first edition (1980) of the Orange Book - FDA Law Blog

4. Erythromycin stearate Tablets - All manufacturers of erythromycinstearate tableted products demonstrated the bioequivalency of their productsas a conditien of applicatien approval. These bioequivalence studies wereperformed under fasting conditions and, as a result, all firms were requiredto label their products to be· taken en an empty stomach. Since that timesane firms have demonstrated that their products also may be taken immediatelybefore meals, but not with meals, and still achieve acceptable bloodlevels. On the basis of such studies, FDA has approved those products to belabeled accordingly. At the ·same time, the agency stresses that optimalabsorption for any erythromycin stearate tablet is achieved when the drug isadministered under fasting conditiens, and recorrmends that prescriptionsinclude instructions regarding administratien in relation to meals. Whenerythromycin stearate tablets are to be administered under fasting conditions,the agency believes that any listed brand coded AB may be consideredtherapeutically equivalent. If erythromycin stearatE! is to be takenimnediately before meals, only those products with labeling that providesfor such administratien should be dispensed. Erythromycin stearate tabletedproducts have been designated therapeutically equivalent (AB) in the Listbecause all of the products produce equivalent blood levels provided thedrug is prescribed and administered in accordance with the conditions of usein the labeling. Prescribers and dispensers are advised to be familiar withthe labeling of these products.5. Imipramine HCI Tablets - The agency has determined that certainbrands of imipramine tablets may undergo deterioration in their dissolutionrate as the tablets age on the shelf, even under normal conditions ofstorage. FDA will be proposing to the USP a new dissolutien rate standardto solve this problem. Those products that already meet the proposed newstandard are coded AB. Products without data to support satisfactorydissolution are coded BP.6. Amino Acid and Protein Hydrolysate Injections - Of these tWo typesof products, only parenteral amino acid mixture solutions presently arelisted as approved and marketed under new drug applicatiens. Proteinhydrolysate injections. are omitted because of safety problems. Becausethese products differ by the amount and kinds of amino acids they contain,tooy are not considered pharmaceutical equivalents. Thus, it is on thisbasis that FDA cannot evaluate these products as therapeutic equivalents.At the same time, the agency believes that it is appropriate to point outthat where nitrogen balance is the sole therapeutic objective and individualamino acid content is not a consideration, pharmaceutical alternativeproducts with the same total amount of nitrogen content may be considered astherapeutically equivalent.7. Prednisone Tablets - Because of known bioinequi valence and ther a­peutic inequivalence problems, the USP recently adopted a new in vitrodissolution test correlated with in vivo bioequivalence data. All prOductsI - 18