Contract analysis

I. Executive Summary This memorandum analyzes the legal framework for Institutional Review Board ("IRB") reliance agreements that would permit non-Pennsylvania Veridian Health Research Network ("Veridian" or the "Network") sites to rely on the Veridian Central IRB rather than maintaining separate institutional IRB review for Protocol PPC-4871-III (the "CLARION" trial). The memorandum also addresses the distinct IRB a

II. Background A. The CLARION Trial The CLARION trial is a pivotal Phase III clinical trial designed to evaluate the safety and efficacy of penterafenib (PPC-4871), an oral multi-kinase inhibitor, for the treatment of advanced hepatocellular carcinoma in patients who have progressed on or are intolerant to prior systemic therapy. Penterra submitted Investigational New Drug Application No. IND 157823 to the U.S. Food

III. Regulatory Framework for IRB Oversight of Multi-Site Clinical Trials This section sets forth the principal regulatory authorities governing IRB review of multi-site clinical trials in the United States, with particular attention to the legal basis for the sIRB reliance model that Penterra and Veridian propose to adopt for the CLARION trial. A. FDA Regulations — 21 C.F.R. Part 56 The FDA's requirements for IRB re

IV. Structure of the Proposed IRB Reliance Model for the CLARION Trial A. Overview of the Proposed Model We recommend that Penterra and Veridian adopt a two-track IRB oversight model for the CLARION trial, structured as follows: Track 1 — Graystone University Medical Center (Site 001). Graystone will maintain independent IRB review through the Graystone University Institutional Review Board (IRB Registration No. IRB0

V. State Law Considerations A. Overview The CLARION trial will be conducted at 38 sites across 14 states, creating a complex state regulatory landscape that must be evaluated in connection with the proposed sIRB model. While the federal regulatory framework — principally, FDA regulations under 21 C.F.R. Parts 56 and 312 and the Common Rule under 45 C.F.R. Part 46 — establishes the baseline requirements for IRB oversi

VI. Implications for the MCTA and Ancillary Agreements The IRB reliance structure described in this memorandum has significant implications for the drafting and negotiation of the MCTA between Penterra and Veridian, as well as for the ancillary agreements and exhibits that will govern the conduct of the CLARION trial at individual sites. This section identifies the specific MCTA provisions that must address IRB overs