Active Ingredient: Hydroxyzine
Barr's research has shown, giving a greater opportunity for dissolution of the drug.
As defendants concede, with respect to some products. I 1977 amended 1962, with provisions for premarketing review of new drugs. This review, however, was directed solely to assuring drug-product safety.
It was not until the Act was amended in 1962 that the definition of "new drug" was enlarged to include drugs not generally recognized as safe and effective. The 1962 amendments changed the data-reporting requirements of the "new drug" procedure to require submission of data showing efficacy and, in place of automatic approval of NDAs not disapproved, the procedure under the 1938 Act, the 1962 amendments required positive agency approval to make an NDA effective.
For further discussion of the history of drug regulation by the federal government, see Weinberger v.
Articles of Drug Lannett, 585 F. However, FDA will approve an ANDA only where the "me-too" product is shown to be the therapeutic equivalent of the pioneer and safe and effective in accordance with 21 U.
See Premo Pharmaceutical Laboratories, Inc. United States, 629 F.
See generally Hoffmann-LaRoche, Inc. Weinberger, supra.
II Much of the testimony on this hearing related to bioavailability. Bioavailability is "the rate and extent to which the active drug ingredient or therapeutic moiety is absorbed from a drug product and becomes available at the site of drug action.
See Dorland's Illustrated Medical Dictionary 200 25 th ed. See 21 C.
When two different drug products are to be used interchangeably in the treatment of illness, it can be critical that the products are bioequivalent that is, that there be no significant difference in the products' bioavailability. A drug that is less bioavailable than that for which it is substituted will deliver less of its active ingredient than expected; a drug that is more bioavailable than that which it replaces presents the danger of overdosage.
The Government argues that physicians and patients generally believe or assume that generic versions of "brand-name" products are bioequivalent to the respective pioneer drugs themselves. Because the generic versions are usually significantly less expensive than the pioneer drugs, they are frequently freely substituted for their more expensive counterparts.
Thus, the Government contends, it is crucial that the products be, in fact, bioequivalent. Contending that, because so many factors independent of a product's active ingredient and even, as indicated below, of its inactive ingredients can affect a drug product's bioavailability and thus its bioequivalence to an FDA-approved medication, the Government concludes that absent preclearance of each of Premo's products named in the complaint, there can be no assurance of its safety and effectiveness, and it must be considered a "new drug" within the meaning of section 321 p of the Act.
Premo argues that so long as the active ingredient in its product is the same as the active ingredient in the approved pioneer drug all other questions are irrelevant because the active ingredient, the "drug, has been recognized as safe and effective by the FDA.
There are many factors that can affect a drug's bioavailability. Among these are the particle size and crystalline form of the active ingredient; the choice of inactive ingredients excipients, such as binders and fillers; the facilities and controls used in the manufacture and processing of the drug; and the environmental conditions during manufacture and storage.
This, in turn, can affect the bioavailability of the active ingredient itself.
Diluents, used to provide tablet bulk, can affect bioavailability in numerous ways, such as by interfering with the drug's absorption.
And disintegrants and surfactants, added to tablets or capsules to cause them to break up after ingestion, can also affect the drug's dissolution and thus its bioavailability. In fact, as set forth in an affidavit submitted on behalf of the Government, Dr.
In addition, a multitude of other factors can affect bioavailability. NDBI 30. The takes of the possible practices used in the manufacture of Premo's depends are not known by to experts either Tr.
I 1977 consulted 1962, 21 U.
Although defendants have included arguments to the affected, with provisions for premarketing development of new drugs, results in an undesirable of C max and AUC of ropinirole by 60 and 84.