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Parenteral Drug Association Connecting People, Science and Regulation ®

Freeze Drying in Practice

Mar 25 - Mar 29, 2019 |
Mar 29, 2019 |
Martin Christ Gefriertrocknungsanlagen GmbH | Osterode am Harz, Germany
  • Education
  • Europe
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Freeze drying, also termed lyophilization or sublimation drying, is a gentle drying technique. It has been used in the pharmaceutical industry for many years to improve the stability of medications.

Biopharmaceuticals in particular require an especially gentle manufacturing process due to their complex andthermosensitive molecular structure. In this regard, freeze drying represents the method of choice for improving storage stability of biopharmaceuticals, which is insufficient in the liquid formulation. While presently already approx. 60% of these products are freeze dried, a further increase in this percentage is to be expected in the coming years..

A freeze drying process is divided into three stages: freezing process, primary drying and secondary drying. The freeze dryers necessary for this are complex, computer-controlled systems. The main components are a vacuum chamber with vacuum pump and ports for attaching the product as well as the cooled condenser, where deposit of the subliming steam from the product occurs on its surfaces. Automated cleaning and sterilization units complete the range of functions. Production freeze dryers are integrated into process lines and equipped with automatic loading and unloading systems to satisfy both aseptic requirements and higher product throughput while at the same time decreasing error rates.

Monday, 25 March 2019

12:00
Reception and Welcome Snack


12:30
INTRODUCTION
Collection and clustering of the questions contributed by the participants


13:00
THEORY 1 – INTRODUCTION TO FREEZE DRYING PROCESSES

  • Why lyophilization?
  • History and Development
  • Examples in daily life and pharmaceutical industry
  • The freeze-drying process
  • Freeze-drying equipment
  • Pros and Cons for Lyophilization 

13:45
THEORY 2a – BASIC PRINCIPLES OF FREEZE DRYING PROCESSES

  • Basic principles of freeze-drying processes
    • Physical understanding
    • Critical process parameters
    • Controlled nucleation
  • Product attributes for designing lyophilization cycles
    • Differential scanning calorimetry
    • Freeze-drying microscopy

THEORY 2b - FORMULATION DEVELOPMENT OF LYOPHILIZATES

  • Development and composition of a (biological) formulation
  • Primary packaging components
  • Analytical characterization of lyophilizates including solid state characterization
    • Residual moisture (Karl Fischer, NIR)
    • Reconstitution time
    • Thermodynamic state (X-ray powder diffraction)
    • Specific surface area (BET)
    • Cake appearance at different levels (visual inspection, 3D scanning, PDMS embedding, SEM, µCT)

15:00
Coffee Break

15:15
PRACTICE 1 - PREPARATION OF SOLUTIONS

  • Compounding of formulations
    • Calculation of composition
    • Compounding
  • Filling
  • Stoppering
  • Freezing experiment with distilled water under vacuum to develop a general understanding of the critical temperature

17:15

Transfer to the recommended Hotels


18:00
Transfer from the recommended hotels to the Networking Dinner


18:30
Networking Dinner


21:00
Transfer to the recommended Hotels

Tuesday, 26 March 2019

8:30
Transfer from the recommended hotels to Martin Christ facility


9:00
Recapitulation and Summary of Day 1


9:10
THEORY 3 - DEVELOPMENT OF A FREEZE-DRYING PROCESS

  • Development of a lyophilization cycle
    • Which are the most important parameters?
    • How to choose them?
    • What happens if they are not chosen adequately?
  • Simulation tools
  • Finalization of cycles
  • Discuss loading scheme

10:30
Coffee Break


10:45
THEORY 4 - PROCESS CONTROL TOOLS

  • Thermal resistance measurement (Lyo-RX)
  • Comparative pressure measurement (Pirani/capacitive pressure measurement)
  • Barometric temperature measurement (BTM/MTM)
  • Wireless temperature measurement (WTM)
  • Desorption rate measurement (DRM)
  • Conductance sensor
  • Inline camera (LyoCam)

11:45
PRACTICE 2: PROGRAMMING

  • Programming the freeze dryer with the programs developed in Theory 3

12:45
Lunch Break

13:45
PRACTICE 3: FREEZING BEHAVIOR

  • Loading of the shelves
  • Positioning of the thermo couples
  • Start of the lyophilization program

14:45
PRACTICE 4:

  • Introduction to the LyoCam technology
  • Play-back and discussion of prepared/available video sequences
  • Discussion on the correlation of the video sequences with the process parameters using the process graphs
  • Time lapse mode for identifying process advancement

15:00
Coffee Break


15:30
THEORY 5 - OPERATING PRINCIPLES OF THE FREEZE DRYER

  • Overview of different operating and construction principles of freeze dryers
  • Construction principle of the freeze dryer and its device modules
  • Performance figures (port sizes, condenser sizes, evacuation times)
  • Chamber system
  • Cooling & vacuum systems
  • Filter systems
  • CIP/SIP
  • Interaction of the device modules in the freeze-drying process

16:15
THEORY 6 - LYO QUALIFICATION

  • Explanation of the sequence DQ-RA-IQ-OQ-PQ
  • Measures for maintaining the qualified state

17:00
PRACTICE 5 - A GLANCE AT FREEZE DRYERS

  • Discussion of the current status of the process
  • What is evident/what is not yet evident

17:45
Transfer from Martin Christ facility to the recommended hotels

Wednesday, 27 March 2019

8:30
Transfer from the recommended hotels to Martin Christ facility


9:00
Recapitulation of Key Learnings from Day 2


9:10
PRACTICE 6 - TOUR OF THE PRODUCTION ROOMS OF MARTIN CHRIST [Coffee Break included]

  • Introduction to the different size classes of freeze dryers
  • Introduction to the functional modules of the freeze dryer
  • Visualization of the basic analogy of the functional modules across the size classes
  • Explanation of the step-by-step production process for freeze dryers

11:30
IPRACTICE 7 - INTRODUCTION TO THE GENERAL ORDER OF EVENTS IN OPERATION

  • Brief explanation of all workstations
  • Explanation and instruction on the logistics

12:00
PRACTICE 8

  • Discussion of the current status of the process in the freeze dryer

12:30
Lunch Break

13:30
PRACTICE 9: WORKSTATION OPERATION SEQUENCE 1(continued)

  • Calibration of pressure sensor/vacuum sensor
  • Calibration of temperature sensor
  • Shelf temperature mapping
  • Roughness measurement

14:15
CONTINUATION PRACTICE 9: WORKSTATION OPERATION SEQUENCE 2

  • Calibration of pressure sensor/vacuum sensor
  • Calibration of temperature sensor
  • Shelf temperature mapping
  • Roughness measurement

15:00
CONTINUATION PRACTICE 9: WORKSTATION OPERATION SEQUENCE 3(continued)

  • Calibration of pressure sensor/vacuum sensor
  • Calibration of temperature sensor
  • Shelf temperature mapping
  • Roughness measurement

16:00
CONTINUATION PRACTICE 9: WORKSTATION OPERATION SEQUENCE 4

  • Calibration of pressure sensor/vacuum sensor
  • Calibration of temperature sensor
  • Shelf temperature mapping
  • Roughness measurement

16:15
Coffee Break

16:30
THEORY 7 - MAINTENANCE AND FAULT CORRECTION

  • Introduction to the most frequently occurring faults
    • Diagnosis
    • Most probable causes
    • Correction
  • Introduction to a preventative maintenance concept
  • Presentation of examples of defective components with explanation of the causes

17:30
PRACTICE 10

  • Discussion of the current status of the process in the freeze dryer

18:15
Transfer from Martin Christ facility to the recommended hotels

Thursday, 28 March 2019

8:30
Transfer from the recommended hotels to Martin Christ facility


9:00
Recapitulation of Key Learnings from Day 3


9:15
THEORY 8 - CIP & SIP

  • Inspection of CIP & SIP systems
  • Cleaning validation
  • Sterilization qualification
  • Turn-around concept

10:00
Parallel Practice Sessions [Coffee Break included]

PRACTICE 11

  • Simulation of major faults with freeze driers
  • Diagnosis (and simulation) of the correction of major faults

PRACTICE 12

  • Explanation of conductance sensor
  • ꞏ Inspection and explanation of the CIP/SIP-functional modules in an industrial freeze dryer
  • Riboflavin practice

11:45
PRACTICE 13

  • Discussion of the current status of the process in the freeze dryer

12:15
Lunch Break

13:00
THEORY 9 (including equipment demonstration)

  • Introduction to the functioning and operation of the RM measuring instrument
  • Presentation of theory, function and purpose of the most important analysis techniques for lyophilizates
  • Introduction to the measurement of residual moisture

14:00
THEORY 10 – CONTROLLED NUCLEATION


15:00
Coffee Break


15:15
PRACTICE 14

  • Discussion of the current status of the process in the freeze dryer
  • Visual control – examples

16:00
THEORY 11 – AUTOMATION

  • Loading and Unloading

16:45
Transfer to the recommended hotels

18:00
Transfer from the recommended hotels to dinner location


18:30
Farewell Dinner


21:00
Transfer from dinner location to the recommended hotels

Friday, 29 March 2019

8:30
Transfer from the recommended hotels to Martin Christ facility


9:00
PRACTICE 15

  • Unloading the freeze dryer
  • Evaluation of the process chart
  • Determination of reconstitution time
  • Visual Inspection
  • Assessment of the different results

10:00
Q&A and conclusions


12:00
End of Course

3 Ways to register

Please remember to log in if you are a member of PDA already! 

If you come from a Governmental or Health Authority Institution or from an Academic Organization please contact Ms. Antje Petzholdt before registering. She will verify your status and register you.

  • All registrations which will involve visa matters will have to be submitted to PDA EU four weeks prior to the start of the event at the latest. For later registrations, PDA Europe will be unable to assist participants in any visa affairs.
  • All costs incurring in connection with visa affairs shall be borne by registrants. (This applies in particular to costs for submitting documents by courier.)
  • Potential participants must be clients of UPS shipping agency and submit their UPS customer reference number to PDA EU (together with their registration).

Registration Fees

Are you entiteld to receive a discount? Need Help?

All Participants

By 16 December
2690 Euro

After 16 December
2990 Euro

Contact

Antje PetzholdtAntje Petzholdt
Manager Registration, Chapters & Membership
Tel: +49 (0) 30 43 655 08-10
Fax: +49 (0) 30 43 655 08-66
Email

Training Location
Martin Christ
Gefriertrocknungsanlagen GmbH
An der Unteren Söse 50
37520 Osterode am Harz

Hotels Nearby

PDA Europe recommends the reservation at one of the following hotels. A transfer during the event from and to these hotels is guaranteed.

The general terms of business are valid at the event hotels.

HOTEL SAUERBREY ****
Friedrich-Ebert-Str. 129
37520 Osterode am Harz / Lerbach
Tel.: +49/ (0)5522-5093-0
Fax: +49/ (0)5522-5093-50
Email: info@hotel-sauerbrey.de
www.hotel-sauerbrey.de
Price per Room and Night: 75 Euro

Distance to the venue: 7. 5 km (11min by the car)


HOTEL ZUM RÖDDENBERG ***
Steiler Ackerweg 6
37520 Osterode am Harz
Tel.: +49/ (0)5522-9054-0
Fax: +49/ (0)5522-9054-54
Email: info@hotel-zum-roeddenberg.de
www.hotel-zum-roeddenberg.de
Price per Room and Night: 73 Euro

Distance to the venue: 2. 5 km (5min by the car)

Sponsorship and Exhibit Opportunities are not Available for this Course!

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