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Contract Manufacturing Services for
Pre-filled Syringes
From Standard Solutions to Complex Products
Stefan Czvitkovich, PhD
Director Product Partnering Sterile Pharmaceuticals
Central Europe
CPhI woldwide 2017 Booth 41K02
Fresenius Kabi Product Partnering
Fresenius Kabi
Product Partnering
dedicated to:
Contract Development &
Manufacturing Services of
Sterile Pharmaceutical
Finished-Dosage Forms
© Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th, 2017 2
20+ R&D & manufacturing sites
© Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th, 2017 3
Contract manufacturing services forfinished-dosage forms in pre-filled syringes
© Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th, 2017 4
Graz, AustriaWilson, North Carolina
Plant Graz, Austria: Facts & Figures
Competence center for aseptic manufacturing
~800 Employees & commercial manufacturer of
products in pre-filled syringes & other containers:
glass vials and bottles, glass ampoules, bags
Annual capacity: > 10 Mio pre-filled syringes
Formulation technologies: aqueous solutions, oil-based
formulations, emulsions, suspensions, lyophilisates
Aseptic filling since 1990 (& terminal sterilization)
Pilot plant for process optimization and clinical supply
Global regulatory approval
(incl. US-FDA, EU & Asia)
© Copyright Fresenius Kabi AG 5CPhI worldwide, Booth 41K02, Oct 24-26th, 2017
Plant Wilson, NC, USA: Facts & Figures
Fully dedicated manufacturing site for pre-filled syringes
> 120 employees, manufacturing area: 125,000 ft2
Annual capacity: > 25 Mio pre-filled syringes
DEA Schedule II, and IV controlled drugs
Compounding in fixed tanks (250-900L) with CIP/SIP
or mobile tanks (150 L)
Aseptic manufacturing capabilities
with in-line E-Beam decontamination
100% automated inspection of
filled syringe, product, stopper, tip cap
Regulatory approval by US-FDA
© Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th, 2017 6
Typical manufacturing of pre-filled syringesat manufacturing site in Graz, Austria (1/2)
© Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th, 2017 7
Bag opening
Tyvekremoval
Filling Stoppering
InspectionFinal assemblyLabelingPackaging
Autoclave
Typical manufacturing of pre-filled syringesat manufacturing site in Graz, Austria (2/2)
© Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th, 2017 8
AutoclaveVisual
InspectionFinal
AssemblyLabeling
Blistering /Packaging
FinishedProduct
Sterile Pharmaceuticals in Pre-filled Syringes
Syringe types
Glass and plastic syringes
Luer cone, luer lock and staked needle
Format range from 1 mL to 50 mL
Filling volumes starting at 0.1 mL
Experience with main syringe suppliers
Stoppers
Ready-to-use stoppers for
optional aseptic manufacturing using port system
© Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th, 2017 9
Formulation technologies & API handling
© Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th, 2017 10
Formulation technologies
for pre-filled syringes:
Aqueous solutions
Emulsions
Oil-based formulations
Suspensions
Liposomes
CapabilitiesTerminal
sterilization
Aseptically
High viscous
Oxygen sensitive
Lightsensitive
Small molecules& biologicals
Non-sterile and sterile APIs
High potent APIs
Water-free products
Customer-dedicatedmobile vessel system for high flexibility
Disposable compounding containers
Mobile vessel system
Design acc. to products requirements
On-board-automation system
Connection to media-systems
close to the filling line
Cleaning at CIP/SIP-stations
(Aseptic ) connection to weighing isolator
for transfer of high potent APIs or sterile APIs
Dedicated and multi-purpose
© Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th, 2017 11
Compounding with high-potent APIs
Manipulation of highly active substances
Mobile vessels connected to isolator
High potent API transfer into isolator
Weighing of high potent API
High potent API transfer into mobile vessel
Cleaning
Manipulation of sterile substances
Mobile vessels connected to isolator
Isolator is sterilized via peroxide
API-container is connected aseptically (via port system)
Weighing of sterile API
Transfer of sterile API into mobile vessel
Cleaning
© Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th, 2017 12
Filling of sterile pharmaceuticals inpre-filled syringes
Technologies
Nested syringes, ready-to-fill
Aseptic and non-aseptic filling
Filler with cRABS technology
Filling Techniques
Rotary piston pumps
Peristaltic pumps
Stoppering Techniques
Insertion tube
Vacuum
Further capabilities
Oxygen reduced filling
Dedicated, multi-purpose & disposable equipment
VHP sterilization
© Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th, 2017 13
Filling line for pre-filled syringes in Graz, Austria
Autoclaving & Visual Inspection
Terminal sterilization by autoclaving
100% automated inspection at Wilson
Semi-automatic visual inspection at Graz
Manual visual inspection
for small batch sizes
© Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th, 2017 14
Seconary Packaging of pre-filled syringes
Bulk packaging of pre-filled syringes for
auto-injector assembly at customer or external CMOs
Labeling
Assembly of plunger rod, backstop, finger flange
Assembly of safety devices
according to customer‘s requests and guidance
Implementation of serialization requirement in process
© Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th, 2017 15
Packaging configurations for pre-filled syringes
© Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th, 2017 16
Sealed (barrier) blister
High-end packaging option for large-volume PFS and kits
Functional barrier packaging for O2 protection possible
Rigid thermoformed tray providing shock protection and fixed arrangement of components
Single carton
Side loading carton for emergency care products requiring tamper evidence
Minimized storage foot print for single cartons
Highly flexible machine concept regarding product-specific sizes
Flow pack
Sealed over-bag (printed or unprinted) as tamper evidence feature or alternative to barrier blister
Intensive care products used frequently, e.g. anesthetics; minimized storage footprint essential
A B C
Process development and clinical manufacturing
Formulation and Process Development
Aqueous and oil-based formulations
Analytical method development
Compatibility studies for container closuresystems, stainless steel, silicone, etc.
ICH stability studies (thermal, light, etc.)
Process optimization by DoE
Clinical manufacturing
FDA & EMEA approved plants for
global clinical supply
cGMP batch sizes: 5 L to 900 L
Secondary packaging for clinical studies
© Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th, 2017
Quality Target Product Profile (QTPP)
Risk Analysis and Identification of Critical Quality Attributes (CQA)
Formulation & Process Development
Optional: Design of Experiments (DoE) for Design Space Definition
Upscaling in the pilot plant to commercial batch sizes
17
Summary (1/2)
Contract manufacturing services for
pre-filled syringes in glass and plastic from 1 – 50 mL
Aseptic filling and terminal sterilization
Handling high-potent APIs incl. biologicals
High flexibility with various formulations
Adaptable flexible line:
mobile vessel, disposable equipment etc.
Full secondary packaging capabilities
Gobal supply
© Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th, 2017 18
Summary (2/2)
Experience with development, clinical
and commercial manufacturing
Experience with diverse customer base
from biotech to big pharma
Global supply incl. regulatory approval
Professional project management structure
Fresenius Kabi is a key player in the pharmaceutical
industry for parenteral dosage forms looking
for long-term partnership
© Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th, 2017 19
Let‘s fill syringes!
© Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th, 2017 20
Meet us at our booth 41K02
Lora Peknik-GrahamDirector Product Partnering
Plants North America
Fresenius Kabi USA, LLC Three Corporate Drive
Lake Zurich, Illinois 60047 T: +1 847-550-2048 C: +1 847-212-0315
Stefan CzvitkovichDirector Product PartneringCentral Europe
Fresenius Kabi Austria GmbH Hafnerstrasse 36A-8010 GrazT: +43 (0) 316 249 1366C: +43 (0) 664 8372481
More information at www.freseniuskabi-productpartnering.com