During the course of a drug or drug product’s development and as the product is nearing completion, it needs to be tested to ensure that it performs as expected, within the specified limits as mentioned in the compendia, drug master file, or drug application. When it does not and falls outside the specified limits, it is said to be OOS or out of specification. If this happens often, it is an indication of the manufacturing and analytical procedures not being in control. It can lead to frequent customer complaints and the rejection of commercial batches. As a result, the pharmaceutical business will face a heavy inventory loss. It may also compromise the safety of patients and their handlers. Therefore, any incident of OOS result occurrence must be investigated and the root cause addressed.
Typically, the specified limits are detailed in documents such as the compendia, drug master file, or drug application. This happens right at the product design stage after the product has been conceptualized and the details of the nature of the product, its goals, and the raw materials to be used are specified. The testing criteria are also laid down at this stage, explaining how the product should be tested and who will be testing it.
From the time of design to the time of manufacturing, the design undergoes several changes. Due to these changes or due to process errors, deviations may be introduced at the time of manufacturing too, This can cause Out of Specification. Some of the common factors of Out of Specification (OOS) include:
- Deviations during the product manufacturing process
- Errors during testing due to incorrect procedure
- Errors caused by malfunctioning analytical equipment
Therefore, to understand whether the error is due to the product not conforming to the specifications or other factors, a root cause analysis must be performed to identify the true cause. The OOS causes can be classified as
- Assignable: When the error is identified.
- Non-assignable: When the error is not identified.
On observing an OOS result, a laboratory preliminary investigation (Phase-I) is recommended to identify the assignable cause. Based on the findings, further investigations will be conducted. If no error was found, then too, the batch may need a QA to be performed.
These decisions are communicated by the QC team to the designated personnel on OOS being reported, who will be responsible for classifying the OOS as the assignable or non-assignable cause.
