If you saw two products on the shelf that were essentially the same, but one was less expensive, which would you buy? Most would choose the more economical item. But some would purchase the higher-priced product, thinking that higher price—and perhaps brand name—translate into higher value.
It’s the same quandary some dairy producers experience when trying to determine which vaccine, antibiotic or other drug to choose for their animal health programs. They can choose between brand name “pioneer” drugs or generic drugs.
The term pioneer is used to describe drugs researched and developed—and usually patented—by a company for a specific purpose, using a trademarked “brand” name. Because of the patent, typically valid for 20 years from date of patent application, other manufacturers cannot produce or sell the same drug product for the duration of the patent period.
However, when that patent expires, other pharmaceutical companies can legally use the same compound—or make a product that is “bioequivalent” to the pioneer drug. These products are generic drugs. Of course, these generic drug manufacturers cannot use the pioneer company’s brand name, but they reference the underlying safety and efficacy data from the pioneer drug’s approval by the Food and Drug Administration (FDA). The end result is generic drugs bring more value to the cattle or dairy producer.
In spite of the price advantage, though, some producers—and even some veterinarians—are more comfortable with the established brand. Some even doubt the safety and effectiveness of generics.
To get the facts about this sometimes-perplexing choice, Bovine Health Watch talked with two generic animal drug professionals: Bill Zollers, Ph.D., vice chair of the Generic Animal Drug Alliance and director of regulatory affairs at Norbrook, Inc., and Terry Christie, B.S., vice president, research and development at AgriLabs. Here’s what they had to say.
Are generic drugs as safe and effective as pioneer drugs?
Zollers: In a word, yes. Like pioneer animal drug products, generic animal drugs must comply with the Federal Food, Drug, and Cosmetics Act and all applicable FDA regulations. The pioneer drug company must prove its drug is effective and that it does what it is designed to do. They also must do extensive safety testing to show that the drug is not going to hurt animals that receive the drug—or the humans who consume the animal product.
Since the FDA has already approved the pioneer drug, the provisions in GADPTRA allow the generic drug to gain approval based upon the safety and effectiveness data already established by the pioneer. To use the pioneer data, “bioequivalence” must be demonstrated between the generic drug and the pioneer drug. Two products are considered bioequivalent when they are equally bioavailable—that is, the active drug is delivered into the animal’s bloodstream in the same amount over the same period of time, and becomes available at the site of drug action.
Does a generic manufacturer use a different formulation? If so, why?
Christie: Different formulations sometimes result when the exact formulation of a pioneer drug is not available. In general, animal-injectable products list the exact formulation, including inactive ingredients, on the label. In these cases, where the exact formulation is provided on the label, the generic product is virtually the same as the pioneer product. If the formulation is the same and the product is a true solution, the FDA’s Center for Veterinary Medicine (CVM) will grant a waiver from conducting in-vivo (in the animal) bioequivalency studies.
On the other hand, certain dosage forms, such as boluses, tablets and liquid suspensions, don’t generally list the inactive ingredients on the label. When that information is not available, the generic company conducts analytical testing on the pioneer product to arrive at a formulation that is as close as possible to the original. For these dosage forms (not true solutions), in-vivo bioequivalence must be demonstrated to gain FDA approval. This is true even if the generic formulation is the same as the pioneer.
What is bioequivalence and how is it determined?
Zollers: A generic drug that is bioequivalent produces the same effect in the same part of the body as the original pioneer drug and has equal bioavailability. If the generic company can demonstrate bioequivalence, they can rely on the safety and efficacy trials of the pioneer drug. But, establishing bioequivalence is not a simple task. The generic company must conduct a bioequivalence study, following a set of very strict scientific rules and equations. Designing, conducting and analyzing a bioequivalence study can take as long as two to three years to complete. A protocol must be submitted to the FDA for review and concurrence. A study is then conducted, including drug administration, blood sample collection, sample analysis, statistical analysis, report development and finally submission to the FDA. The FDA review process through product approval can take another two to three years, depending on the completeness and quality of the information presented and the questions that arise. So, the total process can easily take five years or more. The bottom line is: establishing bioequivalence is time-consuming and scientifically challenging.
If you demonstrate bioequivalence, FDA approval is likely, provided the chemistry and manufacturing aspects of the application are sufficient. If you cannot demonstrate bioequivalence, the drug is not approved. As a consumer—and as a manufacturer of generic drugs—I want the FDA approval process to be thorough. No one wants problems with a drug after it is approved and goes on the market.
Are there other things about generic drugs that could be different than pioneer drugs?
Zollers: A generic animal drug is typically the ‘same’ as its pioneer counterpart. It contains the same ingredients in the same concentrations, the same dosage form and the same route of administration. Its label must also include the same warnings, as well as information about safety and withdrawal times. Even the pH range of the generic drug must be the same as that of the pioneer drug.
What about manufacturing standards? How do they stack up for generics?
Christie: In some cases there has been a perception that pioneer products are manufactured under stricter standards. The fact is that all drug products must be manufactured using FDA current good manufacturing practices (cGMPs). FDA investigators use these same cGMP requirements when inspecting pioneer or generic manufacturers. In fact, these are the same requirements investigators utilize for inspecting human drug manufacturers.
What are some of the other misconceptions about generic drugs?
Zollers: Some people think generics have inferior ingredients, and that’s not true at all. All the active and inactive ingredients are held to the same standards as those approved for the pioneer. When the generic drug company submits chemistry and manufacturing information, every ingredient must meet the same United States Pharmacopeia (USP), United States National Formulary (USNF) or other acceptable standards as those of the pioneer drug in order to assure the quality of the ingredients is the same.
Another misconception is that the pioneer drug has a better carrier, so it helps the drug get released into the bloodstream quicker. That’s simply not true. Carriers in generic drugs have to meet the same standards as those for the pioneer drug. In some instances, generic drugs may have a different carrier, but that carrier must meet the same standard and have the same effect as the carrier in the pioneer formulation. If a generic drug carrier is inferior, this will be determined in a bioequivalence study—resulting in a failed study and the generic product not receiving approval.
Christie: Sometimes there is also a mistaken impression that generics are formulated at lower levels of active than pioneers. On the contrary, cGMPs require that active ingredient levels must be formulated at 100 percent of label claim.
How much do producers save buying generic drugs?
Christie: Generic drugs are a good value because they have been demonstrated to be just as safe and effective as pioneer products—and, they are often significantly less expensive. For example, when Ivermectin Pour-On was on the market by itself, it cost more than $500 for five liters. Today, a generic version sells for $60-$90 for the same-size package. The price difference between pioneer and generic drug prices depends on the number of generic competitors. With two or more generics competing in the marketplace, as there were in the case of Ivermectin, the savings can be significant.
Zollers: Generics put price pressure on pioneer products when they come to the market. The effect on the animal drug market-place is not as dramatic or immediate as it is on the human drug side, but it does exert pressure, and pioneer product prices come down.
What influence does the “brand name effect” have on the animal drug buying decision?
Christie: If a producer has used a particular pioneer product for years, there may be a bias toward that product, even though the generic has been proven as safe and effective. But for the most part, especially in today’s economy, the value of the generic drug comes through, whether to the producer or veterinarian. With the volume of drugs they buy, producers have to make decisions that are economically sound.
In addition, many important animal health drug products are available only in the generic version because the pioneer companies have chosen to discontinue manufacturing and marketing them.
So, what is the bottom line for generic drugs?
Zollers: What we want producers to take away from this discussion is that a generic animal drug is approved by the CVM by a rigorous process to ensure that the safety, effectiveness, quality and consistency are the same as the pioneer animal drug.