Focus on Biologics Technology - 2018 ISPE Europe Aseptic Conference

Keynote Presentations

Jörg Zimmermann, Pharma Vetter GmbH

Key trends and developments were presented by Jörg Zimmermann, Vice President at Vetter Pharma (see Figure 1). These 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 personalized medicine with falling prices; and technology companies 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 noncommunicable 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 prefilled 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.

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.

KYMRIAH is a one lot per patient process, as patient-specific cellular material is collected under nonaseptic 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.

Genomics, metabolomics, and proteomics information is leading to new drug discoveries and personalized medicine.

An interesting question-and-answer session followed and posed the questions as to whether new regulation is needed, as the product cannot be called “sterile,” and is the term “aseptic processing” still correct? A clear statement from Andy Hopkins, Expert GMDP Inspector at MHRA, clarified the MHRA viewpoint: “The fact that a product comes from a nonsterile starting material does not really matter.”

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 nonsterile products. There were concerns that Annex 1 could be used globally for nonsterile 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 in 2005.

Andy Hopkins, MHRA

Andy Hopkins, Expert GMDP Inspector for 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.

Andy Hopkins’s statement and conclusion about QRM in aseptic 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.”

Additional Presentations

After the keynote presentations, 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 from participants, including regulators, about the program, including the presentation content and speakers, the D/A/CH Affiliate committee has committed to repeating the conference within the next two years.