Since the publication of the ISPE Drug Shortages Survey report in June 2013, many new association and regulatory initiatives have been initiated. This presentation will bring delegates up to date with these initiatives, especially with the recent multi-association team that is responding to an EMA request for proposals regarding the prevention of shortages.
Dr. John Berridge, Strategic Advisor, ISPE
Falsified medicines are a growing threat also in Europe. Therefore the European Union has published a directive to fight against this thread. This directive has to be implemented by every member state. In Germany the securPharm project was founded to design and set up the corresponding national system. The speaker will introduce the project, talk about the results of the pilot-phase and the lessons learned. To complete the picture, the integration in a European wide network will be shown.
Dr. Martin Bergen, Managing Director, SecurPharm, Germany
Joseph A. DeFeo, 25 years as a Sr. Consultant, Author and CEO of Juran Global, as well as the successor to Joseph M. Juran, will provide a view from outside of the pharmaceutical industry. His perspective will encourage all organizations to look outside to adopt a new quality philosophy and framework that best fits the diverse needs and risk associated with our industry.
In his engaging style, Mr. DeFeo will discuss and answer these questions:
Joe DeFeo, President and CEO, Juran Institute, Inc.
If we look back to Biotech in Pharma in a few years, we will recognize that in this year Biopharma entered a new cycle of its development. On the one hand maturing with much higher productivity, which is urgently needed due to severe pressure in the markets and Pharmacos entering emerging markets with biologics to allow access to their products for the world majority of its population. But also with the need to generate profitability to invest in innovation again to develop products like e.g. a vaccine against ever more spreading Dengue Fever.
On the other hand also new, enabling technologies are in a stage providing serious alternatives for development, analytical characterisation and manufacturing. As in any industry, with maturity comes more continuous manufacturing with higher quality demands. And what has been set up in the past to work globally will have to be modified due to a strong increasing demand of regionalization and localization. Standardisation of facilities, higher degrees of flexibility in relation to geography and demand are only some of the consequences.
I would like to draw the participants’ attention - who are all outstanding experts in their respective fields to the higher level of a strategic direction - what do we have to consider beyond our passion for innovation and technology, how will states and their healthcare systems, payers, patients, economics impact the future of Biotech in Pharma? There is a strong need in bioprocessing for a real shift to data driven science and much more professionalism in a sense of a mature industry. We have to make processes much more predictable and reliable, in and across all scales. And second it is our ethical responsibility to make our drugs accessible to all in the world.
That is not the case, because we have not been able to develop and manufacture for a cost which would allow us to reinvest the profitability for new Innovation globally. There are a lot of real exciting technologies out there which really significantly improve benefit for patients. And the most successful ones very often combine different areas of science. One of the most exciting for me is the sRNI/mRNA delivery which I hope we will see continuous positive results in clinical Trialsor cellfree production.
Prof. Dr. Wolfram Carius, Senior Vice President Biopharma Strategy and Member of the Global Leadership Team, Sanofi Frankfurt
An Industry Perspective on the challenges of:
And how a Quality Culture can become a competitive advantage in the face of these challenges.
John Pinion, Global Head of PT Quality & Compliance, Roche
This presentation will discuss the EMA-FDA pilot program for the Parallel Assessment of Quality by Design regulatory applications from an industry perspective.
Dr. Graham Cook, Sr. Director, Pfizer Global Quality Strategy
The procedure for implementing QbD will be illustrated by a case study where QbD elements such as Real Time Release Testing were realized for a legacy product. In the presentation the establishment of the design space as well as the validation of supporting PAT models will be explained highlighting the encountered challenges of this pilot project.
Furthermore lesson learned will be presented as well as the next future steps and projects.
Dr. Lorenz Liesum, Senior Process Analytical Expert (PAT), Novartis
This presentation addresses the on-going problem of disagreements between industry and regulators in European procedures. The EU interpretation of the current guidelines will be presented, and the requirements for the dossier explained. Finally, some examples of regulatory decisions and the rationale behind them will be presented.
The current global regulatory framework for controlling post-approval CMC changes does not facilitate a streamlined, strategic approach to managing CMC across the product life-cycle, nor does it promote continual improvement or innovation in pharmaceutical manufacturing.
The life-cycle management of CMC is becoming increasingly important as a result of factors including the implementation of ICH Q8-Q11, globalisation of the development and manufacture of pharmaceuticals, and increasing complexity of supply chains. A framework for facilitating life-cycle management of CMC which builds on existing regional initiatives is desired and emphasis will be placed on opportunities to provide:
Dr. David Tainsh, Chief Product Quality Officer, GSK
After seven years of experience with enhanced (‘Quality by Design’) approaches to commercial product development, regulatory submissions presenting this information continue to be a minority of new submissions. Regulators have appreciated the extensive level of scientific and technical investment in process understanding and product knowledge, but expectations for regulatory submissions have increased concomitantly and divergently within, as well as across, Boards of Health. Everyone sees risks differently. An individual’s frame of reference, i.e., personal knowledge, experience and individual roles and responsibilities influence the level of risk tolerance. Based on experience to date, these differences can be observed in the understanding of how risk-based decisions are made:
Lack of clarity and alignment has discouraged industry from introducing QbD and enhanced approaches in regulatory submissions because the regulatory benefit for doing so has been limited. In addition, divergent perspectives between regulators in US, EU and industry on what details constitute compliance commitments in regulatory submissions has significantly impacted operational flexibility and effective CMC lifecycle management. As a complement to the EMA QbD workshop, this presentation introduces constructive opportunities to explore differences in understanding and promote alignment of expectations for the preparation and review of regulatory submissions.
Roger Nosal, VP CGMC, Pfizer Inc.
Wendy Zwolenski-Lambert, Global Validation Leader, Technical Operations, Novartis
In considering what lies ahead for the future of pharmaceuticals, biotechnology and medical devices, this presentation will attempt to consider future challenges and opportunities for the industry, and consider these in relation to the importance and requirements of the quality system, maintaining a strong quality culture as the foundation to address these challenges, together with effective understanding and management of risk, to enable industry to develop and supply safe, effective and patient focused therapies, balancing safety with innovation to meet patient needs.
The presentation will aim to ask the questions that we need to proactively prepare for on this cultural journey.
Carol Bye, Head Pharmaceutical Sciences Quality Assurance Global Quality Operations, Pfizer
Since more than ten years a discussion is ongoing on the new paradigm in pharmaceutical quality. The output of this discussion was the adoption of the ICH guidelines on pharmaceutical development (Q8), Quality Risk Management (Q9), Pharmaceutical Quality System (Q10) and Development and Manufacturing of APIs (Q11). Further Q&As, training materials and reflection papers have been published.
The presentation will provide a survey of the current status of implementation together with some examples, indicating the challenges for both industry and regulators and proposing some way forward. And will give introduce the recent EMA EFPIA QbD workshop which will presented later by both regulator and industry.
Dr. Jean-Louis Robert, LNS, France
Jan 2014, at EMA with 40 regulators and all EU agency connected via WebEx, was set up a QbD workshop where 6 real case studies of real QbD application was shared publicly. Each presentation was an opportunity to identify remaining challenges and key learning associated to QbD submission in order to facilitate future submission. As one of the key regulatory sponsors of the workshop, Evdokia Korakianiti will share the key learning and the way forward for future application from the EMA regulator point of view.
Dr. Evdokia Korakianiti, Head of Procedure Management Department, EMA
For 2014, WHO identified convergence as one the key objectives. Very recently, an International Coalition of Medicine Regulatory Agency, including FDA, EMA, China was initiated in order to address the challenge associated to the globalization at more senior level. As a conceptual approach QbD is a cultural change which take time to be integrated internally by pharmaceutical industry and another challenge is associated with the regulatory alignment and acceptance in this global Regulatory environment. The presentation will put in perspective the cultural aspect associated to the global environment, remaining challenges, and the way forward.
Dr. Georges France, Region Head Quality Europe, Novartis
The European Pharmacopoeia (Ph.Eur.) defines legally binding standards for the quality control of medicinal products and their components. These standards need to be frequently reviewed to ensure they reflect scientific/technical developments and changes in medical practice.
This is why the Ph.Eur. closely follows developments in its regulatory environment and the pharmaceutical industry; for example, the change in paradigm in the recent ICH guidelines on pharmaceutical development, quality risk management and quality systems. While defining legally-binding standards that will be used as a reference in disputes, the Ph.Eur. must allow for sufficient flexibility to avoid stifling innovation; for instance, in the development and implementation of process analytical technology (PAT) and the concept of Quality by Design, in the production or control of active substances or finished products. In doing so, it is important to set up a tiered system, considering equally the different needs of the globally-acting pharmaceutical industry and small and medium-sized enterprises, while ensuring protection of public health.
The presentation will provide an overview of measures taken in this direction, including the work of the Ph.Eur. PAT Working Party.
Dr. Susanne Keitel, Director, EDQM
The manufacturing of pharmaceuticals heavily relies on the analytical results generated as in-process, release, retest and stability controls. A high number of analytical controls ensures the stability of the manufacturing process and the quality and safety of the finished pharmaceutical product. These analytical control procedures are similarly regulated as manufacturing processes. For frequent use in the QC environment, precise, accurate and robust methods with appropriate balance of innovative technology/costs is required.
The presentation will give an oversight on Analytical Quality by Design (aQbD) Concepts and good method development practices for analytical methods. Opportunities arsing from some elements of the aQbD concepts within the currently available regulatory framework will be presented. In particular, the use of post approval change management protocols as a novel regulatory tool will be explored. Finally, consequences for the regulatory documentation framework, such as specifications, monograph descriptions and method validation will be discussed.
Dr. Oliver Grosche, Governance & Regulations Lead, Novartis
Learn how to change the current paradigm used in the management of quality systems and achieve a 50% decrease in the number of human errors and a drastic reduction in your total cost of quality.
ICH Q9 (Quality Risk Management) has been around years. It highlighted the importance of intelligent, structured risk management as a core business competence. Eight years on how has the pharma industry benefited? The answer for many is ‘not a lot’.
The good news is that some pharmaceutical companies have excelled at using QRM to drive continuous improvement as well as reduce business risk. This interactive session will describe the Top Ten ‘Best In Class Practices’ observed by NSF DBA. Drawn from over 1,000 client audits we will share how the best in class apply Quality Risk Management for business benefit.
Martin Lush, Vice President, NSF-DBA Ltd
QRM, a regulatory requirement, successfully integrated into the business, drives scientific rigour, improves decision making and allows resources to be focused in the best interests of the patient.
Specifically the presentation will consider the integration of QRM into the European guidance’s and how companies can incorporate this into their business and quality management systems.
The importance of a well organised approach, training, sponsorship and governance will be discussed as well as looking at some of the pitfalls.
Ultimately a strong QRM system can improve product quality and enhance facility and equipment performance throughout their lifecycles, bringing benefits for the business and more importantly for the patient.
Dr. John Kerridge, Quality Leader, EU Quality Assurance Systems and External Advocacy, Eli Lilly
Updates from current PQLI PV Implementation Team activities including:
Wendy Zwolenski-Lambert, Global Validation Leader, Technical Operations, Novartis
Quality Risk Management (QRM) principles described in ICH Q9 are fully applicable to the control of cross contamination in multi-product manufacturing facilities, also referred to as “shared facilities”. The revised versions of chapters 3 and 5 of the EU GMP Guideline state that dedicated facilities are required for manufacturing of a medicinal product if the risk of cross contamination cannot be adequately controlled by operational and/or technical measures, or if a threshold value cannot be established based on scientific data, or if the threshold is too low for being detected or controlled by analytical methods. Such threshold values have to be derived from toxicological evaluations of the products being manufactured. For this purpose, the CHMP/Safety Working Party (SWP) developed a draft guideline on setting health based exposure limits for use in risk identification in the manufacturing of medicinal products in shared facilities. The presentation shows how QRM principles can be applied to controlling cross contamination, explains basic methodology of deriving health based exposure limits/threshold values, and gives some insight into practical experience from an industry point of view.
Dr. Thomas Pfister, F. Hoffmann-La Roche Ltd
What is the true cost of compliance for both industry and the public? Through using some real life case studies this presentation will show the global impact of shortages resulting from compliance issues. Experience from the use of QRM principles in the management of critical supplies across international boundaries will be presented. Strategies to help companies seek a better path of compliance and also recent regulatory changes will also be explored.
David Churchward, Expert GMDP Inspector, MHRA
How does a national regulator use Quality Risk Management approaches? This presentation will explore how compliance risks are managed through scheduling, inspection conduct and surveillance between inspection cycles. Ways in which regulators are seeking to work closer together to share the inspection burden will be presented. Additionally it will look at how the wider regulatory framework is utilising QRM principles.
Mark Birse, Group Manager GMP/GDP Inspection, MHRA
This presentation will underline why and how both EU and PIC/S have taken into account QRM principles in their inspection process. Elements regarding GMP guides and planning of inspection will be addressed specifically.
Dr. Jacques Morenas, Deputy Director, Inspectorate and Companies Department, ANSM
Overview of industry interpretation of QRM application in GDP, focusing on transportation strategy, quality oversight of logistics service providers, and implications in product supply.
Simon White, Regional Leader, Quality Operations, Pfizer
In this presentation Brendan Cuddy will summarise the various EMA regulatory activities on the drug shortages.
Dr. Brendan Cuddy, Scientific Administrator, EMA
In response to European Medicines Agency initiatives on drug shortages -- including a Reflection Paper and Public Workshop -- working in collaboration with regulators and stakeholders, PPTA has recently launched a program that reports European distribution data on plasma protein therapies. The presentation will focus on the operational details and benefits of this European Data Program. It will also provide a few real world example of the program's utility, drawn from 15 years of experience with a similar PPTA data program in North America.
John Delacourt, Vice President, Legal Affairs, Plasma Protein Therapeutics Association (PPTA
The presentation is reflecting on key trends affecting pharmaceutical manufacturing today and in the future.
Trends such as blockbuster patent cliff, smaller products, smaller batch sized, increased flexibility, increased regulatory requirements, market globalization and others make facilities of the future different form the past. This is well described in ISPE’s ILF GPS document.
Introduction of the two-day track programme of Facilities of the Future.
New concepts for a highly flexible machine platform open the eye for future scenarios in manufacturing of small batch parenterals. These concepts involve isolator technology, robotics and a variety of fill techniques including single use fluid path. The concepts could be a blueprint for manufacturing of personalized medicines in the future.
New sensor data exchange techniques can support this approach and combine high flexibility with highest efficacy. A scenario extracted from these ideas predicts change of paradigms in pharmaceutical manufacturing.
Dr. Johannes Rauschnabel, Engineering Pharma Processing, Bosch
There are different approaches and challenges to gain operational excellence for a CMO in the pharmaceutical industry. One key performance indicator is the OEE (Overall Equipment Effectiveness). In the presentation will be shown different solutions and necessary facts to improve both certain manufacturing processes and the OEE based on the experience of a CMO for aseptic production. For that a new high-performance filling line is presented as well as potential measures on the way to gain operational excellence.
Gerald Buerkle, Director Pharmaceutical Production, Vetter Pharma-Fertigung GmbH & Co. KG
The first edition of the Biopharmaceutical Manufacturing Facilities Baseline® 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 Biopharmaceutical 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.
Mark von Stwolinski, Vice President Facility Integration, CRB
Pfizer has recognized the need to develop more flexible manufacturing options for drug products. The presentation will address our approach to developing a portable, continuous and miniature manufacturing platform for tablets and capsules. With specific focus on integrating process analytical technology (PAT) and advanced process controls (APC) to ensure product quality is maintained in a continuous manufacturing process.
Brian Henry, Executive Director, Head of Drug Product Design, Pfizer
In this presentation, the ConsiGma™ continuous manufacturing platform will be discussed.
The system satisfies the pharmaceutical industry’s demand for continuous production to provide improved quality, flexibility, agility, consistency and cost reduction for pharmaceutical processes.
Topics that will be highlighted are among others the modularity, process and technical advantages when using ConsiGma™ technology for continuous powder dosing, inline blending, wet granulation, direct compression, tableting and coating.
Kris Schoeters, Product Manager Continuous Processing, GEA Pharma Systems
Niels Guldager, Senior Technology Partner, NNE Pharmaplan
Presentation gives and overview on the realization of the continuous manufacturing approach for commercial manufacturing of tablets at TEVA Operations in Germany. Following the project timeline from project design via installation and process qualification to commercial operation, the key success factors at the different stages are highlighted.
Frank Streil, Head of TSA (Technology & Scienticic Affairs), Teva
In this presentation the current industrial needs are determined in order to demonstrate that pharmaceutical companies are in compliance with regulation, self-identified procedures and business processes. Transparency of data used and generated in end-to-end supply chain functions and business processes is the new standard and regulatory expectation. Quick access to all compliance relevant data and reports is prerequisite for quality oversight and management awareness and responsibility, proactively and retrospectively.
This presentation will offer a new way to get this data while meeting the future needs of quality metrics. The approach is based on orchestrated systems like ERP, EQM, ECM and ExM and subsequently linked with cross-functional business processes. Finally, it is combined with the quality metrics metadata level, applicable to any existing IT landscape or architecture.
The presentation will cover a case study on the Merck new greenfield facility for Vaccine and Biologics Sterile Facility (VBSF) in Carlow, Ireland. This project was a category winner (operational excellence) in the 2013 ISPE FOYA. The VBSF Project delivered significant innovations in the facility and process design and demonstrated excellence in project execution. The team followed Lean Six Sigma methodology during design and project execution to deliver a flexible and expandable site that is aligned with the Supply Chain Network, is forward looking from a regulatory perspective, and is adaptable to the rapidly changing external environment. The design allows the simultaneous manufacturing of two separate products on individual filling lines, with shared infrastructure and support systems, while providing an ‘over the horizon’ facility of the future for the manufacture of life saving medicines.
Sarah Fitzgerald, Associate Director, Global Eng Svcs, Merck
Two main developments will impact future biopharmaceutical manufacturing concepts. First one to be named is the interest of the growth markets to have production sites in their regions. There are indications that in the long run decentralized supply chain concepts may be advantageous. Second one is the increasing pressure on drug prices. While cost of goods may not be the main contributor on the price of a drug, the pressure on manufacturing will still increase steadily. Both developments are asking for lower cost smaller size biopharma production concepts.
The efficiency of the biology has already increased significantly and allows for smaller size systems. Innovative production technologies offers single use solutions resulting in a rather simplified facility concept with no need for CIP and SIP systems. However until today all systems are operated in batch.
About two years ago Bayer Technology Services started to look into continuous processing of biopharma products. Target of the project was and is to build up a demonstrator which is fully integrated (upstream and downstream), fully single use and continuous. Such a system will allow to operate 24/7 and therefore lead to another significant step in reducing the required manufacturing space. Strictly single use applications allow to decouple the building from the process and guarantees a highly flexible system. Conti processing allows for a fully automated process - operation and product sampling.
This presentation will showcase the status of the project and will discuss what kind of anticipated benefits can be achieved and what kind of challenges of a fully continuous biopharma production line are still ahead.
Dr. Thomas Daszkowski, Vice President Process Development and Optimisation, Bayer Technology Services
In this presentation, Dr. Brendan Cuddy will outline the major regulatory developments from EMA perspective and what implications they might have for the Facilities of the Future.
Dr. Brendan Cuddy, Scientific Administrator, EMA
A discussion of the compliance issues facing sterile drug manufacturers and the need to relook at pharmaceutical quality within this sector of the industry.
Dara Corrigan, Director, Europe Office, FDA