Shawn Kinney, CEO, Berkshire Sterile Manufacturing
Shawn Kinney, CEOManufacturing injectable medicines have never been more relevant, and though we may not have been aware of it, we have benefited from several astounding and recent improvements in the industry. A critical aspect of injectable manufacturing is ensuring sterility. If a non-sterile drug product were administered to a patient, it could cause severe illness and potentially be fatal depending on the extent of contamination and delivery mechanism. In addition to patient safety concerns, a contaminated drug product lot could set back or end a clinical study and prevent a new treatment, cure, or vaccine from making it to commercialization where it could improve patient survival and outcomes.

While large manufacturing sites have adopted several advanced technologies to help improve the sterility assurance of parenteral, small-batch fill-finish companies that produce products for clinical trials or rare diseases have been slower to adopt this technology. This has not been out of lack of care but rather because the technology did not offer the flexibility that smaller batch filling required.

This was the case until a Massachusetts-based biotech company, Berkshire Sterile Manufacturing (BSM), entered the field in July of 2014.

The battle between flexibility and sterility assurance

Operator involvement is closely tied with sterility assurance. The more involved operators are in the filling process, the more likely sterility assurance failures may occur. One technology that drastically improves sterility assurance by removing operators from the filling environment is isolators.

Isolators appeared in the ’80s and were slowly adopted into filling lines by the pharmaceutical industry. Like any new technology, isolators were clumsy and awkward at first, with some significant weaknesses. Despite their ability to effectively remove the operator from the drug product filling, they came with several drawbacks. They were very expensive relative to traditional grade A cleanrooms, they had long sanitization and aeration times, and they were not ergonomic or flexible as they were designed for particular activities.

Clinical scale fill/finish CMOs manufacturing drug products for clinical trials, or small commercial needs found they could not accommodate different container types and sizes in a single isolator-based filling line. Changeover times were long, and the line preparation was complex. It was unaffordable to develop an isolator-based line for each container type. Thus they invested in restrictive area barriers (RABs) that required a separate grade A cleanroom.

Berkshire Sterile Manufacturing : Innovative Sterile Manufacturing of Injectable Drug Products

Our philosophy is to offer quality, and innovation to customers, utilizing new technologies to improve the sterility assurance and quality of the products while ensuring regulatory compliance

This protected the sterile core from the operators and reduced the risk of contamination, but it did not offer the advantages of isolators by eliminating operator impact.

Improving the Standard in Fill Finish

Berkshire Sterile Manufacturing (BSM), a small-scale sterile drug manufacturer, was established in 2014 by three industry professionals with over 50 years of combined experience in fill-finish. Their mission was to utilize new technology in the industry to enhance the sterility assurance of parenteral for clinical and small-scale commercial production.

Aiming to serve the industry better, BSM’s team worked with several leading equipment suppliers to design their ultra-flexible and isolator-based filling line. This line was one of the first small-scale filling lines capable of filling syringes, cartridges, vials (either RTU or bulk), and lyophilized products. BSM started with a manual filling isolator in 2016, added a semi-automated filler in 2018, and has grown exponentially.

BSM continues to redefine the quality standard in the small-batch filling. The company is currently installing a fully robotic, ultra-flexible, isolator-based filling line that will be operational by March 2022. This line is part of a $20M facility expansion to increase their capabilities and improve fill-finish standards. In designing this new line, BSM combined a standardized process module with advanced robotics. A double-headed filler provides exceptional flexibility and would be able to deliver increased fill speed to increase capacity. Robots were included to perform all the handling activities, such as loading and unloading the filler. They provide complete automation of the filling without the need for operator intervention. Despite designing the filling line to be completely automated, glove ports were still installed to serve as a precaution in unforeseen issues. As Shawn Kinney, the CEO of Berkshire Sterile Manufacturing, concludes, “Our philosophy is to offer quality, and innovation to customers, utilizing new technologies to improve the sterility assurance and quality of the products while ensuring regulatory compliance.”

This approach offers a lot of flexibility with a minimal footprint. The system could fill all the popular container types and sizes and multiple product types, including high viscosity fill. Adding robotics and automation to the system has also created more rapid and robust VHP decontamination cycles, improved line ergonomics, and sped up the changeover times between setups. Other technology such as 100% IPC (in process weight checks), decontamination of RTU tubs with pulsed light, the connection of the lyophilizer and lyophilization system to the isolator, and the ability to add lyophilizer in the future were all incorporated into this unique line. Many additional innovations will be employed in the future, and sterile filling companies are beginning a significant shift towards these types of technology.

As pharmaceutical companies begin to embrace this type of innovation, advanced automation, robotics, remote monitoring, and other technologies will change how drug manufacturing is performed. Incorporating technology into pharmaceutical training, compliance, monitoring, and testing will enable the production of higher quality products. The future is bright for this industry, and BSM is one of the first companies to showcase this new technology transformation.