Investigations are very important as these help company to solve the issues. It helps finding the solution of deviations, failures, market complaints, out of specifications. It helps us to reach the root cause of the problems.
It we will not investigate any issue in depth then its high possibility that we will reach wrong conclusion and hence there will be mistake in taking the accurate CAPA.
What will be the result of taking wrong CAPA?
The deviation or problem will not be solved. The issues wont stop. Every day you will face new problems. Because due to that CAPA the actual problem will not be solved.
This is the reason that about 122 pharmaceutical companies got Warning Letters due to the inadequate investigations.
We are discussing this topic since last few articles and in these we see different angles and mistakes which lead to critical non compliances and companies got Warning Letter.
Lets discuss this new case study.
The firm failed to adequately perform a timely and thorough investigation into the in-process OOS results obtained for (b)(4) tablet drug products. For example, FDA investigators found that approximately 27 validation and commercial batches of (b)(4) tablets with different strengths failed blend powder drum assay acceptance criteria and were compressed and released before being adequately investigated.
Now what do you think with this case where batches released before the investigation is closed?
When one do not know that the batches are complying with the acceptance criteria or not and batches are released. What will be its impact on the patient's life? What will be its impact on the brand of the company?
How these batches will give rise to the business of any organization?
During the inspection, firm generated a technical report explaining the OOS results were related to the drum sampling process. Specifically, it stated that the angle of insertion of the sampling thief was insufficiently shallow and resulted in the application of extra force.
In the response, firm provided investigation. The investigation is deficient in that it only considered (b)(4) batches and not extended to all similarly impacted drug product.
Furthermore, firm's response concluded that additional OOS results for the drum samples tests did not require investigations. However firm submitted the Risk Assessment report.
The response was found to be inadequate.
As per the authority firm is responsible for conducting a thorough investigation when it become aware that a product fails to meet any of its established specifications. The firm failed to assess other sources of variability, allowed the continued use of flawed sampling processes and did not identify correct CAPAs.
Furthermore, timely investigations are essential when data indicates a problem with a system or process.
o Determine whether the scientific justification and evidence relating to the invalidated OOS result conclusively or inconclusively demonstrates causative laboratory error.
o For investigations that conclusively establish laboratory root cause, provide rationale, and ensure that all other laboratory methods vulnerable to the same or similar root cause are identified for remediation.
o For all OOS results found by the retrospective review to have an inconclusive or no root cause identified in the laboratory, include a thorough review of production (e.g., batch manufacturing records, adequacy of the manufacturing steps, suitability of equipment/facilities, variability of raw materials, process capability, deviation history, complaint history, batch failure history).
Provide a summary of potential manufacturing root causes for each investigation, and any manufacturing operation improvements.
o Quality unit oversight of laboratory investigations
o Identification of adverse laboratory control trends
o Resolution of causes of laboratory variation
o Initiation of thorough investigations of potential manufacturing causes whenever
a laboratory cause cannot be conclusively identified
o Adequately scoping of each investigation and its CAPA
o Revised OOS investigation procedures with these and other remediations
Read this case study and article multiple times and review investigations on your site.
In case you find any gap fill the gaps and make your system in compliance.