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Drug review steps Preclinical (animal) testing:

A designation of “not approvable” describes deficiencies significant enough that it is not clear that approval can be obtained in the future, at least not without substantial additional data. Common problems include unexpected safety issues that crop up or failure to demonstrate a drug’s effectiveness. A sponsor may need to conduct additional studies including perhaps studies of more people, different types of people, or for a longer time period. Manufacturing issues are also among the reasons that approval may be delayed or denied. Drugs must be manufactured in accordance with standards called good manufacturing practices , and the FDA inspects manufacturing facilities before a drug can be approved. If a facility isn’t ready for inspection, approval can be delayed. Any manufacturing deficiencies found would need to be corrected before approval. The FDA outlines the justification for its decision in an action letter to the drug sponsor. When the action is either approvable or not approvable, CDER gives the sponsor a chance to meet with agency officials to discuss the deficiencies. At that point, the sponsor can choose to ask for a hearing or correct any deficiencies and submit new information, or they can withdraw the application. The quality of clinical data The FDA relies on data that sponsors submit to decide whether a drug should be approved. To protect the rights and welfare of people in clinical trials and to verify the quality and integrity of data submitted, the FDA’s Division of Scientific Investigations (DSI) conducts inspections of clinical investigators’ study sites. DSI also reviews the records of institutional review boards to ensure they are fulfilling their role in patient protection. DSI seeks to determine such things as whether the study was conducted according to the investigational plan, whether all adverse events were recorded, and whether the subjects met the inclusion/exclusion criteria outlined in the study protocol. Following each inspection, FDA investigators prepare a report summarizing any deficiencies. In cases where they observe numerous or serious deviations, such as falsification of data, DSI classifies the inspection as “official action indicated” and sends a warning letter or a Notice of Initiation of Disqualification Proceedings and Opportunity to Drug nomenclature Three name classifications of drugs are the chemical, or scientific name; the generic name; and the brand or trade name: ● Chemical (scientific) name : Drugs often have several names. When a drug is first discovered, it is given a chemical name, which describes the atomic or molecular structure of the drug. The chemical name is thus usually too complex and cumbersome for general use. Next, a shorthand version of the chemical name, or a code name (such as RU 486), is developed for easy reference among researcher. ● Generic name : The generic or official name of a drug is assigned by its producer in collaboration with the Food and Drug Administration and Council on Drugs of the American Medical Association. The United States

1. An investigational new drug application (IND) outlines what the sponsor proposes for human testing in clinical trials. 2. Phase 1 studies (typically involve 20 to 80 people). 3. Phase 2 studies (typically involve a few dozen to about 300 people). 4. Phase 3 studies (typically involve several hundred to about 3,000 people). 5. The pre-NDA period, just before a new drug application (NDA) is submitted. A common time for the FDA and drug sponsors to meet. 6. Submission of an NDA is the formal step asking the FDA to consider a drug for marketing approval. 7. After an NDA is received, the FDA has 60 days to decide whether to file it so it can be reviewed. 8. If the FDA files the NDA, an FDA review team is assigned to evaluate the sponsor’s research on the drug’s safety and effectiveness. 9. The FDA reviews information that goes on a drug’s professional labeling (information on how to use the drug). 10. The FDA inspects the facilities where the drug will be manufactured as part of the approval process. 11. FDA reviewers will approve the application or find it either “approvable” or “not approvable.” Explain (NIDPOE) to the clinical investigator, specifying the deviations that were found. The NIDPOE begins an administrative process to determine whether the clinical investigator should remain eligible to receive investigational products and conduct clinical studies. CDER conducts about 300 to 400 clinical investigator inspections annually. About 3 percent are classified in this “official action indicated” category. The FDA established an independent Drug Safety Oversight Board (DSOB) in 2005 to oversee the management of drug safety issues and communication to the public about the risks and benefits of medicines (FDA, 2016). The board’s responsibilities include conducting timely and comprehensive evaluations of emerging drug safety issues, selecting drugs to be placed on a drug watch website for health professionals and patients, and ensuring that experts both inside and outside of the FDA give their perspectives to the agency. Adopted Names (USAN) assigns the generic name, which may be used by any interested party. A generic drug name is not capitalized; for example, aluminum hydroxide. ● Brand, proprietary or trade name : Trade names are copyrighted terms selected by a manufacturer to designate a particular product. Copyright laws prevent any other person from using the name, and other laws prevent pharmacists from substituting chemically identical products for the trade name article. When there are no longer any legal restrictions on the use of a brand name, the most widely accepted and familiar name may become the official or generic name. (Smith-Marsh, 2018)

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Book Code: MIL1224

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