Inspection Parenterals

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  • Topic: Carbon, Particle, Raman spectroscopy
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  • Published : December 19, 2012
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Bethesda 2005 PDA Visual Inspection
The Top Ten compounds of particulate contamination in parenterals Markus Lankers Rap.ID Particle Systems GmbH

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Bethesda October 20, 2005

Liquid Particle Explorer: Number Size, Composition in Minutes

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Liquid Particle Explorer®
Number

Particles >2µm
•Fully Automated •Easy Calibration

Size Shape Chemical Composition (ID)

Liquid Particle Explorer: Number Size, Composition in Minutes

Visual Inspection - Production
given: product free of visible (foreign) particles (>50 µm) results: 1. 100 % visual inspection 2. separation of rejects 3. removal of rejects 4. reject rate (PM): 0.2-3%

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Liquid Particle Explorer: Number Size, Composition in Minutes

Know Your Particles
particle !

Source !
source ?

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Liquid Particle Explorer: Number Size, Composition in Minutes

Particle Characterization in the Lab
method light microscopy EDX analysis IR – microscopy RAMAN microscopy meaning colour + form e.g.: black fibres elements e.g.: 96% Fe, 4%Cr,.. compounds e.g.: Teflon, PE, compounds e.g.: Teflon, PE, TiO2

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time/particle 1-5 min 60-180 min 60-180 min 60-180 min

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Chemical Analysis

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Polyethylene
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Measurement
•membrane filtration 1 •measurement 3

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2 1

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Liquid Particle Explorer: Number Size, Composition in Minutes

Filter

Scan Fields

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•Membrane (0.8 µm, 3 µm) RAMAN inactive

Liquid Particle Explorer: Number Size, Composition in Minutes

Image Analysis
5µ m

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Liquid Particle Explorer: Number Size, Composition in Minutes

8µ m

Automated Spectroscopy

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Liquid Particle Explorer: Number Size, Composition in Minutes

RAMAN Spectroscopy
laser spectrometer

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nodge

ccd- detector

Liquid Particle Explorer: Number Size, Composition in Minutes

Documentation

data tracking

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hypertext document Scanning picture

number and size of particles original spectrum and ranking of the data bank Liquid Particle Explorer: Number Size, Composition in Minutes

Protein Solution @ 25 µm
Protein A > 250 µm

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Cellulose > 50 µm

Fluorescence > 25 µm

Liquid Particle Explorer: Number Size, Composition in Minutes

Example 1: Troubleshooting
Observation: Rejects from visual inspection Pool of 3 samples Defect filter element Substance Amorphous Carbon UPO Fluorescence Polyester all particles Number 5 4 9 475 493 >=25 4 2 5 372 383 Size distribution [µm] >=50 1 1 2 82 86 >=100 0 1 2 21 24

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Liquid Particle Explorer: Number Size, Composition in Minutes

Importance of small particles
1. In ~ 75 % of our troubleshooting applications we observed a few visible particles in a huge amount of smaller particles of the same substance You can avoid a lot of trouble and troubleshooting by continuous monitoring of your particle (particulate process profiling)

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2.

Liquid Particle Explorer: Number Size, Composition in Minutes

Example 2: Protein aggregation
Monoclonal antibodies: Rejects in visual inspection: Aggregation of product or foreign particle ? Visible particles identified as protein Substance Silicone oil Polystyrene carbon Fluorescence Protein all particles Number 4 2 4 3 72 85 Size distribution >=2 0 0 0 0 0 0 >=5 1 0 2 1 14 18 >=25 3 2 2 2 30 39 >=50 0 0 0 0 12 12 >=75 0 0 0 0 16 16

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Liquid Particle Explorer: Number Size, Composition in Minutes

Top Ten
1872 measurements of 303521
Number >=10 % Number >=50 % Cellulose 15582 7,1 8411 9,9 Longchain hydrocarbon 8731 4,0 2551 3,0 Polyester 7115 3,2 3708 4,4 Talcum 1903 0,9 205 0,2 Silicone oil 6281 2,9 2778 3,3 Protein (Keratin) 6255 2,9 2748 3,2 Polystyrene 4993 2,3 1575 1,9 Polypropylene 2979 1,4 2655 3,1 Carbon 7670 3,5 3648 4,3 Titandioxide 3627 1,7 632 0,7 Organic substance 19626 9,0 3632 4,3 Fluorescence 28980 13,2 7434 8,8 Other compounds 105188 48,0...
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