Prof Dr Thomas de Beer, University of Ghent
Dr Ranjit Dhenge, GSK
Dr Giustino Di Pretoro, Johnson & Johnson
Dr Sau (Larry) Lee, FDA, Deputy Director; Emerging Technology Team Chair, US FDA
Roger Nosal, Pfizer
Dr Salvatore Mascia, Continuus Pharmaceuticals
Nuno Matos, Hovione
Dr Moheb Nasr, Nasr Pharma Regulatory Consulting & formerly FDA
Dr Frank Streil, TEVA
It is the aim of this conference to show how a transition from batch to continuous manufacturing for small molecules can look like.
Questions regarding technology, process development and GMP/Quality Assurance and Regulatory Affairs will be discussed.
Solid dosage forms are still the most common dosage form, first and foremost tablets without any pioneering developments in the recent years. But driven by only a few pharmaceutical companies more and more of the global players started to invest in continuous manufacturing. Companies like GSK, Pfizer; Johnson & Johnson and Vertex have been in the news lately. A shift from batch to continuous manufacturing could be one of the largest paradigm changes since the system of validation & qualification came up years ago.
Continuous manufacturing is data driven and by gaining this flood of information two topics become very important: process control and process monitoring. A vast amount of data has to be evaluated in order to control the process and to decide whether material can be collected or has to be rejected.
Regulating authorities, first of all the FDA, also encourage the transition from batch to continuous production. They expect an increase in product safety while equipment suppliers promote a decrease of production costs. But with a continuous mode of operation new and already answered questions raise:
- How should a batch be defined? Is there a difference between lot and batch?
- What risks does a continuous process involve?
- How can a continuous line look like?
- Which concepts are conceivable for continuous processes
- How can a continuous process be kept in a controlled state?
- How is a continuous system validated?
- How to determine the ResidenceTimeDistribution – what about material traceability?
- How should deviations in a continuous process be handled?
Listen to companies who already did the transition and learn about advantages / disadvantages and how they answered the questions above.
This conference is directed at
- Decision makers dealing with the question whether continuous manufacturing should be implemented
- Executives from engineering, production and QA responsible for the implementation of continuous manufacturing
Regulatory considerations of continuous manufacturing
Past, Present and Future for Continuous Manufacturing: FDA/CDER Perspective (remote presentation)
Global Regulatory Implementation of Continuous Manufacturing
- The progress that FDA has made in CM will be discussed
- The current expectations will from FDA will be highlighted: Submission review, Facility evaluation
- The recent trends and future challenges will be described
Regulatory Experience with Manufacturing Innovation including Continuous Processes
- Impact of current regulatory system on implementation of CM
- Points to consider prior to the implementation of CM
- Filing requirement and expectations – Global perspective
- Remaining regulatory challenges
- Future regulatory guideline – ICH and regional
- Innovation can improve, manufacturing capacity, process efficiency & quality assurance. However global regulatory trends have been a barrier to innovation. Global implementation is increasingly confronted by punitive rather than incentive-based regulatory expectations.
- Acceleration only increases the challenge for CMC development & sustainable product commercialization
- This presentation describes regulatory experience, opportunities & challenges, with manufacturing innovations including continuous manufacturing
Development & control of continuous processes
PAT for model based design, optimization, monitoring and control of continuous manufacturing
Control Strategies in Continuous Processing – taking control to the next level”
- Linking a raw material property data-base to the performance of the unit operations of a DC line
- PAT for process understanding & process modeling of continuous manufacturing technologies
- PAT for process monitoring & control of continuous manufacturing
- Model based PAT implementation
- Model based design of continuous manufacturing technologies
Adoption of a batch oriented QA system to Continuous Manufacturing
- Update on the Janssen’s journey to Drug Product Continuous Manufacturing
- Control Strategies in Continuous
- Residence Time Distribution in the control strategy
- How stable is a CM process? – development insights on the first Janssen’s NME in continuous manufacturing
- Batch definitions
- Validation of continuous processes
- Handling of deviations
- Batch release
Technology & Equipment
In this part, practical solutions for continuous manufacturing will be presented and explained by selected suppliers.
In continuous processing various unit operations get seamlessly combined. One of the most critical steps is the preparation of the feed material for the tablet presses. In this chapter/session key vendors explain concepts both for
- Continuous mixing and direct compression
- Continuous granulate drying
Additionally it is discussed how these can be by combination with further up- and downstream processes such as dispensing, compression and coating, further developed into fully Integrated continuous manufacturing lines
Rainer Lemperle, Director of Sales, Gebrüder Lödige Maschinenbau
Dr Robin Meier, Manager Scientific Operations, L.B. Bohle
Dr Harald Stahl, Group Director Application & Strategy Management, GEA
Pharmaceutical Case Studies
Case Study TEVA: Continuous manufacturing of direct compression tablets
Case Study GSK: Continuous Tablet Manufacturing using Wet Granulation
- Implementation of CM in commercial manufacturing
- Field report - Challenges and Benefits of CM
- Experience gained
- Introduction to Continuous Tableting Line (CTL): Twin screw granulation
- Design selection considerations for twin screw granulation
- Process development and scale up and operations challenges on CTL
- Considerations for development of platform control strategy
- Current status and challenges for automated testing to enable real time release
Continuus Pharmaceuticals: Integrated continuous manufacturing with novel technologies
The development of novel manufacturing technologies has the potential for reaping the full benefits of continuous manufacturing. Moreover, their integration into a modular plug-and-play, end-to-end continuous manufacturing process, including both chemical and pharmaceutical operations, i.e. integrated continuous manufacturing (ICM), can open a new manufacturing paradigm for this industry.
The development of an integrated control strategy for ICM is crucial to ensure release of pharmaceutical products that conform to specifications. ICM relies on proven principles of quality by design and the use of process analytical technologies to monitor and control the manufacturing operation.
ICM will enable “on-demand” manufacturing of pharmaceuticals: high quality medicines will be produced quickly when needed, and a significantly reduced cost.
- Layout motivations for changes in pharmaceutical manufacturing
- Identification of the need for improving quality in pharmaceutical manufacturing
- Presentation of a case study on end-to-end (chemical + formulation) integrated continuous