The pharmaceutical industry is becoming increasingly globalized. Not only are more companies looking to sell their drug products in multiple markets across the globe, but they are also sourcing supplies of active pharmaceutical ingredients (APIs), as well as packaging and other commodities from overseas suppliers.

COVID-19 has added to the complexity. The supply chain disruption experienced during the first global lockdown in March 2020 led many companies to diversify their supply chains, beginning relationships with new suppliers and partners in a greater array of territories than ever before.

The pandemic also played a key role in establishing outsourcing, development and manufacturing to contract partners as a widely accepted integral part of the drug development journey, even for larger pharma companies.

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The race to develop viable and effective vaccines meant that many pharmaceutical firms sought out the support of contract development and manufacturing organizations (CDMOs). They took advantage of these companies’ existing specialist infrastructure and expertise to help bring their vaccines to clinical trial and to commercialization faster than anyone thought possible.

Keeping up with demand
This new acceptance of the role of CDMOs is, of course, good news for these partners, but it does bring with it challenges, particularly when it comes to keeping up with surging demand for their services. CDMOs now face even greater competition than before to attract new drug developer customers while maintaining optimum productivity and efficiency.

This poses a challenge for CDMOs who may feel under pressure to invest in specialist production lines to attract high-value projects that may not be needed once the project is finished. Particularly for CDMOs looking to attract specialist projects that require sterile processing, or the handling of highly potent APIs (HPAPIs) that pose a safety risk to operators. This investment may be wasted or may require additional costly work to upgrade for new projects.

With this in mind, CDMOs need new manufacturing solutions to help them attract lucrative projects, while offering them the agility to meet the needs of a diverse and ever-changing array of customers. In particular, they need added flexibility in their operations to switch lines over to new production requirements with minimal downtime or financial outlay. This is a particular challenge when it comes to sterile processing, whether containment controls add an extra layer of complexity. How can this flexibility be achieved, while also ensuring optimum productivity and minimum downtime?

Production equipment holds the key
To support CDMOs in expanding their capacity and upgrading it to ensure it meets growing customer demand for greater flexibility, production line technology is adapting quickly.

One way that production line equipment is evolving to support CDMOs in meeting agility goals is the rise of hybrid Single Use Technology (SUT).

There are a number of key advantages to using SUT equipment to create more flexible and agile drug development and manufacturing infrastructure. SUT is easy-to-use with no need for extensive training, without requiring upgrades to existing production lines.

Crucially, SUT is specially designed to be used once before disposal, which means it can streamline cleaning and validation procedures while reducing production downtime. This is particularly valuable for production lines involved in aseptic processing—sterile disposable equipment can help maintain sterility and optimize integrity without the need for added washdown regimes.

Moreover, by minimizing cleaning procedures, SUT equipment can ensure true containment, whether to maintain sterile integrity or to protect employees from contact with a highly potent API (HPAPI). They can also ensure optimum containment during transit between, as well as within, manufacturing facilities.

All in all, SUT offers the potential for firms to ensure optimum product quality, while helping to maximize process efficiency and reduce production costs.

The flexibility benefits of SUT
A good example of single use technology that is helping drug developers to enhance flexibility on busy production lines is the split butterfly valve (SBV). These allow contained transfer of powders, including drug substance and drug product, into and out of process equipment during the pharmaceutical manufacturing process.

Two key components make up an SBV: an active half connected to the production line equipment and a passive half attached to a filling container. When fitted together, these two halves create a single plate that allows product to flow from the line into the container via the interior surface of each half, without any product coming into contact with the exterior environment. As such, SBVs allow true containment of the product, and can help maintain sterile integrity.

Disposable SBVs can help achieve the same level of containment—aseptic or otherwise—during processing as standard reusable SBVs while significantly enhancing efficiency. As they don’t need to be cleaned after use, the SUT component can simply be disposed of between fillings, increasing productivity, and streamlining the product changeover process.

The disposable passive half of the SBV can also be connected to a SU flexible bag to enable the contained and sterile transfer of pharmaceutical powders between each step in the manufacturing process, as well as between facilities. This further ensures containment and sterile integrity while minimizing downtime from cleaning components after use or between projects.

SBVs that have been specially designed for sterile processing can further ensure aseptic integrity while enhancing efficiency. They can offer functions, such as the ability to be autoclaved or SIP (steam in place) and with integral bio-decontamination utilizing H2O2 vapor to perform a qualified 6log sterility assurance. Here a hybrid SBV design can optimize performance and downtime with a multi-sue Active half that can be steam sterilized alongside the process equipment, and a SUT passive half that is produced in cleanroom environments, Gamma Sterilized, used and then disposed of alongside the product container.

No matter what sterilization process is used, this step means that such components are suitable for use by CDMOs in a wide range of projects, including those demanding a level of particulate and bioburden control to the most rigorous aseptic processing environments or stringent containment to safeguard employees.

More advances to enhance line flexibility and efficiency
SU equipment is not the only innovation in production line equipment that can support CDMOs in delivering a more flexible and agile development and manufacturing offering to their customers. The development of “smart factory” technology also has exciting potential to optimize production line efficiency, as well as achieve other specialist project goals, such as sterile integrity or containment. 

Under the principles of the “smart factory”, smart monitoring technology must be integrated into pharmaceutical production lines in order to deliver rich and in-depth real-time information on the status of key manufacturing equipment installed on the line.

This real-time information can help CDMOs’ line operatives to identify where maintenance is needed well before productivity is affected, helping them to plan preventative action in a way that minimizes downtime. In doing so, it can ensure that SBV maintenance can be performed proactively, helping to enhance efficiency, while minimizing the risk of any failure of containment or sterile integrity.

Smart monitoring offers more opportunities for CDMOs looking to deliver a flexible offering to customers, particularly those with sterile or contained production needs. Being in possession of such real-time equipment usage data can enable CDMOs to generate audit trails much more quickly than before. It can allow individuals responsible for regulatory compliance to proactively manage validation programs on their lines—aseptic or otherwise—to support customers in demonstrating conformity to legislative standards. It can also allow internal health and safety teams to ensure they are maintaining optimum containment to safeguard employees’ wellbeing.

This smart data can be viewed using an online dashboard, or even from a mobile device, allowing for remote access and analysis, so responsible persons can monitor the usage of valve components while they are on the move. It is even possible to monitor SBVs in different facilities.
With all of this in mind, smart monitoring technology can revolutionize the containment or sterile processing strategies traditionally used by CDMOs, providing a fully automated means of understanding the health status of the valves on production lines.

The right equipment is the key to optimum CDMO flexibility
The challenge of meeting the booming demand for support from pharma companies quickly and efficiently is becoming ever more pressing for CDMOs. They need to find a way not just of future-proofing by expanding their infrastructure, but of making the most of their existing capability at the same time. Simultaneously, they must ensure their capacity is as flexible as possible to give them the ability to meet each of their clients’ unique project needs.

Advanced SU equipment, combined with innovations such as smart monitoring tools, can be an important step in this direction. By delivering marginal gains in saved downtime, they can achieve a tangible improvement in production efficiency. In doing so, they can optimize line productivity on both existing and new lines, while also offering additional specialisms for customers, from sterile processing, to the handling of challenging materials, such as HPAPIs. 
 

Ben Wylie is Senior Product Manager at ChargePoint Technology. For more information, visit www.thechargepoint.com.