Detection System

Objective FDA requires an instrument that offers high throughput quantification of binding kinetics parameters for the mAbs as well as other proteins in simple solution phase measurements, such as an Octet RED96e system brand name or equal to. CLIN Description Price 0001 Detection System $ Shipping $ Total Cost $ Background A majority of therapeutic protein drugs that are regulated by FDA act via protein-ligand interactions and measurement of such interactions in vitro serves as a surrogate for the drug-efficacy in vivo . Monoclonal antibodies are a significant sub-class of the FDA-approved protein-therapeutic drugs that are used in a number of disease conditions that vary from life threatening cancers to rheumatoid arthritis, auto-inflammatory disease, severe psoriasis and psoriatic arthritis, allergy associated asthma and multiple sclerosis. Protein attributes that are critical to the mode of action are considered as critical quality attributes (CQAs). Characterization of monoclonal antibodies (mAbs) in terms of their binding kinetics is therefore important since binding affinities for specified ligands is a CQA for the mAbs. Therefore, both in upstream production research involving the drug substance as well as the downstream production research involving formulation and product assessment require analysis of this CQA for mAbs. The Division of Product Quality Research (DPQR) is establishing a continuous platform for a mAb produced by a Chinese Hamster Ovary (CHO) cell line to understand the product quality risks associated with continuous manufacturing. A bioreactor will be operated for extended durations of time (≥25 days) under perfusion mode and will utilize several other supporting instruments and systems to enable drug substance production up to a capture step. The mAb needs to be assessed for binding kinetics parameters as a requirement for understanding its quality during drug substance production as well as further when tested for different formulations for a lyophilization process. The division proposes to acquire Octet RED96e system manufactured by ForteBio, Fremont, CA or such other instrument that meets the enlisted system requirements criteria. This instrument shall offer high throughput quantification of binding kinetics parameters for the mAbs as well as other proteins in simple solution phase measurements using specially designed sensor chips by an established principle such as bio-layer interferometry and meets the laboratory requirements. Requirements The protein interactions measurement system/instrument or its equivalent for the measurement of binding kinetics parameters of mAbs shall meet the following salient characteristics: The instrument shall be bench top, compact and shall measure binding parameters in solution phase, independent of buffer or buffer pH. Shall measure at least 8 samples simultaneously for affinity, kinetics or protein titer determination and up to 96 samples to be able to accommodate a common 96-well plate reader format. Shall include affinity/kinetic analyses constants (kobs, ka, kd, and KD) arising out of protein-protein or protein-ligand interactions. Shall determine active protein concentration with a standard curve. Shall measure pairwise interactions for epitope binning analysis for an 8 x 8 pairwise interactions matrix per run. Shall be compatible with samples of varying purity levels, including crude samples. Shall involve non-destructive measurement to provide recovery of the unused sample proteins devoid of cross-contamination. Measurements shall be fast for antibody concentration determination to meet real-time monitoring of protein production. For example, a typical 96-well plate IgG samples shall be measurable within 35 min. Shall provide disposable biosensors that may be regenerated for repeat use. The measurements shall not be influenced by whether the chip-ligand immobilization occurs inside the instrument or outside for flexible workflow. Measurements shall be of high resolution for precise kinetic characterization for not only protein-protein interactions but also for protein-small molecule interactions. Shall offer simultaneous comparison of up to 8 different buffer conditions. Shall be flexible for the adaptation of ELISA (enzyme-linked immunosorbent assay ) assays into fast low affinity binding interactions. Shall not require more than 0.05 µg/mL of IgG for measurement and shall be linear even at 1-2 mg/mL. Shall have long unattended experiment run time (≥12 hours). Place of Performance The system that meets above requirements or its equivalent and other accessories shall be complete and should be delivered to: U.S. Food and Drug Administration Center for Drug Evaluation and Research Division of Product Quality Research 10903 New Hampshire Avenue Building 62 Loading Dock Silver Spring, MD 20993 Schedule: Delivery shall be no later than 30 days after contract award Inspection and Acceptance Criteria The Government shall have 30 working days to inspect and verify that the equipment and its operational software are functional and demonstrate performance. Period of Performance The period of performance is 12 months from the successful completion of installation of software, hardware, and training of FDA scientists.