Integrated Development Advantage

Customer operating a 21 step synthesis process for API with final yields approx 5%. The synthesis is a convergent synthesis with two side chains involving 7 & 6 steps respectively integrating at stage 14. First GMP step required at stage 14 with non-GMP supply of intermediates up to stage 13, provided the impurities are well characterised

Drug in Phase II and options to telescope process exist but also risk associated with process changes is high

Customer Needs

1. Improve yields in current process and supply clinical trials API quantity
2. Preference of customer to have final API from North American site for regulatory purposes
3. Identify partner for scale up and long term cost effective supply
4. Evaluate telescoping of current process to reduce steps and hence improve overall yields

1. Supply of Clinical Trials API quantity from North American location - Advanced intermediates were synthesised at Chennai facility in India at large scale at highly competitive rates and transferred to Toronto site for finished API manufacture
2. Process development team dedicated to process telescoping and yield improvements
3. Capability of supply for large scale requirements mapped out at UK API facility and India facility as per customers long term supply preference
   

Reduction in COGS by over 30% while retaining supply chain flexibility and high service levels

Customer sources drug product from European site. The drug is in late life cycle and generic versions were launched in 2006 and hence price pressure on Cost of goods is high. Product supply involves a number of SKUs across a number of countries in Europe and hence supply and distribution from a European site is preferred as it gives flexibility in managing SKUs as per market demand variances

1. Manufacture and supply of bulk tablets from India plant to UK plant at competitive prices
2. Incoming material QP release by on-site QPs in UK
3. Packaging on high speed blister lines in UK, artwork management, warehousing and shipping from UK site which has been a launch site for a number of products under Searle/Pharmacia/Pfizer ownership
4. Release of Finished dosage form from UK by on-site QPs

Reduction in COGS by over 30% while retaining supply chain flexibility and high service levels

Customer sources drug product from European site. The drug is in late life cycle and generic versions were launched in 2006 and hence price pressure on Cost of goods is high. Product supply involves a number of SKUs across a number of countries in Europe and hence supply and distribution from a European site is preferred as it gives flexibility in managing SKUs as per market demand variances

1. Manufacture and supply of bulk tablets from India plant to UK plant at competitive prices
2. Incoming material QP release by on-site QPs in UK
3. Packaging on high speed blister lines in UK, artwork management, warehousing and shipping from UK site which has been a launch site for a number of products under Searle/Pharmacia/Pfizer ownership
4. Release of Finished dosage form from UK by on-site QP

Overall savings of 4 months in clinical study timelines

Late life cycle product already generic for two years. The product is in a niche therapeutic area hence annual volume of API is approximately 5 MT and doses around 250 million only. Current supplier base for both API and formulation are high cost suppliers in USA. The customer does not own the DMF but owns the ANDA for the drug product

Customer requires competitiveness for the long term to be established. It is hence important to address the cost of goods in both the API and the formulations conversion areas

1. Piramal Pharma Solutions able to develop the process for generic API at lab scale through development centre in Mumbai and carry out scale up studies and commercial manufacturing from USFDA approved site in 8 months
2. DMF filed for API from Piramal site in India after 3 months stability in 11 months from start of project
3. While API is in scale up studies, Piramal able to use lab scale API and carry out preliminary formulation development using customer ANDA – making minimal changes to be within Type I variations and be able to attain the same in-vitro characteristics as current approved drug product
4. API from process validation batches taken to manufacture drug product validation batches from USFDA approved formulations site in India
5. Regulatory team from Piramal helps compilation of the supplement to ANDA for source change and filing in 16 months from
   

Achieved over 35% reduction in COGS of final formulation with process managed across API+Formulations in 16 months