Safety and effectiveness of veterinary generic drugs (Proceedings)
Ever wondered how a veterinary generic drug is assumed to be interchangeable with the pioneer drug in a clinical setting? What is the process by which it is approved by the Food and Drug Administration/Center for Veterinary Medicine (FDA/CVM)? What does pharmaceutical equivalence and bioequivalence really mean? Many veterinarians confidently choose to prescribe generic drugs to our patients for the sole reason that it is cheaper than the pioneer drug. There is nothing wrong with that, however if you are curious to find out about the safety and effectiveness of generic drugs approved in the US, this presentation will enlighten you.
1. Provide the practitioner with an overview of how veterinary generic drugs are approved in the US by the FDA/CVM.2. Provide the practitioner with a general understanding of bioequivalence and its implications in the approval of veterinary generic drugs.
3. Provide the practitioner with a general understanding of blood-level studies, pharmacological endpoint studies and clinical endpoint studies used for confirmation of bioequivalence.
4. Provide the practitioner with some insight on which drugs may qualify for biowaivers.
What is considered a generic drug?
A generic drug is the term used for a product that contains the same medicinal ingredient(s) as the off-patent original brand name (pioneer) product, but is generally cheaper in price. The generic and original pioneer products are referred to as pharmaceutically equivalent.
What is an original pioneer drug?
A pioneer drug is the first approved and marketed drug product in the US. The original pioneer drug is also referred to as the reference formulation used for in vitro comparative studies and in vivo bioequivalence studies with the generic formulation.
What does pharmaceutical equivalence mean?
Pharmaceutical equivalence between two formulations is confirmed when they both contain the identical amount of the identical medicinal (active) ingredients in the same dosage form but do not necessarily contain the same excipients (inactive ingredients), provided they are not known to influence the absorption characteristics of the active ingredients.
What is bioequivalence?
Bioequivalence is demonstrated when the rate and extent of absorption of two formulations of drugs (test and reference) are sufficiently similar, within pre-determined allowable limits, when administered under similar experimental conditions. The underlying principle is that the products should be therapeutically equivalent if the products show bioequivalence with respect to each other and hence, be interchangeable in a clinical setting. Thus, the rate and extent measures of absorption become surrogate indicators of therapeutic outcome.
What constitutes a bioequivalence study?
A bioequivalence study is a useful surrogate in vivo study used to demonstrate comparable safety and efficacy in several situations such as between generic (test) and reference products, for registration of multiple products with the same active ingredient but in different concentrations, to support approval of an alternate route of administration or dosage form, of a minor formulation change or of a manufacturing change which may affect bioavailability. Although it would be difficult to account for all situations, a common template to assess bioequivalence results is desirable.
The FDA/CVM may approve a veterinary generic drug based on the demonstration of comparable safety and efficacy data to the veterinary pioneer drug, when filed as an Abbreviated New Animal Drug Application (ANADA). In order to do that, several studies may be conducted such as in vivo bioequivalence studies and/or in vitro comparative studies. The CVM has a Guidance for Industry document that help pharmaceutical companies conduct the appropriate studies needed for the approval of their proposed generic drug formulation. This Guidance document #35 can be found at the following website: (http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/ucm052363.pdf).