The Reality of Continuous Pharmaceutical Manufacturing

Taking place on 26–28 March 2019, GEA, Siemens and Perceptive Engineering will host an inaugural three-day conference to examine the fact and fiction of continuous manufacturing (CM) in the pharmaceutical industry.

The event will comprise two days of presentations from early adopters, one of which will take place at the National Formulation Centre in Sedgefield, UK, courtesy of the Centre for Process Innovation (CPI), and a chance to visit the MSD, Cramlington plant, who have recently installed a CDC 50, two ConsiGma™ Coaters, a Bruker Tandem and are utilising Siemens PAT technology.

With an expected attendance of 80–120 delegates and focusing on the real-life experiences of existing users of CM technology in the development and manufacture of oral solid dosage (OSD) forms, topics on the agenda will include the current status of “going conti” as well as future plans and expectations.

Confirmed speakers include representatives from 

AstraZeneca – Bayer – CMAC – GSK – Janssen – MSD – RCPE – UCB Pharma – University of Sheffield

(find more details in the TAB above).

To promote awareness of the benefits of continuous manufacturing in the pharmaceutical industry and spread the word as far as possible, we're delighted to offer free attendance at the this event. Delegates are, however, required to cover their own travel and accommodation costs. Hotel reservation information is available on the registration page [LINK] and taxi transfers from Newcastle International Airport can be booked.

Register now >>

GEA has been pioneering continuous manufacturing (CM) solutions for the past 14 years and helping customers to develop, evaluate and optimize continuous processing techniques to enable them to bring new products to market faster and cheaper.

Perceptive Engineering develops and deploys advanced analytics and intelligent control systems to blue-chip clients around the world.

Siemens is a world-leading provider of digital solutions for the entire value chain and, in particular, of PAT Data Management platforms for continuous pharmaceutical manufacturing.

Now gaining momentum in the pharmaceutical industry, CM presents a new approach to OSD form production and meets the industry’s demands for faster product development, reduced costs and increased manufacturing flexibility.

Providing higher yields, lower utility consumption and reduced waste, CM is enabling drug makers to move away from stepwise and time-consuming batch processing to a fully integrated and closely controlled process that gives excellent product consistency by intrinsic design.

The use of CM technologies and inline PAT monitoring is a key driver of building quality by design (QbD) into the complete product lifecycle, from R&D through to manufacturing, with the ultimate aim of getting safer medicines to market in a more efficient and cost-effective way.

Using model-based supervisory advanced process control (APC) to capture unique equipment, material and PAT characteristics creates a system that increases precision and optimizes the yield, capacity and OEE of the CM equipment.

Environmentally friendly with a much smaller footprint, CM is helping the pharmaceutical industry to produce higher quality products, enhance drug safety and reduce its industrial footprint, which provides significant advantages to governments, companies and patients alike.

Further information to follow.

DEVELOPMENT AND CONTROL STRATEGIES FOR A CONTINUOUS DIRECT COMPRESSION PROCESS
Bernd Van Snick, Scientist, Continuous manufacturing - Janssen

GSK R&D PERSPECTIVES OF PAT FOR CONTINUOUS API AND DRUG PRODUCT MANUFACTURE
Ian Barylski, Scientific Leader R&D PAT team - GSK

In common with most other pharma companies GSK is developing continuous processes for both API and drug product manufacture. This presentation will give an overview of some of these processes and the PAT applied to them. The benefits, barriers to implementation and thoughts on the future direction of PAT will also be shared.

CONTINUOUS MANUFACTURING RESEARCH: PROGRESS & PITFALLS
Professor Alastair Florence, Director of the EPSRC Future Manufacturing Research Hub - Continuous Manufacturing and Advanced Crystallisation (CMAC)

Continuous manufacturing is seeing increased adoption in industry with a number of products now supplied via this approach. With a wide range of capabilities available for flow synthesis, workup, crystallisation, isolation, drying, formulation and secondary processing of finished product available across lab and commercial scales there is increasing focus on the successful integration of unit operations, coupled with robust modelling, online measurement and advanced control techniques. The talk aims to provide an overview of developments in continuous manufacturing research, highlighting recent progress across continuous drug substance and drug product processing activities with updates from the industry demand led research programme at the UK Continuous Manufacturing and Advanced Crystallisation (CMAC) Manufacturing Research Hub. The challenges and opportunities arising from increased need for digital design and manufacturing methods will be highlighted as well as selected areas where scientific and technological gaps remain.

ONLINE-MONITORING OF CONTINUOUS PHARMACEUTICAL PRODUCTION PROCESSES AT BAYER AG
Dr. Sven-Oliver Borchert, Technology Expert Process Performance Improvement - Bayer

Continuous processing presents a promising technology for the manufacturing of pharmaceutical products. Higher flexibility, smaller facility footprints and deeper process insight are some of the advantages of this production mode. However, compared to classical batch pro-cesses, online-monitoring of critical quality attributes (CQAs) in continuous processes is essential for a reliable operation. To this end, two examples which outline the potential of SIMATIC SIPAT for the implementation of monitoring CQAs will be presented.

1st Example: Bayer´s MoBiDiK platform focuses on the purification of monoclonal antibodies (mABs). MoBiDiK stands for modular, biological, disposable, and continuous. Single-use technology and aseptic connections between unit operations offer superior protection against bioburden ingress and other forms of contamination. Furthermore, the technology offers the potential for tight control of critical process parameters (CPPs). A high degree of automation reduces the risk of operator induced errors, thus improving quality assurance. Chromatography systems for capture and purification of the mABs are integral parts of the process. Asymmetry factor (AF) and height equivalent to theoretical plates (HETP) are commonly used as indicators for column performance. Results of an online data analysis for monitoring column integrity will be presented.

2nd Example: ConsiGma 25 is a technology platform provided by GEA for continuous production of oral solid dosage (OSD) forms. It combines the process steps: twin-screw granulation, blending, tableting and film coating. Bayer is going to use the technology in a launch facility for R&D and GMP purposes. As an important part of the quality control strategy, blend uniformity is estimated from spectral NIR measurements. In this case, SIPAT will be used to enable a process control strategy based on spectral measurements. A concept will be presented which demonstrates how Bayer is going to implement a closed-loop quality control for the continuous manufacturing plant.

BUILDING A FACILITY BASED UPON CONTINUOUS MANUFACTURING FOR OSD
Dr. Franco Colacino, Process Engineering Manager - UCB Pharma

Design of the continuous manufacturing line

• Review of available options for line subparts, pro and con, assembly
• Design of the control strategy in the prospect of Real-time Release implementation, considering the Drug product specification
• Design of the PAT instrumentation according to the control strategy

Design of the facility

• Room layout and facility organization for GMP manufacturing
• Utilities and HVAC
• Design of the IT architecture to manage the Continuous Manufacturing line and IPC

 Lessons learned during the project execution, equipment installation and qualification, building the facility and its qualification.

TBA
RCPE - Massimo Bresciani, Executive Director, Scientific Operations

INTRODUCTION TO CPI AND ITS NATIONAL FORMULATION CENTRE AND OUR ROLE IN ENABLING INNOVATION IN THIS SPACE.
Dr Graeme Cruickshank, Director of CPI’s National Formulation Centre - National Formulation Centre

Overview of capabilities developed to de-risk innovation journeys in continuous learning and spark horizontal innovation across the formulated goods sector and in particular tools to better enable understanding and control of continuous manufacture in the formulated products industry.

TOUR OF NATIONAL FORMULATION CENTRE

CONTINUOUS MANUFACTURING OF PHARMACEUTICAL PRODUCTS: DIAMOND INTEGRATED PILOT PLANT DiPP- THE UNIVERSITY OF SHEFFIELD
Dr. Chalak Omar, Research Associate, Particle Products Group - University of Sheffield

Manufacturing of formulated products in the pharmaceutical industry involves a series of unit operations which are traditionally operated in batch mode. The history of research in granulation of pharmaceutical products started with limited knowledge and understanding of the mechanisms happening during the process. With the development in research in the last two decades, more and better knowledge was then gained on processing of formulated products, e.g. the creation of regime map, PAT tools and the development of characterisation techniques, etc. Nevertheless, batch mode is still known to be time-consuming, labour-intensive, difficult to control. Recently, continuous manufacture of formulated products in the pharmaceutical industry has become increasingly popular. The growing interest in continuous processing has arisen from the change in the regulatory environment and the need to reduce both R&D and manufacturing costs to improve process control and provide more affordable drugs. The University of Sheffield has made a significant investment in expanding the current facilities in the pharmaceutical powder processing to build a two-floor pilot plant with integration of all unit operations [powder feeding, twin screw granulation, drying, milling, blending and tableting] required for the continuous pharmaceutical solid oral dosage form manufacturing. This is a continuous powder to tablet line, coupled with PAT tools, and it is used for research, teaching and training purposes in the brand new £86m flagship building ‘Diamond’. This is a unique continuous powder-tablet line based within UK academia, which give students a strong hands-on experience in undertaking chemical engineering experiments and reinforce the basic principles. It is also providing an exclusive platform to unite and integrate the expertise in the area of pharmaceutical solids manufacturing and address the challenges in the field.

AstraZeneca – TBA 

MSD – TBA

A chance to visit the MSD, Cramlington plant, who have recently installed a Continuous Direct Compression (CDC 50), two ConsiGma™ Coaters, a Bruker Tandem and are utilizing Siemens PAT technology. (limited places available).