Name of Work:Selection of CRO for Purification, API Synthesis, Formulation Manufacturing, Formulation Development {Under GMP Requirements} and Stability Studies of New Chemical Entity (IND Candidate ) for FIH Clinical Studies
Sl. No.
Item Description
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Activtiy-1
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a) Purification of Rohitukine from 60-70% rohitukine enriched extract (provide by client, CSIR-IIIM, Jammu)b) CRO may first isolate non-GMP batch of initial 10-20 g of final compound with right quality and quantity followed by make process fit to purpose. Extensive process development efforts are not desired but CRO should make the process fit to the purposec) Requirement: Quantity: [~500 g x 3 batches = ~1500 g].d) Certificate of analysis (CoA) of respective batches including other characterization data such as NMR, HRMS, IR, optical rotation. e) CMC with purity profiling including Quantification and method validation. a. Documents required: Drug Master File and Form-29 license
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Activtiy -2
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a) The synthesis of API IIIM-290 from rohitukine using Claisen-Schmidt Condensation with 2,6-dichlorobenzaldehyde. b) The starting material (rohitukine) will be supplied by the sponsor (if the API synthesis is not done at the same firm).c) Complete CMC of API as per regulatory requirements (NCE requirements specified by CDSCO) is to be done by the firm. d) CRO may first synthesize non-GMP batch of initial 10-20 g of final compound with right quality and quantity followed by make process fit to purpose. Extensive process development efforts are not desired but CRO should make the process fit to the purposee) Requirement: Quantity: [300 g x 3 batches = 900 g].f) Certificate of analysis (CoA) of respective batches including other characterization data such as NMR, HRMS, IR, optical rotation. g) CMC with purity of >99 along with impurity profiling including Quantification and method validation. h) Documents required: Drug Master File and Form-29 license.i) The process and documentation should be suitable for clinical studies.
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Activity-3
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Activity-3: Formulation Manufacturing under GMPThe formulation type for this API is solid dispersion which is to be filled in hard gelatin capsules. Complete CMC of formulation as per regulatory requirements (formulation/ product requirements specified by CDSCO) is to be done by the CRO firm.• Quantity: [2000 capsules x 3 batches = 6000 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).• The validated analytical method is available with the sponsor. The same can be used by the firm for CMC documentation.Details of formulation are -: Dosage form:Hard gelatin capsulesFormulation type:Solid dispersion formulationFormula: Each hard gelatin capsule contains IIIM-290: 90 mg PVP-K30: 360 mgCapsule weight……………………….~500 mgWeight of contents in each capsule = 450 mgThe 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.
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Activity-4
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Activity 4 : Stability Studies of API and formulation as per CT rules 2019a) 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.
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