P121: A Contract Research Organization's (CRO) Experience Serving as a Regulatory Sponsor
Julia Solarczyk Donnelly
Regulatory Affairs Director
Westat United States
Westat, a CRO, served as the regulatory Sponsor of government funded clinical trials. We successfully navigated regulatory filings and communication with FDA, and present here critical considerations and our experiences in this role as they pertain to risk and resource needs.
Between 2018 and 2021, Westat served as the Sponsor for two U.S. Phase 2 clinical trials funded by the Department of Defense (DoD). Asked to assume this role after the contract was awarded, Westat obtained corporate approval and managed the subsequent interactions with FDA and the clinical sites.
Prior to committing to the role of Sponsor, Westat clinical trials’ staff performed an in-depth analysis of 21CFR312.50. The associated advantages, challenges, and risks were evaluated and presented to corporate leadership. Westat’s liability coverage was reviewed and deemed adequate given it was a government funded study. As such, Westat assumed indemnification associated with trial-related injury which would be the responsibility of the subject and/or clinical sites. The analysis also identified the need for additional qualified and trained regulatory staff and a clinical trials attorney. In the context of these considerations and the specific trial to be conducted, corporate leadership granted approval. As a CRO sponsoring the study, clinical sites considered Westat as a commercial sponsor, meaning not all of them would assume the responsibilities of subject indemnification and site agreements were re-negotiated.
Unanticipated non-clinical studies were required in response to our 2019 FDA pre-IND meeting. Upon their completion, the IND application was submitted to the FDA in 2020, 18 months subsequent to the pre-IND meeting and in the midst of the COVID-19 pandemic. The IND was placed on clinical hold pending the results of additional non-clinical studies that had to be conducted by laboratories under strictures posed by the pandemic. Labs temporarily closed or were operating under reduced staffing. Westat however successfully submitted the additional data and responses to the FDA. Factoring in the delays encountered in performing the additional studies and that FDA’s resources were understandably focused towards the pandemic, Westat noticed a significant turnover of FDA review staff during our interactions. In response to the submission of our results, the hold was not lifted and the FDA requested additional non-clinical studies. Westat, with direction from the DoD, retracted the IND in late 2021 due to the unanticipated delays and resources.
CRO Sponsorship of trials requires a strong regulatory department, a critical understanding of sponsorship responsibilities, and a careful assessment of risks and adequate resources. A CRO considering the role of sponsorship must have inputs from corporate management and legal counsel, robust capabilities, staff in all service areas related to clinical trials, and the ability to manage nonclinical studies. A cohesive, energized project team, led by a Principal Investigator with relevant scientific expertise and a Project Director with experience and strong leadership skills, is imperative as well as having a regulatory affairs department adept at providing strategic regulatory guidance and with the technical capabilities for regulatory filings. CROs may need to establish partnerships with qualified laboratories experienced in the design, conduct, and analysis of nonclinical studies. While development timelines account for additional requests and questions from the FDA when reviewing regulatory submissions, there is the potential for turnover of FDA review staff, which can present challenges in the continuity of interactions.
There are multiple scenarios where CROs may be presented with the opportunity to serve as a regulatory Sponsor. These may include investigator-initiated trials, early trials with small biopharmaceutical companies that lack adequate in-house support, and foreign entities with an interest in the U.S. market. As such, there is a market space for CROs to serve in this role. Understanding these unique scenarios and the inherent risks that CROs need to carefully consider before committing to being a Sponsor, each opportunity needs to be analyzed individually before making a final decision.
Additional authors: Melissa King, Megan Johnston, Cristina Rabadan-Diehl, David Burgess
Acknowledgement: Work performed under USAMRMC Contracts #W81XWH15C0128 and #W81XWH20C0122 managed by the Naval Medical Research Center Naval Advanced Medical Development