Challenges and opportunities in establishing scientific and regulatory standards for assuring therapeutic equivalence of modified-release products: Workshop summary report

Chen, Mei Ling; Shah, Vinod P.; Ganes, Derek; Midha, K. K.; Caro, James; Nambiar, Prabu; Rocci, Mario L.; Thombre, Avinash G.; Abrahamsson, Bertil; Conner, Dale P.; Davit, Barbara M.; Fackler, Paul; Farrell, Christine; Gupta, Suneel; Katz, Russell; Mehta, Mehul; Preskorn, Sheldon; Sanderink, Gérard; Stavchansky, Salomon A; Temple, Robert; Wang, Yaning; Winkle, Helen; Yu, Lawrence X.

doi:10.1016/j.ejps.2010.03.017

Cited by 21 publications

(18 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A number of questions should be addressed in determining whether to apply a pAUC metric to a bioequivalence study of a given product (25). For example, (a) is there a pharmacodynamic sensitivity with respect to onset/offset; (b) what is the methodology used to establish the appropriate pAUC cutoff sampling time(s); and (c) what will be the appropriate bioequivalence acceptance criteria.…”

Section: Measures For the Determination Of Bioequivalence Of Modifiedmentioning

confidence: 99%

Summary Workshop Report: Facilitating Oral Product Development and Reducing Regulatory Burden Through Novel Approaches to Assess Bioavailability/Bioequivalence

Polli

Cook

Davit

et al. 2012

AAPS J

View full text Add to dashboard Cite

Abstract. This summary workshop report highlights presentations and over-arching themes from an October 2011 workshop. Discussions focused on best practices in the application of biopharmaceutics in oral drug product development and evolving bioequivalence approaches. Best practices leverage biopharmaceutic data and other drug, formulation, and patient/disease data to identify drug development challenges in yielding a successfully performing product. Quality by design and product developability paradigms were discussed. Development tools include early development strategies to identify critical absorption factors and oral absorption modeling. An ongoing theme was the desire to comprehensively and systematically assess risk of product failure via the quality target product profile and root cause and risk analysis. However, a parallel need is reduced timelines and fewer resources. Several presentations discussed applying Biopharmaceutics Classification System (BCS) and in vitro-in vivo correlations in development and in post-development and discussed both resource savings and best scientific practices. The workshop also focused on evolving bioequivalence approaches, with emphasis on highly variable products (HVDP), as well as specialized modified-release products. In USA, two bioequivalence approaches for HVDP are the reference-scaled average bioequivalence approach and the two-stage group-sequential design. An adaptive sequential design approach is also acceptable in Canada. In European Union, two approaches for HVDP are a two-stage design and an approach to widen C max acceptance limits. For some specialized modified-release products, FDA now requests partial area under the curve. Rationale and limitations of such metrics were discussed (e.g., zolpidem and methylphenidate). A common theme was the benefit of the scientific and regulatory community developing, validating, and harmonizing newer bioequivalence methodologies (e.g., BCS-based waivers and HVDP trial designs).

show abstract

Section: Measures For the Determination Of Bioequivalence Of Modifiedmentioning

confidence: 99%

Summary Workshop Report: Facilitating Oral Product Development and Reducing Regulatory Burden Through Novel Approaches to Assess Bioavailability/Bioequivalence

Polli

Cook

Davit

et al. 2012

AAPS J

View full text Add to dashboard Cite

show abstract

“…The improved characterization methods, particularly those showing critical elements influencing the therapeutic effects, should support both the product equivalence and the variation reduction between batches. in vitro methods to evaluate the performance of controlled release formulations, delivery systems using carriers, formulations administrated through non-oral routes, and drug-device combinations (e.g., inhalation and nasal spray) are becoming increasingly important for the development of new generic drug products (Chen et al 2010). For example, a generic version of microsphere formulations containing leuprolide acetate was approved in 2014 in Japan.…”

Section: Future Prospectsmentioning

confidence: 99%

Scientific and regulatory approaches to confirm quality and improve patient perceptions of generic drug products in Japan

et al. 2016

View full text Add to dashboard Cite

The rapidly growing medical expense going with aging population in Japan requires the use of generic products derived from off-patent active pharmaceutical ingredients (APIs) formulations to reduce the financial burden for the national health insurance system, while at the same time avoiding undermining the quality of medical care. This article provides an overview of the regulatory approaches available to confirm the quality of generic products and gain their greater acceptance by patients. Among several approaches taken by the Ministry of Health, Labor, and Welfare (MHLW), designing systems to supply higher quality products, and providing scientific information to patients and healthcare professionals are key elements to promote the voluntary choice of the generic product. The revision of bioequivalence guidelines and the enhancement of good manufacturing practice (GMP) requirements facilitate the rational development and manufacturing control of generic formulations. A program termed Quality Reevaluation of Ethical Drugs was carried out from 1997 to 2012 using dissolution tests to avoid any significant bioINequivalence between originators and generic oral formulations. The evaluation of product quality and the assessment of the literature information by the Expert Committee on Quality of Generic Drug Products have provided a unique science-based and patient-focused approach for the distribution of reliable generic products. Some current and future issues regarding complex generic drugs are also discussed.

show abstract

“…In most cases, this supposition is reasonable and correct (2). A report (43) stated, summarizing a recent workshop on standards for assuring the therapeutic equivalence of MR products, that "the current regulatory approaches and criteria for evaluation of bioequivalence are considered adequate to ensure therapeutic equivalence and interchangeability of drug products in conventional monophasic (or monolithic) MR products. "…”

Section: Single or Multiple Drug Administrationmentioning

confidence: 99%

Metrics for the Evaluation of Bioequivalence of Modified-Release Formulations

Endrényi

Tóthfalusi

2012

AAPS J

View full text Add to dashboard Cite

Abstract. Metrics are discussed which are used for the evaluation of bioequivalence of modifiedrelease formulations. In order to ensure the therapeutic equivalence of the compared drug products, it would be important to contrast measures which are additional to area under the curve (AUC) and C max . For delayed-release products, the assessment of lag times is informative. For extended-release dosage forms, comparisons of the half-value duration and the midpoint duration time are useful. For some modified-release formulations with complicated, multiphasic concentration profiles, the comparison of partial AUCs is important. In determinations of the bioequivalence of extended-release dosage forms, investigations performed under steady-state conditions rather than after single dosing can yield enhanced probability of therapeutic equivalence, especially with substantial accumulation of the drug products. In steady-state investigations of bioequivalence, evaluation of the trough concentration and of the peak trough fluctuation is informative.

show abstract

Challenges and opportunities in establishing scientific and regulatory standards for assuring therapeutic equivalence of modified-release products: Workshop summary report

Cited by 21 publications

References 2 publications

Summary Workshop Report: Facilitating Oral Product Development and Reducing Regulatory Burden Through Novel Approaches to Assess Bioavailability/Bioequivalence

Summary Workshop Report: Facilitating Oral Product Development and Reducing Regulatory Burden Through Novel Approaches to Assess Bioavailability/Bioequivalence

Scientific and regulatory approaches to confirm quality and improve patient perceptions of generic drug products in Japan

Metrics for the Evaluation of Bioequivalence of Modified-Release Formulations

Contact Info

Product

Resources

About