For-cause inspection

The FDA carries out two types of inspections surveillance inspections and compliance inspections. Surveillance inspections are the biennial inspections. Compliance inspections are to follow-up on previous corrective actions. Compliance inspections also include For Cause Inspections, which are inspections to audit a specific problem that has come to the FDA s attention, for example, product recall and industry or public complaints. There are two options of inspections (1) the Full Inspection Qption and (2) the Abbreviated Inspection Qption. 

The FDA s Bureau of Drugs requested a for-cause inspection of the manufacturer s laboratories to determine the cause and extent of the discrepancies. A for-cause inspection is one initiated at the request of an agency unit when there is reason to suspect a problem in an FDA-regulated product. The authority to make for-cause inspections is a general one imder the FFDCA, but one that had rarely been apphed to animal laboratories. 

One approach would have been to continue the program of for-cause inspections, but they would be triggered only by perceived deficiencies in the data after submission to the agency, and thus would not have provided systematic assurance that all studies were valid or guidance to laboratories on standards for conduct of studies. 

Before 1992 FDA normally provided at least 1 weekly advance notice of a GLP inspection except in the case of for-cause inspections, which usually occurred without advance... 

The second type of GLP inspection is the directed, or for-cause, inspection. The directed investigation is more comph-cated by its nature than the routine and is less frequently performed in the GLP program. These constitute only about 20% of the GLP investigations completed since the regulations were invoked. 

In addition to the for-cause inspections, the FDCA mandates that the FDA routinely inspect a manufacturer s facilities for cGMP compliance every two years. This applies to domestic and foreign facilities which manufacture drugs for sale within the United States.7 Unfortunately, this two-year mandate is rarely satisfied because the FDA s district offices, which are charged with the responsibility for the inspections, lack sufficient resources to conduct regular cGMP compliance inspections. 

Compliance inspections are for the purpose of evaluating or verifying compliance corrective actions after a problem has been identified and regulatory action has been taken. Compliance inspections cover the areas found deficient and subjected to corrective actions. One type of compliance inspection is a for-cause inspection, which is conducted to investigate a specific problem that has come to the attention of the FDA. The sources that trigger a compliance inspection include field alert reports, industry complaints, and recalls. 

Auditors should select the audit method most appropriate for their intended audit purpose. Initial quality system audits or regularly scheduled audits are likely candidates for the top-down approach, while audits conducted as part of a root cause analysis, for example, may best employ a bottom-up approach. The FDA employs a similar approach to inspections. Regular scheduled biennial inspections are more likely to employ a top-down methodology. For cause inspections conducted in response to a specific product issue such as a recall are more likely to employ a bottom-up approach. FDA investigators may employ a combination approach during biennial inspections if investigators are aware of specific quality problems that they wish to include in the inspection. 

As a result of these FDA observations, for-cause inspections were performed at a number of institutions conducting preclinical safety studies. The results of these inspections were reported to the U.S. Senate in July of 1975, by the then FDA commissioner, Dr. Alexander M. Schmidt. The findings for these for-cause inspections showed problems in the design, conduct, and reporting of preclinical safety studies. These problems were deemed so serious as to question the validity of some studies. The following examples are illustrative of the magnitude and seriousness of the problems uncovered in these for-cause inspections carried out by the FDA. 

An audit at Searle found a number of similar problems. For example, the audit or for-cause inspection carried out by the FDA showed [10] the following ... 

Although not specified in the FDC Act, internal audit data as it relates to compliance with cGMP requirements, are typically not subject to FDA review, but the agency might seek confirmation that audits were performed. FDA has described situations, such as a for-cause inspection or during litigation, in which it might seek a review of this type of information. 

The FDA s Bureau of Drugs requested a for-cause inspection of the manufacturer s laboratories to determine the cause and extent ofthe discrepancies. A for-cause inspection... 

Before 1992, the FDA normally provided at least one weekly advance notice of a GLP inspection except in the case of for-cause inspections, which usually occurred without advance notice. Current FDA policy, however, is to conduct all GLP inspections in the United States without advance notice. Generally the FDA continues to provide advance notice of GLP inspections outside the United States. 

---