EuPAT: an initiative to promote progress in the science underpinning PAT

A new initiative launch has been announced that aims to promote progress in the science underpinning Process Analytical Technology. The core purpose of the EuPAT meeting is the creation of an open and neutral scientific forum for sharing and discussing new findings in cutting-edge scientific research, development of enabling technologies and development of innovative applications. Building on the successful EuPAT1 conference in Gothenburg, November 2006; the EuPAT2 conference has been announced for November 2007 in Copenhagen.

Background

Fundamental scientific understanding of processing and manufacturing is pivotal for Europe in the facilitating of continuous improvements, and the sharpening of competitiveness within the processing industries. These include the following industry areas; Pharmaceutical; Food; Agrochemical; Paper and Pulp and the Fine Chemical industries. In recent years, it has also been highlighted that a holistic approach to process, quality and logistics is key in strategies for driving improvements in efficiency and effectiveness. In addition, the holistic approach to processing and manufacturing also applies to the entire product and process life cycle; from design through to manufacturing.

The availability of enabling technologies and multidisciplinary scientific/engineering approaches is therefore a prerequisite for success when building quality into processing and products. This rests heavily on the access to a science platform from which to develop new tools and methods to enable predictability of product design, manufacture and quality. In this context, and specifically in the Pharmaceutical Industry, an integrated systems approach to process design, analysis, and control has been referred to as Process Analytical Technology (PAT). Indeed, in the US, FDA issued the PAT guidance 20041 with the aim of encouraging innovation within the manufacture of drug products. Consequently PAT has been recognised as a strategic area of new technology that can have a major impact on the pharmaceutical industries’ future methods of operation1,2. In addition, it has also been featured in significant recent changes to the regulation of drug product quality; for example the ICH guidance Q8 on pharmaceutical development that, based on a quality by design philosophy; comprises the new regulatory concepts, PAT and Design Space. Moreover, both the ICH Q8 guidance and the new ICH Q9 guidance on Quality Risk Management constitute key elements of a modern Quality System, which is the scope of another emerging ICH guidance, Q10. Interestingly, an EFPIA expert group also recently discussed the application of these new concepts on PAT3. By developing a MOCK submission for a fictitious tablet product, they demonstrated new possibilities for a method of implementing a PAT based approach to pharmaceutical development.

In spite of these recent important developments in Regulation, it is interesting to reflect that the scientific basis of PAT is not new; it builds on a framework which was already available in the mid 1980s; an example is Kowalski’s reference to this concept as ‘Process Analytical Chemistry’ (PAC)4. Though it is beyond the scope of this particular paper to discuss the general history of Process Analytics in the pharmaceutical industry, this restrospective insight confirms that it takes an astonishingly long time for new scientific findings and technologies in the field of process analytics to be adopted in a highly regulated environment.

Why is there a need for a EuPAT initiative?

In Brief: for successful implementation of holistic science-based methods of designing and manufacturing products, that is, using PAT based approaches. This rests on the availability of reliable tools, proven science based methodology and people with appropriate training and skills. In any PAT based approach ‘Process’ and ‘Analytical’ encompass an integrated scientific and engineering philosophy accommodating multidisciplinary competencies such as: chemistry, physics, material science/structures, biotechnology/microbiology, mathematics/computation, risk analysis and engineering. For PAT approaches in practise, achieving in-depth process understanding is vital, this requires fundamental knowledge of materials, processes and interactions. To clarify the rationale behind the EuPAT initiative; Figure 1 depicts the way in which PAT science underpins the use of specific PAT tools such as those for measurement. To enable innovation in the greater inter-disciplinary area of PAT science, it is continually important to strengthen the research base and the core competencies in individual subject areas. The simple thinking behind this is that innovation and new thinking feeds from fundamental and mechanistic understanding/knowledge. Clearly, continuous progress and achievement of true multidisciplinarity in the science areas underpinning PAT will benefit from establishing collaborative networking. Ideally, this networking should link ‘new thinking’ to ‘design and manufacturing science’, and to PAT implementation. In particular, by acting as a resource and ‘neutral’ debating forum they can stimulate and promote fundamental scientific/engineering research and innovative approaches in PAT, delivering science into the public domain for the benefit of all, including users and communities. As such, this forum should be ‘neutral’ to nurture and catalyse research, innovation and debate.

The EuPAT Mission

Based on the rationale for PAT science, as described in the previous section, the mission of the EuPAT Conference Series was developed through interdisciplinary networking. The purpose of the EuPAT is to unite scientists, engineers and other specialists in the various scientific fields underpinning PAT to encourage innovation, promotion and scientific discussion. The EuPAT conference series should be a meeting place for sharing and discussing new findings in cutting-edge scientific research, development of enabling technologies and development of innovative applications. The multidisciplinary scientific approach in focus for the EuPAT conference series expects participation from a range of disciplines such as process and chemical engineering; analytical chemistry; material science; modelling; and knowledge engineering.

In an attempt to conceptualize the scientific cornerstones that enable the application of PAT, and on which the EuPAT initiative is built, at least four scientific areas where identified that cut across any branch of application. These four scientific cornerstones are depicted in Figure 2 together with three typical branches of applications, which are physical, chemical and bioprocessing. The four cornerstones which require discussion and promote cutting-edge scientific research, development of novel enabling technology, development of innovative applications and methods are:

• Information-rich process sensors
• Advanced process and in-process material characterisation
• Process modelling, simulation and control
• Real-time process and quality informatics

From EuPAT1 towards EuPAT2

The first EuPAT conference was successfully held in Göteborg, Sweden, on November 21-22, 2006. More than 100 delegates from 13 countries in Europe gathered together in an informal, open atmosphere. Scientific discussion and debate sparked from lectures, poster presentations and through networking . The first EuPAT conference also became a reality through pioneering initiatives from the European PAT Science Network of the European Federation of Pharmaceutical Sciences (EUFEPS) and the Nordic Affiliate of the International Society of Pharmaceutical Engineering (ISPE), supported by the ISPE Community of Practices (CoP) of PAT. Both acting as key sponsors, together with additional co-sponsors. This in itself demonstrates how bridges are built between key communities such as Pharmaceutical sciences and Engineering sciences.

Building on the success and learning from EuPAT1, a new forum for scientists and engineers, dedicated to encouraging and promoting progress in the science behind PAT is now emerging as an annual event. In November 13-14, 2007, the EuPAT2 conference will be organized in Copenhagen, Denmark. The scientific cornerstones as depicted in Figure 2 will continue to constitute the core potential of this meeting place. In addition, for EuPAT2, special focus will be placed on the progress within these areas for bioprocessing. It is noteworthy that the scientific discussion and debate at EuPAT aims to be purely science focused and is therefore not limited to Pharmaceutical processing applications only; it aims at going beyond the traditional application branch boundaries.; the same PAT science for bioprocessing is often equally relevant for applications in Pharmaceutical and Food Industries. For information and contact details for the EuPAT2 Conference, visit the web sites of EUFEPS and ISPE Nordic: www.eufeps.org and www.ispe.org/nordic, respectively.

References

1. http://www.fda.gov/cder/OPS/PAT.htm
2. http://www.emea.eu.int/Inspections/ PAThome.html
3. C. Potter, S. Folestad, R. Beerbohm, G. Muirhead, S. Roenninger, A. Coupe, A. Swanson, F. Erni, G. Fischer, A guide to EFPIA’s mock P.2 document, Pharmaceutical Technology International, 18(12) 39-44 (2006).
4. J.B. Callis, D.L. Illman, B.R. Kowalski, Anal. Chem., 59 (1987) 624A-635A.

Prof. Peter York

Professor york’s research focuses on drug delivery and ‘molecular pharmaceutics’ in which definition and description of the molecular detail of pharmaceutical materials provide the basis for predicting their properties and processing characteristics important in the design of drug delivery systems. Information from molecular modelling and chemical structure coupled with crystallographic knowledge give molecular architecture and surface detail. A wide range of high resolution solid state, surface, particle and mechanical testing apparatus, as well as processing equipment, is available to test predictions and evaluate materials. Recent research includes work with supercritical fluids, using molecular organics, polymers and biologicals, this has provided breakthrough manufacturing processes for controlled particle formation. This is a key enabling technology which provides creative opportunities for extending ‘molecular pharmaceutics’ concepts into crystal engineering, particle design for drug delivery and biopharmaceutics.

Rasmus Bro

Teaching

• Advanced Chemometrics – Ph.D. course on multi-way analysis
• Food quality – aroma, sensometrics and chemometrics (Danish)
• Matlab courses
• Netmaster in statistics
• Industrial chemometrics course (Danish)
• Nordic Institute for Chemometric Education (NICE)

Current Projects

• ODIN – industrial consortium
• Mathematical resolution of complex chemical measurements
• Cheese monitoring during storage by fluorescence spectroscopy and chemometrics
• Tri- and multi-linear methods for Signal Processing In Communication
• Flavour and taste in vegetables
• Datamining in the herring industry
• Blind PARAFAC Antenna Receivers for DS-CDMA Systems
• ERCIM working group on Matrix Computations and Statistics

Prof. Staffan Folestad

Prof. Staffan Folestad obtained his PhD. in Chemistry from the University of Göteborg in 1985. As an Associate Professor he directed research activities comprising development of Capillary Separation Techniques, Laser-Based Spectroscopy and Ultra-Trace Analysis. In 1994 he joined AstraZeneca (ex Astra Hässle); in his role as a Senior Principal Scientist he has been leading global R&D activities in Process Analytical Technology (PAT) for the past decade. As a Leader for the AZ Center of Excellence for PAT his research comprised development of advanced in-situ Process Sensors and in silico Process Modeling. Between 1999 and 2006, he held a part time position as Professor in Analytical Chemistry at Uppsala University. Among several external appointments he is a member of the Royal Swedish Academy of Engineering Sciences, as well as a board member of the Center for Chemical Process Engineering at Chalmers University of Technology, and has been a member of the EFPIA PAT Topic Group.