Pierre Fabre immunology centre is the biotech division of the group combining high level antibody research & development specifically in the field of oncology. As part of its expansion strategy the group decided to develop monoclonals up to clinical phase and to build and design their own facility.
The project was driven by key high level objectives:
Considering the initial and future capacity requirements along with the requirements for flexibility single-use disposable systems for manufacturing to be integrated as far as possible throughout the process were the obvious choice.
Process technologies were carefully selected through a structured stepwise approach and measures for preservation of the environment were a constant concern. The facility was awarded by the French HQE certification for its high performing environmental profile.
The facility was built for a total budget of USD$18M including all equipment for process and QC. A facility expansion (that was planned for at the design phase) is envisioned in the near future as part of Pierre Fabre strategy.
Dr Olivier Cochet, Director Industrial Biotechnoloy, Institut de Recherche Pierre-Fabre
One of the biggest challenges or barriers to further disposables implementation today is the lack of harmonised industry standards whether it be in the field of leachables and extractables testing, quality and manufacturing standards to which the single-use suppliers are working, standardization of design, level of testing on single-use systems that is appropriate or what should the single-use supply chain look like? This presentation will outline the key industry standardisation issues and how the six industry associations, suppliers and end users are addressing this.
One of the key questions put during this presentation will be: who should define the industry standards for disposables? User, supplier, independent third party Engineering company , regulator or standards organization
Case studies will be presented providing practical recommendations on
Miriam Monge, Vice President Sales & Marketing, Biopharm Services Ltd
Dave Wolton, Biotechnology Consultant, PM Group
We have evaluated the freezing/thawing of cells in bags for fully closed operations from thawing to 1250L Bioreactor inoculation. A first trial on 7 different CHO cell lines was performed and demonstrated the feasibility of this approach. This first improvement was combined to SUB that are now commonly used for process development and as seeding or production bioreactors. During the period 2010-2012, we performed a study in order to evaluate the performances of SUB at various scale from 3L to 200L. The evaluation was performed both for seeding application and for clinical material production. Several clinical runs at 200L and 1250L scale were performed to ensure a meaningful comparison. These performances were also compared to glass and stainless steel bioreactors of different sizes ranging from 3.6L and 1250L. Coupling cell freezing in bag and disposable bioreactors up to production scale allowed us to develop a fully closed USP process.
Aurore Lahille, New Technology Manager, Merck Biodevelopment
The technical and economical benefits of Single-Use in bio-manufacturing are well known and our industry is broadening their adoption in all steps of commercial production. In parallel, the improvement in protein titer and purification yields help reduce the scale of Bioprocesses and hence accelerate the penetration of Single Use against traditional stainless steel processes.
The presentation reviews the new challenges associated with the growing adoption of Single-Use Technologies in more critical process steps of cGMP commercial productions and the solutions offered by a leading supplier to improve quality, assurance of supply, change control, product integrity and extractable validation.
The lecture introduces a new supply chain management strategy that involves partnering with polymers and film suppliers to enhance assurance of supply and change control of resin materials and films used for the manufacture of single-use bags.
This new strategy follows the concepts of quality by design and design space and relies on business contingency plans to create unprecedented level of quality and security for the end users. In addition, the paper describes how the establishment of resin specification instead of general trademarks can facilitate change control in the future.
The author further explains how transparency on resin and additive formulation followed by a fully controlled manufacturing process of the plastic films ensure the generation of extractable data are relevant and meaningful. End user can then use supplier data to perform toxicity assessment and support the utilisation of SU systems in their process.
The author will conclude with describing the latest single-use technology advances towards new generation of films and bag integrity testing at the supplier and at the point of use.
Katell Mignot, Head of Application Specialist SE & NEMEA, Sartorius Stedim Biotech
GSK is boosting life cycle management as the company recognises the challenges to manage product quality, complexity, costs and… the biological nature of the products. The major part of the vaccines were developed decades ago are today in a maturity stage and thus require extensive life cycle management to fulfil current requirements. The mission of Technical Live Cycle Management (TLCM) within GSK is being re-defined as to maintain and evolve the current GSK Vaccine portfolio to assure the supply of safe and compliant drugs with robust and economically sound manufacturing processes. To gather a momentum for this, all business functions are involved. In the new vision, TLCM manages the complexity and provide knowledge, assess the risk and lead change projects, defining a clear implementation strategy that accommodate regulatory needs and ensuring the continuous supply of the product within the quality specifications locally approved at a specific time.
During the presentation, the key steps of the lifecycle value stream are exposed:
Philippe Ronse, Director, Head Technical Lifecycle Management, GlaxoSmithKline Vaccines Biotech
This presentation will identify the key challenges that many biopharmaceutical companies currently face when managing their process data from early phase development through scale up to manufacturing.
Crucell (a J&J company) will explain how process models are used within their organization to become more efficient in terms of optimizing and managing their processes in development, by getting a better understanding of their different process options, evaluating the impact for example of new technologies such as disposable systems, but also expression platforms, such as high density cultures, and comparing these to traditional platforms.
In the case study presented, Crucell will show:
After the session participants will be able to:
Keywords: Process Modeling, Cost Evaluation, Facility Design, CAPEX, Vaccine Production, Process Optimization
Kai Touw, Process Engineer USP, Crucell / J&J
Wiebe Van Vuure, Process Engineer DSP Development , Crucell / J&J
Potentially beneficial innovations have become available to the industry in the field of production line design, build and operation. However, there is considerable inertia for any company seeking to benefit from these innovations, both internally and externally.
This presentation takes a scenario in which biotech processes are operating in a controlled, non-classified space and takes a risk based approach to considering how operational approaches would differ from a more traditional design of facility. Whilst still under development, the objective of this work is to provide increasing assurance amongst key stakeholders, that safety and quality can be delivered, whilst improving the economics of facility building and management.
The presentation builds on Area Classification work undertaken by a cross-industry collaboration team, facilitated by the BioPhorum Operations Group.
Delegates will gain from this presentation:
Robin Payne, Facilitator, BioPhorum
Process Development, scale-up and robust supply are key factors for successful biosimilar development. For each individual molecule, a broad screening of process conditions is required to match the desired product quality and in-depth process understanding is needed to ensure reliable supply at scale. It will be described how biosimilar process development requires a different approach compared to what is needed for novel biologics. The presentation will outline the evolution from process development platforms to a biosimilar process development toolbox focusing on IgG molecules. Ultimately, biosimilar process development will drive an increasing scientific understanding on how combinations of key process parameters relate to distinct product quality attributes that are post-translationally determined throughout the manufacturing process.
Hitto Kaufmann,Vice President Process Science, Boehringer Ingelheim
The construction cost of a Future Facility / Flexibility Facility as presented in this Guide can allow a 40% reduction over traditional facilities. The first edition of the ISPE Biopharmaceutical Manufacturing Facilities Guide was issued in June 2004. The concepts developed at that time have been accepted and implemented in a phased approach over the years. Since its issue, the Industry, processing technology and views to manufacturing have dramatically changed. This new Biopharm Facility Guide collects and integrates the current industry Future Facility and Flexible Facility concepts into a single document. The Guide addresses many factors that drive facility design. The factor with the greatest impact to facility design is closed processing. Closed processing disconnects the process from the facility allowing for new and innovative design solutions, including multi-product production ballrooms.
Delegates will gain a better understanding of:
Mark Von Stwolinski, Vice President of Architectural Services, CRB
The consistent and integrated use of disposable technologies enables fast and reproducible GMP manufacturing and allows a significant cost reduction for clinical supply.
In 2010, Rentschler successfully implemented the first 1000 L disposable manufacturing line, and was awarded with the “Facility of the Year Award” for its second 1000 L fully disposable manufacturing line.
Over the last three years Rentschler has successfully executed a significant number of various customers processes in its 1000 L fully disposable manufacturing area.
Continuous improvement and optimization of the facility and its processes has made the utilisation of disposable technologies more robust and effective.
The presentation will focus on the gained experience, lessons learned, current and remaining challenges. Subjects as “Leachables and Extractables”, “Material Flow”, “Maintenance”, “Difficulties in Operation”, will be addressed.
Peter Rogge, Vice President USP Production, Rentschler Biotechnologie GmbH
Fujifilm Diosynth Biotechnologies (FDB), an industry-leading cGMP Biologics CMO is meeting the challenge of maintaining flexible yet dependable manufacturing operations through establishing communities of learning throughout the organization.
These communities are underpinning compliance and right-first-time manufacturing with rich visual knowledge. The capture, conveyance and retention of operational best practice is enabling the use of visual content; pictures, videos, sounds etc., to be deployed in support of manufacturing. For example; a visual guided tour of how to assemble chromatography systems.
The browser based digital solution is being used to provision R&D with the knowledge of manufacturing operations enabling development teams to maximize process fit and to minimise the need for manufacturing changes. Access to subject matter experts previously restricted by day-to-day manufacturing demands are now available through our communities of learning.
Paul Bird, Head of Development Engineering, Fujifilm Diosynth Biotechnologies
This presentation is based on the article 'Risk Analysis and Mitigation Matrix (RAMM) - A Risk Tool for Quality Management', which won the ISPE 2012 article of the year award. RAMM is a risk tool developed to be incorporated into a risk management system and align with the latest FDA guidelines, especially the requirement of lifecycle risk management.
For those familiar with the tool, this will also provide and update from the previous year on implementation of the tool in specific case studies.
Daniel Abrahamsson, Validation Engineer Consultant, NNE Pharmaplan
Why should a new manufacturing building employ modular construction instead of conventional standard (= stick-built) construction?
The presentation starts with a brief introduction of the modular concept, showing the configuration and
building of a new biopharmaceutical facility, including a short overview of available solutions on the
The results of a comparison study, developed during an early phase of an investment project, will be presented, evaluating the pros and cons of a modular approach.
Based on several case studies of operational modular facilities, the presentation highlights specific challenges associated with the modular approach and demonstrates how these challenges can be understood, assessed and mitigated.
Thorsten Kimmel, Senior Project Engineer, F. Hoffmann-La Roche
The development and scaling up of processes is a cornerstone of success for the biopharmaceutical industry in making safe and effective medicinal products.
These processes are required to meet cGMP regulations wherever products are marketed, while remaining in compliance with all other governing codes, laws, guidelines, and regulations.
This Guide focuses on the development, process approaches and practices involved in providing cost effective, regulated manufacturing of biopharmaceutical products in a timely manner that meet their intended use. It is intended to be used by industry for the design, development and scaling up to regular production, all leading to processes meeting the requirements from FDA, EMA, JMHLW, PMDA, WHO or other health authorities.
Robert Dream, Principal, HDR COMPANY LLC
Ease the factory-school will be located in Strasbourg within the centre of Europe. It will cover all steps of pharmaceutical production chains. This training centre offers to the pharmaceutical companies and their partners facilities to train their staffs in immersion and “a la carte”. All roles within the chain from the cleaning technician to the head of pharmaceutical operations could be trained in EASE in initial or continuous education. The equipment and training programs to meet industry’s needs in “GMP-like” production facility for bio-manufacturing, liquid Sterile forms and solid dosage on manufacturing processes and supporting processes (utilities, maintenance, automation, QA/QC…). Ease is a co-founder with BTEC North Carolina of the BTEC international training network.
Constance Perrot, Operational Project Leader, European Aseptic and Sterile Environment Training Centre