Friday, June 21, 2013

Tips On How To Investigate Laboratory & Manfacturing Sterility Failures

Sterility can be defined as the freedom from the presence of viable microorganisms. However, the conditions that guarantee absolute sterility are usually too harsh for active ingredients, and the definition of sterility for a medicinal product must be defined in functional terms.

What do you do when you encounter a sterility failure?

It depends on your perspective!

If you are a Lab Technician you get worried and cry……….if you are a Lab Manager you get furious and try to find out who messed up………if you are QA you reject the batch…………….and if you are part of the manufacturing unit you reject the batch.
How can you settle all these concerns methodically?

The problem can be solved by conducting root cause of the failure.

Investigate:

    What went wrong?
    Where did it go wrong?
    What went wrong?
    How did it go wrong?
    How can it go wrong?
    What & who all are involved?

Investigate the Procedure
The investigation shall be done by a team of professional experts based on company specific written procedures and SOP’s.

Conduct based on Risk
Sterility Failure investigation shall be conducted on a System based Approach.
Laboratory System Investigations

Culture Media

    Media Preparation Details (in-house / ready to use / dehydrated media)
    Negative controls results (passes / fails)
    Growth promotion test results (passes / fails)

Sterilizer & Sterilization

    Media sterilization details
    Sterilizer filter Integrity testing records
    Sterilizer Qualification Reports – any cold spots?

Test Procedure

    Test Procedure / SOP
    Sterilizer filter Integrity testing records
    Analytical manipulations done during testing : Reconstitution / Mixing of the Product

Test Equipment

    Open Sterility Equipments -Requires independent Sterilization and assembly
    Closed Sterility Equipments- Ready to use containers

Test Samples

    Sample Transportation and Handling Procedures
    Records of Sanitization / Decontamination of the sample surface

Analyst

    Qualified
    Training Records
    Self Assessment During Stress Conditions
Environmental Monitoring

    Trend Analysis: Recent Out of Trend data
    Comparison of the recovered organism with that of data bank
    Identification of the organism to species level
    Any typical or atypical organism observed
Cleaning & Disinfection

    Records of preparation of the solution
    Filter integrity testing records
    Reports of disinfection agent effectiveness on the recovered organism



Test Environment

    Sterility Performed in a Uni-Directional Air Flow unit in a classified cleanroom
    Investigate reports for : Preventive maintenence , Air velocity, differential pressure, leak rates , sanitization cycles, cleaning records
    Sterility Performed in an Isolator

No comments:

Pharmaceutical Validation Documentation Requirements

Pharmaceutical validation is a critical process that ensures that pharmaceutical products meet the desired quality standards and are safe fo...