SELECTION OF CRO FOR GMP FORMULATION OF NEW CHEMICAL ENTITY

ACTIVITY # 1: Formulation Manufacturing under GMP The formulation type for this API is solid dispersion which is to be filled in hard gelatin capsules. Complete CMC and stability studies of formulation as per regulatory requirements (formulation/ product requirements specified by CDSCO) is to be done by the CRO firm. • Quantity: [~3000 capsules x 3 batches = ~9000 capsules]. • Raw materials, KSMs to be procured by the quoting firm. • The API will be supplied by the sponsor (if the API synthesis is not done at the same firm). • Method validation including CMC and other requirement essential for clinical trial as per CDCSO guidelines. Details of formulation are provided below: Dosage form: Hard gelatin capsules Formulation type: Solid dispersion formulation Formula: Each hard gelatin capsule contains IIIM-290: 90 mg PVP-K30: 360 mg Capsule weight……………………….~500 mg Weight of contents in each capsule = 450 mg The constituted drug product is prepared by formulating it as a solid dispersion with PVP-K30 polymer. IIIM-290 was dissolved in a combination of chloroform and methanol (API: Solvent ratio: 1:5 w/v)*. PVP-K30 was dissolved in methanol. These two solutions were mixed under mechanical stirring. The solvent was evaporated under reduced pressure at 50 °C and 50 rpm using a rotary evaporator. The obtained dry solid dispersion formulation was ground using mortar and pestle, sieved through #30 mesh, and stored in a desiccator until further analysis and characterization (% assay, in-vitro dissolution) [Lit. Reference: Int J Pharm. 2019, 570, 118683]. The formulation is to be filled in air-tight PTFE containers. * The above process may be optimized/modified by the selected CRO as required to meet GMP and CDSCO requirements, with prior approval from CSIR-IIIM. The formulation shall be evaluated for assay, content uniformity, in-vitro dissolution, related substances and residual solvents and other as per CDSCO guidelines as applicable.

ACTIVITY # 2: Stability Studies of API FORMULATION as per CDSCO guidelines* a) Long-term 30°C + 2° Cl 75% RH ± 5% RH (24 months) b) Accelerated 40°C ± 2° CI 75% RH ± 5% RH (6 months) *The process and documentation should be suitable for clinical studies as per CDSCO guidelines and CRO should provide the stability data every 3 months for both long term and accelerated stability studies.