Quality Control and Troubleshooting Arista Biologicals Inc.

Quality Control Incoming Raw Materials QA/QC In Process QC Final Product Testing and Release Arista Biologicals Inc.

Development Process Product control is very important in both the research and development phase as well as in full production. Identify characteristics of components important for acceptable behavior in the test system Sensitivity Specificity Stability Test several lots in order to determine acceptable range of these characteristics in order to determine final raw material specifications. Arista Biologicals Inc.

Standard Operating Procedures Analytical methods (measurement techniques) Equipment operation, maintenance, and calibration Preproduction planning procedures Specific product procedures Product preparation In-process testing Raw materials acceptance procedures Storage and control Shipping and limitations Quality control and GMP compliance Validation of all the above Arista Biologicals Inc.

Incoming Raw Material Manufacturing Quarantine and sample all materials associated with the production of the final product. Verify specifications of raw materials by testing characteristic requirements defined in the development process. Maintain retention samples of raw material. Arista Biologicals Inc.

Typical Specifications for Materials used in Rapid Diagnostic Tests Membranes Wicking Rate (raw and processed) Length Thickness Protein Binding Capacity (functionality testing) Hydrophobicity (line quality and wetting) Overall Consistency thru lot (random sampling) Plastics Consistent dimensions No solvent leaching Color Flexibility Characteristics Arista Biologicals Inc.

Typical Specifications Cont… Conjugates and Antibodies Concentration Immunological Reactivity (functionality) Absorbents and Pads Density Thickness Hydrophobicity Consistency Arista Biologicals Inc.

Typical Specifications Cont… Desiccants Weight Moisture Content Moisture Capacity Indicator status (if applicable) Pouches Integrity Dimensions Arista Biologicals Inc.

Typical In Process Testing and Quality Control Documentation: Process and Control Instrument and Equipment Validation: pH meters, balances, dispensers, spectrophotometers, slitters, sealers, etc. Buffers: pH and conductivity measurements Reagent Concentration Verification: Verifying concentration of working dilutions. In Process Testing: Wicking rate, sensitivity, specificity, stability, etc., including within lot analysis and sampling. Parameters predetermined during the development stage and piloting. Arista Biologicals Inc.

Final Product Testing and Release Finished Product testing Accelerated Stability Studies and Tracking Final Documentation for Release Customer Complaints Arista Biologicals Inc.

General Troubleshooting Raw Materials Laminated Plastic Sheets Adhesive loses solvent which modifies membrane structure or immunological activity of reagents. Adhesive loses ability to bind to membrane or pads upon addition of liquid sample. Adhesive builds up excessively on strip cutter or slitter Sample and conjugate Pad Materials Inconsistent density or thickness causing flow problems or reagent capacity differences upon soaking of reagents. Hydrophobicity differences from lot to lot causing flow problems or nonspecific binding of reagents or sample. Fragile materials fracturing or fraying upon handling. Materials retaining analyte, conjugate, or other component of assay nonspecifically because of variation in pad material. Arista Biologicals Inc.

General Troubleshooting Cont… Raw Materials Cont.. Membranes Nonconsistent flow characteristics and/or pore size. Hydrophobic or hydrophilic behavior changes causing wetting, nonspecificity or line broadening problems. May be surfactant variation incorporated into the membrane either post or during membrane manufacturing. Protein capacity variation causing sensitivity changes. Inconsistent blocking causing flow or specificity problems. Conjugates and Antibodies Variation in sensitivity or specificity which may or may not be able to be compensated by concentration optimization. Release of conjugate variation and/or stability problems. Overloading of capture material or conjugate causing flow problems. Arista Biologicals Inc.

General Troubleshooting Cont… Raw Materials Cont… Equipment Dispenser not consistent within one continuous line or from sheet to sheet causing line quality and/or sensitivity or specificity problems. Dispenser causes inactivation of the reagent being dispensed onto membrane. Dispenser damaging membrane (contact systems) Drying not complete due to lack of moisture removing capability or capacity. Slitters or cutters damaging membrane causing structural damage to membrane or pads. Improper assembly or positioning of strip components causing flow problems ultimately causing assay failure. Improper assembly of strip to device causing flow problems also causing assay failure. Improper heat sealing of packaging causing stability problems. Arista Biologicals Inc.