Cancer Treatment Today

All generic medications must undergo testing for bio-equivalence before the U.S. Food and Drug Administration (FDA) decides if the generics are equivalent to the brand-name medications and assigns a rating to each one.

For FDA approval, a generic drug must:

Contain the same active ingredients as the innovator drug (inactive ingredients may vary)
Be identical in strength, dosage, form and route of administration
Have the same use indications
Meet bioequivalency criteria of 80 to 125 test reference ratio
Meet the same batch requirements for identity, strength, purity and quality
Be manufactured under the same strict standards of FDA’s Good Manufacturing Practice regulations as the innovator drug
What must be taken into consideration, however, is that some variability occurs in the manufacturing of both brand and generic drugs. The FDA limits the amount of variability, outlining acceptable standards.

In the case of Gleevec, however, there is a study by Islamagic et al that concluded that generic imatinib as second-line therapy does not have deleterious effects on patient outcomes. Reduced efficacy was only seen with other versions of generic imatinib, several of which were reported by single authors. Contradictory results with the same generic product were reported in two larger case series (90% response11 vs. 33% relapse).However, there is significant concern about whether actual clinical effectiveness is the same. Islamagic found that first-line generic imatinib showed suboptimal efficacy compared with branded imatinib. Overall, 52% of patients switched from first-line generic imatinib to nilotinib owing to treatment failure and side-effects.

Bioequivalence does not necessarily mean therapeutic equivalence. To be therapeutically equivalent, a drug should have the same clinical effect and safety profile. These are not demonstrated in a bioequivalence test.

Islamagic, Erna et al. The Efficacy of Generic Imatinib as First- and Second-line Therapy: 3-Year Follow-up of Patients With Chronic Myeloid Leukemia Clinical Lymphoma, Myeloma and Leukemia ( in-press)http://dx.doi.org/10.1016/j.clml.2017.02.001

BC Cancer Agency, GENERIC IMATINIB: REVIEW OF THE LITERATURE ON CLINICAL EFFICACY 2017