Reference-listed drugs

To document the bioequivalence of the drug product for which the manulacture has been changed, as defined in this guidance, compared to the drug product manufactured prior to the change or compared to the reference listed drug (RLD). 

Changes requiring completion of studies in accordance with 21 CFR part 320 to demonstrate equivalence of the drug to the drug as manufactured without the change or to a reference listed drug (506A(c)(2)(B)). 

Reference Listed Drug The listed drug identified by FDA as the dmg product on which an applicant relies in seeking approval of its abbreviated application (21 CFR 314.3). 

Statement that the route of administration, dosage form, and strength are the same as those for the reference listed drug and a... 

Information that shows that the product is bioequivalent to the reference listed drug Results of any bioavailability or bioequivalence testing performed in support of a petition Methods and GLP statement for any in vivo bioequivalence studies... 

Statement on proposed labeling that the labeling is the same as the labeling for the reference listed drug with the exception of changes noted in the annotated proposed labeling... 

If a USP method is not available, the FDA method for the reference listed drug should be used. 

For example, a 505(b)(2) application would be appropriate for a controlled release product that is bioinequivalent to a reference listed drug where... 

An application in which the only difference from the reference-listed drug is that the extent to which the active ingredient(s) is absorbed or otherwise made available to the site of action is less than the listed drug [21 CFR 314.54(b)(1)] or... 

IF AN ANDA, OR AADA. IDENTIFY THE REFERENCE LISTED DRUG PRODUCT THAT IS THE BASIS FOR THE SUBMISSION Name pf Diug HohMr 0 Approved Appficatton... 

On February 17,2004, Nastech Pharmaceutical Company announced its filing of an ANDA for a salmon calcitonin nasal spray drug product for the treatment of postmenopausal osteoporosis. As with Fortical, Novartis s Miacalcin was cited as the reference listed drug however, Nastech chose to submit an ANDA via the 505(j)(l) route, rather than a 505(b)(2) application. 

On the other hand, the comparability of the drug substance and excipients with those of the innovators product listed by the FDA as the Reference Listed Drug (RLD), assumes (under the FDA s SUPAC guidelines) considerably greater importance for sterile and non-sterile semisolid formulations than, for solid oral dosage forms. With the semisolid dosage forms, the FDA uses various types of diffusion analyses in lieu of dissolution as a surrogate for in vivo bioequivalence. 

---