title: Challenges and opportunities in establishing scientific and regulatory standards for determining therapeutic equivalence of modified-release products: Workshop summary report.
abstract: BACKGROUND
  Modified-release (MR) products are complex dosage forms designed to release drug in a controlled manner to achieve the desired efficacy and safety profiles. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity.
  
  
  OBJECTIVE
  This paper is a summary report of the American Association of Pharmaceutical Scientists, International Pharmaceutical Federation, and Product Quality Research Institute workshop titled "Challenges and Opportunities in Establishing Scientific and Regulatory Standards for Assuring Therapeutic Equivalence of Modified Release Products", held October 1-2, 2009, in Baltimore, Maryland.
  
  
  METHODS
  The workshop provided an opportunity for pharmaceutical scientists from academia, industry, and regulatory agencies to discuss current regulatory expectations and industry practices for evaluating the pharmaceutical equivalence and bioequivalence of oral MR products.
  
  
  RESULTS
  In the case of conventional monophasic MR formulations, the current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and inter-changeability of drug products. Additional measures may occasionally be needed to determine the bioequivalence of multiphasic MR products. The metric of partial AUC proposed by the US Food and Drug Administration received broad support as an additional measure for evaluating bioequivalence of multiphasic MR products designed to have a rapid onset of drug action followed by sustained response. The cutoff for partial AUCs may be based on the pharmacokinetic/pharmacodynamic or pharmacokinetic/ response characteristics of the products under examination. If the new metric is highly variable, the bioequivalence limits may be set based on the known within-subject variability for the reference product.
  
  
  CONCLUSIONS
  The current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and interchangeability of conventional monophasic MR products. Additional measures may occasionally be needed to establish the bioequivalence of multiphasic MR products, and development of such measures is an important objective. The metric of partial AUC was proposed for products designed to have a rapid drug action followed by sustained response.
authors.affiliation: US Food and Drug Administration, Silver Spring, Maryland 20993–0002, USA. meiling.chen@fda.hhs.gov
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Chen
authors.forename: Vinod P
authors.initials: VP
authors.lastname: Shah
authors.forename: Derek
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authors.lastname: Ganes
authors.forename: Kamal K
authors.initials: KK
authors.lastname: Midha
authors.forename: James
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authors.lastname: Caro
authors.forename: Prabu
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authors.lastname: Nambiar
authors.forename: Mario L
authors.initials: ML
authors.lastname: Rocci
authors.forename: Avinash G
authors.initials: AG
authors.lastname: Thombre
authors.forename: Bertil
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authors.lastname: Abrahamsson
authors.forename: Dale
authors.initials: D
authors.lastname: Conner
authors.forename: Barbara
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authors.lastname: Davit
authors.forename: Paul
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authors.lastname: Fackler
authors.forename: Colm
authors.initials: C
authors.lastname: Farrell
authors.forename: Suneel
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authors.lastname: Gupta
authors.forename: Russell
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authors.lastname: Katz
authors.forename: Mehul
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authors.lastname: Mehta
authors.forename: Sheldon H
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authors.lastname: Preskorn
authors.forename: Gerard
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authors.lastname: Sanderink
authors.forename: Salomon
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authors.lastname: Stavchansky
authors.forename: Robert
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authors.lastname: Temple
authors.forename: Yaning
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authors.lastname: Wang
authors.forename: Helen
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authors.lastname: Winkle
authors.forename: Lawrence
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authors.lastname: Yu