Regulatory Inspections Get Serious

Q. Are inspections getting tougher?

A. Many reviews of regulatory inspection activities focus on the top 10 citations/findings, which say a lot about the areas of concern, but little about how these inspections are conducted or whether or not inspections are getting tougher. Several agencies publish their inspection standard operating procedures (SOPs) or how they inspect (1, 2). This gives the industry a good idea how the inspection will be conducted and what areas will be looked at. The industry has studied these documents and learned from inspections over the years. Consequently, one should assume that all is well under control, but is it?

Siegfried Schmitt

FDA inspections

Feedback from both inspected companies and consulting firms points to a significant change in the focus of FDA inspections of foreign drug establishments and the expected response by the inspectors. This change has caught many companies by surprise. The following examples clarify the observed change:

• A multinational European manufacturer had been inspected regularly and apart from the occasional observation on form FDA-483 did not have any issues of note. During the most recent inspection by FDA, the same common areas, such as deviation management and the associated corrective and preventive action (CAPA) process were scrutinized. There was no lenience when it came to incomplete or ambiguous records for root cause analysis or delayed completion of CAPA. The argument "but we have always done it this way" only contributed to FDA's issuance of a warning letter.

• A large Asian company with a good history of compliance received a series of FDA-483 observations to which they responded in the same manner as for previous inspections. However, where it had been sufficient in the past to describe CAPA actions specific to the findings, FDA dismissed their response as not addressing the totality of the findings in a holistic and encompassing way. Where FDA now states that they consider the integrity of the quality system compromised, a review of the entire system is expected. Any response that falls short of this expectation can have serious consequences, such as an import ban.

• Another company learned that implementation of International Conference on Harmonization (ICH) Q7, Q8, Q9, Q10, and Q11 guidelines is now also expected by FDA. FDA inspectors were no longer satisfied with being presented the odd risk assessment, rather than a company-wide approach to quality risk management.

Other regulatory agencies

Though the given examples resulted from US FDA inspections, there is no reason to believe other agencies do not or will not apply a similarly tough approach. In these and similar cases, the issue was that companies either failed to maintain their quality management system in a state of compliance with the applicable regulations and guidances, or that their attitude to resolving identified issues was neither holistic, nor investigative enough. This is a clear sign that there just is no room and time for complacency and failure to keep up with the developments in regulatory expectations. Just because inspectors sometimes provide industry with some leeway during inspections does not give them any right to flaunt the regulations and compromise compliance. Compliance really is an attitude, one that has to be understood, embraced, and implemented by everyone in the organization, including top management.

References

1. FDA, Compliance Program Guidance Manual, 7356.002F, www.fda.gov/ICECI/ComplianceManuals/ComplianceProgramManual/ucm2005382.htm, accessed July 15, 2013.

2. EMA, Compilation of Community Procedures on Inspections and Exchange of Information, EMA/INS/GMP/459921/2010 Rev 13.