Seidenader

Seidenader Maschinenbau GmbH

Inspektionssysteme Pharma

Automatic Inspection of Prefilled Syringes

A3P Congress Biarritz France October, 2001

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Agenda
Intro Seidenader Maschinenbau Syringe inspection Material handling Vision system Particle inspection Cosmetic inspection Validation approaches Training requirements References

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Company profile
Founded Annual turnover Employees, total Total staff vision system development, integration, installation : Products 1895 20 mio 150 52 Inspection machines Vision systems Vial and ampule washers Tablet sorting and inspection Markt Schwaben/Munich SVResearch,Harrisburg, PA Seidenader Equipment, Florham Park, NJ Agents and tech. support partners 49 worldwide

Locations

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New Building for future Growth for Seidenader Maschinenbau and SVResearch, Germany
MUC Airport

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Office space: 2,100 sqm Factory space: 2,100 sqm 130 employees

- New Vision Laboratory - Training facilities - New workflow philosophy

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Total sales / Automatic inspection machines

100 %

Semiautomatic&others Automatic machines

1996

1997

1998

1999

2000

2001e

Company growth driven by automatic inspection machines

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Accumulated Inspection Experience
Total Semiautomatic inspection machines ca. 650 Last 3 yrs ca. 120

Automatic inspection machines Vision systems/processors integrated

79 1500

45 350

Total staff vision system development, integration, installation: 52

Seidenader is an experienced player in both worlds

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Semiautomatic inspection machines

- For ampules, cartridges, vials and bottles - Particles and cosmetic defects - Freeze dried products - Prefilled syringes

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Automatic inspection machines

- For ampules, cartridges, vials and bottles - Particles and cosmetic defects - Freeze dried products - Prefilled syringes

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Agenda
Intro Seidenader Maschinenbau Syringe inspection Material handling Vision system Particle inspection Cosmetic inspection Validation approaches Training requirements References

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Prefilled syringe processing Industry trends Heparin manufacturers are increasing syringe manufacturing capacity

Growing market of vaccines in classic and needle less syringes

Manufacturers in Japan,Europe and USA start to build up filling capacity for prefilled plastic syringes

- Greater variety of syringe types - Greater demand for automation of the inspection process

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What makes syringe inspection different? Material handling challenges

Products are delivered to the machine in hanging position Standard methods of conveying and buffering cannot be used Typical handling is with starwheels, vacuum star wheels, clips and grippers

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Machine overview

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Material handling challenges

Avoid timing screws and guide rails - they potentially scratch the syringe or the print - they tend to wear quickly by broken syringes

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Material handling challenges

Needle up particle inspection for syringes > 10mmdiameter - provided liquid moves freely - product does not tend to foam or bubble

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Material handling challenges

Needle down particle inspection for syringes < 10mm diameter - liquid cannot move freely due to siliconisation,surface tension or viscosity of the product

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Agenda
Intro Seidenader Maschinenbau Syringe inspection Material handling Vision system Particle inspection Cosmetic inspection Validation approaches Training requirements References

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Controls architecture of vision systems

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SVIM-Processor

A complete vision engine: - Dual Pentium I III power for easy and complex Vision applications. - Standard PC Interfaces for easy and standarized communication. - 4 asynchronous camera inputs for 4 independant inspections. - Windows NT - a well-known and secure operating system. - SVObserver The Interface for easy configuration contains an extended catalogue of tools, no programming is necessary

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What to look for in a syringe ? Inspection areas
Finger flange Plunger Fill level Liquid/ particles

Tip cap/ needle shield position Sidewall above / below plunger

More components than in ampules + vials More fragile than most vials Therefore more images have to be taken in order to perform a thorough inspection

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Agenda
Intro Seidenader Maschinenbau Syringe inspection Material handling Vision system Particle inspection Cosmetic inspection Validation approaches Training requirements References

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Particle inspection station

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How to look for defects ? Particles

Good

Glass Chip and dust

Defects Glass Rubber Fibers moving / non-moving

Method Backlight Polarized backlight Darkfield 2 x 4 images Imagesubtraction

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Particle inspection

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Particle inspection

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Detection performance Particle inspection
120% 100% 80% 60% 40% 20% 0% 30 Automatic inspection Manual inspection

50

75

100

200

300

Source : Abbreviated version of data published by Dr. John Shabushnig, Pharmacia Corporation, USA Seidenader tests on Pi 30 machines with calibrated glass particles

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Particle detection performance comparison Machine vs machine Product 1 Line Sensor Polymers< 100y Glass fragments 100-200y Glass fragments 500y Glass fragments >1,0mm Fibers 500y - 1,0mm Floaters 75,9 57,8 85,2 93,3 75,1 60,0 Seidenader 99,4 68,9 84,7 99,3 93,5 100

Source :Thesis by Dr.J Peters, Roche, Basel, Switzerland

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Particle detection performance comparison Double blind study Product 2 Line Sensor Seidenader Human

Glass fragments 100y-1,0mm 55,6 Fibers Empty Underfill 5% Underfill 10% Overfill 10% 60 100 80,0 100 93,3

96,6 87,3 100 100 100 100

55,1 42,1 100 18,2 70.4 51,9

Source :Thesis by Dr.J Peters, Roche, Basel, Switzerland

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Detection performance comparison Knapp samples AventisPasteur, France

AventisPasteur collected Knapp set to evaluate performance of new Seidenader SI machine, built for AvP, Swiftwater, PA. A set of 215 syringes (148 good, 67 particle defects) was put together and run on the machine on May 17-19th, 2001 at SVResearch,Harrisburg. After the test runs, the data was compared to the data from human inspection and the existing machine at AvP, Val de Reuil, F. The product was influenza vaccine, a light suspension, based on aluminium hydroxide

Source :Test data from comparative study by SVResearch and ,AvP, F

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Detection performance comparison Knapp samples AventisPasteur, France Defect Glass, large (>5mm) Glass,mid size (1-5mm) Glass, small (100-1000u) Plastic White fiber White particles Colored particles/fibers Overall False rejects Manual 100 99 62 71 45 45 60 79 1,50 Existing 100 100 71 65 52 39 61 79,1 2,20 Seidenader SI 30 100 100 77 91 99 100 62 89 1,20

Source :Test data from comparative study by SVResearch and ,AvP, F

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Detection performance comparison Knapp samples AventisPasteur, France Biggest Challenges White particles/fibers in suspension Seidenader have developed special vision tools and light technique to enhance the contrast of these defects. A combination of light absorption and light scattering methods are used in conjunction with double polarisation Large, non moving particles / Chips A special inspection window is used to detect light absorbing or reflecting edges/lines in the bottom part of the syringe Airbubbles in the liquid A contour tool was used in conjunction with the standard blob analyzer, to allow separation of small glass and plastic particles and airbubbles by their profile. This allowed to inspect at a higher sensitivity without increasing the false reject rate for these defects.

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Agenda
Intro Seidenader Maschinenbau Syringe inspection Material handling Vision system Particle inspection Cosmetic inspection Validation approaches Training requirements References

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How to look for defects ? Flange defects

Defects Chips Broken edges Concentricity

Method Ringlight 1 image

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How to look for defects ? Flange defects

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How to look for defects ? Sidewall defects

Pic 1

Pc 2

Pic 3

Good

Cracks

Fill level

Defects Particles sticking to sidewall Fill level Cracks above / below the plunger Presence of print

Method Backlight 6 images

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How to look for defects ? Sidewall defects

Pic 1

Pc 2

Pic 3

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How to look for defects ? Plunger defects

Good

Liquid between ribs

Damaged plunger

Defects Position / Orientation Liquid between the ribs Rib geometry

Method Backlight 6 images

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How to look for defects ? Plunger defects

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How to look for defects ? Needle shield / Tip cap defects

Good

Wrong position

Needle shield bent

Defects

Method Backlight 3 images

Gap to shoulder Banana shapes

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Agenda
Intro Seidenader Maschinenbau Syringe inspection Material handling Vision system Particle inspection Cosmetic inspection Validation approaches Training requirements References

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Validation support Team of 4 dedicated specialists in Seidenader No external consultants or third party Experience of over 50 IQ/OQs on Seidenader machines in US and Europe Kick off meeting/ Audit / Validation matrix Protocol design and review Execution of protocols w/ Seidenader specialists support on site Standard protocols or completely customized and execution by Seidenader available as option

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Validation approach 1 OQ Focus on samples PQ

A Performance existing inspection

Specification sample set

B >/ = A

1. PQ Batch Reinspect manually Adjust Y/N

2. PQ Batch

B Performance automatic inspection machine

AQL met ? Y/N

3. PQ Batch AQL met ? Y/N

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Validation approach 2 Focus on Production

Vendor selection Specification

FAT/SAT

IQ/ OQ

PQ Reinspect Good and Bad manually Repeat 2 x Inspect production on machine

Sample set

Define capabilities

Samples vs. specification

compare Data

Overall machine must outperform manual method Inspect production manually Reinspect Good and Bad on machine

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Agenda
Intro Seidenader Maschinenbau Syringe inspection Material handling Vision system Particle inspection Cosmetic inspection Validation approaches Training requirements References

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Different levels of Training

Basic SVIM Training

Vision application training

Operator & Maintenance Training To understand how to operate and maintain m/c, cleaning, status messages, documentation, simulations Training on machine at customer 3-4 days after installation

To understand principles of vision processor, light, inspection tools, filters, etc Training courses regularly in MUC and HBG 3-4 days before FAT

To understand features used in specific application

Training on machine at customer 3-4 days after SAT

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Agenda
Intro Seidenader Maschinenbau Syringe inspection Material handling Vision system Particle inspection Cosmetic inspection Validation approaches Training requirements References

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Experience w/ automatic inspection of syringes

SI 20/30/40 Syringes up to 400/min Leo Pharma, Vernoillet, F Aventis Pharma, Maison Alfort,F Aventis Pharma, Le Trait, F Rovi, E Federa, B Solvay, NL Aviron, USA Schering Plough, USA Becton Dickinson, USA 2x 3x 2x