The Evolving Aseptic Processing Landscape

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The past year has been dominated by the COVID-19 pandemic, which has posed challenges similar to that typically faced in the aseptic pharmaceutical processing market, where the rapid development and deployment of vaccines has proved to be a stern test of the capabilities of both manufacturers and suppliers. The speed at which sterile vaccines needed to be produced has brought some key challenges to the forefront, even as demand for the same production remains high today.

Because the pandemic occurred against the backdrop of a rapidly changing industry landscape, bio/pharmaceutical companies need to be aware of changes in regulations as well as the greater pressure that industry supply chains have been put under. In addition, there are more sterile drug products in development, and there is a wider shift toward outsourcing the manufacturing work for these products in development. This is only a small sample of the shifts that are occurring.

Booming market

It is without doubt that manufacturers in the aseptic processing space have a number of challenges to face down, but one of the major challenges is a positive one: demand. Manufacturers are facing unprecedented demand, which is exerting added pressure on both facilities and equipment. The latest estimation suggests that the overall global aseptic processing market will grow to be worth $73.6 billion by 2027, up from $62.2 billion in 2020 (1).

A significant driver of this growth is COVID-19 and the vaccines that were quickly developed to counter the pandemic. As people are expected to need booster vaccinations in the years to come, this is likely to become a stable foundation for continued demand for the sterile production of vaccines.

Broader than this, there has been a general movement in the pharma industry toward providing patients with more individualized treatments, which has been reflected in the rapid growth of cell and gene therapies. The growth of individualized treatments in development has resulted in a greater number of aseptic products that require a different kind of manufacturing process than those at large scale. This shift toward small-batch production necessitates the adoption of new technology to maintain speed of production and the integrity of the process.

Adapting to the pressure

Regardless of the drug product involved, the basic objective remains the same: to produce safe medicine for patients as efficiently and effectively as possible. Errors and missteps can have disastrous effects. Any issues during the aseptic processing steps could lead to risks in patient safety and can result in product recalls, logistical delays, operational disruption, and increased costs.

The demand for vaccine manufacture, as a result of the COVID-19 pandemic, proved to be a test for the industry, not least of which was determining how quickly vaccine production could be sped up. The pandemic shone a spotlight on the capacity available of a particular type of facility due to the spike in demand. Producing sterile vaccines is far from simple, and a complex task such as this questions whether or not the industry is set up to meet the challenge of producing a product at the speeds needed. The demand highlighted the requirement for manufacturing facilities that are flexible and able to turn around a quicker response to immediate need.

The pressure the industry came under initially was evident when vaccine developers experienced issues with being able to provide the number of doses initially estimated. The supply chain was heavily disrupted in the early stages of the pandemic, which led to shortages of ingredients for products and the materials required for packaging.

With many more moving parts involved due to the pandemic, there was also the issue of transfer and logistics through the manufacturing process. The transfer of ingredients into and out of critical areas, such as isolators, has always been a challenge for the industry. With manufacturers partnering with a greater number of contract manufacturers and other partners, there is an on-going discussion regarding the ease of transfer of product from site to site.

Regulatory changes

Beyond the immediate pressures of the pandemic, there remains the significant challenge regarding the broader move toward increasing regulation. A final version of the European Union’s good manufacturing practices (GMP) Annex 1 (sterile products) will be introduced in 2021, with a consultation draft previously published in February 2020 (2). Annex 1 will have wide-ranging implications for aseptic processing and containment, especially regarding contamination control strategy (CCS) in cleanroom zones.

A section has been added regarding closed systems, which provides additional stipulations that pharma manufacturers will need to comply with. This means that pharma manufactures will have to reduce the number of manual interventions to ensure sterility. As a result, emphasis will need to be placed on carrying out risk assessment and the monitoring of data integrity, which will require additional methods to be put in place to comply with regulation.

An evolving industry

Facing down these challenges meant that the industry has had to adapt, especially in reaction to the pandemic. Numerous trends that were already underway have been accelerated as the need for flexibility and speed became paramount.

Single-use technology solutions

One of the major prevailing trends in recent years has been the uptake of single-use technology (SUT), which nearly 85% of operations at clinical or process development scale use, research suggests (3). One piece of SUT that can support drug developers is the split butterfly valve (SBV). This technology provides a solution for the sterile transfer of powders, including drug substance and drug product. The valve enables the transfer of powders into and out of process equipment during the pharmaceutical manufacturing process.

The SBV is made up of two components: a passive half that connects to a filling container and an active half, connected to the production line equipment. This allows the product to transfer from the line into the container via the interior of each half. The end result is that the power does not come into contact with the surrounding environment and thereby maintains aseptic integrity through the process. There is also a disposable version of the passive components, with the principal benefit being to manage the same quality of aseptic processing but with the improved efficiency that comes with using a disposable system.

Maintaining sterility during transit

Another area of the process that has become increasingly important is ensuring sterility while transferring from facility to facility or to another geographic region. This has become a pressing need because the trend toward outsourcing manufacturing is accelerating as pharma manufacturers choose to select a partner specializing in the manufacture of a particular product or delivery formulation. This trend was particularly seen when pharma vaccine developers looked to contract manufacturing partners once a viable vaccine candidate had been found. The fragmentation of manufacturing led pharma companies to engage with multiple partners to handle different parts of the manufacturing journey.

As manufacturers look for seamless integration from drug substance to drug product site, single-use products are gaining ground because of the ability to reduce risk by eliminating double handling. This posed the problem of maintaining sterility during transit and the additional cost that comes with purchasing reusable solutions. However, there are SU bags available on the market that are contained and maintain sterility during the transfer of powders through the manufacturing process, as well as between facilities. In addition, because SU equipment is discarded after use, this significantly speeds up the hygiene procedures required to maintain a sterile environment. As a result, production downtime is reduced compared to reusable alternatives.

Bringing data to bear

The revolution that is occurring across industry lines is the utilization of data, which can be regarded as an opportunity to aid the aseptic processing industry. The “smart factory” concept allows pharmaceutical production lines to view real-time usage data of the equipment on their processing lines.

This comes with various benefits, but the principal one is to ensure the health status of valves on the processing line, with fully automated monitoring being possible. Those working on the line are able to receive information remotely. The real-time data generated can help line operatives determine exactly where and when maintenance is needed, allowing for intervention prior to a situation where aseptic integrity or productivity is affected.

The data can also be made accessible through a mobile device or through an online dashboard to the health and safety team, who can then remotely assess the health of the processing line. This remote assessment also works for viewing the functioning of valves located in different facilities when the individuals accessing the information are not in the same location.

Opportunity for the future

There is no doubt that, since the beginning of the pandemic, the pharmaceutical industry has faced a number of new challenges. However, from these challenges, the industry has emerged better equipped and more resilient for future challenges that may come. The demand of aseptic manufacturing will continue to grow and, therefore, investing in the ability to ensure product quality at faster speeds and with more flexibility will always be worthwhile.

References

1. Reportlinker, “Global Aseptic Processing Industry,” Press Relase, Oct. 27, 2020.
2. European Commission, Annex 1: Manufacture of Sterile Medicinal Products, Revision draft (February 20, 2020).
3. K.J. Morrow, Jr. and E.S. Langer, “Rise of Single-Use Bioprocessing Technologies: Dominating Most R&D and Clinical Manufacture,” www.americanpharmaceuticalreview.com, Feb. 27, 2020.

About the author

Ben Wylie is senior product manager at ChargePoint Technology.

Article Details

BioPharm International
Vol. 34, No. 8
August 2021
Pages: 34–37

Citation

When referring to this article, please cite it as B. Wylie, “The Evolving Aseptic Processing Landscape,” BioPharm International 34 (8) 34–37 (2021).