Metered-dose inhalers generic

Adams, W.P. Poochikian, G. Taylor, A.S. Patel, R.M. Burke, G.P. Williams, R.L. Regulatory aspects of modifications to innovator bronchodilator metered dose inhalers and development of generic substitutes. J. Aerosol Med. Deposition, Clearance, and Effects in the Lung 1994, 7 (2), 119-134. 

The most significant developments in metered-dose inhaler technology to occur since the early 1990s have been the introduction of hydrofluoroalkane (HFA) systems as alternatives to chlorofluorocarbon (CFC) systems [174]. This has largely been caused by the link between the use of CFC systems and ozone depletion in the upper atmosphere [152,175]. Albuterol and beclomethasone have been reformulated in HFA products, but as yet the CFC products are still subject to an annually renewable medical exemption. The Food and Drug Administration has recently published its position on alternative propellant formulations, which should initiate the phase-out of CFCs [176]. In the meantime, a number of generic CFC products of albuterol have been manufactured. The opportunity for reformulation of products as they come of patent is likely to increase research and development in this area in the near future. New formulation opportunities will also arise from these developments, including solutions [177], micellar [178,179], and microemulsion [180]. 

As with the metered-dose inhalers, some old drugs have been repackaged in new devices. For dry powder inhalers these are not true generics but have a similar impact on the marketplace. Most notable of these in the Clickhaler (Innovata Biomed), which is marketed in Europe, for the delivery of albuterol (salbutamol) and beclomethasone. 

Interim Guidance for Documentation of in Vivo Bioequivalence of Albuterol Inhalation Aerosols (Metered Dose Inhalers). Division of Bioequivalence, Office of Generic Drugs, Center for Drug Evaluation and Research, FDA, January 27,1994. 

This raises the issue whether there can be any general standard of equivalence. Two matters which are surely of some relevance are the therapeutic window for treatment and the batch-to-batch variability. Some drugs, such as procainamide, have a very narrow therapeutic window, others such as propranolol have a much wider one (Rowland and Towzer, 1995). On the other hand, for certain products, such as those delivered by transdermal patch or metered-dose inhaler, or generally active at extremely low concentrations, the variability from batch to batch or even from sample to sample may be considerable. As Rhodes (1994) has pointed out, it seems to be unreasonable to require a generic to be equivalent to a brand name if the latter is not equivalent to itself. In particular, the combination of wide therapeutic window and high batch-to-batch... 

Blake KV, Harman E, Hendeles L. Evaluation of a generic albuterol metered-dose inhaler importance of priming the MDI. Ann AUergy 1992 68 169-174. 

Chenge JK, Chrystyn H. Volumatic usage some generic salbutamol metered dose inhalers can be used. Thorax 1994 49 1162-1163. 

Clark DJ, Gordon-Smith J, McPhate G, Clark G, Lipworth BJ. Lung bioavailability of generic and innovator salbutamol metered dose inhalers. Thorax 1996 51 325-326. 

Wong and Hargreave (245) have written an excellent review about the bioequivalence of metered-dose inhaled medications. The article is written for comparisons of generic drugs with the original. It is, however, also relevant for comparison between different administration systems. The authors discuss the criteria for equivalence of medications in in vitro studies it should be close to 15% of the innovator. They also discuss the different main types of inhalation drugs (e.g., bronchodilators, steroids, and antiallergic aerosols). 

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