Equivalence of Generic Drugs

by Food and Drug Administration (FDA)

When Stuart Addison goes to the pharmacy in Margate, Fla., he has the pharmacist fill his prescriptions with generic drugs. Addison, a retired federal government auditor, is one of many Americans who are choosing generics when they buy drugs.

"My motivation is to keep the prices down," said Addison, noting that his insurance plan pays for his prescriptions. "My pocketbook is not directly affected, but in the long run, I'm helping to keep down insurance premiums."

Although not all approved drugs are available in a generic version, those that are can offer substantial savings to consumers. For millions of Americans, the less-expensive drugs could mean the difference between getting necessary therapies and not being able to afford proper medical treatment.

Insurance companies' recommendations to policy holders that they choose generics over brand-name drugs whenever possible, coupled with the promotional efforts of large drug chains, have helped heighten consumer awareness of the availability of generics. The result has been that generic sales have been booming most of the years since 1984, when Congress passed the Drug Price Competition and Patent Term Restoration Act. This act expanded the number of drugs eligible to be manufactured as generics. The new rules eliminated the need for duplicate safety and efficacy testing for generics, saving industry time and money. The Food and Drug Administration also developed and issued explicit guidelines for a generic product's bioequivalency (see accompanying article) and stability, ensuring that products retain potency. In addition, products must meet specifications set by the U.S. Pharmacopeial Convention, a private scientific organization that sets standards for drugs and drug products in the United States. Almost 80 percent of U.S. generic drug production is done by brand-name firms in modern manufacturing plants.

In 1991, consumers spent about $5.5 billion for generics and are expected to spend more than $15 billion in 1995, according to a report issued earlier this year by Frost & Sullivan International, a health information research organization. The report found that expiring patents on pioneer (brand-name) drugs, coupled with increased attention to containing health-care costs, will play important roles in the growth of the generics industry in the next decade.

Since 1984, there has been a succession of top-selling drugs that have lost their market exclusivity and been challenged for market share by generic brands. An average of about 15 pioneer drugs lose patent protection annually, and FDA has prepared for an expected explosion of new generic drug applications through the end of 1995. Among the top-selling brand-name drugs scheduled to lose protection are Eli Lilly's anti-infective Ceclor, Marion Merrell Dow's calcium channel-blocker Cardizem SR, and the firm's non-sedating antihistamine Seldane. Also scheduled to lose their exclusive market niche are the anti-inflammatories Anaprox by Syntex and Voltaren by Geigy, hypoglycemics Glucotrol by Roerig and Micronase by Upjohn, and Squibb's antihypertensive Capoten.

Scandal Rocks Industry

Popularity of the copycat products grew significantly after 1984, when the approval process was widened. But that popularity took a downturn in 1989, when scandal rocked the industry. Federal investigators uncovered such problems as illegal gratuities, fraud, obstruction of justice, and noncompliance with various manufacturing procedures by some industry officials.

The investigations revealed that several FDA employees had accepted money or other compensation in exchange for information and assistance that gave certain firms an advantage in the approval procedure. Investigators also uncovered submissions of fraudulent data by several manufacturers. In one case, a company submitted the pioneer drug disguised as a generic version with its bioequivalence studies.

Subsequently, FDA investigators rushed to reevaluate data presented in hundreds of generic drug applications. More than 2,550 samples of the top 30 prescribed generic drugs — or about 30 percent of all generic drugs on the market — were collected and laboratory-tested. The agency conducted intensive inspections of 36 of the largest generic drug firms and 12 contract laboratories.

Agency Steps Up Testing

In early 1990, more than 300 scientists at 17 FDA labs tested samples from generic drug companies. The agency determined that only 27 samples, or approximately 1 percent of those tested, did not comply with standards of potency, dissolution, content uniformity, product identification, moisture determination, or purity.

FDA also tested 429 samples representing at least three different batches of all 24 then-currently-marketed, narrow-therapeutic-range drugs (those in which the difference between a therapeutic dose and a toxic dose is small) made by 73 brand-name and generic drug manufacturers. The 24 drugs were selected because of their high potential for adverse reactions or therapeutic failure if they lacked bioequivalency. Only five of the samples — all aminophylline tablets, a bronchodilator — failed to meet USP standards. None of the defects in the generic drugs posed a public health hazard.

Based on these results and the fact that brand-name products experience similar failures at a similar rate, the agency recommended that doctors continue to consider prescribing generic drugs when appropriate, to offer lower-cost products to consumers.

FDA investigators continued to scrutinize operations at dozens of plants, and, in response to government findings, a number of firms made voluntary drug recalls due to manufacturing deficiencies. FDA's Office of Generic Drugs, directed by Roger L. Williams, M.D., is charged with conducting reviews and is responsible for the subsequent approval of the imitator products. The office interacts with a national network of FDA field offices to monitor the production methods of generic makers. Williams said, "the office's increased emphasis on quality, integrity and performance in the development, manufacture and review of generic drugs has led to a strong industry, a better review process, and better generic products for the consumer."

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.