Other Regulatory Authorities

Unlike in the US and Europe, only certain research centers and hospitals are especially designated by the Chinese SDA for the conduct of clinical trials. 

In May 2001, the SDA approved the conduct of a multicenter Phase II trial on liver cancer. The compound is MTC-Doxorubicin from FeRx Inc., US. It was the first time that a trial had been approved in China for a compound that was not previously approved for commercial use in the US, Europe or Japan. 

Drugs are classified into several categories. These are synthetic drugs, TCM, and biological products. The SDA stipulates compliance to cGMP for medical products, GCP for clinical trials and GLP for non-clinical drug safety research. 

The SDA has set up fines for the manufacture and distribution of fake and inferior drugs. There are also strict controls on advertising drugs these prohibit the use of certain words, phrases and unscientific claims. 

Argentina National Administration of Drugs, Foods and Medical Technology 

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Tlie views expressed in this chapter are those of the author and do not necessarily represent the views or the opinions of the Medicines Control Agency, other regulatory authorities or any of dieir advisory committees. 

Analytical chemistry is a critical component of worker safety, re-entry, and other related studies intended to assess the risk to humans during and subsequent to pesticide applications. The analytical aspect takes on added significance when such studies are intended for submission to the U.S. Environmental Protection Agency and/or other regulatory authorities and are thus required to be conducted according to the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) Good Laboratory Practice (GLP) Standards, or their equivalent. This presentation will address test, control, and reference substance characterization, use-dilution (tank mix) verification, and specimen (exposure matrix sample) analyses from the perspective of GLP Standards requirements. 

Up until this point, it was assumed that naked DNA injected into animals would not be spontaneously taken up and expressed in host cells. This finding vindicated the cautious approach taken by the FDA and other regulatory authorities with regard to the presence of free DNA in biophar-maceutical products (Chapter 7). 

The aim of the FDA, and of other regulatory authorities who have taken up this theme, is to move from an industry that relies heavily on validated and fixed processes where quahty is ensured by end-point testing to one whose process are well understood and controlled. In other words, quahty is to be built into a product by design since it cannot be built in merely by testing. This begs the question of what is meant by a well-understood process. The Agency s own interpretation [43] is that a process is well understood when... 

In the absence of Food Safety Standards on POPs specific to Hong Kong, the level of POPs contamination in marine fish and shellfish sampled in the local waters was examined against Food Safety Standards/Action Levels published by other regulatory authorities (Table 7.20). The level of POPs contamination in marine fish and shellfish from Hong Kong waters was well below (by 1-2 orders of magnitude) the Food Safety Standards/ Action Levels set by the US, Mainland China and/or the European Community. 

Other data that may be required for deriving EQSs under the EU Water Framework Directive (also required by most other regulatory authorities)... 

Historically, the United Kingdom and some other regulatory authorities have based EQS values on single-species tests and only used mesocosm data as corroborative evidence. Under the WFD, however, mesocosm no-effect data have recently been used directly to set a freshwater EQS for chlorpyrifos in the European Union, and similar action has been taken for atrazine in the United States (USEPA 2003a). It is clear that such data are more relevant to the natural environment than laboratory-based single-species tests. 

Similar validation is conducted by some other regulatory authorities. For example, it was shown in an Australian study that there was no effect on sensitive species at concentrations 10 times above the EQS values for metals in sediments because of the EQS derivation method in which toxicity was equally ascribed to cooccurring chemicals (leading to concerns over the ecological realism of sediment metal EQS values) (Simpson et al. 2005). In Canada, no formal validation programs of this type have been undertaken. 

The FDA and other regulatory authorities require that all major items of equipment be uniquely identified. All the specified components of the system should be present and correct including printers. Visual Display Units (VDUs) and touch screens, keyboards, and computer cards. The identifying serial numbers and model numbers of all the major items must be recorded. The question as to whether units of equipment need to be dismantled in order to check their component details is often raised. If a unit is sealed in such a way that dismanthng would invalidate the manufacturer s equipment warranty, then disassembly should not be attempted it is not required in these circumstances. The IQ should simply check the unique identity of the sealed unit. Processing boards that are clip-fastened into slots in a rack should have their serial numbers recorded, along with their slot position within the rack. It is worth checking with suppliers in advance of delivery whether their equipment does in fact have unique identifiers. 

Other regulatory authorities expect pharmaceutical and healthcare companies to make their own determination based on pnblished GxP regulations and guides on what critical records iu their computer systems are and to apply electronic record controls accordingly." ... 

The FDA has now reconsidered and at present only requires the meaning and content of electronic records to be preserved. This is achieved typically through appropriate validation of supporting computer systems and by applying audit trails where necessary to individual electronic records. Metadata will normally be managed through computer validation rather than as part of the electronic record as required previously by the FDA. This is consistent with other regulatory authorities who only expect constructive evidence to support the accuracy of electronic records. 

The FDA has until recently only considered hybrid solutions as an interim measure until new eomputer systems can be implemented which fully comply with all 21 CFR Part 11 requirements. This position has now changed and the FDA, in line with other regulatory authorities, will allow the use of a hybrid solution as part of a final system. In either case, robust proeedures must be implemented for hybrid solutions to ensure electronic records are contemporaneous with printed copies. 

However, the FDA and other regulatory authorities expect more than planning to take place. Meaningful progress is expected. Prioritization is accepted as it is widely recognized that it will take some time for all computer systems to come into full compliance. In the transition period, procedural controls are expected to be put in place to compensate for any technical deficiencies. 

The FDA has recently highlighted the importance of risk management as part of 21st century compliance. Other regulatory authorities such as MHRA share this perspective. Without risk management, computer validation costs can quickly become prohibitive. Taking the highest level of compliance for all aspects of a computer system will not necessarily lead to discernible, increased patient/consumer safety. 

Environmental control in drug manufacturing facilities has drawn increased attention from the FDA and other regulatory authorities in the 1990s. Section 46 of the U.S. Code of Federal Regulation for Good Manufacturing Practice states that ... 

The FDA expects (and many other regulatory authorities require) that the QCU will have full independence from other units. This is to provide the maximum degree of assurance that the QCU s decisions will be free of conflicts of interest and other impediments. Normally, the expectation is that the head of the QCU will report to a very senior level person (CEQ, President, COO, etc.) of the company, and that there will not be a situation where the head of the QCU reports to manufacturing, marketing, or other similar functions. 

In conclusion, clinical trials have shown that COX-2-selective NSAIDs seem to be less toxic to the gastrointestinal mucosa than traditional ones. However, life-threatening ulcer complications have been reported in patients taking both celecoxib (81,96,97) and rofe-coxib (79). The FDA and other regulatory authorities require that drug information sheets for celecoxib and rofecoxib carry gastrointestinal ulcer warnings similar to those for older NSAIDs. 

Six parties to ICH represent the regulatory bodies and research-based industry in the three regions, Europe, Japan, and the United States, where the vast majority of new medicines are currently developed. These Six Parties are directly involved in the decision making process and were selected as they represent the regulatory bodies and the research-based industry in the European Union, Japan, and the United States. However, the Conference, its preparations, and follow-up activities are conducted in an open and transparent manner and the presence of observers from other regulatory authorities and WHO is welcomed as a means of ensuring that the benefits of progress towards harmonization can be utilized worldwide. The Six Parties are as follows ... 

Regulatory To interface with FDA and other regulatory authorities... 

For many years, combination products were discouraged by the FDA and other regulatory authorities. The treatment of AIDS has highlighted the need for combination tablets, which have advantages as well as disadvantages. If the drug dose ratio required depends on the pharmacogenetics, then this is the opportunity for 3DP approaches or other forms of production flexibility. 

This chapter has described and discussed the various modules of a Common Technical Document (CTD) as presented in ICH M4. A sponsor preparing a marketing application for submission to any of the three ICH regions and to most other regulatory authorities around the world can, and probably should, utilize the recommend orders of presentation outlined in the ICH CTD guideline for quality, nonclinical, and clinical results generated to support the characterization and development of a drug candidate. 

Web site for other regulatory authorities Local regulatory guidance http //www.pharmweb.net/... 

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