Post on 09-Jun-2020
March 13, 2018COMPANY CONFIDENTIAL 11
Apply for R&D and Producing 适用于研发和生产
1. Potent Compound SDD’s (Spray Dried Dispersions) 高毒性化合物SDD(喷雾干燥分散体)
2. Sterile powders for parenteral drug delivery 无菌注射用药粉
SPX FLOW Aseptic Spray Drying 无菌级喷雾干燥技术
实现连续生产、帮助提高产能、降低投资成本
By Oule Geng, SPX (Shanghai) FLOW演讲人: 耿志林 , 来自斯必克(上海)流体技术有限公司
Cell Phone: 13818568632 E-mail: Oule.geng@spxflow.com
March 13, 2018COMPANY CONFIDENTIAL 2
AnhydroBrand Overview
HistoryFounded in 1948Developed the Anhydro Triple-A Dryer in 2006Launched “Sustainable solutions for tomorrow´s generation” in 2009Acquired by SPX in 2010Leading supplier of evaporator and dryer solutions to the dairy, food, chemical and pharmaceutical industries worldwide – strong Anhydro brand recognition in all industries
Core Markets
2
Dairy
Food
Chemical
Pharmaceutical
Main Locations
Soeborg, Denmark
Sao Paulo, Brazil
Shanghai, China
Paris, France
Maryland, US
Moscow, Russia
Test Centre,Soeborg
Primary Products
Evaporator Spray dryer Spin Flash dryer
Fluid bed Small Scale Parts & Service
Integrated processesEvaporatorsSpray DryersSpin Flash DryersFluid Bed Technologies
Small Scale PlantsBag FiltersParts & Service
• 21 CFR parts 210 and 211.
• 21 CFR part 11 electronic signatures
• ICH Q7A API
• Guidance for Industry
Sterile Drug Products
Produced by Aseptic Processing —
• Current Good Manufacturing Practice
The Joint IPEC – PQG Good Manufacturing Practices Guide FOR PHARMACEUTICAL EXCIPIENTS
• GAMP V Quality system to develop controls
Pharmaceutical Regulations USA
March 13, 2018COMPANY CONFIDENTIAL 3
Process robustness
High level of Reproducibility
High efficiency (95%+ recovery possible)
Predictable scale up
Is more gentle than Freeze drying / lyophilization
Controls product characteristics better than other processes
Is a continuous process with large throughputs
Spray drying Advantages
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Viscosity Less than 1500 cp
Low glass transition temperature Tg
The dried powder should not be sticky
Solutions OK
Suspensions OK
Properties that make for a good spray drying candidate
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MS-35
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MS-75
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MS-150
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Anhydro Ref. - page 9
MS 35 20
MS 75 30
MS 400 40-80
MS 1250 80-100
Typical Particle for Each Processor
Anhydro Ref. - page 10
Drying of Spray & Particle Morphology
Anhydro Ref. - page 11
Shrivelled particle
Solid particle with satellites
Solid particle
Hollow particle
Cenosphere
Disintegrated particle
Highly Potent Active Pharmaceutical Ingredient HPAPI
Spray Dried Dispersion SDD
And
Aseptic Spray Dried Powders
Fastest Growing Applications
March 13, 2018COMPANY CONFIDENTIAL 12
• “All the easy drugs have been found now we have to go after the rocks”
• Majority of new development drugs have poor bioavailability.
• Solid Dispersion Improve bioavailability of insoluble drugs
• Formulators will add excipients to a formulation and spray drying will change the solid form of the substance IE making it more amorphous, and improve bioavailability.
• Make the API more amorphous add other substances Polymers IE HPMCAS, PVP, etc
• May increase Drug bioavailability 1000’s of times
• Solvent drying – Nitrogen inertion- closed cycle systems.
Solid Dispersions
March 13, 2018COMPANY CONFIDENTIAL 13
Anhydro Ref. - page 14
Closed Cycle Spray Dryer
Anhydro Ref. - page 15
Anhydro Ref. - page 16
Bag in Bag out transfer of filters or other items out of or into the process
MS-35 Containment
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Containment with Open Door
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Isolator RTP
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Anhydro Ref. - page 20
Dock Lock Open/Close Unlock/Undock
Split Butterfly valve – Principal of Operation
Milling Compression Filtration & Drying Isolator Charge/Discharge
Used for both Highly Potent API and Aseptic processing
Anhydro Ref. - page 21
Transfer via ChargeBottle™
Maximum Containment w/ EXCEL Vortex Valve
Transfer via ChargeBag™Improved Containment w/ exhaust shroud
Pressure Rated Valve with Sight Glass Option
A biologic is manufactured in a living system such as a microorganism, or plant or animal cells. Most biologics are very large, complex molecules or mixtures of molecules. IE proteins.
These molecules are too large to pass through the walls of the digestive system.
They must be injected, inhaled, absorbed through the skin (patch), implanted devise.
Large Molecule Drugs Biologic
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Why do we dry?
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Anhydro Ref. - page 23
• Stabilization of protein by drying
Water removal
• Water is a good medium for degradation
Reactions
• Oxidation, surface adsorption
Denaturation aggregation
• In solid state Low molecular
Hydrolysis Minimized
• Storage stability better in solid state
than in solution
March 13, 2018COMPANY CONFIDENTIAL 24
Anhydro Ref. - page 24
Spray Drying
AdvantagesContinuous process
Low capital /ops cost
Flowable powders allows diverse delivery options
Particle production
Particle engineering possible
A stable spray dried powder requires no salt/cryoprotectants
Process speed
March 13, 2018COMPANY CONFIDENTIAL 25
Anhydro Ref. - page 25
Aseptic Spray Dryer Vs LyophilizersComparing Processor Throughput
Spray Dryer can replace• 12 Lyophilizers (56,000 vials)
• 6 Large Lyophilizer (112,000 vials)
MS-1250
MS-1250
=
=
March 13, 2018COMPANY CONFIDENTIAL 26
Anhydro Ref. - page 26
Aseptic Spray Drying
Aseptic Spray Drying Applications:
Vaccines
Proteins and Peptides
Live Cells
Inhaleable Powders
Antibiotics
March 13, 2018COMPANY CONFIDENTIAL 27
Anhydro Ref. - page 27
Aseptic Spray Drying
Design Features:
Cleaning in Place (CIP)
Sterilization in Place (SIP) 6 Log reduction
Depyrogenation in Place 3 Log reduction
Filter Integrity Testing (bubblepoint)
Depyrogenation Endotoxin Reduction
March 13, 2018COMPANY CONFIDENTIAL 28
Pyrogen a substance that causes fever.
When microbes die the cell wall are made up of Lipopolycaccharides when these enter the blood stream they cause fevers, endotoxins
Steam sterilization will not remove endotoxins
The endotoxins must be washed off the equipment
March 13, 2018COMPANY CONFIDENTIAL 29
Anhydro Ref. - page 29
Aseptic Spray Drying
Relationship of steam pressure to sterilization temperature
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Vacuum cycles to remove non-condensables
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Aseptic MS-1250
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Sterilizing Filters
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Anhydro Ref. - page 34
Anhydro Ref. - page 35
Anhydro Ref. - page 36
Anhydro Ref. - page 37
Aseptic MS-35
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MS-75 SIP Steam
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Anhydro Ref. - page 40
Aseptic spray dryingRequire Sterile filling Technology to fill bulkPowders into vials
Anhydro Ref. - page 41
MICROFILL 400
NEW IN-LINE FILLING & STOPPERING MACHINE FOR INJECTABLE POWDER
Aseptic spray dryingRequire Sterile filling Technology to fill bulkPowders into vials