Dr. Janet Woodcock’s exhortation (ISPE Annual Meeting, 7 November 2005) that 21st century life science manufacturers should be ‘maximally efficient, agile and flexible’ and produce high quality drug products ‘without extensive regulatory oversight’ has been widely reported as a wake-up call to our industry.
In June 2006, the EMEA called for nominations from companies to participate in the pilot phase of a worksharing exercise for Quality variations1. Worksharing is a key element in the revisions to the variations proposed by the European Commission, which are intended to streamline the process for making changes to Marketing Authorisations, reducing the regulatory burden and encouraging innovation2. The worksharing procedure is intended where variations to the same nationally authorised product are submitted to the different National Competent Authorities (NCAs). All NCAs are eligible i.e. potentially all 29 EU/EEA states could be involved in the procedure.
The ease in making process analytical measurements (typically spectroscopic) in manufacturing has provided a unique opportunity to obtain up-to-date information for making timely process correction decisions. At-line methods provide near-time information without the need for elaborate process control interfacing upfront. This approach works well for batch processing applications or unit operations when process decisions can be made during a defined operation. Effective use of at-line methods includes the measurement of raw materials, premix batches, or quality check point monitoring before finished product is sent to the finishing lines.
The biopharmaceuticals industry has undergone a number of revolutions in the past decade, not least the variety of ‘omics’ that focus on high throughput technologies to identify new product targets and can rapidly characterise those targets at small scale. However, it has been widely recognised that the technology used in the manufacturing of these in new products has lagged behind. In many respects, Process Analytical Technology (PAT) is a new ‘omics’ for biopharmaceutical manufacture.
Since the FDA revolutionary white papers in 2004, the industry has talked non-stop about the potential of PAT (Process Analytical Technology) and more recently, QbD (Quality by Design). These topics have found regular spots in conferences, press and internal company discussions. It has been widely stated that the benefits are potentially huge and that this way of developing and manufacturing life science products offers the opportunity to ‘catch up’ with other industries such as food and electronics, which have their processes down to a ‘science’ rather than an ‘art’.
The pharmaceutical industry has, for many years, operated in a special environment with strong regulation and patent protection. Production efficiency and yields have not, as in many other industries, been the major competition parameter and, as a result of this, pharmaceutical manufacturing has a low manufacturing performance compared to other industries.
The process analytical technology guidelines have been a hotly debated topic within the pharmaceutical industry ever since they were made public in 2004. This also holds true at Johnson & Johnson Pharmaceutical Research & Development (J&JPRD), Division of Janssen Pharmaceutical N.V. In recent years, the company has introduced PAT tools in its manufacturing operations and in its development organisation on a project-by-project basis. Several of these projects have resulted in a better insight into critical manufacturing processes and have led to significant optimisations.
This article discusses ISPE’s Product Quality Lifecycle Implementation (PQLI) initiative, which is to provide practical guidance for implementation of ICH Q8, Q9 and Q10. It represents the author’s individual opinion. It should be noted that PQLI is an evolving work area and so will continue to develop beyond the position explained at the time of writing this article.
European Pharmaceutical Review presents a comprehensive guide to PAT addressing the challenges and advancements that are impacting upon PAT implementation in 2008 and beyond.
ASTM Committee E55 formed in April of 2003 as a result of FDA’s GMPs for the 21st Century Initiative and the subsequent Guidance, “PAT – a framework for innovative pharmaceutical manufacturing and quality assurance.” Focusing on process understanding and flexible manufacturing, FDA encouraged the pharmaceutical industry to utilise the consensus standards approach to enable implementation of PAT principles into their manufacturing processes.
The FDA’s recent guidance regarding Process Analytical Technology (PAT) offers the pharmaceutical and biotech industries an unprecedented opportunity to leverage hard-won experience with scientific inquiry and innovation. However, the leap to PAT is significant for even the most rigorous development program. Many aspects of Six Sigma; including its use of statistical tools and its phase- or toll-gate approach to project management, can facilitate and accelerate a PAT initiative. Rather than advocating company-wide Six Sigma adoption as a prerequisite to effective PAT implementation, an eight-phase Design for Lean Six Sigma approach is recommended that can be used on a project-by-project basis.
Biopharmaceuticals are the fastest growing sector of the pharmaceutical industry1; with monoclonal’s being the key biopharmaceutical products representing a significant proportion of the current business focus. It is anticipated that this new generation of biopharmaceuticals will revolutionise clinical medicine over the next 5-10 years.
European Pharmaceutical Review brings you a comprehensive guide to the current developments and possible future innovations within Process Analytical Technologies.
Process analytical technology (PAT) and design science are interrelated; although the leading idea of PAT is to develop quality by design in the pharmaceutical manufacturing process. Surprisingly, few attempts have been made to apply fundamental design theory in keeping with the routine practices of other engineering disciplines.
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.
This case study provides a comprehensive look at Talecris1 Biotherapeutics’ approach to PAT and automation followed by examples of PAT deployed on a bioprocess. It introduces the concept of integrated and scalable automation, provides a comparison of automation concepts and explains how the selected automation effectively supports initiatives such as PAT.
Since its creation in December 2003, ASTM International Committee E55 on Manufacture of Pharmaceutical Products has grown in size as well as global relevance. Recent liaison relationships have been established with the ISPE and the European Compliance Academy (ECA) regarding their internal distribution of E55 draft standards for the purpose of gathering member feedback and, in September 2006, several E55 officers addressed the European Medicines Agency (EMEA) with the goal of creating a similar relationship.
Is the pharmaceutical manufacturing environment of today becoming more challenging? There is increasing pressure to control or reduce costs because of the limitations on healthcare budgets. Asset utilisation, operating efficiencies and cycle times in the pharmaceutical industry generally compare unfavourably with other high technology industries. Despite the resources invested in compliance, many companies continue to struggle to meet the regulatory requirements, as evidenced by warning letters and consent decrees.
So far in 2006 we have published contributions on a variety of PAT-related topics, including training (Issue 1), NIR (Issue 2) and the role of PAT in biotechnology (Issue 3). In this article Jean-Marie Geoffroy reports on the business case for PAT with his own interpretation and charts the road ahead.
Product quality of pharmaceuticals manufactured in biotechnology processes is to a large extent synonymous with the reduction and control of unwanted biological side-products. Production of biopharmaceutical proteins and secondary metabolites such as antibiotics are the result of biosynthetic capacity of the microbes or cells used. But this capacity may also contribute to turn the product molecules into molecular forms unacceptable in the final product, form side-metabolites that could harm the cell physiology and release contaminating cellular components. The main task for the ensuing process steps, the downstream procedures, is to reduce these impurities to acceptable levels that comply with the regulatory quality criteria.
APACT 06 is organised by the Centre for Process Analytics and Control Technology (CPACT), and is designed to be an open forum for the presentation and discussion of recent advances in engineering and scientific topics relevant to process analytics and control technologies.
Due to the need for improvement in the cost structure and efficiency of the pharmaceutical industry, the introduction of NIR analytical techniques in combination with PAT applications is a promising opportunity for cycle time reduction and machine utilisation increase.
There can be no doubt that the FDA’s initiative on Process Analytical Technologies (PAT) has had an enormous impact on the pharmaceutical industries. However, the emergence of ’born again‘ PAT devotees in pharma companies has caused mild amusement in other industries where on-line analysis has been an integral part of process monitoring and control for a long time.
Optical techniques can not address every application need, so the well-equipped PAT toolbox must include a broad array of technologies. One analytical tool that has been less-published but no less useful than the optical methods is mass spectrometry. This article provides a brief review of some of the published uses of process mass spectrometry, and provides some specific examples from the authors’ labs that demonstrate the value and utility of this technique.
While the current attention and focus on Process Analytical Technologies (PAT) may make you believe otherwise, PAT measurement systems have been used in the pharmaceutical industry, Pfizer included, for some time, albeit often to a limited extent.
The pharmaceutical industry plays a major role in the lives of individuals by providing critical therapeutic medicines. This places the industry in the public eye, as does drug pricing, safety and efficacy, the stock markets and courting with several different regulatory bodies, with differing legal requirements, around the world. The industry also employs, directly and indirectly, large numbers of people.
