Using Root Cause Analysis to Find Pharmaceutical Manufacturing Deviations

Using Root Cause Analysis to Find Pharmaceutical Manufacturing Deviations

September 26th, 2018 // 1:36 pm @

Investigating the cause of a drug quality failure is something that all drug manufacturers must do, and some must do so more frequently than others. FDA 483s and warning letters often cite improper corrective and preventive action (CAPA) as a major problem with compliance. How do you ensure that your CAPA program is on the right track? Many experts in the CAPA field say that the more comprehensive and structured your CAPA program is using root cause analysis, the more successful it will be.

While CAPA will be handled in different ways at different pharmaceutical companies, best practices for dealing with investigations and complaints revolve around common core activities and basic processes.

One of the biggest problems that drug companies have is breaking down the various silos in the firm, each of which could have several different CAPA processes and technologies they are using in different departments or buildings. These companies may have several different CAPA methods in their organizations, but they lack a common way to perform trending and put preventive actions into place across the entire organization.

Many smaller companies are actually more effective handling their CAPA complaints than the big companies. At a single site company, workers are more likely to work as a team. But with big companies, silos are common and there is a greater need for a systematic approach to CAPA.

Many CAPA problems that are cited in warning letters and 483s boil down to a lack of process requirements and written procedures. Having no systemic management processes to handle CAPAs means the company cannot audit their processes and take strong preventive actions across multiple sites.

Most CAPA investigations are initiated by an abnormal event, such as a lab investigation, manufacturing issue, an FDA inspection or a customer complaint. These items are entered into the CAPA system and starts the CAPA investigation. But this is often too late. The heart of a strong CAPA is defining the problem and assessing who, what and where is  a risk, and the impact on the company if the problem grows.

Generally, CAPA experts recommend that a root cause analysis investigation follow these steps:

  • Identify the problem
  • Evaluate the size and magnitude of the problem, including risk assessment
  • Investigate the issue and assign responsibility
  • Analyze and fully document what the root cause of the problem is
One of the most challenging parts of the CAPA issue is determining exactly what the problem is. The hardest part of this problem solving is getting a consensus among stakeholders about what the problem is. You need to identify what is happening and what is likely to happen.
For example, pills frequently show silicone contamination when they are manufactured. The drug company must know exactly how much silicone will be in the pill in the perfect circumstance. Drug companies are loathe to admit it, but there is always a certain amount of contamination from the machinery and valves. Knowing what the baseline is will be vital to determine the level of deviation.
Companies must be sure that their root cause analysis CAPA investigates all potential causes and tests the most likely one to be sure that it is the real problem cause. Distinguish between symptoms that are observed and the root cause. Be sure your people are fixing the actual issue and addressing the real cause of the CAPA.


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