Lyophilization – Modern Techniques & New Requirements

Objectives

Take advantage of the opportunity to focus on freeze drying technologies and processes and get a first-hand demonstration of solutions for diverse requirements. Further, you will learn how the freeze drying output is affected by different equipment, parameter changes, solvents, etc.

Registration

Background

Lyophilization (or freeze drying) is one of the most exciting technologies in the pharmaceutical industry, although it is a very old process for the preservation of unstable materials. Trends are growing towards using non-aqueous systems.
Additionally, Process Analytical Technology (PAT) / RTRT (Real Time Release Testing, Annex 17 of the EU GMP Guide) systems for in-line process monitoring are used to control and determine critical processing parameters. PAT plays also an important role in continuous lyophilization processes. According to ICH´s new guideline Q13 “continuous manufacturing (CM) has potential for improving the efficiency, agility, and flexibility of drug substance and drug product manufacturing”. Regulatory agencies have seen more companies engaged in the development and implementation of CM in recent years than in the past.
Modern QbD (Quality by Design) development following ICH Q8, Q9 and Q10 is based on the objective to design a lyophilization cycle applying a systematic and scientific approach instead of trial and error. Sufficient process understanding is essential to achieve a robust production process and efficient handling of post-approval changes (life cycle management according to ICH Q12) of a freeze-drying process.
There is an increasing trend in aseptically produced lyophilized products, including peptides and proteins. Owing to the nature of these biological products, the lyo-cycle is more complicated and, in most cases, even longer than for other medicinal products.
The utility of lyophilization goes far beyond the vial. Principles of low temperature, low pressure can be applied to stabilize substances ranging from high potent APIs, novel medical devices, biologics and nanomaterials, freeze drying offers multiple opportunities.

Target Audience

This conference addresses specialists and executives working in the fields of pharmaceutical manufacture, research and development and quality control, as well as engineers, project/facility engineers, especially those involved in the implementation of new monitoring methods for controlled nucleation, risk-based scale-up models and process technology for freeze drying processes. The conference is also of interest for participants working in the areas of container development and manufacturing process/packaging.

Moderator

Dr Ingrid Walther, Pharma Consulting Walther

Detailed Programme

Tuesday, 19 March 2024

Regulatory Overview, Annex 1 Impact and Inspection Experience
Dr Frank Sielaff, Hessian State Office of Health and Care, Germany

  • Regulatory framework (EU), impact for Lyo-Products
  • Impact of new Annex 1
  • Inspection experience

Process Validation of Lyophilized Products and ongo-ing Lifecycle Verification
Dr Andrea Weiland, ExplicatPharma

  • Critical quality attributes (CQAs) and critical process parameters (CPPs):
    • Assessment of CPPs through robustness testing to establish the process boundaries as the basis for the transfer from lab to commercial scale
  • Freeze drying scale-up and validation:
    • Process qualification/validation in lyophilization strategies in relation to FDA/EMA modern process validation guidelines
  • Process control strategies:
    • Hot and cold spot determination to allow for process control by using a product temperature PAT device

Lyophilized Plasma Products - Experience and Technical Challenges in Refrigeration
Frank Heck, CSL Behring

  • The operator's point of view:
  • Freeze technology through the ages
  • Freeze drying, but please climate friendly
  • Plate cooling and the requirements for technical components in the product environment
  • Methodologies for condition-based technical monitoring
  • Outlook

Atmospheric Spray Freeze Drying
Prof Alf Lamprecht, University of Bonn

  • Process understanding, monitoring & control
  • Design of continuous lyophilization

Continuous Freeze Drying
Dr Friedrich Haefele, formerly Boehringer Ingelheim Pharma

  • Freeze drying in Food and Pharma
  • Market survey
  • Batch process lyophilization
  • Applications for continuous lyophilization
  • Outlook

Improving the Sustainability of Pharmaceutical Freeze Drying
Dr Benjamin Ledermann, GEA
Thomas Beutler, GEA

  • Natural refrigerants
  • Microwave-assisted freeze drying
  • Atmospheric spray freeze drying
  • Drying time reduction
  • GWP reduction

Wednesday, 20 March 2024

Vials and Stoppers for Lyophilization
Francis Carroll, West

  • Primary packaging aspects for lyophilization
  • Considerations for lyo stoppers
  • Considerations for lyo vials
  • Volatile Extractables
  • EU GMP Annex I

Container Closure Integrity
Matthias Schaar, Novartis

  • Applicable CCIT and Process Analytical Technologies via non-destructive methodologies
  • Examples

Aseptic Process Simulation (Media Fill)
Alexandra Stärk, Novartis

  • Media Fill Design
  • Worst-case parameters for Media Fills
  • Validation of lyophilization processes with Media Fills
  • Requirements for Media Fills
  • Trends with regards to Media Fills

Annex 1 Upgrade of Aseptic Filling and Lyophilization of Parenterals in RABS
Dr Tino Galgon, Lyocontract

  • GAP analysis in relation to the new Annex 1
  • Risk-based determination of monitoring points for the B area
  • Risk-based upgrade of monitoring in the aseptic core zone (RABS)
  • Implementation of a new stopper sterilization and drying system
  • Integration of a glove lifecycle including testing, cleaning and sterilization

Aseptic Lyophilization with the Help of Protective Membrane Bags
Rolf Lenhardt, Teclen

  • Annex 1 requirements for aseptic lyophilization processes
  • Lyophilization protection with membrane technology for vials
  • Sterile bagging unit for small sterile batches with open RABS or Isolator
  • Are pilot freeze dryer without CIP/SIP suitable for aseptic processing in combination with sterile bagging unit
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