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Piramal says pharmaceutical companies should strive to improve their processes, not just for original patented products but efforts should go beyond DMF and ANDA submissions.
Piramal Enterprises' Pharma Solutions division issued a call encouraging pharmaceutical companies to implement green chemistry earlier in the drug development cycle. According to the CDMO, it is imperative to improve the mechanism by which drugs are discovered. It is high time the industry puts quality-by-design (QbD) principles into practice at all stages to ensure product and process quality through advances in process analytical technology (PAT).
Piramal Pharma Solutions noted that most companies tend to examine process efficiency only in later stages of drug development, if at all. Piramal has launched a series of green chemistry initiatives and is calling partners to evaluate the greenness of the chemical pathways they are using in any project. More than 100 kg of waste can be generated during the manufacture of 1 kg of API or advanced intermediate.
Piramal highlights two potential areas for implementing greener processes in drug development. Phase II is a good starting point, after the drug has demonstrated efficacy because this is when the clinical risk is reduced and companies can begin investing R&D resources into developing more efficient and greener routes. Another area is during the lifecycle management of post-commercialization stage, where the onset of generic drug manufacture requires more efficient processes to remain competitive.
“Green Chemistry by design (GCbD) presents us with a great opportunity to look at the bigger picture during route scouting and move ahead with green chemistry principles,” Vivek Sharma, CEO of Pharma Solutions, Piramal Enterprises commented in a press statement. “I am sure that further down the line, the FDA will look at bringing in these principles more formally, but as an industry we should be taking action and doing this now. The routes used for many drugs-whether generic or patented-are often atom inefficient and have significant room for improvement using route scouting methodologies including GCbD principles. We need to start the GCbD process early-not after a new drug application (NDA) or drug master file (DMF) has been filed, but as early as Phase I for innovators and as early as NDA approval for generic players. This is where the greener routes are established, after which they tend to remain with the product through its life cycle, and that is where the fundamental change needs to occur.”
To be able to go green, new chemistries for improved routes based on QbD are needed, observes Piramal. There are already a number of tools available, according to the CDMO, from changing the initial routes, using biocatalysis, flow systems, and chemo catalysis, and by implementing a key R&D function called “route scouting.” Several CMOs are developing new chemistries that enable greener reactions using GCbD principles but it is important that pharma makes it a priority to improve its overall greenness and efficiency in the first place. According to Piramal, the industry as a whole is still reluctant to move out of its comfort zone. Going green would mean that drugs can be produced at a significantly lower cost, with reduced footprints.
As an example, Piramal scientists have re-designed the route for a patented product during the development of a new generic, resulting in more than a 25-fold improvement in efficiency. Dr. Dhileepkumar Krishnamurthy, vice-president & head of R&D (API), Pharma Solutions, Piramal Enterprises, pointed out that waste was reduced from 1500kg/kg down to under 50kg/kg. “Even in the generic industry, where reducing cost is a key, re-examining routes is not a regular occurrence prior to DMF filing. Therefore, we, as a collective industry, need to invest in investigating potential new routes for patented products that drive atom efficiency and a step change reduction in costs, instead of doing incremental improvements for a quick DMF and ANDA submission,” Krishnamurthy said.
According to Sharma, at CPhI Worldwide, Piramal will be urging partners and the wider industry to take up greener and more cost-effective routes. “We believe that as an industry, we have a greater responsibility to reduce our carbon footprint while also assisting patients. In what is largely unique to pharma, once approval is granted, there is little incentive for continuous process improvement as regulatory hurdles present significant challenges to rework routes. As an industry, we need to change this paradigm by investing in GCbD principles, early and to drive cost effective and elegant chemical transformations,” he said.
Piramal has instilled and nurtured a green culture over the past few years and is currently exploring a number of new, green, chemical processes. At CPhI, the company will be looking for new partners to commercialize these waste-reduction technologies.