CAPA and Root Cause Analysis

Some companies have implemented electronic solutions for pieces of the CAPA process. “But very few pharmaceutical firms have implemented a comprehensive process” like the one Fetterman is installing for his current client, he says. “They had a totally manual process before,” he adds.

People issues

In Fetterman’s experience, it is extremely difficult to get people across all sites to follow the CAPA complaint and investigation process in the same way. “The biggest challenge we had with this global rollout was coming up with a consistent and reliable approach to handling CAPA complaints and investigations worldwide,” he says.

To establish consistency, companies must have a strong directive from senior management for the project, and a commitment by the organization that “this is the way we are going to handle it,” he says. “You just don’t want to have separate workflows for different sites.”

Of course, even the best technologies and processes are only part of the solution. The cultural issue of getting people in the organization to perform their CAPA responsibilities is the key to any successful program for dealing with CAPA complaints and investigations. “How to incent employees to work on the same page is important,” says AMR’s Jacobson. “The technology is the enabling component, but someone has to own responsibility for the process. A lot of companies have put together cross-functional teams.”

FDA-certified consultants who specialize in CAPA can facilitate its acceptance, Jacobson says. “Having a credible outside voice to come in is helpful,” he points out.

This is especially true for pharmaceutical companies that plan to install a specific software package for CAPA. “For a system like TrackWise, you do need specific expertise on how to configure it,” Fetterman says.

But CAPA technology and consultants will take a company only so far, says Wade Speir, senior consultant in the life sciences practice at Kepner-Tregoe, Inc., a Princeton, N.J. consulting firm. “The software is only a part of the solution,” he says. “There are the process issues, which often require changing people’s behaviors.”

The bearer of bad news

The most difficult aspect of CAPA problem solving is getting a sharp fix on exactly what constitutes the problem at issue, Speir says. “By far the hardest part of problem solving is getting a clear consensus of what the problem is,” he says. “You need to identify what’s actually happening as well as what is expected to happen.”

For example, pills often show silicone contamination from the production process. The manufacturer needs to know exactly how much, if any, silicone was expected to appear in the pill under optimal circumstances. Though drug companies may not admit it, “There’s always some contamination from all the valves and machinery,” Speir says. Knowing the proper baseline — whether there is zero or the most minute amount of contamination — is essential to determining how much actual deviation exists.

To identify the root cause of a CAPA problem, the manufacturer must first specify what the problem is, where it occurs, how often, and how big the problem is. It must also test possible causes against the facts of the occurrence. The idea is to see which cause explains the problem. At the same time, this process also should point out the possible problems that could occur and why they are not.

“The idea is to be able to explain why this batch was bad, as well as why the preceding lot and the one after the bad one were okay,” Speir says. Once the company has a hypothesis for what caused the problem, the next step is to test it — either by experimentation, or by fixing it and seeing if this solution works.

Companies need to be sure that their CAPA root cause analysis investigates all possible causes and tests the suspected one to make sure it is, in fact, the real cause of the problem. It’s important to distinguish between the observed symptoms of a problem and the fundamental or root cause. “You want to be sure people are fixing the right issue and addressing the right cause,” says John McLaughlin, principal consultant at Taratec Development (Bridgewater, N.J.). “You don’t want an engineer putting a fix on a problem without addressing the underlying issues.”

The root cause analysis involves answering a battery of questions that ask “why” with the goal of digging deep until the reason for the problem is identified. Sometimes the cause of the problem may only be a symptom of a more pervasive issue. For example, if a poorly trained operator was the immediate reason for the production of a bad batch, the root cause analysis should delve deeper to determine if the plant’s training program itself is at fault. The question should be asked, could other operators be poorly trained in the future?

“Pharmaceutical firms should be looking across the organization to see if a larger problem exists,” adds McLaughlin. “The good news is always great to hear, but the bad news is what you really want to hear. Companies should remember that, at the end of the day, the CAPA process is supposed to help them.”

All this activity must be documented to prepare a full investigation report for the FDA. Much of this information can be drawn from the batch record, which in many instances, can be found in binders of information. “For many companies this is quite a challenging effort,” Speir adds. “And usually the people doing it are not the highest paid in the organization.”

Identifying the root cause of a CAPA event is only part of the overall CAPA action to be taken. The other half of the process is determining what actions can be taken both to correct and prevent such occurrences.