Regulatory authorities clinical trial authorization

The CA in whose territory the CT takes place enters the details into a new European Drug Regulatory Affairs Clinical Trial (EUDRACT) database. It allocates a unique EUDRACT number that cannot be reallocated to another trial if the original one does not proceed if an International Standard Randomized Controlled Trial Number (ISRCTN) is available, this detail is also entered. These EUDRACT entry data are accessible only to the CA, the EMEA, and the Commission and details the request for authorization, the protocol, any proposed protocol amendments, approvals by the CA and IEC, any suspension, the declaration at the end, and reference to any GCP inspections. 

The regulatory authorities must be informed of any planned recall actions (see Chapter 12). Procedures are also required for emergency un-blinding of materials undergoing clinical trial. The responsibility for complaints and the initiation of product recalls should be assigned to designated individuals. 

In Australia, approval of clinical trials involves both the regulatory authority and an ethics committee. Under the Clinical Trial Exemption (CTX) scheme, a clinical trial proposal must first be evaluated by the TGA, and then approved by an ethics committee on-site. Under the Clinical Trial Notification (CTN) scheme, a trial is evaluated and approved by the local ethics committee, and then notified to the TGA. 

Despite the anecdotal nature and sometimes poor documentation, publication of case reports in journals remains one of the most useful primary sources of information on ADRs. ADR reports in the literature can be identified in several different ways. Prepublication manuscripts describing a spontaneous case report or an event from a clinical trial are sometimes provided by authors to the manufacturer of the drug and the regulatory authority in that country. Pharmaceutical companies are required to be aware of the literature as to the safety of their approved therapeutic products, and are assumed (by law) to be cognizant of such. 

Phase Illb. Clinical trials conducted after regulatory submission of an NDA or other dossier, but prior to the medicine s approval and launch. These trials may supplement earher trials, complete earlier trials, or may be directed toward new types of trials (e.g., quality of life, marketing) or Phase IV evaluations. This is the period between submission and approval of a regulatory dossier for marketing authorization. 

The intention of this book is to provide an overview of how a drug is discovered, the amount and types of laboratory tests that are performed, and the conduct of clinical trials before a drug is ready to be registered for human use. Of importance is the role of regulatory authorities in these processes. Through... 

Repeated dose chronic toxicity studies are performed on two species of animals a rodent and nonrodent. The aim is to evaluate the longer-term effects of the drug in animals. Plasma drug concentrations are measured and pharmacokinetics analyses are performed. Vital functions are studied for cardiovascular, respiratory, and nervous systems. Animals are retained at the end of the study to check toxicity recovery. Table 5.2 shows the duration of the animal studies, which depends on the duration of the intended human clinical trial. Appendix 6 summarizes the information to be submitted to regulatory authorities. 

Government bodies have on occasion accelerated clinical trials against advice from researchers, in response to public demands (Exhibit 6.15). The climate today is that due diligence regarding safety has to be performed before the drug is administered to human subjects and that clinical trial submissions have to be approved by the regulatory authorities before the trial commences. 

Regulatory authorities play an important and active role to ensure regulatory compliance in the conduct of a clinical trial. Agencies such as the FDA inspect clinical studies. An inspection of a trial may reveal that the protocol is not being followed strictly, the Investigator may not be involved with the project as much as is expected, there may be a lack of patient care, changes to the protocol may not have been relayed to the IRB, and so on. In such cases, corrective actions have to be implemented immediately and the FDA must be satished before the trial can continue. Deficiencies found are reported on Form 583. 

Regulatory authorities stipulate the need for ethical principles to be observed when conducting clinical trials. Clinical trials should never be conducted to gain knowledge per se. They should be based on risk-benefit considerations, informed consent, and respect for human individuals. Furthermore, subjects should be protected without being taken advantage of. 

Due to problems in some early clinical trials, where subjects were taken advantage of, regulatory authorities require that clinical subjects be treated fairly. Ethical considerations should be undertaken to safeguard subjects safety and well-being. 

Regulatory authorities perform the watchdog role to ensure that animal studies comply with Good Laboratory Practice (GLP), clinical trials are... 

Similar to the US requirements, there are two regulatory steps to go through before a drug is approved to be marketed in the European Union. These two steps are clinical trial application and marketing authorization application. There are 27 member states in the European Union (as of August 2007) clinical trial applications are approved at the member state level, whereas marketing authorization applications are approved at both the member state or centralized levels. 

It is conceivable that, in the not too distant future, biogenerics will be approved with applicants supplying certain preclinical data and clinical trial information to prove comparability and bioequivalence. At the same time, the regulatory authorities will rely on their experience and expertise in approving innovator biologies to guide them as they evaluate biogenerics. 

When all criteria are met, the optimized lead becomes a drug candidate. Typically, one in 100 000 HTS actives reaches this stage [20]. Following approval from regulatory authorities, drug candidates proceed to clinical trials. If all three phases of clinical trials prove successful, which only one in 10 candidate drugs [21] does, the compound is approved and becomes a launched (or marketed) drug. 

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