Contract Manufacturing Services for Pre-filled Syringes · Contract manufacturing services for pre-filled syringes in glass and plastic from 1 –50 mL Aseptic filling and terminal

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


Contract manufacturing services forfinished-dosage forms in pre-filled syringes


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


Typical manufacturing of pre-filled syringesat manufacturing site in Graz, Austria (1/2)


Bag opening

Tyvekremoval

Filling Stoppering

InspectionFinal assemblyLabelingPackaging

Autoclave

Typical manufacturing of pre-filled syringesat manufacturing site in Graz, Austria (2/2)


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


Formulation technologies & API handling


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


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


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


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


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


Packaging configurations for pre-filled syringes


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


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


Let‘s fill syringes!


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

[email protected]

Stefan CzvitkovichDirector Product PartneringCentral Europe

Fresenius Kabi Austria GmbH Hafnerstrasse 36A-8010 GrazT: +43 (0) 316 249 1366C: +43 (0) 664 8372481

[email protected]

More information at www.freseniuskabi-productpartnering.com

Documents

Contract Manufacturing Services for Pre-filled Syringes · Contract manufacturing services for pre-filled syringes in glass and plastic from 1 –50 mL Aseptic filling and terminal