FDA inspector exposes most common regulatory violations at BWB

At Biotech Week Boston (BWB) on Tuesday, Wang discussed how companies can better prepare for inspections by the Center for Biologics Evaluation and Research (CBER) to ensure their manufacturing processes are in line with regulatory expectations.  

During her talk, Wang gave an overview of CBER’s objectives and what the organization looks for when they perform facility inspections. On inspection day, manufacturers can expect CBER to verify compliance with cGMP and the accuracy and completeness of information that has been submitted. CBER also reviews additional related documentation, evaluates manufacturing controls, and observes critical manufacturing processes, including aseptic processing. 

“The most common observations that we have are in quality, facility, and equipment,” Wang said, reminding the audience that observations are not fully representative of a determination of compliance by inspectors. “You can always discuss observations during inspection.” 

The most common inspection issues that Wang observed included lapses in documentation. She said that organizations sometimes fail to observe good documentation practices, resulting in written procedures that are incomplete or improperly followed. At times, data is not adequately secured, maintained, and managed.  

In her discussion of quality system observations, Wang said that deviation management has also proven insufficient for some companies. She added that organizations often fail to initiate deviation reports or lack a complete root cause analysis after initiation. “I hear ‘Based on this and that we don’t think this is a non-conformity,’” she said, cautioning that in cases when a drug product is affected by an event, a timely investigation and root cause analysis is necessary. 

Companies sometimes fail to effectively implement corrective and preventive action (CAPA) plans or manage them correctly. Training as well is sometimes inadequate, particularly for aseptic techniques, which can be compounded by a lack of quality oversight.  

Wang also discussed common facility and equipment system observations. She said that companies sometimes lack air monitoring of cleanroom areas. She said that companies sometimes mistakenly think they can do without this capability during certain operations, “but that’s a 483 [observation].”  

At times, cleaning-procedure documentation is not specific enough to ensure consistent execution. She added that one of the most important aspects of cleaning validation is ensuring that it is adequately conducted to support multiple product use, which is a weakness for some organizations. 

Other commonly cited observations include deficiencies in qualification of equipment, unplanned maintenance being performed without quality oversight, and deficient effectiveness studies on the disinfectant that companies use.