Biological assays (bioassays) provide critical measurements of the activity of complex biological drug products(proteins, vaccines, cell therapy, and gene therapy products) particularly during product development andproduction quality control. These assays use living systems for measurement and have special designs andanalyses to accommodate the large variation and confounding factors involved. Common lab bioassaysimpose complex statistical structures that, if not designed and analyzed properly, lead to poor precision forestimates of potency and limited capabilities to monitor assays for developing problems. These problemscontribute to lot release failures for manufacturers and slow down or block the development ofbiopharmaceutical products for consumers.Precision Bioassay provides statistical services for bioassays, helping organizations that develop, use,perform, validate, monitor, and regulate bioassays use modern methods to get better information andperformance, ultimately improving the quality and accelerating the discovery of biopharmaceutical drugproducts. The proposed research will lead to three new tools that will improve bioassay design, analyses andmonitoring, each will become a new product (a combination of software and consulting support). New bioassaydesigns that exploit the capabilities of modern robots will, in combination with good analyses, separateimportant sources of variation that are confounded with current designs and analyses; this improvedinformation will accelerate bioassay development and enhance monitoring of bioassays. Improved methods forselection of which sources of variation to include in bioassay analysis models (equivalence-based randomeffects model selection) will improve estimation of important sources of variation that are often ignored withcurrent analysis methods; this will substantially improve bioassay monitoring. Limiting bias of potency isessential to ensuring that a bioassay is fit for its intended use: a new approach to setting bounds forequivalence tests of similarity of test samples to standards will limit bias of potency associated with allowednon-similarity to pre-specified levels, ensure that most samples that are similar will pass similarity, andestimate the assay size required to achieve this performance target.In Phase II we will extend the proof-of-concept results from this research using prototype software able toaddress practical cases. The products from this research will become additional packages in our existingsoftware and consulting services that will accelerate the development of biopharmaceutical products.
Public Health Relevance Statement: Biological assays provide critical and particularly relevant measures of the activity of biotechnology products
(proteins, vaccines, cell therapy, and gene therapy products) which are used in quality control and product
development. The goal of this SBIR is to develop improved statistical designs and analyses to exploit the
capabilities of modern laboratory robotics improving the precision, lowering the bias, and lowering the cost of
bioassays. This will improve quality control and reduce an important barrier to development of novel products
to address currently unmet medical needs.
Project Terms: Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Biological Products ; Biologic Products ; Biological Agent ; biopharmaceutical ; biotherapeutic agent ; Biological Response Modifier Therapy ; Biologic Therapy ; Biological Therapy ; biological therapeutic ; biological treatment ; biotherapeutics ; biotherapy ; Biotechnology ; Biotech ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; gene therapy ; DNA Therapy ; Gene Transfer Clinical ; Genetic Intervention ; gene-based therapy ; genetic therapy ; genomic therapy ; Goals ; Laboratories ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Methods ; Modernization ; Organism ; living system ; Production ; Proteins ; Quality Control ; Random Allocation ; Random Selection ; Research ; Risk ; Robotics ; Computer software ; Software ; Technology ; Testing ; Vaccines ; Generations ; Measures ; base ; improved ; Area ; Specific qualifier value ; Specified ; Phase ; Variant ; Variation ; Biological ; Medical ; Non-linear Models ; Nonlinear Models ; Ensure ; Failure ; Measurement ; cell mediated therapies ; cell-based therapeutic ; cell-based therapy ; cellular therapy ; Cell Therapy ; Robot ; tool ; Knowledge ; Complex ; Source ; Consult ; Services ; consumer product ; experience ; Performance ; Structure ; novel ; Statistical Methods ; Modeling ; Sampling ; native protein drug ; pharmaceutical protein ; protein drug agent ; therapeutic protein ; statistical service ; Manufacturer ; Manufacturer Name ; Address ; Data ; randomisation ; randomization ; randomly assigned ; Randomized ; Collection ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Monitor ; Process ; Development ; developmental ; Output ; cost ; design ; designing ; novel strategies ; new approaches ; novel approaches ; novel strategy ; manufacturing process ; commercial application ; prototype ; product development ; software as a service ;
