Broad Implementation of a universal solution for quality control modernization in PET radio-pharmaceutical manufacturing industry.

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This project’s broad long-term objective is to enable the PET drug manufacturing industry to supply the most diverse portfolio of imaging products demanded for most effective diagnostic imaging across a range of clinical indications. Current limitations are in throughput and regulatory compliance of PET drug manufacturers. Proposed project addresses both of these limitations by modernizing the most complex and subjective aspect of PET drug production – quality control. It builds on the success of the prior U01 project that has delivered a solution, called Tracer-QC for one most common PET tracer (18F-fluorodeoxyglucose) and expands the validated benefits to the full portfolio of PET drugs. Several barriers need to be addressed before Tracer-QC can deliver an industry-wide impact in PET drug manufacturing. (1) Currently each new PET drug requires development of an analysis method and a unique disposable kit tailored to that drug. Trace-Ability has developed and validated 3 drug-specific kits to date. But with close to 100 (and growing) PET products in use and clinical trials, we cannot keep pace by deploying kits for each new PET drug. (2) While use of Tracer- QC is very efficient, its deployment at each new site followed by detailed review by the FDA is lengthy and requires the resources that many PET drug manufacturers do not have. (3) Innovative kits developed to date had efficiency and reliability as key criteria for success, which unfortunately led to their high cost which is another obstacle to industry-wide adoption. Proposed project will address the 3 roadblocks to adoption and enable the whole PET industry as well as the FDA inspectors to benefit from the unique simplicity, safety, uniformity and compliance offered by Tracer-QC innovation. Specific Aim 1: Universal Tracer-QC solution configurable by the user to support QC of any PET Drug. This solution will allow the user to choose any combination from a list of 20 (and growing) possible QC tests on-the-go without method development for their tracer of interest. Specific Aim 2: Validated production of kits that can be offered to the end user at $100 or less without compromising quality. This aim would require redesign of both the kit and its manufacturing processes. Specific Aim 3: Regulatory “rollout vehicle” that allows commercial PET drug manufacturers to implement Tracer-QC for any tracer via CBE-30 mechanism. In order to achieve this aim, we will need to develop and validate the “rollout vehicle” in close collaboration with the FDA, for which the U01 mechanism offers a unique opportunity. There are several envisioned mechanisms including comparability protocol or DMF with uniform PQ procedures among others. The “rollout vehicle” will be first validated at an academic site followed by implementation and assessment at commercial PET drug manufacturing sites, thus making the critical step to industry-wide adoption of Tracer-QC. Expected outcomes: (1) Improved quality of PET drugs and efficiency of release testing across the whole industry; (2) Modernization of PET drug production body of knowledge making it more robust, predictable and cost-effective; (3) 21 CFR Part 212 compliance issues addressed at the industry level: (4) Simplified oversight of PET drug production by the FDA; (5) Science-based quality standard; (6) Operator safety; (7) growth of PET drug production industry delivering broader portfolio of PET products to patients and doctors nationwide.