Regulatory requirements summary

Name and description of the investigational product(s). A summary of findings from non-clinical sfudies and from clinioal trials that is relevant to the trial. Summary of the known and potential risks and benefits, if any, to human subjects. Description of and justification for the route of administration, dosage, dosage regimen, and treatment period(s). A statement that the trial will be conducted in compliance with the protocol, GCP and the applicable regulatory requirement(s). Description of the population to be studied. References to literature and data that are relevant to the trial, and that provide background for the trial... 

Once the determinative or confirmatory method has been developed to take full advantage of the chemical properties of the analyte molecule, a study is necessary to prove that the method is valid. Criteria for method validation are outlined in guidelines from the US FDA, US EPA, and EU. A summary of the differences in regulatory requirements for method validation is provided in Table 3. The parameters addressed by all of the regulatory guidelines include accuracy, precision, sensitivity, specificity, and practicability. 

In this guidance the FDA offers some direction for the demonstration of comparability. They request that the manufacturer provide evidence that the methods, facilities, and controls that were used to manufacture previous products conformed to cGMPs and to other applicable regulatory requirements. In addition they request the submission of validation summaries, as well as product characteristics such as total nucleated cell count, viable CD34 cell count, and number of colony-forming units. Stability data and information from the scientific literature can also be used. Clinical outcomes can be part of the comparability demonstration. 

Many of the recommendations of the ICRP and other radiation protection groups regarding radiation exposure have been incorporated into regulatory requirements by various countries. For the U.S. Department of Energy facilities, radiation exposure limits are found in Title 10, Part 835 of the Code of Federal Regulations (10CFR835). Table 3.1 provides a summary of the dose limits for occupational external exposures. 

Apart from compliance with SOPs for biostatistics and report writing, the statistical analysis plan, the trial protocol, regulatory requirements and guidelines (ICH E3, 1995 ICH E9, 1998 ISO 9000 2005, 2005), QA auditors check the internal consistency of the trial report and appendices and between data in tables, figures and graphs and numbers cited in the text. All numbers and percentages must be substantiated by attached tables and listings. In summary, the trial report should be an accurate representation of the clinical data. Allocation of trial... 

This short summary demonstrates that each company has selected a niche application to focus on for their success. The wound dressings have been in the market for some time, while the thermogel applications are apparently still in the regulatory approval process. This is more an indication of the divide in meeting regulatory requirements between external medical products and internal implants rather than product shortcomings. Clearly, this overview indicates that chitin and chitosan-based medical products can be termed commercially successful and this augments well for the future of chitin and chitosan in biomedical research and applications that reach commercialization. 

The Expert Report is a particular requirement of the European pharmaceutical regulatory system. It is intended that the Expert Report submitted by the applicant should include an accurate summary of the supporting evidence for the application and that it should also include a critical discussion of that information. Expert reports were originally required when a requirement for an Assessment Report was imposed on the member states the intention was that the Expert Report should form the basis for that Assessment Report. 

In summary, transcription of the Cdc25-type phosphatase encoded by string limits the progression of many embryonic cell cycles, which are rapid (1—3 h) and require little cell growth. The massive ofi-regulatory region of string acts as a sophisticated pattern sensor that is influenced by a wide variety of cell type-specific transcription factors (Fig. 2A). 

In view of the regulatory delay that was caused by the need to apply for a CTC, a Statutory Order (SI 1974/498) was made during 1974, to provide an exemption from the need to hold a CTC in such cases, subject to certain conditions. This order applied to trials conducted by doctors and dentists on their own responsibility (DDX). The basis of the clinical trial exemption (CTX) scheme, introduced in 1981, to include studies initiated by the pharmaceutical industry, was that together with a detailed clinical trial protocol and summaries of chemical, pharmaceutical, pharmacological, pharmacokinetic, toxicological and human volunteer studies, a clinical trial in patients may proceed without the need for the additional details normally required for a CTC or Product Licence application. This exemption scheme was based on the requirements that ... 

As provided in the Botanical Guidance, clinical studies have been permitted for many botanical preparations prior to a complete set of conventional animal toxicity testing. The decisions were not difficult for submissions with substantial and well-documented history of past human use. But some other applicants had not presented an adequate summary of the past human experiences and had failed even to document well-known toxicity of the herbal ingredients. Between these two extremes, how to adjust the requirements of animal toxicity data and substitute that with large quantity but poor quality of human experiences is another big challenge to the regulatory agency in the review of botanical applications. 

A detailed method validation report may not be necessary until submission of the final market application. However, summary reports should be available to facilitate efficient data retrieval and fulfill requests from regulatory agencies for the information when required. 

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