable endeavours to assist the other Party (and where appropriate its Sublicensee), at the other Party’s cost, to register the Drug Product for use in the Field in its Territory accordance with the Regulatory Plan, and to answer questions from any Drug Regulatory Authority with respect to the API and the Drug Product
Use of Regulatory Dossier and References
5.7 Each Party (and where appropriate its Sublicensees) shall be entitled, without the approval or consent of the other Party, to have full access to the Regulatory Dossier submitted to the FDA and the EMA by Entasis, to use it with any Drug Regulatory Authority in its Territory and to exercise its licensing rights (including sublicensing rights in accordance with this Agreement.
5.8 The Party submitting a filing to a Drug Regulatory Authority (the “Filing Party”) shall have discretion to decide the documents (or extracts thereof) which will be included in the particular Regulatory Dossier that it submits and to modify and translate such documents as required. Promptly after such submission, the Filing Party shall notify the other Party (the “Non-Filing Party”) that such regulatory filing has been made, and upon the request of the Non-Filing Party, provide it with a copy of each such submission. Each Party shall update the other Party as to the status of each Regulatory Dossier within the different countries where it is submitted in its Territory, and will provide the other Party through the JSC with a report on its exchanges with the applicable Drug Regulatory Authority.
5.9 The Filing Party shall provide to the Non-Filing Party (and use commercially reasonable endeavours to procure that its Sublicensees provide) in writing letters of reference, granting the Non-Filing Party Sublicensees behalf) to the extent available to Filing Party, and to all applicable Marketing Authorisations for such products in the Filing Party’s Territory. Such rights of reference shall expressly be binding on any assignee or transferee of the Filing Party’s rights to such filings and such Marketing Authorisations.
5.10 If any Drug Regulatory Authority in a Territory requires access to certain portions of any filing or Marketing Authorisation related to the API or the Drug Product for legal or regulatory purposes in connection with the Non-Filing Party (or its Affiliates’ or Sublicensees’) development, Manufacturing and/or Commercialization efforts, then the Filing Party shall reasonably cooperate with such Drug Regulatory Authority and seek to make such portions available to the Drug Regulatory Authority and, if legally required for the Non-Filing Party (or its Affiliates or Sublicensees) to submit or pursue an application for Marketing Authorisation, to the Non-Filing Party, solely for such purpose, and the Filing Party shall use reasonable efforts to obtain similar cooperation from its Sublicensees.
9. Safety Reporting, Recalls And Information Exchange
9.1 Each Party will be responsible for ensuring that it complies with its regulatory obligations as either sponsor or as Marketing Authorisation holder, and for the management of clinical safety and pharmacovigilance with regard to the Drug Product in its respective Territory.
9.2 Within ninety (90) days from the Effective Date or such other period as the Parties may agree before enrolment of the first trial subject in the QT (TQT) Study, the Parties will conclude a pharmacovigilance agreement to govern the investigation of and action to be taken with regard to Drug Product related adverse experience reports, to enable each Party to comply with its legal obligations (“Pharmacovigilance Agreement”).
9.3 Each Party shall exchange with the other Party all relevant information that relates to the safety and efficacy of the Drug Product as set out in the Pharmacovigilance Agreement. Each Party will reasonably co-operate with the other Party to ensure that regulatory requirements concerning drug safety surveillance are complied with in all countries in which the Drug Product is developed, Manufactured or Commercialised both in the Field and for any Future Indications.
9.4 Entasis will be responsible for setting up a worldwide Drug Product safety database, the details of which will be set out in the Pharmacovigilance Agreement.