Lyophilisation: Scientific Issues of the Process and Introduction to Risk-based Approach

3–4 December 2008
Barcelona, Spain

Seminar Leaders
Miquel Galan, Telstar Lyo (Spain)

Pierre Le Meur, SPEC Conseils (France)

A complete update on scientific and technical issues
Outline of new methodologies, processes and trends
Understand the regulatory expectations for lyophilisation and lyophilised products

Using a series of workshops and case studies, this comprehensive two-day seminar covers the key issues involved in applying a risk-based approach to lyophilisation. Covering theory and practice, sessions will combine specific aspects of risk assessment, identification of new technologies and techniques (including sterilisation methodologies, the development of PAT tools and new control methods) and trends in monitoring.

Taking a pragmatic approach to the problems and pitfalls of this complicated practice, speakers from a range of backgrounds and approaches – industry, suppliers and manufacturers – take a lifecycle approach to addressing some of the challenges and risks. Regulatory expectations, including the application of GMP Annex 1 are covered.

Speakers include industry experts, academics, practitioners, suppliers and manufacturers to give a full and rounded view of the latest technologies, tools and approaches.

Take Back to Your Job

An understanding of regulatory requirements involved in lyophilisation processes
New trends and approaches in controlling lyophilisation processes
Knowledge of how and when to apply risk assessment and risk control

Agenda

Wednesday, 3 December

10.00 – 10.15 Welcome and Introduction
Miquel Galan, Telstar (Spain)
Pierre J. Le Meur, SPEC Conseils (France)

10.15 – 11.00 Freezing: A Critical Step for Freeze-drying Cycle Development and Product Stability
Fernanda Fonseca, AgroParisTech/INRA (France)

Identifying stresses encountered during freeze-drying, and in particular during freezing. How to limit them?
Determining the critical events (nucleation) and temperatures affecting product stability and cycle efficiency
Improving product stability and cycle efficiency through formulation and/or process parameters
Exploring two kinds of bioproducts: proteins and bacteria

11.00 – 11.45 Regulatory Expectations for Lyophilisation and Lyophilised Products
J. David Doleski, FDA (USA)

Stay tuned for future session updates

11.45 – 12.30 Understanding, Monitoring and Controlling the Freeze-drying Process by Means of Model-based Tools and Computational Fluid Dynamics
Antonello A. Barresi, Politecnico di Torino (Italy)

Computational fluid dynamics and two-scale models can strongly help in improving the product uniformity of the batch
The model-based control can guarantee the quality of the product and reproducible process conditions
Detailed modelling of the apparatus can help to improve the reliability of the monitoring sensors (model-based monitoring) and thus of the control system, taking into account variable gradients in the chamber

12.30 – 14.00 Lunch and Networking Break

14.00 – 15.30 Workshop 1: Predicting the Operating Parameters of a Lyo cycle
Miquel Galan, Telstar (Spain)

Rationale
Choice of two ‘hands-on’ case studies - define complete cycle parameters
Participants will use the provided software tools

15.30 – 16.00 Coffee and Networking Break

16.00 – 16.45 Parameter Characterisation of a Lyophilisation Cycle
Enric Jo Cardoso, Reig Jofré Group (Spain)

Thermal principles and the thermal fingerprint in lyophilisation
Lyophilisation recipe: Application of the thermal outcomes
Procedure to define the process set points: From the formulation knowledge to the industrial plant, and the security zone
Different case studies: Shortening of cycles – how to avoid the bottom from breaking; how to face formulations with very low critical temperatures; comparison of different cycles

16.45 – 17.15 Questions and Answers, Close of Day 1
Miquel Galan, Telstar (Spain)
Pierre J. Le Meur, SPEC Conseils (France)

17.30 – 18.30 Networking Reception

Thursday, 4 December

9.00 – 9.15 Review of Day 1, Introduction to Day 2
Miquel Galan, Telstar (Spain)
Pierre J. Le Meur, SPEC Conseils (France)

09.15 – 10.00 Vials Class A Capping in the Lyophilisation Chamber
Philippe Legall, BIOCORP (France)

Crimp sealing: Regulatory compliance
Crimping options: Operational, quality, regulatory and marketing perspectives
Several packaging concepts provide means to crimp-seal vials in the freeze dryer meeting the regulation without a need for new equipment or clean rooms
Their design criteria, characteristics, implementation in a pharmaceutical operation and performance profile will be discussed and compared

10.00 – 10.30 Coffee and Networking Break

10.30 – 11.15 GMP Manufacturing of Highly Potent Freeze-dried Parenterals for Clinical Studies Phases I and II. The Feedback of a Pharmaceutical Contract Manufacturer
Maxime Laugier, MP5 Laboratory (France)

Manufacture of investigational medicinal products: Follow the lead of GMP Annex 13
A flexible and reliable manufacturing organisation to meet a wide range of process and highly potent products
Manufacturing of highly potent freeze-dried products: Presentation of some case studies
Some advice prior to clinical manufacturing of a highly potent parenteral freeze-dried product

11.15 – 12.00 Non Invasive Data Acquisition During the Freeze-drying Process
Pierre Chouvenc, Sanofi Pasteur (France)

Why the need for non invasive data acquisition during the freeze-drying process?
- Critical parameters during the process
- What are the limitations of invasive data acquisition?
Non invasive data acquisition
- Non exhaustive list of techniques available for R&D and industrial equipment
- Pros and cons from an industrial point of view
- Focus on manometric temperature measurement
Non invasive data acquisition to ensure freeze-drying process robustness

12.00 – 13.30 Lunch and Networking Break

13.30 – 15.00 Workshop 2: Risk Assessment
Pierre J. Le Meur, SPEC Conseils (France)

Audience being divided in several groups, each group will perform the risk assessment of part of typical lyophilisation equipment and will present the result to the other groups. Documentation about the equipment will be presented and assessed

15.00 – 15.45 Modern Freeze-drying Production Facility. Description and Technical Challenges
Ernesto Renzi, IMA EDWARDS (USA)

Project definition
Aseptic room classification
Equipment layout and material flow
Freeze-drying equipment main characteristics
Loading - unloading configuration
Project technical challenges

15.45 – 16.15 Questions and Answers, Close of Seminar
Miquel Galan, Telstar (Spain)
Pierre J. Le Meur, SPEC Conseils (France)


Conference Programme General Information Venue and Area Information Networking Evening Sponsorship Opportunities Table Top Exhibition Registration Information Download Brochure Current as of 18 August Delegates See the company and country background of already registered delegates !	Lyophilisation: Scientific Issues of the Process and Introduction to Risk-based Approach 3–4 December 2008 Barcelona, Spain Seminar Leaders Miquel Galan, Telstar Lyo (Spain) Pierre Le Meur, SPEC Conseils (France) A complete update on scientific and technical issues Outline of new methodologies, processes and trends Understand the regulatory expectations for lyophilisation and lyophilised products Using a series of workshops and case studies, this comprehensive two-day seminar covers the key issues involved in applying a risk-based approach to lyophilisation. Covering theory and practice, sessions will combine specific aspects of risk assessment, identification of new technologies and techniques (including sterilisation methodologies, the development of PAT tools and new control methods) and trends in monitoring. Taking a pragmatic approach to the problems and pitfalls of this complicated practice, speakers from a range of backgrounds and approaches – industry, suppliers and manufacturers – take a lifecycle approach to addressing some of the challenges and risks. Regulatory expectations, including the application of GMP Annex 1 are covered. Speakers include industry experts, academics, practitioners, suppliers and manufacturers to give a full and rounded view of the latest technologies, tools and approaches. Take Back to Your Job An understanding of regulatory requirements involved in lyophilisation processes New trends and approaches in controlling lyophilisation processes Knowledge of how and when to apply risk assessment and risk control Agenda Wednesday, 3 December 10.00 – 10.15 Welcome and Introduction Miquel Galan, Telstar (Spain) Pierre J. Le Meur, SPEC Conseils (France) 10.15 – 11.00 Freezing: A Critical Step for Freeze-drying Cycle Development and Product Stability Fernanda Fonseca, AgroParisTech/INRA (France) Identifying stresses encountered during freeze-drying, and in particular during freezing. How to limit them? Determining the critical events (nucleation) and temperatures affecting product stability and cycle efficiency Improving product stability and cycle efficiency through formulation and/or process parameters Exploring two kinds of bioproducts: proteins and bacteria 11.00 – 11.45 Regulatory Expectations for Lyophilisation and Lyophilised Products J. David Doleski, FDA (USA) Stay tuned for future session updates 11.45 – 12.30 Understanding, Monitoring and Controlling the Freeze-drying Process by Means of Model-based Tools and Computational Fluid Dynamics Antonello A. Barresi, Politecnico di Torino (Italy) Computational fluid dynamics and two-scale models can strongly help in improving the product uniformity of the batch The model-based control can guarantee the quality of the product and reproducible process conditions Detailed modelling of the apparatus can help to improve the reliability of the monitoring sensors (model-based monitoring) and thus of the control system, taking into account variable gradients in the chamber 12.30 – 14.00 Lunch and Networking Break 14.00 – 15.30 Workshop 1: Predicting the Operating Parameters of a Lyo cycle Miquel Galan, Telstar (Spain) Rationale Choice of two ‘hands-on’ case studies - define complete cycle parameters Participants will use the provided software tools 15.30 – 16.00 Coffee and Networking Break 16.00 – 16.45 Parameter Characterisation of a Lyophilisation Cycle Enric Jo Cardoso, Reig Jofré Group (Spain) Thermal principles and the thermal fingerprint in lyophilisation Lyophilisation recipe: Application of the thermal outcomes Procedure to define the process set points: From the formulation knowledge to the industrial plant, and the security zone Different case studies: Shortening of cycles – how to avoid the bottom from breaking; how to face formulations with very low critical temperatures; comparison of different cycles 16.45 – 17.15 Questions and Answers, Close of Day 1 Miquel Galan, Telstar (Spain) Pierre J. Le Meur, SPEC Conseils (France) 17.30 – 18.30 Networking Reception Thursday, 4 December 9.00 – 9.15 Review of Day 1, Introduction to Day 2 Miquel Galan, Telstar (Spain) Pierre J. Le Meur, SPEC Conseils (France) 09.15 – 10.00 Vials Class A Capping in the Lyophilisation Chamber Philippe Legall, BIOCORP (France) Crimp sealing: Regulatory compliance Crimping options: Operational, quality, regulatory and marketing perspectives Several packaging concepts provide means to crimp-seal vials in the freeze dryer meeting the regulation without a need for new equipment or clean rooms Their design criteria, characteristics, implementation in a pharmaceutical operation and performance profile will be discussed and compared 10.00 – 10.30 Coffee and Networking Break 10.30 – 11.15 GMP Manufacturing of Highly Potent Freeze-dried Parenterals for Clinical Studies Phases I and II. The Feedback of a Pharmaceutical Contract Manufacturer Maxime Laugier, MP5 Laboratory (France) Manufacture of investigational medicinal products: Follow the lead of GMP Annex 13 A flexible and reliable manufacturing organisation to meet a wide range of process and highly potent products Manufacturing of highly potent freeze-dried products: Presentation of some case studies Some advice prior to clinical manufacturing of a highly potent parenteral freeze-dried product 11.15 – 12.00 Non Invasive Data Acquisition During the Freeze-drying Process Pierre Chouvenc, Sanofi Pasteur (France) Why the need for non invasive data acquisition during the freeze-drying process? Critical parameters during the process What are the limitations of invasive data acquisition? Non invasive data acquisition Non exhaustive list of techniques available for R&D and industrial equipment Pros and cons from an industrial point of view Focus on manometric temperature measurement Non invasive data acquisition to ensure freeze-drying process robustness 12.00 – 13.30 Lunch and Networking Break 13.30 – 15.00 Workshop 2: Risk Assessment Pierre J. Le Meur, SPEC Conseils (France) Audience being divided in several groups, each group will perform the risk assessment of part of typical lyophilisation equipment and will present the result to the other groups. Documentation about the equipment will be presented and assessed 15.00 – 15.45 Modern Freeze-drying Production Facility. Description and Technical Challenges Ernesto Renzi, IMA EDWARDS (USA) Project definition Aseptic room classification Equipment layout and material flow Freeze-drying equipment main characteristics Loading - unloading configuration Project technical challenges 15.45 – 16.15 Questions and Answers, Close of Seminar Miquel Galan, Telstar (Spain) Pierre J. Le Meur, SPEC Conseils (France)

Lyophilisation: Scientific Issues of the Process and Introduction to Risk-based Approach

3–4 December 2008 Barcelona, Spain

Agenda

3–4 December 2008
Barcelona, Spain