ISO 24190:2023

INTERNATIONAL ISO
STANDARD 24190
First edition
2023-05
Biotechnology — Analytical methods
— Risk-based approach for method
selection and validation for rapid
microbial detection in bioprocesses
Biotechnologie — Méthodes d'analyse — Approche basée sur
les risques pour la sélection et la validation de méthodes pour la
détection microbienne rapide dans les bioprocédés
Reference number
© ISO 2023
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ii
Contents Page
Foreword .v
Introduction . vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 General considerations .7
5 Risk management for microbiological contamination. 7
5.1 Risk management in manufacturing process . 7
5.2 Risk management in microbial testing . 8
6 Selection of a fit-for-purpose assay .9
6.1 General . 9
6.2 Assay selection . 10
6.3 Kit or system selection . 10
6.4 Considerations for various test types . 11
6.5 User requirement specifications .12
6.5.1 General .12
6.5.2 Speed .12
6.5.3 Sample volume .12
6.5.4 In-process versus final release testing .12
6.5.5 Specificity . 12
6.5.6 Sensitivity . 13
7 Validation . .13
7.1 General concepts . 13
7.2 Selection of microorganisms for validation . 14
7.3 Quality by design of method validation . 15
7.4 Revalidation method . 15
7.5 System validation . 16
7.6 Use of reference material in validation . 16
7.7 Acceptance criteria of targeted validation parameters . 16
7.8 Precision . . . 17
7.9 Detection limit . 17
7.10 Accuracy . 17
7.11 Robustness . 18
7.12 Ruggedness . 18
8 Use and application of rapid microbial tests .18
8.1 Number and type of samples . 18
8.2 Testing environment . 18
8.3 Sensitivity . 19
8.4 Analytical specificity (microorganism detection) . 19
8.5 Comparable test data . 19
9 Investigation of positive sterility results .20
10 Training .20
11 Documentation .21
12 Test report .21
Annex A (informative) Exemplary framework for identifying microbial contamination .22
Annex B (informative) Risk analysis with cellular therapeutic products related to input
materials — Donor selection .23
iii
Annex C (informative) Risk analysis with cellular therapeutic products related to input
materials — Cell transformation and expansion .24
Annex D (informative) Risk analysis with cellular therapeutic products related to input
materials — Packaging storage and administration .26
Annex E (informative) Risk-based classification for monitoring practices for cellular
therapeutic product manufacturing .27
Annex F (informative) Validation of rapid microbial test methods .28
Annex G (informative) Microorganisms for validation of rapid microbial test methods .30
Annex H (informative) Methods for rapid microbial testing .34
Annex I (informative) Environmental control .41
Bibliography .42
iv
Foreword
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v
Introduction
Patient safety is essential in providing cell-based therapies. However, novel cell-based therapies
present many challenges with respect to the timely assessment of microbial contamination. Since
many cell-based therapies have short shelf lives, they are administered to patients within hours after
formulation. In addition to final product testing, testing on cell banks and product intermediates is
common. Microbiological testing includes bacteria, fungi, my
...