Contract Manufacturing Services for Pre-filled Syringes

Transcription

1 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

2 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,

3 20+ R&D & manufacturing sites Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th,

4 Contract manufacturing services for finished-dosage forms in pre-filled syringes Wilson, North Carolina Graz, Austria Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th,

5 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 CPhI worldwide, Booth 41K02, Oct 24-26th,

6 Plant Wilson, NC, USA: Facts & Figures Fully dedicated manufacturing site for pre-filled syringes > 120 employees, manufacturing area: 125,000 ft 2 Annual capacity: > 25 Mio pre-filled syringes DEA Schedule II, and IV controlled drugs Compounding in fixed tanks ( L) 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,

7 Typical manufacturing of pre-filled syringes at manufacturing site in Graz, Austria (1/2) Bag opening Tyvek removal Filling Stoppering Autoclave Inspection Final assembly Labeling Packaging Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th,

8 Typical manufacturing of pre-filled syringes at manufacturing site in Graz, Austria (2/2) Autoclave Visual Inspection Final Assembly Labeling Blistering / Packaging Finished Product Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th,

9 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,

10 Formulation technologies & API handling Formulation technologies for pre-filled syringes: Aqueous solutions Emulsions High viscous Oxygen sensitive Light sensitive Small molecules & biologicals Non-sterile and sterile APIs Oil-based formulations Suspensions Aseptically High potent APIs Liposomes Terminal sterilization Capabilities Water-free products Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th,

11 Customer-dedicated mobile 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,

12 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,

13 Filling of sterile pharmaceuticals in pre-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 Filling line for pre-filled syringes in Graz, Austria Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th,

14 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,

15 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,

16 Packaging configurations for pre-filled syringes A B C Sealed (barrier) blister High-end packaging option for large-volume PFS and kits Functional barrier packaging for O 2 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 productspecific 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 Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th,

17 Process development and clinical manufacturing Formulation and Process Development Aqueous and oil-based formulations Analytical method development Compatibility studies for container closure systems, 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 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 Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th,

18 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,

19 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,

20 Let s fill syringes! Lora Peknik-Graham Director Product Partnering Plants North America Fresenius Kabi USA, LLC Three Corporate Drive Lake Zurich, Illinois T: C: Lora.Peknik-Graham@fresenius-kabi.com Stefan Czvitkovich Director Product Partnering Central Europe Fresenius Kabi Austria GmbH Hafnerstrasse 36 A-8010 Graz T: +43 (0) C: +43 (0) Stefan.Czvitkovich@fresenius-kabi.com More information at Meet us at our booth 41K02 Copyright Fresenius Kabi AG CPhI worldwide, Booth 41K02, Oct 24-26th,