Ramesh E., Director, DS Manufacturing (Upstream), Kemwell Biopharma Pvt. Ltd.
Large-molecule biologics (such as monoclonal antibodies) are used in many lifesaving therapies and have been witnessing significant growth due to rapid scientific and technological advancements. Many pharmaceutical companies (large and medium) do have significant number of promising pipeline products at various stages of development. In addition to the ever-expanding product pipelines, pharmaceutical companies – as a growth strategy – also look for opportunities to expand geographically.
While the growth potential of biologics-based therapies continues to be attractive, it is also equally challenging to bring the products to patients at an affordable cost with the highest quality standards. Owing to the scientific complexities and sophisticated high-end technologies involved in the development of large molecules (both novel biologics and biosimilars), pharmaceutical companies face challenges in terms of high investments, relatively long project timelines and extremely tough regulatory expectations and scrutiny. Additionally, rapidly changing market dynamics, pricing pressure from competitors and/or governments and technology shifts make it essential for pharmaceutical companies to be lean and nimble to stay on top of the game.
Challenges in biologics product development:
Challenges differ depending on the type of biologics drug under development (such as novel biologics and biosimilars). Figure 1 depicts the pattern of CMC outlay required for the development of novel biologics and biosimilars.
Biosimilars development requires upfront investments to generate a large volume of CMC data at a very early stage of product development. Generally, product development timelines for biosimilars are back-calculated from loss of exclusivity for a given product. Hence, there is very limited or no cushion in the product development timelines. To be competitive in the market space, pharmaceutical companies need to pursue multiple products in their pipeline. One of the major criteria employed by big pharma companies in the selection of pipeline biosimilar molecules is PTRS (probability of technical and regulatory success). However, in the recent past, there were several instances where big pharma companies had to either discontinue or divest some of the pipeline assets due to ever-changing market dynamics. Though biosimilars have reached major regulated markets including the US, most of the early entrants are backed by big pharma companies. Medium and small companies struggle to overcome the challenges discussed above.
Novel biologics, on the other hand bring a different set of challenges. While there is no direct external pressure on market launch timelines, novel biologics ideally should reach the clinic at a shorter lead time as the fate of the molecule is solely determined by its performance in clinical trials. In the past, there were several examples where novel biologics either failed in the advanced stages of clinical trials or discontinued due to the availability of alternate relatively low-cost therapies. In some of these cases, the dedicated manufacturing capacities for the novel molecules installed by the sponsors turned out to be over capacities due to product failures.
The CMO advantage:
Factors discussed above influence big pharma companies to explore partnership opportunities with CMOs to meet existing supply shortages, balance the market/technology-related risks and defer investments until key milestones in clinical trials and/or market uptake are achieved.
Despite the challenges, market studies reveal that many new players are entering biosimilars business adding more and more products to the pipeline. This is mainly driven by the fact that more legacy reference products will go off-patent in the near future. Medium and small size pharma companies look for long term partnerships with CMOs owing to the immediate availability of manufacturing expertise, highly skilled human resources and state-of-the-art facilities. By this way, medium and small size pharma companies can avoid upfront capital investments to build R&D and clinical manufacturing facilities.
For large, medium and small pharma companies, outsourcing is a viable option as about 60% – 70% of COGS for the manufacturing of biologics products is contributed by fixed costs. In case of dedicated in-house manufacturing facilities, the fixed costs cannot be avoided even during idle conditions. Use of multi-product facilities to produce biologics has been proven to be safe as there is minimal to no risk in terms of product carryover.
In recent years the biopharma CMO industry is extremely active and growing both in terms of business volumes and global reach. New large scale clinical/commercial manufacturing facilties have been commissioned by CMO players in India and China paving way for cost effective manufacturing of biologics with highest quality standards. In particular, India offers abundant talents with global exposure and time-tested expertise in GMP manufacturing and specialty services.