Continuous manufacturing process involves the production of pharmaceutical drug substance in a single run, while operating 24×7. In this process, the drug is developed from its base ingredients / raw materials and processed to the final product in one facility, without any hold time. For decades, pharmaceutical companies have manufactured drugs using batch processing in which a specific quantity of a drug is produced through multiple sequential steps. However, batch processing can be slow and inefficient. As a result, drug developers have begun to adopt continuous manufacturing to streamline drug production process. This can be attributed to the several advantages offered by continuous manufacturing process over traditional batch processing, including reduction in facility footprint (by 70%), reduction in operational and running costs (by 40-50%) and easy scale up of continuous manufacturing process.
Batch Manufacturing vs Continuous Manufacturing
Traditional pharmaceutical batch processing involves series of steps for API manufacturing / drug product manufacturing. Additionally, during batch processing, each batch goes through a sequence of steps, and the entire batch must be completed before a subsequent batch can be processed. Conversely, continuous manufacturing is an uninterrupted production process where raw materials are continuously fed, and drug substance / drug product is continuously manufactured. Moreover, continuous manufacturing provides a real-time quality control, increases efficiency due to uninterrupted production process which further reduces downtime and manufacturing costs.
The abovementioned advantages offered by continuous manufacturing technology over batch processing technology make it a promising technique for manufacturing of small molecule and biologics. Additionally, production of drugs through continuous manufacturing takes less time to get regulatory approval as compared to drugs manufactured using batch processing, which provides an estimated cost saving benefit of around USD171 to USD 537 million to pharmaceutical manufacturers.
Despite the several advantages offered by continuous manufacturing technique as compared to traditional batch manufacturing technique, the pharmaceutical industry seems skeptical about adoption of continuous manufacturing. This may be attributed to some of the challenges associated with this process; the key challenges have been mentioned below:
High Cost of Continuous Manufacturing System / Equipment: The high cost of continuous manufacturing system / equipment is contributed by the incorporation of PAT, process modeling and automation software. Although this process saves losses in production, the initial investment required is very high.
Process Development Restrictions: These restrictions are generally due to different types of technologies which are used to build the continuous manufacturing system. Due to its lack of flexibility, switching from one drug to another becomes challenging.
Investing in the Manufacturing Plant: Significant changes and investments are required to make a facility suitable for continuous manufacturing, which makes it difficult to set up a robust unit in the same premises. For instance, a vertically structured building is preferred in case of continuous manufacturing as it facilitates uninterrupted flow of raw materials from the top and efficient collection of finished product at the bottom. Further, manufactured materials require additional storage facilities, such as silos. In addition, heavy equipment is required to handle large amounts of these materials. This, in turn, demands additional investment for setting up the plant for continuous process manufacturing.
Presently, close to 60 manufacturers have adopted end to end continuous manufacturing and semi-continuous manufacturing process for various types of biologics, including antibodies, enzymes, proteins / peptides, vaccines and viral vectors. It is interesting to note that close to 50% of these companies are large and very large firms, indicating the presence of well-established players in this market. Further, close to 75% of the continuous biologic manufacturers offer contract manufacturing services for continuous manufacturing of the above mentioned biologics. Majority of these manufacturers are headquartered in North America (~40%) followed by Europe and Asia Pacific. Additionally, it is important to highlight that, presently, biologics segment captures the majority share of the continuous manufacturing market.
The small molecule continuous manufacturing companies landscape features close to 50 manufacturers having expertise in end to end continuous manufacturing or semi continuous manufacturing of drug products. The market landscape is well-fragmented, featuring the presence of small, mid-sized, large, and very large companies, which claim to have the required expertise in continuous small molecule API manufacturing and Finished Dosage Form (FDF) manufacturing. It is interesting to highlight that majority (~75%) of the small molecule manufacturers are focused on API manufacturing followed by the companies focused on FDF manufacturing. Further, more than 50% of the continuous small molecule manufacturers are based in Europe, followed by North America and Asia Pacific.
Recent advances in manufacturing technologies have prompted pharmaceutical companies to consider shifting from the traditional multi-step, batch manufacturing processes to faster, and relatively more efficient continuous manufacturing.
Continuous manufacturing can easily accommodate scale-up and post-approval changes in drug production which is advantageous in case of drug shortages. It is worth noting that the Biden administration has supported increased funding of pharmaceutical continuous manufacturing technologies to overcome challenges associated with pharmaceutical supply chain. Such developments will support the continuous manufacturing market growth.
Presently, North America and Europe capture more than 60% of the overall continuous manufacturing biologics market size, and more than 90% of the overall continuous manufacturing small molecule market size. In recent years, adoption of continuous manufacturing in North America has witnessed a tremendous increase owing to the regulatory support and early approval for continuous manufacturing applications by the Food Drug Administration. Several recent developments have taken place in the field of continuous manufacturing. We have outlined some of these recent initiatives below. These developments, even if they took place post the release of our market report, substantiate the overall trends that have been outlined in our continuous manufacturing market analysis.
In May 2023, Sandoz (unit of Novartis) entered into an agreement with Just-Evotec Biologics to develop and manufacture multiple biosimilar candidates utilizing Just-Evotec’s proprietary drug substance development platform and continuous manufacturing technology.
In April 2023, Arranta Bio (a Recipharm firm) signed an agreement with MIT to develop a continuous manufacturing technology for mRNA therapeutics.
In April 2023, Exothera inked a deal with Quantoom Biosciences to gain access to Nfinity, a continuous manufacturing technology / platform for RNA synthesis.
In March 2023, Curia collaborated with Corning to expand and accelerate continuous-flow development and manufacturing programs for the chemical and biopharmaceutical industries globally. The collaboration marks the first global installation of Corning’s G1 production system to support higher-quality API manufacturing using flow-chemistry technology.
Key companies engaged in continuous manufacturing include AbbVie Contract Manufacturing, ACG Group, Boehringer Ingelheim, Corden Pharma, Glatt Group, Kaneka, Phlow and Wuxi Biologics. Examples of companies that have adopted continuous manufacturing for biologics include AGC Biologics, Cytovance Biologics, FUJIFILM Diosynth Biotechnologies, Just – Evotec Biologics and Rentschler Biopharma.