Enabling nationwide AD PET imaging to support most efficient clinical trials by adoption of radically simplified and standardized quality control in commercial production of AD PET tracers.

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Positron Emission Tomography (PET) is the most powerful imaging procedure relied upon in the management of Alzheimer’s Disease (AD). It provides information on the molecular processes in the brain. PET imaging studies require short-lived radioactive contrast agents called PET tracers. Multiple PET tracers have a strong predictive value in AD. The long-term objective of the proposed work is availability of AD PET imaging to broad AD population, which enables (1) detection of disease in pre-symptomatic stage and (2) most effective clinical trials for development of AD therapies. Both of these impacts lead to improved outcomes for AD patients. Thereby, this project is considered highly relevant to the mission of National Institute on Aging (NIA). Trace-Ability plans to enable nationwide availability of AD PET imaging by eliminating production complexity rooted in release testing of AD PET imaging tracers. The enabling solution will be demonstrated with of [F-18]Flortaucipir (leading tau PET tracer with pending NDA) and [F-18]Florbetaben (FDA-approved Beta Amyloid PET tracer), thereby demonstrating solution’s universal applicability to multiple AD PET products. Proposed solution relies on complete automation of release testing on Tracer-QC platform that has been validated earlier with the most common PET tracer, F 18 Fludeoxyglucose (FDG) and demonstrated with [F-18]Florbetaben. Current experience has identified critical gaps that need to be filled in order to achieve broad commercial adoption of these products. By filling these gaps with R&D focused on 2 specific aims, proposed Direct to Phase II project enables rapid expansion of AD PET imaging to the broad AD population. Specific Aim 1: Achieve overall solution reliability required for broad commercial deployment by demonstrating failure of <0.1% at Trace-Ability and <1% in the field. This aim will first require thorough assessment of the currently known issues and potential risk factors. Next, we will define unique innovative technical solutions to each of the identified risks and issues. Then, implementation of each solution will be followed by a solid proof of its effectiveness. Once all solutions have been implemented, we will test the overall resulting reliability of the system in-house. After proving it to ourselves by demonstrating <0.01% failure rate, we will deploy systems in the field to prove the desired reliability of >99% in a variety of commercial AD PET tracer production environments. Specific Aim 2: Automated QC of AD PET tracers qualified at 4 commercial production facilities with a 30-day regulatory mechanism for adding new sites. The regulatory challenge for adoption of automated QC solution at new sites with new AD PET tracers is two-fold: (1) It requires thorough validation at each new site. (2) There is a 10-month FDA approval process for each new manufacturer. Phase II R&D will yield effective and innovative Performance Qualification (PQ) procedures that deliver solid proof of system’s analytical performance against pre-set acceptance criteria with a small number of special test runs at each new facility. In combination with a Type V DMF containing validation reports, such PQ will allow each new site to switch their release testing to Tracer-QC within 30 days following a CBE30 mechanism.