copyright © 2008 | aseptic technologies | all rights reserved crystal , the closed vial technology...

Copyright © 2008 | Aseptic Technologies | All rights reserved

Crystal,

the Closed Vial Technology

A Revolution in Aseptic Filling

Overall Introduction DocumentJanuary 2009


New concept of Crystal® | Process

Sterilization(Gamma

irradiation)

Molding & Closing(Class 100/A/ISO 5)

Assembly(Class 100,000/C/ISO 8)

Capping Laser re-sealing Filling

Filling line under barrier (Class 100/A/ISO 5) Clean & sterile “ready to fill”

vial

Molding site Irradiation unit

Pharmaceutical site


The Crystal® Closed Vial Technology

Key advantages

The Vial

Body made of COC and stopper of thermoplastic elastomer:

• Hydrophobic material to prevent electrostatic interaction with soluble proteins

• Unbreakable vial• Glass-like transparency• Specially designed stopper minimizing loss of residual volume

• Exceptional inertness: low absorption, no ion and very few leachables

• Excellent moisture barrier• Bio-compatible• Ability to reduce oxygen concentration to 0.1%

Crystal® vial is particularly suitable for:•High value products•Toxic products



The Filling process

The Crystal® closed vial enables to:

• Eliminate most complex steps of aseptic filling– no WFI washing– no hot-air tunnel– no siliconization– no stoppering

• Limit risk of batch release thanks to process simplification

• Secure potent and high-value products

Key advantages

Crystal® Technology drastically simplifies aseptic filling operations


Vial description

Ensures sterility assurance level of the piercing area

Ensures closure integrity

Made of Thermoplastic Elastomer (TPE) Allows laser resealing after filling

Made of Cyclo-olefin co-polymer (COC)Contains volume from 0.2 to 20mlVials up to 50 ml are feasible

Ensures mechanical stability

Flip away cap

Top ring

Stopper

Vial body

Bottom ring

Crystal® vial is closed in a class 100 A room before being sterilized by gamma irradiation


Market research results Crystal® vs. glass vial

• 246 healthcare professionals from hospital settings interviewed• 71 doctors, 161 nurses and 14 hospital pharmacists• 134 in Europe (F, B) and 110 in the US (West and East Coasts)

Crystal preferred No preference Glass preferred

87 76

89

85 5

5

10

6Europe

USA

90

85

86

6

14

6

9

4Doctors

Nurses

Pharm.

Full presentation available on request

87% of professionals prefer Crystal®

In each region By each professional


Closed vial filling line | Description

Production line

1 meter3.28 feet

Vial loading area to introduce vials

provided in a sterilized box

E-beam to ensure sterility of the

filling site on the stopper

Floating pulley to move from continuous

movement to intermittent movement

Laser resealing of the needle

piercing trace in the stopper

Vial filling done with a special

needle injection through the

stopper

High-speed capping using

snap-fit technology

CVFS (Closed Vial Filling System) to ensure class 100 condition during all

operations

Laminar airflow


Three formats of line available

• Designed to fill large commercial batches

• Capacity: up to 600 vials/min

• Able to handle all formats of vials (1 to 50 ml)

• Equipped with 6 to 24 filling needles and lasers

• Space needed: 100 m² (machine footprint: 44 m²)

• Capacity increase is feasible by adding filling heads and lasers

Production line (Crystal P6 to P24)

• Designed to fill clinical batches and small commercial batches

• Capacity: up to 75 vials/min

• Able to handle all formats of vials (1 to 50 ml)

• Equipped with three filling needles and lasers (C3)

• Space needed: 40 m² (machine footprint: 9 m²)

Clinical line (Crystal C2 or C3)

• Designed to fill very small batches (<5,000 vials)

• Capacity: about 10 vials/min

• Able to handle all formats of Crystal vials (1 to 50 ml) and glass vials

• Equipped with a robot performing filling, re-sealing and capping

• Space needed: ~8 m² (machine footprint: 1 m²)

Laboratory line (Crystal L1)


Lyophilization in Crystal®

Process

Pusher

1. Normal vial filled but not laser re-sealed

2. Penetrator (funnel shape) placed in line on vial top

3. Lyo shelve moved down to push penetrator and re-open piercing trace

4. Lyophilization done through piercing trace

5. Penetrator withdrawn and vial laser re-sealed and capped

Lyo shelve

Tests conducted using identical cycles compared to glass vials:

Lactose 5 and 10%: successfulSucrose 5 and 10%: successfulViruses: same virus titer as in glass


Key advantages of Crystal® Technology

• For your regulatory team

• For your supply chain team

• For your manufacturing team

• For your QA/QC team

• For your marketing team

• For your financial team

• For your manufacturing team

• For your sales team

For whom?

• Provide a top-class sterility assurance level thanks to a closed ready to fill container

• Secure the products inside an unbreakable and coded container

• Simplify entire filling process (lean manufacturing)

• Quicker initial validation and less follow-up validation work

• Facilitate handle by healthcare specialists

• Reduce capital expenses

• Reduce operating expenses despite vials more expensive than unclean non-sterile glass vials

• Boost sales thanks to better perception by end-users

Why?

SAFER

EASIER

INCREASE PROFIT


The history of Aseptic Technologies

2003 2004 2005 200720062002 2008

Presentation of concept to FDA

& EMEA

1st successful Media Fill

(clinical line)

2nd successful Media Fill

(production line)

Presentation of validation results

to FDA

Contract filling line approved by

EMEA at AT

DMF at FDA for contract filling

at AT

First vial manufacturing line full scale

First prototype of vial

manufacturing line

Creation of Aseptic

Technologies

First collaboration contract signed

with a major CMO: NextPharma

(EU, US)

First production line to be delivered to GSK Biologicals

(Belgium)

2009


Current status of the Crystal® Technology

•Use of technology- One Production line (36,000 vials per hour) sold to GSK Biologicals for vaccine filling

- Stability tests started with two vaccines from GSK Biologicals and several products from biotechs and contract manufacturers

•Vial- Vial made by injection molding (1 and 2 ml) available at industrial scale- Larger volumes (10 to 100 ml) made by injection blow molding

- Design and feasibility pilot phase finalized- Small scale production pilot under development

•Line- Mechanical and pharmaceutical validation performed- Media fill simulation: no contamination in more than 100,000 vials filled

•Filling capabilities- Clinical line installed in our facility - Inspected by EMEA, approval granted for stability batches- Two DMF filed at FDA (both CBER and CDER) - Several partnerships with contract manufacturer, including NextPharma to fill at Aseptic Technologies for partner clients

- Aseptic Technologies site elected as “Facility of the Year” by ISPE for equipment innovation


Aseptic Technologies

•Launched in June 2002 with a capital of 25 Mio EUR with the objective to develop the closed vial and its filling line, capital increased to 55 Mio EUR in 2005

•Subsidiary of GlaxoSmithKline Biologicals

•Current headcount 22 people

•4,000 m² of facility of which 400 m² of clean room

•Collaboration with several partners in the conception and production of vials and lines

- IBA: mini e-beam- Technord: automation- Lasea: laser technology- Sirris: material studies- Rexam: vial manufacturing

•Core technology licensed by Medical Instill Technologies Inc.



•Has a proven track record of biological drug stability

•Protects your products from physical and chemical damages

•Reduces the risk on product loss- Residual volume- Broken vial- Batch rejection

Filling suite in our facility to support your compatibility/stability tests in the Crystal® vials

EMEA approved 2 DMF filed at FDA

Aseptic Technologies S.A.Rue Camille Hubert, 7-9B-5032 GemblouxBelgium

www.aseptictech.com


Benoît VerjansCommercial Director

Tel: +32 81 409 4directFax: +32 81 409 [email protected]

copyright © 2008 | aseptic technologies | all rights reserved crystal , the closed vial technology...

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