Equivalence of Generic Drugs : Part 2

by Food and Drug Administration (FDA)

(Page 2 of 3)

Pre-Approval Inspectors

In 1990, the agency instituted product-specific, pre-approval inspections of manufacturing sites listed in a sponsor's application. During inspections, FDA reviews the step-by-step manufacturing process and monitors how much and what kind of active ingredients, excipients (material added to make products a suitable consistency), flavorings, and other substances will be used. Sponsors must even identify the type of machinery that will be used in each step of the manufacturing process. Just as it does with brand-name drugs, the agency closely regulates generic makers' production sites and blocks the marketing of any drugs produced in substandard facilities. FDA conducts more than 5,000 inspections at drug plants annually.

Agency inspectors also review on-site production records, examine exhibit batches, and determine whether the plant is capable of producing the drug properly before giving a satisfactory recommendation for the drug's approval. Plant managers must be able to show that the operation has sterile production facilities where required, acceptable assembly-line procedures, and that labeling procedures are designed to prevent mix-ups. The company must also prove that finished products are kept in a temperature-controlled storage area and that products can be easily identified to prevent drug mix-ups.

Richard Davis, director of FDA's division of field investigation, said new policies and procedures help prevent fraudulent activities and help ensure the availability of safe and effective generic products.

"We believe we have ferreted out virtually all of the fraud that was involved in the scandal," Davis said. "There shouldn't be any reason to be concerned about the equivalency, safety and effectiveness of generic drugs. We now have a very vigorous pre-approval inspection program."

Other Safeguards

Other safeguards have also been established. In May, President Bush signed into law an act that calls for the mandatory debarment of any individual convicted of a federal felony related to the development or approval of any drug application. The violator will be permanently prohibited from working in any capacity for any individual, partnership, corporation, or association that produces an approved drug and will be fined up to $250,000. A company convicted of a federal felony related to the development or approval of a generic drug application will be prohibited from submitting applications for 1 to 10 years and fined up to $1 million.

Todd Dankmyer of the National Association of Retail Druggists credited FDA's swift actions, comprehensive compliance plan, and the subsequent survey after the generics scandal for restoring the faith of the medical community and consumers in generics.

At the time of the crisis, "physicians were less likely to write prescriptions for generics" because the overall quality and safety were called into question, Dankmyer said. "But it appears to be back where it was before. Pharmacists reevaluated their relationships with suppliers, and if they had been given a clean bill of health by the agency, they continued to sell the company's generic products."

Applications Increase

From 1984 through 1991, the office received 6,635 applications to manufacture and market generic drugs, called abbreviated new drug applications (ANDAs). (Those for antibiotics are called abbreviated antibiotic drug applications [AADAs]). FDA determined that a little more than half — 3,672 applications — completed the agency's requirements and could be marketed. Many others were either dropped by their sponsors or are pending further review by FDA for a variety of reasons. The agency receives thousands more — 5,487 in 1991 — supplements and amendments to supplements that request changes in strength, dosage form, or manufacturing method.

Currently, FDA approves about 200 generic drugs annually. That number is expected to climb to more than 300 over the next several years as more top-selling, brand-name drugs lose patent protection.

Nearly 20 percent of the applications submitted to FDA are rejected within 30 days of submission. The reasons for their rejection range from the firm's failure to provide sufficient stability data, to incomplete sample batch records on bioequivalency testing, to an application that is missing some form of necessary research data.

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.