The sponsor will also want to conduct quality assurance activities at clinical sites during and after a study regardless if
an SMO is involved. Although not specifically required, quality assurance audits are recommended by E6.15 Surveys show that most sponsors conduct audits at sites during the conduct of the study. Additionally, sponsors audit nearly
90% of sites chosen by FDA for inspection.16 These audits occur between the time FDA notifies the site and the start of the inspection, which can happen within less than
one week. Although it might not be practical to audit every site, the sponsor should consider auditing sites that are high
enrollers, have a very large or small number of adverse events, or have compliance issues well before FDA phones to schedule
an inspection.17 Quality assurance audits should be separate from the sponsor's routine clinical trial activities. To encourage quality assurance
activities, the FDA's Compliance Program Guidance Manual for sponsor audits18 prohibits review of QA audit reports under normal circumstances.19 Specialty vendors, computerized systems CROs, clinical laboratories, and SMOs are three of the most common GCP vendors. But there are a number of other vendors, some
of which should be audited. In preparing procedures and audit plans, it is important to remember the two areas of FDA concern: data integrity and subject
protection. Think about how the vendor will impact data and what steps need to be taken to ensure GCP compliance. In particular,
determine whether there is quality control with written procedures at each stage of data handling. An important area to examine with any vendor is computerized systems. The FDA is currently reassessing its implementation
of the Part 11 regulation regarding computerized systems (Electronic Records; Electronic Signatures). It has issued a draft
guidance for clinical trials that is less stringent than previous enforcement efforts.20 The guidance states it contains "nonbinding recommendations." Although they may be nonbinding, they are the best we have
until FDA determines how they intend to regulate computerized systems. In auditing computerized systems, one will quickly discover that everyone believes they have a validated system. However,
by asking a few quick questions, the term validation takes on many different meanings. The FDA guidance document offers a
framework for writing an audit plan that covers Part 11. The guidance offers the minimum, not the maximum, standard that should
be applied. FDA may be using enforcement discretion for the time being, but the day will come when FDA resumes enforcement of Part 11.
If the computerized system is critical for the integrity of the data being submitted to the agency, then the system should
be validated and Part 11 compliant. Conclusion Using specialty GCP vendors is a necessity in conducting clinical research in today's research environment. By developing
a strong, consistent program for quality control and quality assurance, a sponsor can ensure not only compliance with GCP
regulations but also cost-effective quality research. Carl Anderson is a senior consultant at Quintiles Consulting. Cathy Tashiro, PhD, RN, is associate professor of nursing at the University of Washington, Tacoma. Laurie Taddonio* is also with Quintiles Consulting, where she is director of bioresearch, 1801 Rockville Pike, Suite 300, Rockville, MD,
20852-1366, email: laurie.taddonio@quintiles.com
*To whom all correspondence should be addressed. References 1. Code of Federal Regulations, Title 21, Parts 11, 50, 54, 56, 312, 511, 812 (U.S. Government Printing Office, Washington,
DC). 2. Food and Drug Administration Compliance Program Guidance Manual (CPGM) 7348.810, Sponsors, Contract Research Organizations,
and Monitors: Part 1–Background (FDA, Rockville, MD, 2001). 3. Food and Drug Administration ICH E6 Good Clinical Practice: Consolidated Guidance, Section 5.1, Quality Assurance and
Quality Control, Federal Register Vol. 62, No. 90, pp. 25691–25709 (May 9, 1997). 4. Code of Federal Regulations, Title 21, Part 312.52 (U.S. Government Printing Office, Washington, DC). 5. Code of Federal Regulations, Title 21, Part 812 (U.S. Government Printing Office, Washington, DC). 6. Code of Federal Regulations, Title 42, Part 493.3(b)(2) (U.S. Government Printing Office, Washington, DC).
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