Formulation Development: • Well established formulation screening platform for siRNA

• Experienced in formulating siRNA at high concentration with well controlled viscosity, osmolarity and pH

• Capable of achieving concentrations up to 200 mg/mL, with viscosity below 6 cP

• Rigorous assessment of API COA to ensure batch consistency

• Optimized pH titration and dilution processes for batch consistency

Stability Study: • Conduct comprehensive stability studies including:

- Temperature stress tests: 40°C, 25°C, freeze-thaw cycles.

- Mechanical stress tests: agitation.

- Environmental stress tests: light exposure.

- Degradation studies: long-term, accelerated, and forced degradation.

• Conduct container compatibility and clinical in-use studies

Solution Preparation: • Solution preparation conducted in biosafety cabinets (BSC) and isolator

• Utilize multiple operation techniques to enhance dissolution efficiency

• Extensive experience in titration to control pH of siRNA solution

Fill & Finish: • Achieved higher DP yield from lower than industry filling line loss (< 100mL), resulting in significant cost savings for clients

• Experienced in fill & finish of high viscosity and high concentration formulated products

• Aseptic fill/finish line (Bosch isolator, 100,000 vials/batch, 0.4 to 35mL fill volume) meeting typical 0.5~1.5 mL filling requirement for RNA drugs, with fill weight accuracy of <5%

• Completed over 60 DP lots with 100% success rate

Lifecycle Management of QC Method Per ICH/USP/ChP: • Identity: IPRP, AEX, IPRP-ESI-MS, Sequence (MS-MS), Tm (UV), FTIR

• Assay: Slope spectroscopy (UV)

• Purity and Impurity: IPRP, AEX

• Pharmacopeia Method: Appearance, osmolality, visible particles, sub-visible particles, endotoxin, bioburden, sterility, etc.

Project Experience: • Analytical method development, optimization, and qualification

• Drug product specification setting and stability study

• Impurity characterization and particle identification