SBIR-STTR Award

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. Public Health Relevance Statement By expanding availability of Positron Emission Tomography (PET) imaging to broad Alzheimer’s disease (AD) population, proposed work enables disease detection in pre-symptomatic stage. Thereby it is expected to provide an earlier window of opportunity to implement AD treatments or slow down disease progression, leading to improved quality of life for AD patients and their families. This work will further enable most effective clinical trials focused on treatment solutions for AD.

Project Terms:
Achievement ; Achievement Attainment ; Adoption ; Alzheimer's Disease ; AD dementia ; Alzheimer ; Alzheimer Type Dementia ; Alzheimer disease ; Alzheimer sclerosis ; Alzheimer syndrome ; Alzheimer's ; Alzheimer's disease dementia ; Alzheimers Dementia ; Alzheimers disease ; Primary Senile Degenerative Dementia ; dementia of the Alzheimer type ; primary degenerative dementia ; senile dementia of the Alzheimer type ; Amyloid ; Amyloid Substance ; Automation ; Back ; Dorsum ; Brain ; Brain Nervous System ; Encephalon ; Brain Pathology ; Clinical Trials ; Contrast Media ; Contrast Agent ; Contrast Drugs ; Radiopaque Media ; Disease ; Disorder ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Environment ; Family ; Future ; Goals ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Mission ; Optics ; optical ; Patients ; Positron-Emission Tomography ; PET ; PET Scan ; PET imaging ; PETSCAN ; PETT ; Positron Emission Tomography Medical Imaging ; Positron Emission Tomography Scan ; Rad.-PET ; positron emission tomographic (PET) imaging ; positron emission tomographic imaging ; positron emitting tomography ; Production ; Quality Control ; Quality of life ; QOL ; Reliability of Results ; research and development ; Development and Research ; R & D ; R&D ; Risk ; Risk Factors ; Running ; Standardization ; Technology ; Testing ; Travel ; Work ; Amyloid beta-Protein ; Alzheimer beta-Protein ; Alzheimer's Amyloid beta-Protein ; Alzheimer's amyloid ; Amyloid Alzheimer's Dementia Amyloid Protein ; Amyloid Beta-Peptide ; Amyloid Protein A4 ; Amyloid β ; Amyloid β-Peptide ; Amyloid β-Protein ; Aβ ; a beta peptide ; abeta ; amyloid beta ; amyloid-b protein ; beta amyloid fibril ; soluble amyloid precursor protein ; Imaging Techniques ; Imaging Procedures ; Imaging Technics ; tau Proteins ; MT-bound tau ; microtubule bound tau ; microtubule-bound tau ; tau ; tau factor ; τ Proteins ; Outcome Measure ; Treatment Cost ; base ; improved ; Procedures ; Site ; Solid ; Phase ; Failure ; residence ; residential building ; residential site ; Measurement ; Disease Progression ; Plant Roots ; root ; Funding ; Letters ; Life ; Complex ; System ; Country ; experience ; Performance ; Structure ; skills ; Reporting ; drug development ; Manufacturer ; Manufacturer Name ; Effectiveness ; preventing ; prevent ; Detection ; Predictive Value ; Radioactive ; therapy outcome ; therapeutic outcome ; Validation ; Molecular ; Process ; Tracer ; Development ; developmental ; Image ; imaging ; National Institute on Aging ; National Institute of Aging ; cost ; novel strategies ; new approaches ; novel approaches ; novel strategy ; Outcome ; manufacturing facility ; Population ; Coupled ; innovation ; innovate ; innovative ; new therapeutic target ; new drug target ; new druggable target ; new pharmacotherapy target ; new therapy target ; novel drug target ; novel druggable target ; novel pharmacotherapy target ; novel therapeutic target ; novel therapy target ; FDA approved ; Biological Markers ; bio-markers ; biologic marker ; biomarker ; Therapy trial ; improved outcome ; imaging study ; Alzheimer's disease therapy ; Alzheimer's therapy ; Alzheimer's disease patient ; Alzheimer's patient ;

Positron Emission Tomography (PET) is the most powerful imaging procedure relied upon in the management ofAlzheimer's Disease (AD). It provides information on the molecular processes in the brain. PET imaging studies requireshort-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, whichenables (1) detection of disease in pre-symptomatic stage and (2) most effective clinical trials for development of ADtherapies. Both of these impacts lead to improved outcomes for AD patients. Thereby, this project is considered highlyrelevant to the mission of National Institute on Aging (NIA). Trace-Ability plans to enable nationwide availability of AD PET imaging by eliminating production complexity rootedin 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), therebydemonstrating 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 validatedearlier 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 ofthese products. By filling these gaps with R&D focused on 2 specific aims, proposed Direct to Phase II project enablesrapid expansion of AD PET imaging to the broad AD population. Specific Aim 1: Achieve overall solution reliability required for broad commercial deployment by demonstratingfailure of <0.1% at Trace-Ability and <1% in the field. This aim will first require thorough assessment of the currentlyknown issues and potential risk factors. Next, we will define unique innovative technical solutions to each of the identifiedrisks and issues. Then, implementation of each solution will be followed by a solid proof of its effectiveness. Once allsolutions have been implemented, we will test the overall resulting reliability of the system in-house. After proving it toourselves 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-dayregulatory mechanism for adding new sites. The regulatory challenge for adoption of automated QC solution at new siteswith new AD PET tracers is two-fold: (1) It requires thorough validation at each new site. (2) There is a 10-month FDAapproval 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 smallnumber of special test runs at each new facility. In combination with a Type V DMF containing validation reports, such PQwill allow each new site to switch their release testing to Tracer-QC within 30 days following a CBE30 mechanism.

Public Health Relevance Statement:
By expanding availability of Positron Emission Tomography (PET) imaging to broad Alzheimer's disease (AD) population, proposed work enables disease detection in pre-symptomatic stage. Thereby it is expected to provide an earlier window of opportunity to implement AD treatments or slow down disease progression, leading to improved quality of life for AD patients and their families. This work will further enable most effective clinical trials focused on treatment solutions for AD.

Project Terms:
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