FDA Investigation : Generics: Are They as Good?

After Bruce French doubled over at the dinner table with a pain in his chest and was hospitalized with a blood clot in his lungs, he was surprised when his physician insisted that he take a brand-name blood-thinning drug instead of the generic version.

The doctor told French that he was wary of the generic because of what he perceived to be a slight risk of unexpected side effects. He also advised French to change another drug he was on from the generic to the brand-name equivalent.

“My bias and assumption, quite candidly, was that generics and brand names were in fact of the same consistent quality,” said French, a law professor and generic drug advocate who for years had taken nothing but the lower-priced generics. “I was utterly amazed.”

Are generic drugs safe?

The question facing French and millions of other Americans--whether there are differences between generic and brand-name drugs--is at the heart of an expanding federal investigation prompted by reports of corruption within the booming generic drug industry.

Blood-Pressure Drug Doubted

The U.S. Food and Drug Administration announced Monday that it will withdraw approval of the last remaining generic version of a leading blood-pressure drug, Dyazide. The agency said it is no longer certain that the generic is equivalent to the brand-name drug.

So far, there is no evidence that even the generic drugs that have been challenged have caused any harm to patients. But some physicians and consumer activists say the revelations are rattling their confidence in generics and the way they are approved.

“The current situation appears to be a combination of some dishonesty and a lot of slipshod results,” said Dr. Richard F. Corlin, a gastroenterologist practicing in Santa Monica. “It has heightened people’s concerns.”

Generic drug industry officials say they are cooperating fully with the investigations, but they stand by the reliability of their products. And they insist that there have been no scientifically documented cases of patients being harmed by generic drugs.

‘Extraordinary Record’

“We have an extraordinary record of safety and efficacy with generic drugs,” said Jay Molishever of the Generic Pharmaceutical Industry Assn., “despite intense scrutiny from ‘the brands’ who have been looking for a screw-up.”

Indeed, there is much at stake in this battle.

The U.S. prescription drug market is valued at $30 billion annually. Until recently, it was almost exclusively the territory of brand-name manufacturers. But amid rising pressure to control health care costs, generic firms have cornered a larger and larger share.

According to Molishever, about one-third of all prescriptions are filled with generic drugs. Approximately 30% of prescription drug revenues go to generic firms. Some analysts predict that that percentage will rise as high as 65% by 1995.

The FDA investigation presents “a heyday for the (brand-name) firms,” said Max Stollman, who runs a pharmacy in Beverly Hills and favors generic drugs. “It couldn’t have come at a better time or had more impact. They’ve been screaming for years.”

The Pharmaceutical Manufacturers’ Assn., which represents brand-name firms, has declined to comment on the FDA investigation, saying the inquiry is ongoing and no brand-name firms are involved. But the association has in the past expressed concerns that some of the generic copies approved by the FDA for marketing are not “therapeutically equivalent” to the so-called pioneer drugs.

In particular, industry officials have questioned drugs for conditions including arrhythmia and drugs used for long-term maintenance. The industry association has called in the past for the generic drug approval process to be tightened.

Damage Seen as Short Term

Whether the federal scrutiny will put a crimp in the generic drug industry’s growth will depend on whether patients have been harmed, some medical experts and financial analysts say. Others insist that economic pressures will ensure that any damage is short term.

“The generic market is here to stay,” said Arda Minocherhomjee, a health care analyst for the Chicago Corp., who predicted simply a shakeout of weaker generic firms. “The people who pay (health-care bills) cannot afford high-priced brand-name drugs.”

Scrutiny has focused on prescription drugs, although generic firms also make over-the-counter medications for headaches, colds and other common ailments.

Under current U.S. law, prescription generics can be marketed only after the original drug’s 17-year patent expires. The brand-name company has that amount of time to recoup its investment in research, development and marketing. Then generics can enter the fray.

Generics tend to sell for less than the brand-name equivalent. The difference in price varies widely. For that reason, many insurers and third-party payers have created new rules and incentives encouraging patients and pharmacists to use generics.

More than 8,000 generic prescription products covering 170 drugs in different dosages and made by different manufacturers have been approved since 1970, according to Molishever. The FDA contends that there is no difference between those drugs and the originals they followed.

But a key concern of some physicians and experts are provisions in the federal law under which the FDA approves generic drugs. Those rules generally require that generics be equivalent to the brand-name product--within certain limits.

Proof of Potency

Generic drug companies must prove through studies that their drug is of the same potency as the brand-name version; that is, that both versions are absorbed into the blood and maintained at certain levels at comparable rates.

But the FDA allows in most cases “variability” in potency of up to 20%. For example, the generic drug can remain in the bloodstream 20% longer or less long than the accepted standard, experts say. Whether that 20% margin is a problem may depend on the patient, the drug and your point of view, some doctors say.

“Is this 20% acceptable? The answer is, with certain drugs yes, with others, absolutely not,” contended Corlin, citing certain drugs for heart conditions and diabetes. “The only way you can know is to go through drug by drug by drug.”

But generic drug industry officials say that among drugs approved since 1984, the variability is on average just 3.5%. That level is comparable, they say, to the variability found from batch to batch and lot to lot among brand-name drugs.

Furthermore, the industry officials say the FDA standards are stricter for drugs where small variations might make a difference. The agency allows only 10% variability for drugs in which there is a small difference between a therapeutic and a toxic dose.

“I think (patients) can take generic drugs with confidence,” Molishever said.

However, in recent months three former employees of the FDA’s generic drug division have pleaded guilty to charges of taking thousands of dollars in illegal payments from drug manufacturers in exchange for speeding up approval of their drugs.

Two manufacturers have also admitted that they gave the FDA false information in order to win approvals. One company admitted handing in for laboratory scrutiny the original brand-name version of one drug rather than its generic copy.

Increased Authority Asked

As a result, the FDA is asking Congress for increased authority to punish wayward drug manufacturers. It also intends to intensify its surveillance of manufacturers and laboratories that conduct pre-market testing under contract to the firms.

Generic drug industry officials and long-time proponents of generics emphasize that there is no evidence that any patients were harmed by the alleged corruption. Nevertheless, some physicians and others urge caution in the use of generics in certain instances.

Robert T. Koda, an associate professor of pharmacy at USC School of Pharmacy, said any risks are likely to be greatest in the case of those drugs in which there is a relatively fine line between therapeutic benefit and harmful side effects.

As an example, Koda cited anti-coagulants, such as the drug prescribed to Bruce French. Koda said it could theoretically be risky to switch a patient from the brand-name blood thinner to a generic in light of possible differences in potency.

“It’s possible that the person might have a therapeutic failure,” Koda said, “meaning their blood would coagulate faster . . . or the opposite could be true (and) they would suffer a bleeding episode.

“But you have to temper that with the actual data that seems to indicate that the number of therapeutic failures reported in the literature as a result of generic drugs is relatively small. Reports are not frequently seen.”

Corlin, the gastroenterologist, said he would be cautious in prescribing generic drugs for certain heart conditions and cases of diabetes that are especially difficult to control. By contrast, he would have no hesitation in using certain generics for colitis or ulcers.

“In certain drugs, a 20% margin is not crucial,” Corlin said. “ . . . but if you have a person who is a difficult-to-control diabetic taking 20 units of insulin one morning, and they get 16 units one morning and 24 the next, that person is going to be in trouble,” he said.

Others, including Molishever, contend that such cases are rare and the issue of variability is a red herring. Molishever contended that there have been anecdotal reports of unexpected side effects but not a single scientifically documented case.

Task Force Cited

Molishever also noted that an independent task force formed by the FDA in 1986 to investigate the issue of so-called bioequivalence concluded in February, 1988, that physicians could feel secure in substituting generic for brand-name products.

The task force acknowledged that on occasion properly manufactured and administered drugs fail to have their intended effect. But they said it was extremely unlikely that in such cases another version, whether original or generic, would have a different effect.

“Critics who theorize that one FDA standard might permit variations in potency that would permit one generic to be 80% of the original drug and another to be 120% do not take into account all the criteria FDA uses,” the agency wrote at the time.

Stollman, the pharmacist, who estimated that as much as 50% of all prescriptions dispensed at his Family Pharmacy are generic drugs, suggested that much of the concern about generics on the part of patients is unwarranted.

“Like the doctor, they have been brainwashed (by the brand-name industry) to think, ‘It’s my health. I want the best. I don’t care what it costs,’ ” Stollman said. “ . . . I think people need to have faith in their pharmacist. We’re out to help them be sensible users.”

Times staff writer Linda Williams contributed to this article.