Sterility Testing Failure: What Happens Next?

By Andy Whittard


There is no worse feeling than performing a sterility test on a batch of a product only to have the product fail the test and be positive for microbial contamination. It is far from a perfect process, being both time consuming and labour intensive, but it is the safest solution to ensure that when a positive test is indicated, that there is contamination present in the product.

So how should the manufacturing process move on after a batch of the product fails the sterility test? What procedures should be in place to handle such a failure? And how can you turn advance preparation for a test fail into part of your ongoing processes that will help you avoid such an event in the first place?

The sterility test is a critical touchpoint before product release

The sterility test is a microbiological test required by all pharmaceutical regulators. It looks at a portion of batches to see if they produce microbial growth after 14 days of incubation in appropriate media.

Performing the test is crucial because releasing a contaminated batch of a product can carry extremely serious consequences for both public health and business reputation, as so tragically demonstrated in the case of the NECC.

The required, successful completion of the sterility test is often the last step before a product can be released. Failing the sterility test results in quarantining the entire affected batch.

An investigation to determine how the sterility test failure occurred will follow. This will mean suspension of production while every stage of your manufacturing and testing process is examined for potential areas of risk.

The better prepared you are for this potential situation, the quicker you should be back up and running again.

Start by retracing the steps in your aseptic manufacturing process

Every manufacturer of sterile products needs a clear investigation procedure in the event of a failed sterility test. The investigation procedure needs to lay out who is involved and responsibilities, including what should be examined. The best way to tackle this is with a checklist.

Have a checklist of actions to follow after your sterility test fail

As with aviation or surgery, there are a lot of specific, critical steps in every procedure: too many for one person to remember off the top of their head.

Having checklists ensures that those steps have been completed in a consistent and efficient manner, while also freeing the investigator from planning next steps while analysing results.

Checklists during maintenance, the manufacturing process, sterility testing, and sterility test failure investigation will assist the investigative process by making each step and their correct order clear. They will also provide information about the equipment and process leading up to the failure, making it easier to spot and place corrective action. 

Audit your lab and how it is set up to handle sterility testing

Your checklists to handle a sterility testing failure should begin with the test itself. Problems in sterility testing could lead to a false positive and need to be carefully examined.

Using positive and negative controls, like method validation, the experimental setup itself can be examined as a source of the contamination. The testing equipment and environment found in cleanrooms and isolators, need to be certified as sterile, well maintained, and within expiry date.

The checklist of items to review before performing sterility testing is similar to the checklist to rule out laboratory processes in the case of a sterility testing failure. This can be used to pre-emptively check for issues such as expired products and missed maintenance.

Follow your manufacturing and filling process for your failure investigation

Manufacturing and filling processes need to be examined to find potential sources of the contamination.

Materials used in the manufacturing process, the manufacturing environment, the sterilisation procedures, the manufacturing and filling processes, the operators controlling the processes, and even the cleaning and disinfection records must be reviewed.

The checklist here should be used to ensure that the manufacturing and filling process examinations are done thoroughly and safely. This can also be used during routine manufacturing and filling to ensure that the correct records, tools, and manuals are easily available and help prevent future failures by ensuring that maintenance is properly performed. The use of environmental monitoring can be applied to help assess areas and processes for potential contamination.

Preparation ahead of handling a sterility test fail reduces negative impact

Preparing your checklists now, ready to perform in the case of a sterility testing failure, gives you better foundation if an investigation is necessary to find and address a contamination source.

Every facet of your facility, manufacturing and testing processes will fall under scrutiny. Many people will be involved, equipment will be out of commission and you will lose revenue. Planning ahead to monitor and maintain appropriate procedures, including investigation protocol, can only be beneficial for the future.

Preparing in advance for a potential sterility testing failure can also highlight areas of risk in the manufacturing, filling, or testing processes before a failed sterility test, allowing them to be addressed well before an actual problem arises. Additionally, these preparations can be based on, or double as, regular maintenance procedures, ensuring consistency in standards across your facility.

A sterility test failure is a dreaded situation for those involved in the manufacturing of sterile products. However, being prepared for that possibility is the best way to effectively and economically handle a test failure and address the root cause.

Creating checklists that lay out clear response procedures will reduce its impact while maintaining testing integrity. Using those checklists regularly, as a basis for maintenance, will reduce the probability of a failed sterility test and aid  the investigative process if sterility testing does fail.


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