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Unapproved Pancrelipases Give Patients Problems

Kate Traynor

Despite years of regulatory efforts by the Food and Drug Administration (FDA), some older products—including most pancrelipase preparations—are neither innovator drug nor generic.

Like levothyroxine and digoxin, pancrelipase products, which help regulate fat absorption in cystic fibrosis patients and others with insufficient pancreatic activity, were first marketed before Congress passed the 1938 Federal Food, Drug, and Cosmetic Act. Six years ago, however, FDA declared pancreatic insufficiency products to be "new drugs for which approved applications will be required for marketing." That rule, published in the Federal Register, made pancreatic insufficiency products available only by prescription and forbade manufacturers from introducing nonprescription—and, one would infer, prescription—pancrelipase preparations onto the market.

However, some pancrelipase products were introduced to the market after the rule was published.

University of Florida professor Leslie Hendeles, Pharm.D, warns pharmacists against treating all of these new products—some of which he describes as unapproved and untested in humans—as FDA-rated generic equivalents.

Hendeles has recently seen several instances of treatment failure among cystic fibrosis patients who used a newly marketed pancrelipase product instead of their usual product. In at least one case, he says, the product switch occurred because a chain drugstore added the supposed generic to the inventory as the preferred pancrelipase to dispense. Pharmacy staff members, says Hendeles, told him that their company "wouldn’t have [the product] in their computer system if it wasn’t AB rated," or in other words, considered by FDA to be bioequivalent to an innovator product.

Informed of the situation, the pharmacy's national buyer expressed astonishment to Hendeles. That buyer is not alone. "Everybody that I’ve talked to is astonished that this is going on," says Hendeles.

Professor Robert C. Stern, M.D., who treats cystic fibrosis cases at the University Hospitals of Cleveland, says his patients do not always pay attention to product labeling and often may not realize that they received something other than what they expected. The truth comes out when they have adverse effects.

"When the patients come in and we find out they’re on a generic," says Stern, "we tell them it’s not equal…and that they should insist on the original brand." Both Stern and Hendeles advise prescribers to write "do not substitute" or the equivalent on all pancrelipase prescriptions.

Stern adds that patients can suffer even when switched from one well-known brand of pancrelipase to another, since the correct dosage for each patient becomes apparent "after weeks or months of trial and error."

FDA spokeswoman Crystal Rice says the agency will soon issue a rule designed to regulate prescription pancreatic enzymes. "The agency is looking into the issue concerning the substituting of the unapproved microencapsulated pancreatic enzyme products," she says

Although FDA said in 1995 that "a number of" pancreatic enzyme makers had submitted new drug applications, just one pancrelipase preparation—N.V. Organon’s Cotazym—has been approved by the agency so far.

Does your pharmacy sell unapproved generic drugs? Use FDA’s Electronic Orange Book to find out. Search by trade name or active ingredient, and learn whether your generics are AB-rated equivalent products.