A practical approach for evaluating population and individual bioequivalence

Gould, A. Lawrence

doi:10.1002/1097-0258(20001030)19:20<2721::aid-sim541>3.0.co;2-8

Cited by 21 publications

(13 citation statements)

References 55 publications

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“…It is then accepted that, when used as alternatives, the products ⁄ routes can be expected to provide sufficiently similar efficacy and safety to guarantee therapeutic equivalence. The differences between and procedures required to establish average, individual and population bioequivalences are not considered here (see reviews by Barrett et al, 2000 andGould, 2000), as all regulatory authorities require that data satisfy only the criteria for average bioequivalence. Also not reviewed are the arguments for and against the use of chiral ⁄ nonchiral methods for drug residue studies in food-producing species, except to note that residue depletion profiles depend on rate of depletion in the terminal elimination phase.…”

Section: Decision Trees On Choice Of Analytical Methodsmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of stereoisomeric drugs with particular reference to bioequivalence determination

Lees

Hunter

Reeves

et al. 2012

Vet Pharm & Therapeutics

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Drugs containing one or more chiral centres exist in stereoisomeric molecular forms. Most commonly, drugs containing a single asymmetric carbon atom exist in two enantiomeric forms, designated as eutomer (the more potent) and distomer (the less potent). As well as differences in potency and other pharmacodynamic properties, most members of enantiomeric pairs commonly differ also in their pharmacokinetic profiles. This article reviews factors underlying differences in pharmacological properties of enantiomers. The relevance of such differences for studies designed to evaluate the bioequivalence of products containing chiral drugs is also reviewed.

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Section: Decision Trees On Choice Of Analytical Methodsmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of stereoisomeric drugs with particular reference to bioequivalence determination

Lees

Hunter

Reeves

et al. 2012

Vet Pharm & Therapeutics

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“…The ability of traditional statistical techniques to detect subgroup-by-formulation interaction and that of proposed alternatives, PBE and IBE criteria based on two-period crossover trials, 8,15 should be studied alongside the current proposed PBE and IBE criteria. Additional simulation studies related to the sensitivity of the various criteria to single outliers, mean variance trade-offs, and other comparisons between alternative methodologies proposed 8,15 using simulation techniques. Last, the distribution of estimated σ D 2 as a measure of subject-by-formulation interaction under various assumptions would help put into context the relevance of observed values collected over a period of time.…”

Section: Simulation Studiesmentioning

confidence: 99%

“…Given the joint effect between multiple factors, we recommend the minimal sample size in each scenario to be set ahead of time. Alternative statistical procedures 15,16 should be considered.…”

Section: Data Collectionmentioning

confidence: 99%

Population and Individual Bioequivalence: Lessons from Real Data and Simulation Studies

Zariffa

Patterson

2001

The Journal of Clinical Pharma

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The Food and Drug Administration (FDA) has proposed replacing the 1992 average bioequivalence (ABE) with population and individual bioequivalence (PBE & IBE), as outlined in the preliminary draft guidance of December 1997, which was subsequently replaced by the draft guidances of August 1999 and resolved in the final guidance of October 2000. This has led to considerable public debate among regulatory, academic, and industry experts at numerous conferences (e.g., FDA/AAPS March 1998, FDA/AAPS August-September 1999, FDA Pharmaceutical Sciences Advisory Committee September 1999) and in the literature. The final guidance calls for ABE to remain as the primary criterion by which new formulations may be judged ready for access to the marketplace. In addition, the FDA recommends the use of replicate study designs for the specific drug classes of controlled-release formulations and highly variable drugs. The final guidance also alludes to the possibility of a sponsor requesting alternative criteria such as PBE and IBE following consultation with the FDA. This procedure amounts to a data collection period during which data suitable to evaluate the operating characteristics of PBE and IBE would be generated, analyzed, and discussed among interested parties. A comprehensive review of currently available databases is useful in determining the ultimate value of this data collection period. This report provides an update to the previous publication by the authors. In all, 28 data sets from 20 replicate cross-over bioequivalence studies have been analyzed (n = 12-96) using the statistical methodology in the most recent FDA draft guidance. The results are presented below. ABE Pass: ABE Fail: Total: AUC/Cmax AUC/Cmax AUC/Cmax AUC/Cmax Pass PBE & IBE 20/14 1/3 21/17 Pass IBE only 1/0 0/0 1/0 Fail PBE and IBE 0/2 0/1 0/3 Fail IBE only 2/3 4/5 6/8 Total 23/19 5/9 28/28 Review of the database reveals many interesting features, most notably the lack of consistent results within a given data set across all three criteria. The sensitivity of subject-by-formulation interaction to sample size and inherent variability of the compounds is further explored through simulation studies. It is concluded that additional simulation assessments must be considered when evaluating the value of a data collection period for PBE and IBE assessment. It will be shown that definitive conclusions regarding some of the operating characteristics of PBE and IBE can be achieved through a combination of data-driven hypotheses followed by simulation studies to further evaluate the hypotheses. Some recommendations for further data collection will be made.

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“…There has been no published evidence of clinical failure associated with a formulation demonstrated to be equivalent to the reference product under ABE. 28 While there are limitations to ABE as discussed earlier, the proposed criteria for assessing PBE and IBE do not represent a significant improvement, at least in any demonstrable clinical or public health sense. PBE and IBE,at least as proposed, do address some of the limitations of ABE.…”

Section: Recommendationsmentioning

confidence: 97%

PhRMA Perspective on Population and Individual Bioequivalence

Barrett

Batra²,

Chow³

et al. 2000

The Journal of Clinical Pharma

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The Food and Drug Administration (FDA) issued a second-draft guidance in August 1999 on the subject of in vivo bioequivalence, which is based on the concepts of individual and population bioequivalence (IBE and PBE, respectively). The intention of this guidance is to replace the 1992 guidance that requires that in vivo bioequivalence be demonstrated by average bioequivalence (ABE). Although the concepts of population and individual bioequivalence are intuitively reasonable, a detailed review of the literature has not uncovered clinical evidence to justify the additional burden to the innovator and generic companies as well as the consumer that the new guidelines would impose. The criteria for bioequivalence described in the draft guidance employ aggregate statistics that combine information about differences in bioavailability between formulation means and differences in bioavailability variation of formulations between and within subjects. The purely technical aspects of the statistical approach are reasonably sound. However, PhRMA believes that important operational issues remain that need to be resolved before any changes to current practice are implemented. PhRMA believes that the ideals of prescribability and switchability are intuitively reasonable, but it is uncertain of the extent to which the proposed guidance can achieve these goals. It is not clear whether the attainment of such goals is necessary in the evaluation of bioequivalence given the role this plays in drug development, and the lack of clinical evidence argues against a pressing need to change current practice. PhRMA is concerned that the trade-off offered by the aggregate criteria may ultimately represent more harm than good to the public interest. PhRMA recommends more rigorous evaluation of methods based on two-way crossover designs before moving to methods that require more complex designs. One such method is identified herein and contains procedures for estimating prescribability and switchability. The possibility of a phase-in or trial period to collect replicate crossover data to further evaluate IBE and PBE and possibly allow market access based on these criteria as they are being evaluated has been proposed. PhRMA believes this is unprecedented and will offer little additional information beyond that which can be obtained by simulation or has already been collected by the FDA. Simulation studies have the advantage of allowing evaluation of the sensitivity of various procedures to represent the data patterns as created within the simulation. Operating characteristics by which proposed criteria can be adequately judged have not yet been defined. The limitations of ABE for highly variable drugs and narrow therapeutic drugs are well appreciated and may be addressed by means other than a wholesale change in the current criteria.

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A practical approach for evaluating population and individual bioequivalence

Cited by 21 publications

References 55 publications

Pharmacokinetics and pharmacodynamics of stereoisomeric drugs with particular reference to bioequivalence determination

Pharmacokinetics and pharmacodynamics of stereoisomeric drugs with particular reference to bioequivalence determination

Population and Individual Bioequivalence: Lessons from Real Data and Simulation Studies

PhRMA Perspective on Population and Individual Bioequivalence

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