Key points
The globalisation of the pharmaceutical industry has led to increased outsourcing of development and manufacturing. This has resulted in fierce competition for contract development and manufacturing organisations (CDMOs) to attract new drug developer customers and pressure to invest in specialised production lines to secure high-value projects.
Staying ahead of competition from other CDMOs requires innovative manufacturing solutions that offer flexibility to adapt to new production requirements quickly and with minimal downtime or financial outlay.
Tackling these solutions and achieving flexibility will involve novel cleanroom technology — particularly valves — to ensure production line efficiency.
In this article, Ben Wylie, Head of Product Management and Marketing at ChargePoint Technology, explores the challenges CDMOs face when ensuring flexible and agile production and the potential of novel single-use (SU) manufacturing equipment to help achieve multiple project goals, such as containment and sterility during bulk drug powder transfers.
Staying ahead of the competition during drug powder transfers
The pharmaceutical contract manufacturing market is growing rapidly and is projected to expand at a CAGR of 10.3% in the forecast period between 2023 and 2033 [1].
Growth in the contract manufacturing market is being driven by an increasing number of drug developers who are looking to outsource solutions to bring their products to market more quickly and cost-effectively [2].
This has led to a proliferation of CDMOs and a highly competitive marketplace, where attracting new drug developer customers while maintaining optimum productivity and efficiency across the manufacturing processes is essential.
Even small deviations in manufacturing and drug powder transfer parameters like temperature, humidity and air quality can result in significant product quality issues or regulatory noncompliance, exemplifying the importance of this operation.
Advances in technology are driving innovation in the pharmaceutical industry, with new drugs requiring increasingly complex manufacturing processes. CDMOs must continually invest in new technologies to remain competitive and meet the evolving needs of their customers.
Obstacles to flexible production capacity for drug powder transfers
Ensuring that production capacity offers flexibility and agility is a significant challenge for CDMOs as they strive to meet the needs of a diverse and ever-changing array of customers. CDMOs must be able to address several challenges to remain compliant and successful. These include:
- Investment in technology: Although CDMOs continually invest in new technologies and equipment to meet the evolving needs of customers, investment in expensive upgrades can cause multiple issues:
- Lack of flexibility: Specialised equipment is often only suitable for a particular product or process, reducing flexibility when considering future projects.
- Wasted investments: Investments in technology can require significant capital investment and ongoing maintenance and training. There is risk in this type of technology investment as it isolates the production line capabilities to one area and the line may end up unused and wasted if new projects that require the technology are not secured.
- Costly upgrades: As new products and processes are developed, the specialised equipment may require expensive upgrades to remain effective.
- Managing customer priorities: Managing the priorities of multiple customers is especially challenging when customers have different product specifications, quality requirements and timelines.
- Managing supply chain complexities: Complex supply chains, including sourcing raw materials, managing inventory and ensuring timely delivery of finished products are common challenges. Any delays or disruptions in the supply chain can lead to production delays and may impact customer satisfaction.
- Ensuring regulatory compliance: All production processes should comply with regulatory requirements, which are complex and ever-changing. Maintaining compliance across multiple products and customers requires significant expertise and resources.
A lack of flexibility and the need for costly upgrades can create a significant financial risk for CDMOs and hinder their ability to attract new customers and remain competitive. Seeking solutions like SU equipment can allow for greater flexibility when managing multiple projects.
Handling bulk drug powder transfers
Pharmaceutical companies are incentivised by regulatory bodies to review their current manufacturing processes and adjust their facilities to improve manufacturing processes and achieve compliance in the most cost- and time-efficient ways possible.
A significant part of this investment focuses on the transfer and storage of powders, including active pharmaceutical ingredients (APIs), within their facilities. Given that API and highly potent API (HPAPI) powders can be toxic if consumed in high doses pharma companies must ensure the safe containment of these substances.
This necessitates using highly specialised equipment for handling and storage, as well as contained transfer processes to guarantee operator safety and prevent contamination.
To contain powders during storage or transport, manufacturers use sealed transfer bags. However, most of these bags are open-topped, which can lead to the release of hazardous dust and fumes during loading or unloading.
Consequently, after each loading process, surrounding areas must be thoroughly cleaned and validated to maintain HPAPI containment in the zone. This time-consuming process can often result in productivity losses.
Manufacturers must meticulously evaluate the technologies they use to achieve successful containment in powder transfer while maintaining productivity. This will ensure that manufacturers can adapt to existing facilities while remaining flexible to constant market changes.
Evolution of sterile drug powder transfer handling
Another challenge facing drug manufacturers is ensuring sterile integrity when handling powders intended for use in parenteral or ophthalmic formulations. In the past, pharmaceutical manufacturers would handle such powders in a separate room away from production line equipment to prevent airborne contamination.
The industry now has the option of using stainless steel valves that attach to production line equipment, called split butterfly valves (SBVs). This is a hybrid multi and single-use technology that presents a solution to the challenges of both sterile handling and HPAPI containment.
SBV technology
SBV technology is designed to minimise the risk of operator exposure and contamination of ingredients during material transfer.
The key advantage of SBVs is their ability to provide a barrier between the cleanroom and the product. This is achieved by the valve’s unique design, which splits it into two halves. One half of the valve remains attached to the product container (such as flexible bag) while the other half remains attached to the process equipment.
Once the two halves are connected and sealed together, the valve is opened, and material can be transferred between the two sides of the valve. This design helps to prevent contamination of drug powder or potentially harmful HPAPI exposure to personnel entering the cleanroom during material transfer.
Closed processing systems
Another significant advancement in cleanroom technology is the use of closed processing systems. Closed systems are designed to prevent product interaction to the external environment during processing. This minimises the risk of product contamination and exposure to working personnel.
Closed systems such as Isolators can be used in combination with SBVs (a closed system themselves) at critical stages of manufacture such as dispensing and sub-division or powder filling to provide additional protection against contamination during material transfer.
One technology that is being used as part of a closed system is SU chargebags, which are becoming increasingly common in cleanroom processes for the storage and transportation of drug powder materials. These bags can be equipped with the “passive” half of an SBV, allowing them to be connected directly to production line equipment for filling or transferring the drug product material.
Once filled or emptied, the bags are securely sealed, preventing any egress of the material into the surrounding area and reducing risk of product contamination. The SU nature of this technology eliminates the need for cleaning, validation and additional gowning while reducing the need for manual operator intervention that would typically be required for these lengthy procedures.
Using SU chargebags can help pharma manufacturers achieve regulatory compliance and reduce product changeover downtime — ultimately increasing overall productivity. Additionally, the disposable nature of the bags eliminates the need for cleaning and validation, further increasing efficiency.
Advanced filtration technology
The use of advanced filtration systems is also an important technological aspect of cleanroom technology. These systems are designed to remove any potent contaminants from the air within the cleanroom to maintain a controlled environment.
Filtration can be used in combination with closed processing systems, such as isolators, where negative internal pressure is maintained during operation, to minimise the risk of egress of the product from within the processing machinery. SBVs can also help – they can be developed with dust extraction features to further reduce the risk of potent particles becoming airborne.
These advancements have helped to improve the efficiency and safety of processing by reducing the risk of contamination. As the pharmaceutical industry continues to evolve, new advancements will likely continue to be introduced, further improving the quality and efficiency of processing.
Shaping the future of pharmaceutical manufacturing
Technological advancements and a new generation of SU manufacturing equipment has the potential to help achieve multiple project goals, such as containment and sterility, during bulk powder transfers. SU systems offer several advantages over traditional stainless-steel equipment, including reduced risk of contamination, increased flexibility and agility and improved containment during manufacturing processes.
Looking to the future, it is likely that the pharmaceutical industry will continue to advance, with the introduction of new technologies and manufacturing equipment to improve the efficiency and safety of drug manufacturing processes. CDMOs will need to remain adaptable and open to change, with a focus on quality and customer satisfaction.
References
- www.globenewswire.com
- Pharmaceutical Contract Development and Manufacturing Market Size, Share & Trends Analysis Report By Service (API Manufacturing, Finished Dosage Formulation), By Region, And Segment Forecasts, 2019 – 2026
