Regulatory bodies from the European Union and United States encourage the industry to use appropriate technologies to increase the protection of the pharmaceutical products from potential extraneous sources. These authorities are committed to advancing the use and implementation of innovative manufacturing [1, 2]. An International Society for Pharmaceutical Engineering (ISPE) event on 13th of February in Cork, Ireland, brought experts from the industry together to discuss the latest advancements in aseptic processing.
Participants were invited to discuss their knowledge and experience in various break-out sessions and had the opportunity to ask a panel of experts about topics related to aseptic processing. This resulted in an interactive day with various discussions and network opportunities. Presentations included:
- Aseptic processing using gloveless isolator solutions
Human interventions can bring a lot of contamination risks in aseptic processes. Removing the human factor reduces this risk significantly and it can also improve efficiencies and optimizes the process. One of the most common interventions is entering and the removal of materials from an enclosure using a rapid transfer port (RTP). A novel design was presented that allowed opening the RTP door automatically or manually from outside the isolator. Another concept presented was to automatically put the sterilized funnel for loading stoppers in the right position in an isolator without the need for human intervention. While gloveless solutions reduce the need for human interactions within the critical processing zone, these solutions can be less flexible. One option demonstrated to increase flexibility and at the same time reduce risk for glove integrity breaches was the use of so called “on demand gloves”. Here, glove ports were installed on the enclosure and blanked off without the gloves itself present. Gloves could then be aseptically installed and tested for integrity pre- and post-use when required. - Robotics in aseptic manufacturing
Gloveless systems are moving the pharmaceutical industry forward and engineering solutions are available to improve aseptic processes and increase sterility assurance. However, hurdles remain when it comes to limiting human interaction inside the most critical area of an aseptic filling line. The use of robotics can provide a solution to address these hurdles, while increasing flexibility. This was acknowledged in a 2023 publication from BioPhorum [3] which stated that the last decade has seen a fundamental change in technology and solutions. During the event, a gloves isolator with a fully automatic robot line was presented, whereby all process steps — from filling, stoppering, capping, and renesting of filled units — were automated without the need for human intervention. The design demonstrated also allowed for full environmental monitoring and aseptic introduction of materials into the decontaminated enclosure. The design was also presented to FDA’s Emergency Technology Team (ETT) [4] who provided a positive response to the technology and the approach that was taken.
- Designing Risk Decisions
Regardless of whether it is an aseptic process manufacturing an orphan drug or an over-the-counter oral dosage formulation, risk is very much integrated in what the pharmaceutical industry does. ICH Q9 on quality risk management (QRM) provides guidance on the principles and examples of tools that can be applied for different aspects of quality in pharmaceutical manufacturing [5]. From her research, the presenter of the session on risk management stated that the connection between QRM, risk, and decision-making must be more patient-centric. She noted that, despite technological advances, recalls are not going down and the types of findings remain the same. From the data presented, one of the weaknesses appears to be identification of the hazard due to confusion of failure modes and the hazards that may cause patient harm. The question is, what risk truly impacts the patient and how is this risk able to make it all the way through the process to cause the harm? There needs to be an understanding in the relationship between Critical Quality Attributes (CQAs) and critical process parameters (CPPs), the presenter noted. Critical decisions should be well informed, based on scientific data and move from a reactive to a pro-active mode. If the data is inaccurate, subjective, uncertain, or simply lacking, a less meaningful risk-based decision is likely to be made. Good scientific data improves the traceability of decision-making as it allows determination of where a decision is coming from and where is it based on.
About the author:
Patrick Nieuwenhuizen is Director and Principal Consultant at PharmaLex and has more than 30 years of experience in the industry across a variety of platforms including Biologics, Sterile Fill Finish and Solid Oral Dose.
References
- EudraLex Volume 4 Good Manufacturing (GMP) Guidelines – Annex 1, Manufacture of Sterile Medicinal products (2022) . Accessed through: https://health.ec.europa.eu/system/files/2022-08/20220825_gmp-an1_en_0.pdf
- FDA’s Strategy Document on Innovative Manufacturing Technologies (2023). Accessed through: https://www.fda.gov/media/181689/download?attachment
- BioPhorum – User vision for the filling line of the future (2023). Accessed through: https://www.biophorum.com/download/user-vision-for-the-filling-line-of-the-future/
- FDA – Transcript: Emerging Technology Program. Accessed through https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/transcript-emerging-technology-program
- ICH guideline Q9 (R1) on quality risk management (2023). Accessed through: https://www.ema.europa.eu/en/documents/scientific-guideline/international-conference-harmonisation-technical-requirements-registration-pharmaceuticals-human-use-ich-guideline-q9-r1-quality-risk-management-step-5-revision-1_en.pdf
