Audits vs Inspections

Did you know that the terms “Audit & Inspection” are different & are not synonymous with each other?

Please find some referenced quotes from the ICH-GCP guidelines and the US-FDA CFRs to enumerate the same.

Audit

A systematic & independent examination of trial related activities & documents to determine whether the evaluated trial related activities were conducted, & the data were recorded, analyzed & accurately reported according to the protocol, sponsor’s standard operating procedures (SOPs), Good Clinical Practice (GCP), & the applicable regulatory requirement(s). As per ICH – GCP guidelines E.6, 1.6.

5.19 Audit
   
 
If or when sponsors perform audits, as part of implementing quality assurance, they should consider:
       
  5.19.1 Purpose
     
   
The purpose of a sponsor’s audit, which is independent of & separate from routine monitoring or quality control functions should be to evaluate trial conduct & compliance with the protocol, SOPs, GCP, & the applicable regulatory requirements.
       
  5.19.2 Selection & qualification of Auditors
       
    a.
The sponsor should appoint individuals who are independent of the clinical trials / systems, to conduct audits.
       
    b.
The sponsor should ensure that the auditors are qualified by training & experience to conduct audits properly. An auditor’s qualifications should be documented.
       
  5.19.3 Auditing Procedures
       
    a.
The sponsor should ensure that the auditing of clinical trials / systems is conducted in accordance with the sponsor’s written procedures on what to audit, how to audit, frequency of audits, & the form & content of audit reports.
       
    b.
The sponsor’s audit plan & procedures for a trial audit should be guided by the importance of the trial to submissions to regulatory authorities, the number of subjects in the trial, the type & complexity of the trial, the level of risks to the trial subjects, & any identified problem(s).
       
    c. The observations & findings of the auditor(s) should be documented.
       
    d.
To preserve the independence & value of the audit function, the regulatory authority(ies) should not routinely request the audit reports. Regulatory authority(ies) may seek access to an audit report on a case by case basis when evidence of serious GCP non-compliance exists, or in the course of legal proceedings.
       
    e.
When required by applicable law or regulation, the sponsor should provide an audit certificate.
       
Inspection
 
The act by a regulatory authority(ies) of conducting an official review of documents, facilities, record, and any other resources that are deemed by the authority(ies) to be related to the clinical trial & that may be located at the site of the trial, at the sponsor’s & / or contract research organization’s (CRO’s) facilities, or at other establishments deemed appropriate by the regulatory authority(ies). As per ICH – GCP guidelines E.6, 1.29.
       
56.115 IRB records
       
  7 b
The records required by this regulation shall be retained for atleast 3 years after completion of the research, & the records shall be accessible for inspection & copying by authorized representatives of the Food & Drug Administration at reasonable times & in a reasonable manner.
       
  7 c
The Food & Drug Administration may refuse to consider a clinical investigation in support of an application for a research or marketing permit if the institution or the IRB that reviewed the investigation refuses to allow an inspection under this section.
       
56.120 Lesser administrative actions
       
  a.
If apparent noncompliance with these regulations in the operation of an IRB is observed by an FDA investigator during an inspection, the inspector will present an oral or written summary of observations to an appropriate representative of the IRB. The Food & Drug Administration may subsequently send a letter describing the noncompliance to the IRB & to the parent institution. The agency will require that the IRB or the parent institution respond to this letter within a time period specified by FDA & describe the corrective actions that will be taken by the IRB, the institution, or both to achieve compliance with these regulations.
       
  b.
On the basis of the IRB’s or the institution’s response, FDA may schedule a re-inspection to confirm the adequacy of corrective actions. In addition, until the IRB or the parent institution takes appropriate corrective action, the agency may:
       
    1.
Withhold approval of new studies subject to the requirements of this part that are conducted at the institution or reviewed by the IRB;
       
    2. Direct that no new subjects be added on ongoing studies subject to this part;
       
    3.
Terminate ongoing studies subject to this part when doing so would not endanger the subjects; or
       
    4.
When the apparent noncompliance creates a significant threat to the rights & welfare of human subjects, notify relevant State & Federal regulatory agencies & other parties with a direct interest in the agency’s action of the deficiencies in the operation of the IRB.
       
  c.
The parent institution is presumed to be responsible for the operation of an IRB, & the Food & Drug Administration will ordinarily direct any administrative action under this subpart against the institution. However, depending on the evidence of responsibility for deficiencies, determined during the investigation, the Food & Drug Administration may restrict its administrative actions to the IRB or to a component of the parent institution determined to be responsible for formal designation of the IRB.