Regulatory authority, documents

These organisations, and the relevant staff representatives, were identified from EU and national regulatory authority documentation, such as publicly available reports and consultations. 

Only three countries, Tunisia, Uganda and Zimbabwe, do not issue a GMP certificate. The drug regulatory authorities in these three countries do conduct GMP inspections, but do not issue a specific document which indicates that a manufacturing plant has attained GMP standards. The MCAZ does, however, provide a GMP certificate at the manufacturer s request to facilitate international registration and export of products. In Malaysia, various types of certificates are issued GMP certificates Certificate of Pharmaceutical Product for export and Certificate of Free Sale for medical devices and cosmetic products. Cyprus has no clear criteria for issuing a GMP certificate instead. 

Registration requirements, SOPs and decision criteria are documented to ensure transparency of the regulatory process and to facilitate communication between the regulatory authority, the pharmaceutical industry and the public. 

The Electronic Common Technical Document (eCTD) is the vision for future electronic submissions to the FDA. This specification was developed by the International Conference on Harmonization (ICH) as an open-standards solution for electronic submissions to worldwide regulatory authorities. The FDA has adopted the eCTD as the future replacement for its other e-submission guidance, although for now the older guidance is still in effect. Note that the eCTD still depends largely on submitting text documents as PDF files and submitting data sets as SAS XPORT transport format files. 

Reports received by companies via regulatory authorities are often edited and poorly documented, but they cannot be ignored and should be handled alongside... 

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. 

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. 

Regulatory authorities recognize that, in spite of all the control systems put in place, deviations and changes are sometimes inevitable. A robust GMP system includes procedures to handle, review, and approve changes in raw materials, specifications, analytical methods, facilities, equipment, processes, computer software, and labeling and packaging. All the changes have to be documented with references for traceability. 

The Nordic Expert Group for Criteria Documentation of Health Risks from Chemicals (NEG) consisted of scientific experts from the five Nordic countries representing different fields of science, such as toxicology, occupational hygiene, and occupational medicine. The main task was to produce criteria documents (Figure 3.10) to be used by the regulatory authorities of the Nordic countries as the scientific basis for setting Occupational Exposure Limits (OELs) for chemical substances. 

Notification documents and reports in relation to SAEs, etc. for sponsor, lECs and regulatory authorities... 

The ICF consists of two documents - the information sheet and the actual consent form. They must be considered as a pair of documents, not separate entities. Normally, a core ICF should be present in the appendices. The core ICF may need modifications to comply with local regulations. It is the responsibility of the sponsor/ institution, or in an independent study the investigator, to prepare an ICF that meets the requirements of ICH CCP or any additional requirements of the local regulatory authority, and is only used after it has been approved by the relevant I EC. 

The closing down of the clinical trial at the site after the last visit of the last study subject has finished and all the CRFs are completed is an important part of the clinical trial. The process of archiving the documentation, both at the site and at the sponsor office, needs to take place -ideally as soon as possible after the end of the clinical phase of the study. The effort required to do this well is very much less than that which will be required if deficiencies are identified later -particularly if that occurs during a regulatory authority inspection ... 

The common technical document (CTD) (ICH M4) is now a requirement. The CTD is the agreed common format for the preparation of a well-structured application to the regulatory authorities and has had an impact on all organisations as database integration and electronic submissions become more common. 

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