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While supply chain disruptions have resulted in many alterations to workplace practices, they have also presented an opportunity to get ahead of changes to the EU’s upcoming revision of Annex 1.
The supply chain disruptions brought on by the COVID-19 pandemic resulted in significant changes to workplace operations. In the context of aseptic production, the impact on ongoing operations is certainly present, but it can be more clearly felt in the trends beginning to take shape in advance of the European Union’s upcoming changes to Annex 1 regulatory guidelines. These changes, which are largely concerned with overhauls to contamination control strategy and procedures, are poised to enforce changes in the European aseptic manufacturing landscape.
Patrick Nieuwenhuizen, director senior consultant at PharmaLex, notes that in aseptic production, existing contamination control procedures were already in line with the types of measures that were being enacted on a global scale following the onset of the pandemic. Instead, changes in aseptic production workflow were more along the lines of finding ways to get staff that needed to be in the building (e.g., manufacturing personnel, quality control lab technicians, cleaners) present and performing their tasks in a safe and socially distanced manner.
According to Philip Vanek, chief technology officer at Gamma Biosciences, a life sciences tools company backed by private equity firm KKR, the biopharmaceutical manufacturing industry continued to face significant added pressure to consistently meet quality measures. Adhering to good manufacturing practices (GMPs) already significantly limits the ways a company can operate; throwing a pandemic in on top of that necessitates creative thinking as a means of navigating these supply chain disruptions.
“Necessity is the mother of invention,” says Vanek. “Most established equipment manufacturers scrambled to meet demand in the already stressed supply chain. One change that we did observe early on was an increasing expression of interest and demand of equipment and single-use consumables from smaller, lesser known brands that could substitute in the manufacturing workflow [as a replacement for those that were in short supply].”
The short supply of some consumable single-use parts led some to consider stainless-steel alternatives that allow them to rely on in-house procedures rather than continual shipments from an outside supplier. Properly maintained stainless-steel systems can last upwards of 20 or even 30 years without needing a full replacement, adds Nieuwenhuizen.
With single-use-systems, however, the need to clean systems between cycles is eliminated, saving time and money on validation and revalidation procedures. Richard Denk, senior consultant, Aseptic Processing and Containment at SKAN, believes that validation concerns are absolutely front of mind for manufacturers.
“The word ‘validation’ will have a big impact on equipment design and cleaning procedures in the future, as current designs are often not easy to clean and for that reason need to demonstrate a robust validation,” says Denk. “If we look at the pipeline in the future, many new products in development are considered highly potent. [At the same time,] inappropriate cleaning procedures are the most common findings during GMP inspections in shared facilities.”
Single-use systems are just one way companies are attempting to ease the load of maintaining GMP requirements with a compromised workforce. The industry was always going to need to engage in some level of introspection into common methods and practices in advance of upcoming changes to Annex 1.
Following several drafts and comments from various pharmaceutical companies and organizations, the EU’s changes to Annex 1 are set to have a pronounced emphasis on contamination control strategies. Notably, the revised guidelines contain detailed instructions on isolators and restricted access barrier system (RABS) technologies and new sections on form-fill-and-seal systems and single-use systems.
“For the company to demonstrate they have a good understanding about their processes and what risks and controls they have in place was often sufficient to have a validated process,” says Nieuwenhuizen. “Now it becomes more important to provide justification and evidence why the process you have designed as a company and the controls you have implemented are adequate to assure that you have an aseptic or sterile product.”
It is because of this increased scrutiny on holistic process development that companies have begun fine tuning their contamination control strategies. There are various ways to factor optimal contamination control into one’s aseptic production process, says Denk, who was the GMP lead for the development of the SKAN-Groninger robotic filling line. Denk’s line was fully automated, including measures that help in contamination control such as viable monitoring and automatic delivery of indirect product contact parts.
According to Vanek, companies have invested in technologies that de-risk manufacturing, including process analytical technologies and continuous closed manufacturing. “Technologies that improve production efficiency in terms of classified space utilization, such as automation enabled by new process analytics and high-efficiency closed continuous production systems, have been in the spotlight. The momentum towards single-use manufacturing in aseptic processing, both upstream and downstream, is likely to continue and perhaps accelerate with the adoption of new process analytical technologies and the data sciences that support them.”
The upcoming revision to Annex 1 has incentivized manufacturers to do everything in their power to minimize direct contact of product by operators. With this context in mind, the trend toward single-use-systems, automation, and other strategies to close systems and minimize contamination is not likely to go away even after the
pandemic has fully passed.
Vol. 34, No. 12
When referring to this article, please cite it as G. Playter, “Looking Past the Pandemic: The Future of GMPs in Aseptic Processing,” BioPharm International 34 (12) 10–14 (2021).