Nonclinical reports

Most regulatory agencies now request that women be enrolled into the clinical studies as early in phase II as possible. Since thalidomide, reproduction and teratology studies have been required prior to enrollment of large numbers of women in clinical studies, in some cases, depending on the proposed indication for the drug, postmenopausal or otherwise reproductively incapable women can be enrolled. However, the timing of the enrollment of women needs to be understood well in advance so that the lack of appropriate nonclinical reports does not hinder clinical development. 

Test storage temperature range 0°C to +40°C (2 weeks storage without functional losses) Nonclinical report... 

Reporting of study results 9.1. General 9.2. Content of the final report 10. Storage and retention of records and materials Subpart J - Records and Reports Sec. 58.185 Reporting of nonclinical laboratory study results. Sec. 58.190 Storage and retrieval of records and data. Sec. 58.195 Retention of records. 

Raw data Any laboratory worksheets, records, memoranda, notes, or exact copies thereof, that are the result of original observations and activities of a (nonclinical laboratory) study and are necessary for the reconstruction and evaluation of the report of that study. 

Conduct of a nonclinical laboratory study Reporting of nonclinical laboratory study results Storage and retrieval of records and data Retention of records Purpose... 

The CTDs were implemented in July 2003. They are format-based documents for submission to the regulatory authorities the country-specific process of review, for example, via the IND and NDA of the United States or the Centralized Procedure of the EMEA, is not affected. The harmonized CTDs help to reduce cost and accelerate approval time. Figure 7.1 shows the CTD structure five modules with Module 1 for regional administrative information specihc to each country. Module 2 on summary of quality, nonclinical and clinical. Module 3 on quality. Module 4 on nonclinical study reports, and Module 5 on clinical study reports. 

Inspect each (nonclinical laboratory) study, maintain written records of these inspections providing the details of each, and report any problems to the study director. 

For CTAs, the Investigator s Brochure (IB) is an important document, as it generally represents all the nonclinical data submitted. Study reports are not routinely included unless the assessor considers... 

It is important that applicants pay close attention to the questions and suggestions from the assessors. By ensuring that the questions are addressed and the advice followed, it can be possible to preempt questions and concerns with the dossier. In the author s experience, nonclinical scientists are not always included in these meetings, and it is important for the company representatives who do attend to ensure that any relevant information is passed on to the correct scientists. It has also, unfortunately, been the author s experience that most applicants have failed to comply with requests made for specific issues to be addressed in the dossier and the same questions have had to be posed in the assessment report. 

Review the final study report to assure that such report accurately describes the methods and standard operating procedures, and that the reported results accurately reflect the raw data of the nonclinical laboratory study. 

For each nonclinical laboratory study, testing facility management shall...(c) assure that there is a quality assurance unit. (e) ensure that personnel, resources, equipment, materials, and methodologies are available as scheduled, (f) assure that personnel clearly understand the functions they are to perform, (g) assure that any deviations from these regulations reported by the quality assurance unit are communicated.. . and corrective actions are taken and documented. 

Summary and Bibliography of Reports of Scientific Investigations and Literature. You are required to provide a summary and bibliography of reports in the scientific literature that are known, or that reasonably should be known to you, and that were not previously submitted as part of your PMA application [21 CFR 814.84(b)(2)(ii)]. If there are reports or scientific literature on clinical or nonclinical studies of similar devices, we recommend that you include them in your summary and bibliography. 

The CTD consists of five modules, although it must be noted that module 1 is technically not part of the CTD since it is region specific and may contain quite different information from one regulatory submission to another. Module 2 contains a brief general introduction and summary information addressing manufacturing issues (quality) and the safety and efficacy of the drug. Module 3 contains information on quality, and modules 4 and 5 contain individual study reports for nonclinical studies and clinical studies, respectively. 

A Table of Contents should be provided that fists all of the nonclinical study reports and gives the location of each study report in the Common Technical Document. 

Before entering into a clinical evaluation program, a drug candidate is subjected to a number of preclinical studies to further define and characterize its safety profile. The results from the pharmacology, developability, and preclinical studies are documented in technical reports or scientific publications and used to prepare the IND submission. All of the preclinical studies, described in the section below, and nonclinical studies, discussed in the following section, need to be conducted according to GLP regulations. 

The annual report will also contain summary information obtained during the previous year s clinical and nonclinical investigations including ... 

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