Auditing an SMO
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However, the sponsor cannot just sign away its responsibilities and forget about them. Ultimately, the sponsor is always responsible.
After all, it is the sponsor's investigational product, and it is the sponsor who submits the data to the agency. Thus, it
is important for a sponsor to conduct due diligence by auditing the CRO prior to the enrollment of subjects. This is particularly
true if it is the first time the sponsor is using the CRO. The sponsor's clinical quality assurance team or an outside contractor
can conduct the audit.
It is important for a sponsor to have written procedures for audits. A written plan for the specific vendor audit is highly
recommended. The plan should cover each stage of data handling the vendor will be performing. Other areas to cover in a CRO
audit include staff qualifications, experience in the therapeutic area of the study, written procedures, workload, and internal
quality control and quality assurance activities. Sponsors should seek input from each department impacted by a CRO. Clinical development, data management, and drug safety
departments can provide insight regarding CRO qualifications and should be consulted regularly. The most common responsibility transferred to a CRO is monitoring. An important component of monitoring is reviewing CRFs
against source documents for data integrity. But is that the only stage of data handling? Were specimens or ECGs collected?
These are also stages of data handling and need to be conducted under quality control with written procedures. A monitor will also have other responsibilities, including review of regulatory documents for submission of adverse event
reports and IRB approval. A monitor will need to review informed consent forms. This is necessary for the protection of human
subjects—FDA's second major concern—and should be a part of the monitoring plan and procedures. It is important to note that the medical device IDE regulations5 are silent about CROs. Although the FDA realizes that CROs are often used in medical device clinical trials, the regulatory
responsibility always rests with the sponsor. Clinical laboratories If the regulations are clear regarding CROs, the opposite is true for contract clinical laboratories. There is noticeable
regulatory silence when it comes to clinical laboratories. FDA does not have any specific guidance or regulations applicable to clinical labs that support trials. Consequently, many
organizations look to the Clinical Laboratories Improvement Amendments (CLIA) for regulatory guidance. However, CLIA specifically
states that it does not regulate research.6 What to do? In spite of this, CLIA is still a very good place to start. FDA recognizes CLIA certification as the principle
government standard for laboratories, and it is acceptable to FDA as a standard for diagnostic laboratory tests.7 In addition, many industry auditors use the Good Laboratory Practice (GLP) regulations, 21 CFR Part 58, as an audit guide.
These regulations govern FDA's oversight of nonclinical laboratories, primarily animal laboratories, for toxicity and other
safety testing. They are not, however, meant to govern all laboratories that perform analyses for FDA regulated products.
There is no requirement for GLP, CLIA or any other lab certification for a clinical trial. The sponsor is pretty much on its
own when it comes to qualifying a clinical laboratory. So, what criteria should be evaluated in an audit of a clinical laboratory? Once again we start with quality control with
written procedures at each stage of data handling. Follow the flow of a specimen from time of receipt to storage, destruction or return. There should be written procedures at
each stage of data handling. In addition, the audit should determine that employees are qualified, the equipment calibrated,
and that data can be attributed to a specific sample number. Labeling by subject identifiers is essential so that specimens
throughout the analysis and final lab report are accurately correlated by data to subject. The data are worthless if you do
not know which subject you are dealing with.
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