BIO PRODUCTION FORUM: BRIDGING RESEARCH AND INDUSTRY
During the 6th Bio Production Forum, concrete topics were discussed from a scientific, practical and regulatory perspective within the three modules "Drug Product Development", "Process Development, Transfer & Launch Manufacturing" and "Marketed Product Compliance". Alike the Forum the year before, close to 60 delegates had joined the conference conducted by the European Compliance Academy (ECA ) and supported by the University of Munich, the Leiden University, the Swiss Society of Pharmaceutical Sciences, the ETH Zurich, Cilag AG and Merck Serono to get the latest information and some orientation towards future developments.
The key note lecture by Jonathan Barnsley, Senior Vice President of Merck Serono, titled "Biopharma: The Road to Maturity" outlined the path biotechnology will take in the future. The major changes for the future were discussed as the increased medical needs of the aging population, the price pressure of the health systems, competition from Biosimilars and developing countries and patient segmentation. For the road ahead this translates into the need to reinvigorate product development and innovation, increase responsiveness to market opportunities, reduce unit costs, managing a global supply chain and adapting supply to smaller patient segments. Product development will focus on customer convenience for administration, on treatment compliance and on treatments linked to biomarkers. Probably consolidation will continue to leverage development costs globally, in-house research capabilities in big pharma will be downsized whereas collaborations with small biotech and academia will increase. In order to cope with the challenges ahead, biotech industry needs to learn from other industries like electronics to improve capacity utilisation, better automatisation of work flows and data management, more efficient use of staff, reduced inventory, increased flexibility in manufacturing and a return to smaller bioreactors due to more robust processes with higher titers. Biotech industry is past adolescent stage today and needs to become a mature adult now.
The module Drug Product Development placed the focus on protein stability and in particular on the aggregates. It gave deep insight into the causes of aggregation and the range of analytical methods for their characterisation.
Wim Jiskoot discussed protein aggregation and the use of fluorescent dyes to study it. As protein aggregates are correlated to immunogenicity, an understanding of aggregation pathways and mechanisms is crucial. The aggregation pathway was described starting with a partially unfolded intermediate form of the native protein. This intermediate form can either fully unfold and then aggregate, be fragmented and then form aggregated fragments or directly aggregate in the intermediate form. As highly sensitive, selective and versatile tools to study these pathways fluorescent dyes were discussed.
Recommendation
7/8 May 2024
Annex 2 & Co. - GMP Compliance for Biopharmaceuticals - Live Online Training
The aspects of product formulation were described in detail with the example of cyclodextrins. Tim Serno showed the results of the studies of his working group at the Ludwig Maximilians University in Munich about HPßCD, a CD-derivative that is used in approved parenteral products
- HPßCD is the most promising CD-derivative for protein formulation: parenteral applicability and best stabilising properties
- HPßCD provides an alternative to polysorbatein IgGformulation since it stabilises the mAb at the air-water interface and has no negative effect on mAb-stability in the bulk
- Binding to hydrophobic amino-acids in the bulk is not the reason for stabilisation
- No displacement of the mAb from the interface
- Interaction in the interface seems to be the mechanism of stabilisation
Another highlight was the new approach of high-throughput formulation with the emphasis on the speed of analytics and the analytical method-based development of the product formulation ("Therapeomics").
The highly topical concept of "Quality by Design" was elucidated particularly from a holistic and risk-based angle. The studies demonstrated the scientific background and practicalities of risk based QbD along the Product Life Cycle. As a result, QbD based on the causal product and process model opens up the possibility of a multidimensional risk-based process development and of the strategic determination of process control.
A presentation on the latest findings regarding the methods of siliconisation and silicone layer analytics for glass syringes steered the discussion towards primary packaging materials. The compatibility of the materials and the product as well as the potential negative impact on the product (stability, degradation,…) were described in detail.
Dr Frank Böttger from Vetter Pharma-Fertigung used some examples to demonstrate how important it is to better understand the silicone oil film present in any syringe system. Due to the only nanometer thick silicone layer it is essential to use analytics specifically developed for this purpose.
With regard to modern drugs a wrong selection of the siliconisation method and amount can result in an illicitly high number of particles or can - in extreme cases - lead to the generation of protein aggregates.
In the development of autoinjectors it is also essential to optimise and systematically examine the siliconisation due to the attending gliding properties of the syringe. Dr Böttger introduced relevant factors and optimisation strategies for such combination products.
The aspects of distribution (cold chain) and of the various application systems rounded off the issue of product development and represented a suitable bridge to the problems conditioned by production.
The issue of physical stress on the product during fill & finish process was systematically described taking account of all production steps. In particular, the process parameters relevant to product quality were listed and the necessity of model-oriented causal acquisition was pointed out, since this is the only way to also understand the evolution of product quality attributes along that of all production processes and to control them accordingly.
Recommendation
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Blood, Blood Products and Plasma
The last module, "Marketed Product Compliance", began with an exciting look at biotechnological products and processes from a regulatory point of view. The latter underpinned the necessity to thoroughly know the process and the product. The presentations also showed the change of paradigm in the regulatory area with regard to the requirements at the time of registration and implementations of the ICH Q Guidelines.
As some of the conference delegates expressed the conference provided them with some detailed insight which was also supported by the visit of the progressive biotech production of MerckSerono in Aubonne. For 2011 it is planned to conduct the Bio Production Forum in Ulm, Germany, from 8-10 June.
Author:
Axel H. Schroeder
CONCEPT HEIDELBERG
