Perspective:

The following are 10 points to remember about this health policy statement:

1. On average, generic drugs are 75% lower in price compared to brand-name drugs.

2. The 1984 Hatch-Waxman Act authorized the Food and Drug Administration (FDA) to approve generic drugs, which were documented as bioequivalent to the innovator drug. Bioequivalence studies are used to confirm that generic drugs are not less than 80% or 125% more than the innovator drugs. It is often difficult to determine the bioequivalence of fixed-dose combination drugs. Current bioequivalence tests may not be adequate for drugs with narrow therapeutic index.

3. Patents for several biologic products that are manufactured with DNA technology will expire soon. Therefore, policies regarding generic versions of these therapies are needed.

4. Currently, the FDA does not regulate generic substitution, therapeutic interchange, or therapeutic substitution. Product substitutions are made in accordance with individual state regulations. In some states, lists are available which identify products that may be substituted for one another; however, in some states, lists state which drugs cannot have a substitution.

5. Therapeutic interchange is defined as the interchange of one drug for another. Environments such as hospitals may switch a drug such as a statin for another statin due to use of an approved formulary system. Careful discharge planning includes instructions to patients and their families to identify which drugs have changed and if the patient should return to predischarge medications after discharge. The American Medical Association recommends that therapeutic interchange in patients with chronic conditions who are on a stable regimen be discouraged.

6. FDA guidelines exist for determination of margins to be used in noninferiority studies. However, <10% of trials document noninferiority margins based in FDA recommendations.

7. Some drugs that are still on patent in the United States are available in generic form in other countries, including Canada. Importation of such drugs for sale is prohibited at this time.

8. More than 80% of elderly patients take at least one medication. One third of all prescribed drugs are taken by elderly patients. A comprehensive meta-analysis which compared brand-name cardiovascular drugs with generic drugs observed no differences in effect size for beta-blockers, diuretics, calcium channel blockers, antiplatelet agents, angiotensin-converting enzyme inhibitors, statins, alpha-blockers, or warfarin. Generally, starting at a lower dose is preferable when transitioning medications in the outpatient settings.

9. Based on the lack of evidence supporting the assumption of bioequivalence for most therapeutic agents in infants and children, this Committee does not support blanket recommendations for generic substitution. Pharmacokinetics, pharmacogenomics, efficacy, and safety of many drugs in children are often based on data from adults.

10. When considering therapeutic substitution, third-party payers must take into account factors including the strength and level of evidence for the substitution. All payers that consider policies for therapeutic interchange should ensure that adequate information regarding the interchange is available to health care teams.