Quality assurance clinical trials

Program Guidance Manual, 2006), stating Clinical trial quality assurance units (QAUs) are not required by regulation. However, many sponsors have clinical QAUs that perform independent audits/data verifications to determine compliance with clinical trial SOPs and FDA regulations . 

Yen-Lieberman, B et al. (1996). Evaluation of a quality assurance program for quantitation of human immunodeficiency virus type I RNA in plasma by the AIDS Clinical Trials Group Virology Laboratories. J. Clin. Microbiol. 34,2695-2701. 

In Phase III, the final dosage formulation has been established and the pivotal clinical trials are being conducted. Degradation products have been identified, so the method selectivity should be reevaluated to ensure that all degradants can be detected and quantitated. The analytical methods are completely validated, and appropriate for routine quality assurance and control purposes. The type and frequency of system suitable testing (SST) should be determined, and an excellent publication on SST for chromatography systems is available [47],... 

The procedures for assuring quality of clinical trials have evolved over the past 30 years, culminating in several published guidelines. There are three key documents - the GCP guidelines of the ICH, the Code of Federal Regulations (21 CFR) of the United States and the Declaration of Helsinki. " ... 

During the NDA evaluation, the regulator will need to assess the quality of the experimental work and to extract the safety information that is pertinent to assuring the safety of clinical trials in humans. 

The key parameter for any drug product is its efficacy as demonstrated in controlled clinical trials. The time and expense associated with such trials make them unsuitable as routine quality control methods. Therefore, in vitro surrogate tests are often used to assure that product quality and performance are maintained over time and in the presence of change. A variety of physical and chemical tests commonly performed on semisolid products and their components (e.g., solubility, particle size and crystalline form of the active component, viscosity, and homogeneity of the product) have historically provided reasonable evidence of consistent performance. More recently, in vitro release testing has shown promise as a means to comprehensively assure consistent delivery of the active component(s) from semisolid products. 

For an extensive discussion regarding compliance requirements during clinical activities, refer to Chap. 3, Role of Quality Assurance Throughout Clinical Trials. ... 

Stability studies during the IND phase provide not only assurance of the quality of clinical trial material but also the basis for the drug product development program. Stability data are used to evaluate different formulations, methods of manufacture, and container-closure systems, as well as to determine storage requirements, expiration dating periods, and specifications. 

It is clear that the quality assurance organization plays a central role in coordinating facilitating, and documenting the formal investigation of an OOS result, whether the affected batch is utilized prior to approval (i.e., clinical trials, process validation) or postapproval as marketed product. 

Building quality throughout all aspects of the clinical trial process and installing QA oversight early on will not only serve to assure the integrity of the study, but will most certainly support the compliance requirements set forth by FDA. 

Install a quality assurance infrastructure during development and throughout all clinical trial activities. 

---