SPX FLOW Aseptic Spray Drying 无菌级喷雾干燥技术The Joint IPEC – PQG Good Manufacturing...

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: [email protected]


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


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


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


MS-35


MS-75


MS-150


Anhydro Ref. - page 9

MS 35 20

MS 75 30

MS 400 40-80

MS 1250 80-100

Typical Particle for Each Processor


Drying of Spray & Particle Morphology


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


• “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



Closed Cycle Spray Dryer


Bag in Bag out transfer of filters or other items out of or into the process

MS-35 Containment


Containment with Open Door


Isolator RTP



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


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


Why do we dry?



• 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



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



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

=

=



Aseptic Spray Drying

Aseptic Spray Drying Applications:

Vaccines

Proteins and Peptides

Live Cells

Inhaleable Powders

Antibiotics




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


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

Relationship of steam pressure to sterilization temperature


Vacuum cycles to remove non-condensables


Aseptic MS-1250


Sterilizing Filters


Aseptic MS-35


MS-75 SIP Steam



Aseptic spray dryingRequire Sterile filling Technology to fill bulkPowders into vials


MICROFILL 400

NEW IN-LINE FILLING & STOPPERING MACHINE FOR INJECTABLE POWDER

Aseptic spray dryingRequire Sterile filling Technology to fill bulkPowders into vials

SPX FLOW Aseptic Spray Drying 无菌级喷雾干燥技术The Joint IPEC – PQG Good Manufacturing...

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