Test Catalog

Validation of matrices for sterility control (BACTALERT)

Code: 61800, 61801

Type: Control de qualitat de medicaments de teràpia avançada

Technical information

Utility

Bacterial or fungal contamination of human origin products (SoHo) can lead to morbidity and mortality in recipients. Possible sources of contamination include asymptomatic bacteremia in the donor at the time of donation and incorrect execution of aseptic techniques during production.

The European Pharmacopoeia provides in chapter 2.6.27 that automatic sterility control methods can be used. The BACT/ALERT® system uses a detection principle based on the carbon dioxide generated by microbial growth associated with the metabolism of the culture medium substrates, resulting in a pH change, and ultimately causing an irreversible colour change of the bottle bottom indicator. This system is advantageous in terms of the speed it provides in microbial detection and recovery, as results are obtained within a maximum of 14 days through continuous reading, and furthermore, the notification of positive samples is immediate. The samples to be analysed undergo minimal manipulation since only the bottles need to be inoculated and placed in the BACT/ALERT cabinet for incubation. Colour reading is automatic, there is no interference from turbidity, and it is a non-destructive method that allows for subsequent microbial identification and antibiogram, if necessary.

According to the European Pharmacopoeia and good manufacturing practices, before performing sterility control on a medium, reagent, or cellular product, it must be validated that the matrix does not interfere with the control method, leading to false positive or false negative results. For this reason, validation of the matrix must be carried out before using the BACT/ALERT method.

Method

Following the European Pharmacopoeia, the following are validated:

  • Specificity (absence of false positive results)

  • Sensitivity (detection capacity of 100 colony-forming units (CFU) or less) of the strains recommended by the European Pharmacopoeia

  • Reproducibility (3 replicates) of the BACT/ALERT for the matrix under study.

In addition, it is verified with a growth promotion test that the bottles and culture media used are fertile and not contaminated.

In the case of cellular products, chapter 2.6.27 of the European Pharmacopoeia is followed. For media and reagents, chapter 2.6.1 of the European Pharmacopoeia is followed.

The validation codes at the Blood and Tissue Bank are V-LC-020 and V-LMB-007.

Diagnostic Algorithm

If microbial growth is detected, a Gram stain is carried out, plated, and the microorganism is identified using MALDI-TOF.

Results

The expected result is:

  • A NEGATIVE result from BACT/ALERT in the negative control (bottle without inoculated microorganism)

  • A POSITIVE result from BACT/ALERT and the detection of the corresponding strains in the positive controls (bottle with inoculated microorganism)

  • A POSITIVE result from BACT/ALERT and the detection of the corresponding strains in the samples (bottle with matrix and inoculated microorganism)

This expected result indicates that the matrix does not interfere and sterility control can be carried out with BACT/ALERT. Any deviation from the expected result is out of specifications and must be investigated.

Precautions

Validation of the matrix must be carried out before performing a sterility control with BACT/ALERT for the first time on a matrix (reagent, medium, cellular product, etc.)

Response Time

  • 20 days

Specimen information

Sample: Matrix to be validated

Tubes: BACT/ALERT vial (see details in the Sterility Control Test Record)

Stability: Transport as soon as possible to the laboratory.

Transport instructions: Room temperature.

Reason for rejection: Unidentified sample, insufficient sample, etc.

Administrative information

BST Code: 61801 for cellular products and 61800 for reagents

Old BST Code:

Test Description: Profile-Validation BACT/ALERT products and Profile-Validation BACT/ALERT reagents

Synonyms: Matrix validation for BACT/ALERT

Section: Microbiology

BST Rate: Check the updated rates here.

Profiles
Not applicable

References

  • Guide to the quality and safety of tissues and cells for human application. 5th edition EDQM, 2022

  • Farmacopea Europea 11ena edició, 2023

  • NCF: Guía de Normas de Correcta Fabricación de Medicamentos de Uso Humano y Veterinario. Anexo 1

  • NCF Parte IV: Directrices sobre normas de correcta fabricación específicas para Medicamentos de Terapia Avanzada.

  • Guia de l'usuari del BACT/ALERT 3D (Biomérieux)

  • Instruccions dels flascons iFA Plus, iFN Plus, FA Plus, FN Plus, BPA, BPN, iAST, iASN