Download Synthon - Cleanroom Innovation

Cleanroom Innovation Seminar
Semi meets Pharma
16 April 2013 – Koen Kodde (head CIM)
CLEANROOMS BOUWEN
VOOR SPECIALTY PHARMA
Synthon – key facts
• Founded in 1991, privately owned
• 2012 turnover €249 M
• More than €300 M invested in R&D in last decade
• Broad geographical footprint (subsidiaries in 10 countries)
• 1400 Employees of which 360 in R&D
• Focus on autoimmune/neurodegenerative diseases and oncology
• Extensive track record in clinical development & regulatory approvals worldwide
• FDA & EMA approved manufacturing facilities in CZ, ESP, CL, ARG
• B2B model
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Synthon Biopharmaceuticals – key facts
• Financially independent Biotech company
• 150 Employees in US & NL, majority with academic degree (MSc, PhD)
• Focus on autoimmune/neurodegenerative disease and oncology
• Current annual budget: €35 M
• Most progressed platforms: ADCs & SYNLEX™
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The Antibody-Drug Conjugate approach
The Challenge:
• Many antitumor mAbs lack cell-killing capability & efficacy and do not cure
Tumor cell
Inactive drug
Lysosome
Active drug
Linker
Target (antigen)
Antibody
The Opportunity:
• Antibody-Drug Conjugation (ADC): mAb delivers drug inside cancer cell
• Internalization of the mAb-bound target is essential
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GMP manufacturing of ADCs
mAb
ADC
ADC conjugation
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Synthetic Linker-Drug
5
Clean room necessity
Medicines need to be prepared in a highly controlled
environments; controlled rooms, documents and
products are controlled, checked and verified by
multiple different persons
Failure has severe impact which may result in patient
death
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Grades !!??
Volume 4 EU Guidelines to Good Manufacturing Practice
Medicinal Products for Human and Veterinary Use
Annex 1 Manufacture of Sterile Medicinal Products
Based on the work and the risk to the patient safety grades are prescribed
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Clean room specifications
Volume 4 EU Guidelines to Good Manufacturing Practice
Medicinal Products for Human and Veterinary Use
Annex 1 Manufacture of Sterile Medicinal Products
Clean rooms and clean air devices should be classified in accordance with ISO14644
Only measuring 0.5µm and 5.0µm ‘suffices’
Synthon
Clean room specifications
Synthon
Clean room specifications
Volume 4 EU Guidelines to Good Manufacturing Practice
Medicinal Products for Human and Veterinary Use
Annex 1 Manufacture of Sterile Medicinal Products
Tests are to be conducted conform pharmacopeia
An aid can be the ISO 14698
Synthon
Clean room specifications
Generation
Number
Cell
Count
0
1
1
2
2
4
3
8
4
16
5
32
10
1,024
20
1,048,576
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Clean room specifications
Synthon
Clean room design
Flush
Cleanable
Non particle shedding
Temperature
Relative humidity
Coving
Process
Walls
Flooring
Bumper
Glass
Weighing areas
Pressure
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Clean room design – ideal (overpressure)
Pressure [Pa]
Grade D
15
Room/grade
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GRADE A
30
GRADE B
Grade C
45
GRADE C
Grade B
60
GRA
DE D
Grade
A
Clean room design – specialty pharma
GMP emphasizes on
-Patient safety
-Cross contamination reduction
Ergo
-Overpressure clean room
BUT WHAT IF THE MEDICINE IS
-Cytotoxic?
-Radioactive?
Containment is of concern!
-GMO?
-Etc.
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Clean room design – ideal (relative under pressure)
Pressure [Pa]
Grade D
15
Underpressure
Room/grade
Synthon
GRADE A
30
GRADE B
Grade C
45
GRADE C
Grade B
60
GRA
DE D
Grade
A
Clean room design
Bubble
60
45
30
15
Room/grade
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Sink
Clean room design
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Clean rooms for specialty pharma
Conclusion
• Building clean room is a very interesting, but above all challenging task.
• Nothing is fully prescribed in law and legislations.
• Everything is risk based during the process, where the impact can only be
tested at the end (during qualification).
• Building clean rooms for pharma is all about detailing detailed details
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Additional slides
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Clean room specifications
Synthon