Can partnerships with CRDMOs boost biosimilar manufacturing?

The biosimilar manufacturing market is dominated by western companies and in Asia Biocon Biologics is growing strong and has joined the leading ten global biosimilar manufacturers.

India, drug industry,
India is the largest provider of generic medicines, producing 20% of the world’s supply, according to the government’s Economic Survey.

By Dr Mahesh Bhalgat

Biopharmaceuticals, also known as biological medical products, or biologics drugs, are drugs manufactured in, extracted from, or semi-synthesized from biological sources. These agents have been used for treating a myriad of diseases such as cancer, diabetes, and specific immune disorders.

One reason for their rising popularity is that they are highly effective at treating a wide range of conditions and are typically associated with fewer side effects. However, they are one of the most expensive drug treatments available in the market today. Just as generics have brought down the prices and improved access to traditional pharmaceutical drugs, biosimilars offer the same potential for biopharmaceutical agents.

Biosimilars are similar copies of the original biologics where the same protein is used for treatment, although they are produced from different starting materials (seed) grown in bioreactors. Since several biologicals have gone through patent expiry and several others are close to the end of their patent protection period, the biosimilars market offers tremendous prospects.

Biosimilars are becoming indispensable and the global market for biosimilars is expected to expand at a compound annual growth rate of 24.7% from $11.8 billion in 2020 to $35.7 billion by 2025. The biosimilar manufacturing market is dominated by western companies and in Asia Biocon Biologics is growing strong and has joined the leading ten global biosimilar manufacturers.

Biologics manufacturing involves multiple steps and starts with the use of living cells which adds both variability and complexity. The commercialization of a biosimilar comes with challenges, which require extensive research and development. Biosimilars are approved based on the same stringent standards of quality, safety and efficacy that apply to any other medicines.

In addition, there is a requirement that the developed biosimilar must be comparable to the original Biologics drug in terms of its activity and physicochemical properties such as sequence, post-translational modifications, charge variant profile,
product and process impurities, etc. Comparability is an important concept since a biosimilar that is inferior cannot be approved and on the other hand, a biosimilar that is superior becomes a “biobetter” which required more extensive clinical studies (in patients) before seeking approval for market launch.

A critical step in the development of a biosimilar is a thorough understanding (scientifically referred to as characterization) of the innovator biologic that is already approved for treatment. Applying multiple tools (analytical methods), scientists thoroughly understand the primary protein sequence, the 3-dimensional structure (protein folding), its post translational modifications (sugars attached to the protein), charge variants, impurity profile, biological activity, etc. This extensive understanding is then used to design the manufacturing process which involves optimization of the conditions under which the cells can make the same protein, in a high yield, in its right folded form without unexpected variations or impurities.

Cell growth conditions optimization is additionally worth calling out since cells behave differently to change in environment and hence nutrient mix provided to the cells can lead to undesirable changes in the proteins expressed. “Recovering” the protein out of the cells is followed by purifying out unwanted components to provide the pure protein of interest. This part of the process referred to as downstream processing requires additional design and development to ensure the product at the end of this process is still comparable to the innovator biologic. This concept of comparability then needs to extend as the purified protein is filled into vials in high-speed machines to make the marketed biosimilar.

Commercial strategies to manage the competitive pressures and build robust go-to-market strategies Given that all steps of the manufacturing process have to be developed independently by the biosimilar manufacturer, getting a biosimilar on the market relies heavily on strong development and manufacturing capabilities compared to discovery research. The drug discovery activities required to identify and validate the target on which the protein will work, elucidate the mechanism of action, and demonstrate clinical efficacy can be leveraged through the work done on the original biologic by the innovator. Needless to say, a well-equipped analytical facility, process development capabilities, and a state-of-the-art
manufacturing facility are essential, however, come with a significant capex commitment and are associated with long gestation periods.

A reliable and trusted approach to overcome the challenges we are witnessing increased collaborations between large manufacturers/ small virtual biosimilar developers and contract research, development and manufacturing organizations (CRDMO), to manufacture biosimilar products. In 2020 the global biosimilar market was valued at approximately $14B and since then has been expanding swiftly with an anticipated 5-year CAGR of 23% (4). CRDMOs offer a wide range of latest technologies that enable rapid design and development of biosimilars with better-optimized cost. Small companies can reduce the cost of biopharmaceutical drugs as they get expertise with the right sets of knowledge and capabilities for drug development under one roof and avoid intensive capex investments.

CRDMO partners enable biotech companies and biosimilar manufacturers to reach the market faster due to the following benefits:

Reduced development costs: CRDMOs often have expertise that they can apply which reduces the trial and error required to develop a process that can produce a comparable material and do so with an efficient process. Economies of scale can offer better-optimized costs and increase their profitability.

Increased speed: With the help of the resources and infrastructure that is already in place, CRDMOs are able to develocommercial-scaleprocesses that can support large-scale manufacturing operations with process improvements, efficient scale-up approaches, and with regulatory compliance.

Steady supply chain: An integrated supply chain approach can optimize capacity utilization and management, building long-term commercial benefits.            

Customization: CRDMOs are equipped to offer flexible manufacturing services tailored to biotech companies’ needs. They can provide customized processes, formulations, and packaging solutions, which can help biotech companies to differentiate their products and meet their unique requirements.

Knowledge support: CRDMOs often have extensive experience and expertise that spans therapeutic (disease biology), regulatory, CMC (process and analytical) and clinical domain. They can help design strategies and establish bio similarity with innovator product using advanced technologies, navigate complex regulatory requirements, optimize their manufacturing processes, and improve the quality of their products.

Yield: CRDMOs have a deep understanding of protein chemistry, cell culture, and the impact of process conditions on yield and protein structure down to the smallest detail, including changes from lab to GMP scale. They are also able to explore different approaches to yield improvements. For example, Enzene Biosciences is equipped with a novel platform that provides continuous processing for monoclonal antibody production. Along similar lines, Syngene offers an intensified process using perfusion technology which offers high yields with very few changes. It involves constantly removing
cell-culture media containing the product from the bioreactor and substituting it with new media. This method has helped achieve a 3-to-4- a fold increase in productivity.

With the number of biologics which will go through patent expiration in the coming few years, there is no doubt that biosimilars are poised to grow. Biosimilars offer an approach that helps mitigate rising healthcare costs and hence will be an area of interest to governments, payors, medical and biotech professionals. A highly efficient way to gain market access is through the engagement of a CRDMO who has strong expertise in biologics development and manufacturing at a commercial scale in a state-of-the-art facility. This is a win-win permitting low capex investment yet providing high volumes for strong
market growth.

(The author is a  COO, Syngene International. Views expressed are personal and do not reflect the official position or policy of the

Get live Share Market updates and latest India News and business news on Financial Express. Download Financial Express App for latest business news.

First published on: 02-04-2023 at 12:00 IST
Exit mobile version