Over the years, several industries have implemented evolutionary changes in their respective manufacturing processes. One to the most rewarding advancements in this direction, is process automation. In pharmaceutical manufacturing, the automation of various aspects of the production process has led to the establishment of the continuous manufacturing paradigm. However, the transition to continuous manufacturing is challenging and cost intensive; as a result, several companies are still reliant on the traditional batch manufacturing technique for their manufacturing needs. Moreover, with regard to the specific requirements of several modern pharmacological interventions, the continuous manufacturing technology is still considered immature to be adopted / implemented for all product type and scales.
Figure below presents pictorial summary, highlighting the key differences between the integrated continuous and batch manufacturing processes.
Numerous sectors, including food and beverage, chemical, automotive, pulp and paper, steel making, metal smelting, waste-water treatment and electronics industry, have been using continuous and semi-continuous manufacturing equipment and technologies for several years. It is worth mentioning that the continuous manufacturing technique was first used in the 1700s for the production of pig iron in a blast furnace. However, the continuous manufacturing equipment was not used in the pharmaceutical industry till the early 60s, when granulation process was achieved by wet mixing of the particles and shelf drying; this was followed by the adoption of fluid bed granulators in the 70s. This led to the introduction of high-shear mixer granulators, in combination with fluid bed dryers and roller compactor tablet presses, thereby, leading to the development of a continuous process. Later, in 1983, Sandoz (based in Germany), developed and introduced its proprietary continuous wet granulation technique, named the SRS technology.
In the course of time, a number of such equipment capable of continuous manufacturing either small molecule drugs or biologics, have been developed. There are several companies that are now offering continuous manufacturing equipment that contain process analytical technologies (PAT) and advanced sensors. Further, many innovators claim to be engaged in improving the continuous manufacturing process, developing advanced variants of currently available processing systems, and optimizing on the cost of such solutions.
List of Continuous Manufacturing Equipment Providers for Small Molecule Drugs and Biologics
Presently, over 80 companies are focused on developing pharmaceutical continuous manufacturing equipment to offer a variety of solutions featuring continuous processing capabilities for the production of small molecules and biologics. Further, majority of the continuous manufacturing equipment available for small molecules are mixers (31%), followed by granulators (22%) and dryers (18%). Likewise, majority of the continuous equipment available for the manufacturing of biologics are bioreactors (56%), followed by chromatographs (17%) and fermenters (7%).
Majority of the equipment are used for only continuous manufacturing processes for small molecule drugs, while the rest are intended for batch-continuous processes. Majority of the only continuous equipment include (in alphabetical order, no specific criteria for selection) dryers, granulators, mixers and reactors. Example for companies providing batch-continuous processes include (in alphabetical order, no specific criteria for selection) Allagier, coperion and SaintyCo.
Over the years, various pharmaceutical developers have attempted to overcome the existing challenges associated with batch manufacturing. Continuous manufacturing has emerged as a better alternative to traditional production approaches for drug candidates. Several stakeholders have already adopted this advanced technology for the manufacturing of their small molecule drugs and biologics. It is worth mentioning that the ongoing R&D activity in this domain has resulted in a significant increase in the intellectual capital.
Early adopters of Continuous Manufacturing
One of the early adopters of the continuous manufacturing technique include Vertex Pharmaceuticals, a US based biotechnology company. The aforementioned firm received the FDA approval for Orkambi, a drug manufactured using its proprietary continuous manufacturing technology, in July 2015, for the treatment of patients suffering from cystic fibrosis. Following this, in 2016, Johnson & Johnson received the FDA approval for Prezista, which is intended for the treatment of patients suffering from HIV. The continuous manufacturing approach enabled the production of this drug in three days, as compared to the batch process, which took about two complete weeks.
Players offering Continuous Manufacturing
We also came across over 60 players offering continuous processing of drugs using such novel pharmaceutical manufacturing equipment. Presently, most of the companies engaged in this domain are headquartered in Europe (32), followed by those based in North America (23). Within Europe, the United Kingdom emerged as a key hub for continuous manufacturing, followed by Switzerland and Germany. Examples of large companies located in Europe include (in alphabetical order, established before 1886) Bayer, Boehringer Ingelheim, GlaxoSmithKline, Johnson Matthey and Siegfried.
Further, in North America, most of the players are headquartered in the US. Additionally, within Asia-Pacific, China and India emerged as the current hubs for continuous drug manufacturing, featuring the presence of 4 and 3 companies, respectively.
Even though continuous manufacturing has been used across various industries for several decades now, it is still at infancy within the pharmaceutical industry. In other words, pharmaceutical manufacturers still rely on the conventional batch mode of manufacturing.
However, the advantages of continuous manufacturing are numerous and without doubt, this approach to it has the potential to bring about a paradigm shift in pharmaceutical production. Considering the ongoing innovation in biotechnology process development and the efforts being put in by industry stakeholders to automate various steps of healthcare product manufacturing, better and versatile continuous manufacturing equipment are likely to soon enter the market and will consequently drive the future growth opportunity for such equipment providers through the roof.
For further information on this emerging domain, check out the following report: