Generic products, substitution

Some commentators on bioequivalency have voiced concerns as to whether it is appropriate for states to second-guess the FDA on matters concerning bioequivalency. Once FDA has carefully evaluated an ANDA and decided that the generic product should be approved and given a rating that allows for substitution, it seems hard to conceive any likely circumstances under which an individual state should be able to opt... 

The sample involves a regression analysis framework that estimates the effect on price of the number of generic products of the same molecules. Danzon and Chao (2000) also control for the number of therapeutic substitutes, hrst-mover advantages, molecule age, and several other factors. 

Generic products tested by the FDA and determined to be therapeutic equivalents are listed by the FDA in their publication Approved Drug Products with Therapeutic Equivalence Evaluations. These products contain the same active ingredients as their brand-name counterparts and also meet bioequivalence standards. The FDA recommends substitution only among products listed as therapeutically equivalent. 

Additionally, older, now generic products may be packaged in both forms, i.e., protected by the immediate package or only by the secondary package. Such duplicity puts an unusual burden on the user/patient to read the labeling every time they refill their prescription. Because random substitution is allowed for all officially listed generics, many dispensers and users/patients may be very unaware of this problem. 

Under the proposed legislation, pharmacists would be allowed to substitute prescribed products only with a bioequivalent generic therapeutic substitution would not be permitted. Doctors could prevent substitution by marking the script accordingly. Approximately 50 percent of products are not reimbursed. This includes nearly all OTCs, but also minor tranquilizers, some anabolics and amphetamines. 

A city clinic is considering the substitution of generic drugs in order to save money. The clinical pharmacologist is asked to advise on the bioavailability of the generic products. She informs the head of the clinic that the bioavailability of drugs is... 

MacDonald JT (1987). Breakthrough seizure following substitution of Depakene capsules (Abbott) with a generic product. Neurology 37 1885. 

The main consideration where generic substitution is concerned with is that the efficacy and safety of substituted medicinal products should be equivalent to one another. As this is tested during the approval of generic medicinal products, on the basis of bioequivalence studies, it can be assumed that the approved generic products are just as effective and safe as the reference product. However, in conjunction with certain active substances or certain situations, it may be preferable to avoid even the slightest risk (e.g. ciclosporine). 

When in daily practice substitution (e.g. by a generic product) is considered, bioequivalence is of course the first parameter to evaluate. However, other aspects of medicine s use related to both the product and the condition of the patient are to be taken into consideration as well. Among these are ... 

The Textile Eiber Product Identification Act (TEPIA) requires that the fiber content of textile articles be labeled (16). The Eederal Trade Commission estabhshed and periodically refines the generic fiber definitions. The current definition for a polyester fiber is "A manufactured fiber ia which the fiber-forming substance is any long-chain synthetic polymer composed of at least 85% by weight of an ester of a substituted aromatic carboxyUc acid, including but not restricted to terephthalate units, and para substituted hydroxyben2oate units."... 

Pancreatic enzyme replacement is the mainstay of gastrointestinal therapy. Most enzyme products are formulated as capsules containing enteric-coated microspheres or microtablets to avoid inactivation of enzymes in the acidic stomach instead, they dissolve in the more alkaline environment of the duodenum. Capsules may be opened and the microbeads swallowed with food, as long as they are not chewed. A powder form is available for patients unable to swallow the capsules or microbeads, but bioavailability is poor. While products may contain similar enzyme ratios, they are not bioequivalent and cannot be substituted. Generic enzyme products generally display poor dissolution and should not be used.5 Table 13-3 lists commonly used enzyme replacement products. 

There is no evidence that one LT4 product is better than another. However, given the likelihood that these products do have different bioavailabilities, patients should be maintained on the same LT4 product. Given the generic substitution regulations of most states, this is best accomplished by prescribing a brand-name product. The prescriber should not allow substitution in the way mandated by state regulations. 

The growth of generic prescribing and generic substitution will clearly increase the role and responsibilities of pharmacists in drug product selection. This movement will also stimulate in many regions of the world further debate about how bioequivalence should be quantified and when in vitro methods may, in some... 

Some empirical observations are significant in this respect. For example, the demand for brand products is fairly sensitive to the price of generics, and even in some cases to the price of brand name therapeutic substitutes. In an estimate of the parameters of the demand function of brand products and generics in the cephalosporin submarket in the USA, a high price elasticity was observed between brand products and generics, and also in some cases, although to a lesser extent, between therapeutic substitutes.4... 

PCR should be removed from all products that are subject to competition, whether they be generics or therapeutic substitutes for which reasonable elasticity can be expected. 

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