Bioequivalence Of Generic Products Research Articles

Generic orphan drug substitution: a critical analysis of global practices and Saudi Arabia's perspective.

In an era of cost pressure, substituting generic drugs represents one of the main cost-containment strategies of healthcare systems. Despite the obvious financial benefits, in a minority of cases, substitution may require caution or even be contraindicated. In most jurisdictions, to obtain approval, the bioequivalence of generic products with the brand-name equivalent needs to be shown via bioavailability studies in healthy subjects. Rare diseases, defined as medical conditions with a low prevalence, are a group of heterogenous diseases that are typically severe, disabling, progressive, degenerative, and life-threatening or chronically debilitating, and disproportionally affect the very young and elderly. Despite these unique features of rare diseases, generic bioequivalence studies are typically carried out with single doses and exclude children or the elderly. Furthermore, the excipients and manufacturing processes for generic/biosimilar products can differ from the brand products which may affect the shelf-life of the product, its appearance, smell, taste, bioavailability, safety and potency. This may result in approval of generics/biosimilars which are not bioequivalent/comparable in their target population or that meet bioequivalence but not therapeutic equivalence criteria. Another concern relates to the interchangeability of generics and biosimilars which cannot be guaranteed due to the phenomenon of biocreep. This review summarizes potential concerns with generic substitution of orphan drugs and discusses potentially problematic cases including narrow therapeutic index drugs or critical conditions where therapeutic failure could lead to serious complications or even death. Finally, we put forward the need for refining regulatory frameworks, with emphasis on Saudi Arabia, for generic substitution and recent efforts toward this direction.

Dissolution Tests of Loxoprofen Sodium Hydrate Tablets Using Ultra High-speed Liquid Chromatography

Ultra high-speed liquid chromatography (ultra high-speed LC) has become an increasingly popular method in analytical research fields. This novel analytical system provides fast and efficient chromatographic separation over a wide range of flow rate and pressure. In this study, we applied an ultra high-speed LC system to the analysis of active ingredients, such as loxoprofen sodium hydrate and some additives in the drug formulation. As part of the ultra high-speed LC system utilized in this study was a LaChrom Ultra system (Hitachi, Tokyo, Japan) equipped with a L-2455U diode array detector and a LaChrom Ultra C18 (particle size, 2 μm) column ; as a result, short time stability tests of drugs were accomplished efficiently. Loxoprofen sodium hydrate is one of the most popular non-steroidal anti-inflammatory drugs (NSAIDs) used in Japan. The use of generic products has been strongly encouraged in order to reduce healthcare costs. The active ingredients, strengths, dosage forms and regimen of generic products are the same as those of the innovator's products. However, there are many generic products of loxoprofen sodium hydrate. The most important factor in selection is information concerning the quality of the product. For oral drug products, dissolution tests should be performed, since they provide important information concerning the bioequivalence of generic products. After dissolution tests of brand-name drugs and generic products, their elution behaviors were evaluated by high-speed analysis. We achieved a fast analysis of loxoprofen within 1.0 min, and compared the elution behavior between, the brand-name drug and generic products.

Generic substitution: authors' response

We thank Professor Peterson for clarifying the standards by which regulatory authorities consider the bioequivalence of generic products. We did not intend to perpetuate a myth that downplays the quality assurance for equivalence of generic drugs and, if this was the result, we apologise. Since our publication went to press, the Department of Health (DoH) in England (speaking for the whole of the UK) decided against plans detailed within the 2009 Pharmaceutical Price Regulation Scheme (PPRS) for pharmacist-led generic substitution of medicines in primary care [1]. Following a consultation process, the DoH was swayed in its decision by the ‘strong perception (by consultees) that generic substitution poses a threat to patient safety’. However, looking at the responses it seems that many others were in favour of these plans. The DoH was also unconvinced of the cost-effectiveness of generic substitution, recommending instead that other mechanisms should be utilitized to support the use of generic medicines. As noted in our article [2], only in a minority of cases is generic substitution inappropriate, and the proposals permitted the dispensing of a branded medicine when indicated explicitly by the prescriber. Nevertheless, concerns about the minority have seemingly influenced a decision that would have saved the NHS millions of pounds annually. Moreover, in anticipation of the efficiencies achieved from generic substitution which the drug companies involved had agreed to, the PPRS made provisions for a 0.5% compensatory increase in the price of branded medicines, which account for around 80% of the NHS drugs bill, over the next 3 years. Thus while the proposal for generic substitution has been shelved, the costs of branded medicines to the NHS in the UK are allowed to rise. This decision seems perverse at a time of financial austerity.

Physicians Question FDA's Confidence in Generic Drugs' Safety, Efficacy

Physicians Question FDA's Confidence in Generic Drugs' Safety, Efficacy

Availability of Drug Information on Bioequivalence of Generic Products -Findings of Graduate Interns at a University Pharmacy-

Access to drug information (DI) needed to evaluate generic product bioequivalence was studied to identify problems with the current status of DI availability and encourage proper use of DI. Ten items were chosen from among the stock of branded products at the University Pharmacy, and five corresponding generics were selected for each item. Conditions of access to information on pharmacokinetic tests and dissolution tests were rated and the assigned ratings compared. In the case of pharmacokinetic parameters obtainable from makers of generic drugs, we also performed Welch's t-test to compare the difference between values reported for branded and generic products. From the standpoint of individual tests, the pharmacokinetic tests yielded higher scores on the whole than did the dissolution tests, and low scores were obtained for the half-life of blood drug concentration (T1/2). We observed a tendency for the adequacy of information to depend more upon the drug item itself than upon the nature of the test. The percentage of tests allowing for comparison with branded products varied from 0%-75% (average 49%). Parameter by parameter, the range of variation was from 35% of Tmax to 63% of Cmax. Factors precluding comparison included insufficient data on branded products, mismatch in assayed chemical species between branded and generic, mismatch between final sampling time in AUC(t) measurement, dosage inconsistency, and insufficient data on generic products. DI should be provided in a manner that facilitates comparison of information supplied by generic drug makers with data released by makers of branded products.