Regulatory requirements audits

Will the client conduct audits to assure that regulatory requirements are being met ... 

Automated electronic data capture systems have become increasingly important in the laboratory. They have improved the ease of manipulation and reporting of chromatography data. A regulatory requirement is that these systems must generate a permanent audit trail of the parameters employed in the collection and analysis of those data. 

The new European Directive (2001/20/EC) has reinforced the need for European agencies, as well as those of the United States and Japan, to conduct inspections of clinical trials. Sponsors, mindful of the implications of failed inspections, are carrying out audits by their QA units to try to ensure that standards at a particular site meet the regulatory requirements of GCP, and of any future regulatory inspection. Frequently, the inspections will occur 2 or more years after the end of the study. 

The QMS models require periodic audits but do not specify audit frequency. Audit frequency must be determined based on the risk associated with the matters to be audited and other factors including results of previous audits and other quality data. Periodic audits should be conducted over the entire product life cycle and follow-up audits conducted as appropriate to verify that previously identified quality problems have been corrected in accordance with applicable quality system and regulatory requirements. 

Alternatively, the quality audit may be conducted on-site. Again, the audit can be as extensive as a comprehensive GMP, Good Laboratory Practice (GLP), or Good Clinical Practice (GCP) systems audit that reviews all regulatory requirements for strict compliance, or simply a visit to ensure that... 

The appropriate response to this observation would be for the firm to revisit its supplier qualification policy and procedures to ensure that they meet current regulatory requirements as well as internal quality standards. Second, the firm will present the agency with a package of new and improved procedures and an umbrella policy related to a state-of-the-art vendor qualification program. These procedures will ensure that all critical suppliers are audited and monitored appropriately in accordance with predetermined criteria and audit protocols. Audit protocols will be designed to meet the unique aspects of every supplier. 

Quality and Compliance Fulfill regulatory expectations of QA/QC Unit — responsible for interpretation of regulatory requirements into policy and procedures. He or she is responsible for validation oversight (compliance audits and approval of key validation documentation). This role is typically also responsible for inspection-related liaison with regulatory authorities. 

Contracts of supply should exist for all computer systems acquired from external suppliers. The contract should include terms and conditions to dehne individual responsibihties, the assigmnent of responsibilities to third parties, conhdentiality, intellectual property rights (IPR), and terms of payment. It is very important that infringements, liabilities, and insurance are also covered, and it is determined how these are affected by circumstances outside the control of the customer and the supplier. Contract details should be reviewed during Supplier Audits as appropriate. Contract documentation should be retained as specifically required by some regulatory requirements in support of validation. 

Data Historians should be vahdated. Data must be protected from unauthorized and unintentional modification. This might be achieved through locking down data (i.e., no subsequent write permissions given after data created). The requirement for any audit trails needs to be specified. Data retention requirements need to be defined in accordance with company policy and regulatory requirements. Software used to retrieve data should be validated. Any dependencies on storage media need to be understood and managed. Backup and restore are key processes. System interfaces should also be specified and tested. 

The electronic record strategy is fikely to be focused on the role of the Data Historian. General audit trail requirements may be satisfied by the implementation of a transaction log. Particularly critical records may warrant electronic audit trails implemented for individual records. Consideration should also be given to how copies of regulated records, including audit trails, may be provided during inspections and submissions to regulatory authorities. 

ICH GCP (1995) defines QA as All those planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented (recorded) and reported in compliance with GCP and the applicable regulatory requirement(s) . In clinical development of pharmaceuticals, QA usually describes the audit function within a company however, QA should not be limited to auditing. 

QA s task to identify noncompliance with regulatory requirements, the trial protocol and internal procedures such as SOPs is not always an easy job. Communicating deficiencies and highlighting inadequate procedures is certainly a benefit for the company as a whole, but the individual may not appreciate being confronted with audit findings (Winchell, 2004). In order to be efficient and effective in QA, the following should be observed. 

ICH GCP (1995) defines an audit as A systematic and independent examination of trial-related activities and documents to determine whether the evaluated trial-related activities were conducted, and the data were recorded, analyzed and accurately reported according to the protocol, sponsor s SOPs, GCP and the applicable regulatory requirements). ... 

Investigator site audits are probably the most frequent type of audits conducted by clinical QA departments and, therefore, deserve particular attention. The purpose of investigator site audits is to assess compliance with the GCP regulations (with a focus on the country-specific regulatory requirements) and the protocol. Further, thesafety of the trial participants, the ethical conduct of the trial and the validity, completeness and accuracy of the data collected and recorded are verified during the audit. 

A multitude of external providers are used to deliver services in clinical trials, for example CROs, site management organizations (SMOs) and academic research organizations (AROs). To ensure that they are capable of providing the services in a reliable manner and to the standards expected in compliance with current regulatory requirements, capability audits are conducted at service providers prior to contracting. 

The FDA plays a major part in the prevention and detection of research fraud and misconduct. The FDA carries out two different types of reviews. Study-orientated audits are conducted on clinical trial data itself, in order to ensure patient eligibility, and investigator-orientated inspections can be carried out either routinely or because a sponsor has concerns. If the inspectors have reason to believe that a site has not complied with regulatory requirements or has engaged in fraudulent activity - for which the definition in the Federal Code is very similar to that of the Wellcome Trust - they have the power to disqualify the investigator from taking part in further research, or severely restrict his activities. Such findings are widely publicized both within and outside the United States on the so-called Black List . 

The FDA requires each PI to comply with GCP and other applicable regulatory requirements, permit monitoring and audits by the sponsor and the FDA, and maintain a... 

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