More than 200 attendees from manufacturers and key suppliers attended ISPE’s first European conference on aseptic manufacturing in the old capital of the Austrian Hungarian Monarchy Capital, Vienna. Austria is a hot spot for biopharmaceutical manufacturing with a number of global manufacturers or subsidiaries of major pharmaceutical companies. The conference’s focus was on the latest developments in aseptics, the main technology for biologics.
D/A/CH AFFILIATE: 25 YEARS
At the conference, the ISPE D/A/CH Affiliate celebrated its 25th anniversary. Gunter Baumgartner, Chair of the affiliate, highlighted the high level of growth in affiliate membership in recent years with a high global retention rate. The affiliate currently has over 1300 members. The D/A/CH Affiliate has provided a long list of successful events, seminars, trainings and Young Professional and Student activities. The Affiliate received the Excellence Award at the ISPE 2018 Annual Meeting & Exposition in 2018 November, which celebrated the work of the D/A/CH Affiliate. An anniversary celebration dinner at the old Renaissance Palace Ferstel in Vienna included past D/A/CH chairs as honorary guests.
KEY NOTE PRESENTATIONS
Jörg Zimmermann, Pharma Vetter GmbH
Key trends and developments (Fig 4 – Key trends and developments) were presented by Jörg Zimmermann, Vice President at Vetter Pharma, and included increasing regulatory difficulties and cost pressures for European Life Sciences companies; growth in specialty medication especially anti-infectives, oncology, and nervous system disorders; maturing personalised medicine with falling prices; technology companies are entering the health field;
Along with these trends is a change in the conception of health care, Zimmermann said, from caring for the sick to prevention, healthy behavior, and real-time care. About 75% of healthcare spending is now for non-communicable disease, especially cancer, cardiovascular, chronic respiratory diseases, and diabetes.
Genomics, metabolomics, and proteomics information is leading to new drug discoveries and personalized medicine. Big data and mobile apps for healthcare are on the rise with over 20,000 apps available already. Supply chain issues are a challenge for life science companies in forecasting demand and building flexible and reliable supply chains.
Zimmermann predicted the pre-filled syringe market will double between 2014 and 2024, and polymer syringes will enter the markets. For comparison they have already 60% market share in Japan. Also, needleless systems will have more market share as they are painless and so are more appealing to patients.
Fig 4 – Key Notes and Developments
Fig 9 - Picture from Jörg Zimmermann speaking
Paul Fiorio, Novartis
With the example of KYMRIAH for autologous immunocellular therapy, Paul Fiorio, Global Pharma Compliance and Inspection Head at Novartis, discussed the new manufacturing process of a CGT (cellular and gene therapy) product (Fig 5 – CGT „manufacturing and application process“ with KYMRIAH personalised medicine product).
KYMRIAH is a one lot per patient process, as patient specific cellular material is collected under non-aseptic conditions. The microbial bioburden load is dependent of the patient, equipment, and environment conditions. The components for this process are received by qualified and certified suppliers. Measures to reduce bioburden are numerous. The product is manufactured under aseptic conditions and includes the connections between different fittings and syringes and capping/uncapping of sterile ports on bags and containers. Each formulated bulk material is sterility tested with a test for detection of foreign organisms before release. Key controls to aseptic processing cover processing components, personnel, and environment. (Fig 6 – Process flow diagram for CGT product)
Fig 5 – CGT „manufacturing and application process“ with KYMRIAH personalised medicine
Fig 6 – Process flow diagram for CGT product
An interesting question and answer session followed and posed the questions as to whether there is a new regulation needed, as the product cannot be called “sterile” and is the term “aseptic processing” still correct? A clear statement from Andy Hopkins, MHRA clarified the MHRA viewpoint: “The fact that a product comes from a non-sterile starting material does not really matter.”
Fig 10 – Picture from Paul Fiorio speaking
Jean-François Duliere, Chair of ISPE Annex 1 commenting group
Numerous comments from various parties were submitted, collected, bundled, and forwarded on behalf of EMA, to the MHRA rapporteur, Andy Hopkins. Jean-François Duliere, Chair of ISPE’s Annex 1 commenting group, presented a comprehensive overview of the most considered topics.
Various comments went to the Annex 1 link to non-sterile products. There were concerns that Annex 1 could be used globally for non-sterile products. Additional arguments addressed Quality Risk Management with many references to QRM in Annex 1. The word “risk” is mentioned 92 times, indicating its importance to the commenters. Regulators indicate that QRM has been formally required since 2013 after release of ICH Q 9 already in 2005. (Fig 7 – History of Quality Risk Management in EU regulation)
Fig 7 – History of QRM in EU regulation
Fig 11 – Picture from Jean-François Duliere speaking
Andy Hopkins, Expert GMDP Inspector, MHRA
Andy Hopkins, MHRA, provided input about 140 sets of comments on Annex 1 that have been received from industry. All comments have been reviewed. Hopkins noted that there is a certain lack of understanding that Annex 1 does not affect just Europe but also applies to PIC/S and WHO. In addition, Annex 1 covers many types of manufacturing including API, single-unit batch processing, and others. Comments are to a certain extent controversial, ranging from “too prescriptive” to “not prescriptive enough.”
He pointed out that QRM is not a new requirement but already had been formally requested since 2013. Hopkins pointed out that a genuine dialogue between regulators and industry is needed, and should be far more open than currently is the case. Training by industry associations such as ISPE and others is key.
“Bad design” but “good monitoring” is like testing things into compliance and not the right approach, he said. He also noted that contamination control strategy is not a new requirement as mentioned in chapter five in 2015. (Fig 8 – Contamination Control Strategy)
Fig 8 – Contamination Control Strategy
Andy Hopkins’ statement and conclusion about QRM in aseptics processing: “Design the processes, procedures, and facilities not to contaminate the product. Design the monitoring system to detect any deleterious trend and/or failure. Keep reviewing and developing as new information about your processes, procedures and designs comes to light. Keep developing as you become aware of new technological advances.”
Fig 12 – Picture from Andy Hopkins speaking
After that, the conference continued with four dedicated tracks:
Track 1: Quality & Regulatory: Annex 1, Quality Risk management and Data Science
Track 2: Isolator, Barrier, Robotics and Manufacturing High Potent Drugs
Track 3: Aging Facilities - The Way to Facilities of the Future
Track 4: Decontamination, Sterilisation, Transfers, E-Beam, Stoppers, RTU and Disposables
Due to positive feedback about the program from participants including regulators, including the presentation content and speakers, the DACH Affiliate committee has committed to repeating the conference within the next two years.
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