The purpose of an investigation is to determine why an unexpected event occurred and to prevent it from happening again. We call the reasons for the unexpected event the “root causes,” or underlying causes. Once we understand the root causes, we can identify and implement corrective and preventive actions to prevent the problem from recurring.
Preventing the problem from recurring is important for several reasons. Primarily, the goal is to protect patients by ensuring that product is being produced safely, effectively, and consistently. The Food and Drug Administration (FDA) regulations are in place for the same reason – to ensure the safety to consumers. Therefore, complying with the regulations achieves the same goal as protecting patients.
21 CFR Parts 210 and 211 contain the Current Good Manufacturing Practices (CGMP) for Finished Pharmaceuticals. Adherence to these regulations is enforced by FDA.
The CGMPs include specific regulations pertaining to the FDA’s expectations concerning investigations as documented in the box below. To maintain regulatory compliance, and more importantly, to ensure the safety of patients, these regulations must be adhered to.
|CGMP Records and Reports
21 CFR Part 211.192
Any unexplained discrepancy or the failure of a batch or any of its components to meet any of its specifications shall be thoroughly investigated, whether the batch has already been distributed.
The investigation shall extend to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy.
Any written record of the investigation shall be made and shall include the conclusions and follow up.
Form 483’s and Warning Letters
A Form 483 lists observations made during an inspection that is communicated at the conclusion of the inspection. Insufficient investigations are one of the top 10 Form 483 observations. A warning letter is a statement from the FDA indicating that an organization has not complied with the CGMP regulations, thus violating the Federal Food, Drug, and Cosmetic Act, and that the organization has a very limited amount of time to address the problem(s) before the FDA takes further regulatory action.
The following warning letter citations were issued by the FDA to either a pharmaceutical or a biotechnology company, which reflect the FDA’s focus on investigations:
|Warning Letter Citations
“Failure of your quality control unit to investigate thoroughly any unexplained discrepancy or the failure of a batch or any of its’ components to meet any of its’ specifications, and failure to ensure that written records of investigations are made and include conclusions and follow-up.”
“Additionally, it is important that you assess the impact of the investigations findings and take appropriate corrective actions for all of these products that were marketed prior to concluding the investigations. Your response should address this.”
Performing investigations is a critical aspect of patient safety and FDA adherence. Kymanox has expert experience in writing and performing investigations from biotechnology, pharmaceutical, medical device, and numerous other FDA regulated segments of the life science industry. If investigations compliance or training is a gap or concern at your organization, don’t hesitate to reach out to Kymanox for a quick, no obligation discussion.