On-line monitoring, linked to an infrastructure that integrates a company's various data systems, can provide personnel with
excellent visibility of the manufacturing process. But the wealth of information that this infrastructure provides, coupled
with memories of production problems that have brought regulatory scrutiny, can prompt pharmaceutical manufacturers to be
overly cautious with their CAPA programs. "Not all deviations will be CAPAs. I think a lot of people tend to funnel all their
deviations into the CAPA system, and that's not necessarily appropriate," says Schniepp. A deviation should lead to a CAPA
only when the result of that deviation would affect the product's quality and safety.
A common problem in CAPA programs today is many companies' failure to distinguish crucial from noncrucial events. "Events
in a quality system often always become a CAPA, until the company has more CAPAs than it can manage effectively," says Tim
Lozier, manager of strategic development at EtQ (New York). As a result, manufacturers often focus on addressing the most
overdue CAPAs rather than completing those that represent the most crucial events. The excess of CAPAs can create a bottleneck
in an otherwise healthy quality system.
Risk-assessment tools can help companies judge whether or not an event is crucial. First, a company develops risk formulas
based on its past events. When the software system records a deviation, the risk-assessment tools evaluate the threat that
it poses to factors such as compliance, safety, and quality. The company also assesses the deviation's severity and frequency,
and these calculations result in a risk ranking for each deviation. The ranking helps the company decide whether the event
is crucial or not. "This strategy allows for a more focused approach to corrective actions and allows companies to focus their
attention on the events that matter most to the business," says Lozier.
A cosmetic error such as a smudged logo on a finished product may not be deemed crucial, especially if it occurs in a single
lot, and can be immediately corrected. Less crucial events are handled in the event record. A mislabeled finished product,
however, can have a higher risk ranking and be deemed crucial. The definition of a crucial event can vary from company to
company, depending on each manufacturer s history.
The industry is beginning to accept this risk-assessment approach to CAPA as the best practice. For some pharmaceutical manufacturers,
crucial process-parameter deviations automatically trigger a CAPA process. The number of noncrucial deviations that triggers
a CAPA process depends on the culture of the particular company, says Lenich.
Automation for all?
A fully automated CAPA process helps pharmaceutical manufacturers in different ways, and to different degrees, depending on
their size. Although small, medium, and large drug companies face similar regulatory scrutiny and compliance challenges, the
resources available to these companies differ, which may explain why pharmaceutical manufacturers have embraced automation
to different degrees.
Automation is not necessarily cost effective for companies with 100 employees or fewer, says Schniepp. Setting up automated
CAPA systems can be time consuming and might not provide many advantages to firms that manufacture low volumes of a small
portfolio of products. Instead, small drugmakers are likely to rely on their contract manufacturing organizations (CMOs) to
The extent to which small companies are automating their CAPA processes is unclear. Small companies do stand to benefit from
automation, says Lenich, but they often view automation as a cost rather than as a value. This perception is a salient distinction
between small drugmakers and mid- to large-sized manufacturers.
Even if they cannot automate their CAPA systems fully, smaller companies can find automation for specific parts of the CAPA
process, which may help them address performance concerns and focus on continuous improvement, says Kentrup. "The challenge
is to determine a prioritization scheme for automating parts of the process that is consistent with expected business outcomes,"
he adds. Considerations that would promote the automation of a CAPA system include minimizing the initial financial investment,
monitoring process performance, and containing capital-investment costs.
It can be difficult for mid-sized pharmaceutical companies to determine how cost effective it is for them to implement an
automated CAPA system, partly because they are uncertain about whether their products will reach the market. A mid-sized company
with a mixture of small- and large-molecule products will likely want to track the active-ingredient manufacturer, final-product
manufacturer, and packager for each late-stage product. If the company hires 12 CMOs to provide four products, it might consider
automating its CAPA process to keep track of its contractors' operations, says Schniepp.