Drugs, pharmaceutical approvals, process

The federal Food, Drug, and Cosmetics Act of 1938 gave regulatory powers to the FDA. Pharmaceutical companies apply to the FDA for approval to manufacture a new drug. The approval process includes research, testing, and hearings. Once a drug is approved, the FDA determines whether a prescription is required. 

Reasons for chopping clinical candidates at any stage of the drug approval process included (1) stability, formulation, or other pharmaceutical development issues, (2) renal toxicity or neurotoxicity, and (3) insufficient advantage over current chugs. Since 1997, the NCI has also operated a screen for compounds active against the cytotoxic effects of HIV in CEM cells. Of 80,000 compounds tested, 4050 (or about 5%) were active. Of the compounds tested, 2291 have included metals. Of those, 136 (about 6%) were active, and two became clinical candidates. Both were chopped due to toxicity problems. One clinical candidate was a polyoxometallate, and therefore about 80 other similar molecules were tested. These were found to be strongly active in vitro, but too toxic in animal models in vivo. If a way around the toxicity problem can be found, interest in these... 

Drugs are separated into three categories in China Western drugs are reviewed by the Division of Pharmaceuticals, biologies by the Division of Biological Products, and traditional Chinese medicine by the Division of TCM (Section 7.5). The approval process is described in Section 8.5. 

Drug approval processes go through IND and NDA procedures in Japan. The MHLW of Japan has set up the Pharmaceutical and Medical Device Agency (PMDA), which provides technical consultation services for clinical trials. There are four types of consultations before IND, at the end of Phase II studies, before NDA, and consultation on individual protocols. 

An NDA submitted to the MHLW is reviewed by the PMDA. PMDA personnel have the authority to inspect the drug manufacturing facility and clinical trial sites to assess comphance. In the process, the PMDA consults the Pharmaceutical Affairs and Food Sanitation Council (PAFSC). Results of the review are forwarded to the Pharmaceutical and Food Safety Bureau (PFSB), which prepares the final approval through the Minister of the MHLW. Figure 8.10 shows the drug approval process in Japan. The procedure for manufacturing and distribution of drugs for overseas manufacturers is presented in Fig. 8.11. 

Japan Pharmaceutical Manufacturers Association. New Drug Development and Approval Process, http //www.jpma.or.jp/12english/guide industry/new drug/new drug.html [accessed August 8, 2002]. 

Guarino RA New drug approval process. In Drugs and The Pharmaceutical Sciences, vol. 100. Marcel Dekker, 2000. 

Ronald Reagan, Republican president of the United States from 1981 to 1989. Consistent with his free-market and pro-business ideology and policies, his term coincided with expanding use of prescription drugs and increasing success of pharmaceutical companies. His administration supported DTC advertising and a quicker approval process for new drugs. 

That pharmaceutical manufacturers are now totally committed to cGMPs as a fact of life, reluctantly admitted by the newer and inexperienced biopharmaceutical technology-based companies. Indeed, there are examples of young companies going out of business because they felt that this was an unnecessary bureaucratic process that would hinder the application of their wonderful new product. This attitude was perilous in the extreme because, ultimately, the FDA has to approve the drug and its process before it can be marketed. 

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