Regulatory incentives to ensure better medicines for older people: From ICH E7 to the EMA reflection paper on quality aspects.

Biopharmaceutic classification system (BCS) is a substantial part of drug designing and generic product development and has been accepted as a technique to renounce in-vivo pharmacokinetic evaluation (biowaiver). It appeared to be worthwhile and time-saving by means of in-vitro studies in the presence of biorelevant physiological mediums that mimic not only the predictable solubility but also permeability of the multisource product. Such methodology is now applied as a regulatory stamp to support new and generic product approvals based on other than in-vivo equivalence testing. This article outlines the foundation of BCS, its implementation in granting biowaiver, adequacy of in-vitro bioequivalence studies, principles and requirements of BCS biowaiver by four regulatory agencies such as; Food and Drug Authority (FDA), World Health Organization (WHO), European medicine agency (EMA) and International Conference on Harmonization (ICH), potential effect of excipients on solubility and permeability of drug molecules and supplementary data provided by FDA regarding biowaiver approvals. Furthermore, supportive data provided by the International Pharmaceutical Federation (FIP) has also been given for biowaiver sanction of certain drug products. It has been concluded, that although biowaiver is a profitable methodology for generic and new drug product approval, the variance in the standards of governing bodies demands more critical assessment to establish some unified principles to be followed globally.

	Key words: Biopharmaceutics classification system, bioequivalence, biowaiver.

/pdf/comparative-analysis-of-biopharmaceutic-classification-24rzu8qycc.pdf

Comparative analysis of biopharmaceutic classification system (BCS) based biowaiver protocols to validate equivalence of a multisource product

The purpose of this study was to evaluate the similarity of dissolution and permeability properties of commercially available immediate-release metformin hydrochloride (MH) tablets (1000 mg strength) including five generic products obtained from the Turkish drug market (tablets A–E) and two reference products (obtained from the Turkish and European markets). In vitro dissolution studies were conducted in accordance with the MH tablet monograph in the USP (1000 mL, 75 rpm) and with the BCS-based biowaiver guidance in three different media (pH 1.2, pH 4.5, and pH 6.8; 900 mL, 50 rpm). The apparent permeability of MH in all tablets and raw MH was determined in Caco-2 cells. Dissolution studies revealed that neither the generics (except generic tablet B) nor the reference tablets fulfilled the criteria for very rapid dissolution. Although the dissolution profiles of the reference tablets were similar (f2 > 50), none of the generic tablets were similar to either of the reference tablets. Permeability of MH for all reference and generic tablet formulations was similar to that of raw MH (p > 0.05). In contrast, a significant difference in permeability was observed between the two reference tablets (p < 0.05), and only one generic tablet (A) had permeability similar to both reference tablets. As MH has low permeability, potential alterations in permeability due to the dosage form can affect its bioavailability. The results of this study indicate that immediate-release MH tablets do not meet the criteria for very rapid dissolution for the BCS-based biowaiver.

/pdf/comparison-of-dissolution-profiles-and-apparent-23fvp0uwif.pdf

Comparison of Dissolution Profiles and Apparent Permeabilities of Commercially Available Metformin Hydrochloride Tablets in Turkey

The acceptance of foreign comparator products is the most limiting factor for the development and regulatory assessment of generic medicines marketed globally. Bioequivalence studies have to be repeated with the local comparator products of each jurisdiction because it is unknown if the comparators of the different countries are the same product, with the consequent duplication of efforts by regulators and industry alike. The regulatory requirements on the acceptability of foreign comparator products of oral dosage forms differ between countries participating in the Bioequivalence Working Group for Generics of the International Pharmaceutical Regulators Programme. Brazil, Colombia, the European Union member States, Japan, Mexico, South Korea and the United States only accept bioequivalence studies with their local comparator. In contrast, Australia, Canada, New Zealand, Singapore, South Africa, Switzerland and Taiwan accept studies with foreign comparators under certain conditions. Canada limits its use to highly soluble drugs with a wide therapeutic range in immediate release products. Australia requires a comparison of the quantitative composition. In contrast, there are fewer restrictions on the acceptance of foreign comparators in New Zealand, Singapore, South Africa, Switzerland and Taiwan. For the WHO Prequalification of Medicines and for developing generics of the essential medicines the WHO lists comparators from different countries. In conclusion, there is currently no consensus amongst regulators on the acceptability of foreign comparator products.

/pdf/a-survey-of-the-regulatory-requirements-for-the-acceptance-1dlt8ypl5v.pdf

A Survey of the Regulatory Requirements for the Acceptance of Foreign Comparator Products by Participating Regulators and Organizations of the International Generic Drug Regulators Programme.

Dissolution Profile Similarity Assessment—Best Practices, Decision Trees and Global Harmonization

Das Verfahren der gegenseitigen Anerkennung – besser bekannt als Mutual Recognition Procedure oder MRP – stellt zusammen mit dem im Herbst 2005 etablierten dezentralen Verfahren (DCP) das am haufigsten genutzte Zulassungsverfahren in der Europaischen Union (EU) bzw im Europaischen Wirtschaftsraum (EWR) dar Im vorliegenden Beitrag werden beide Zulassungswege miteinander verglichen und ihre jeweiligen Vor- und Nachteile diskutiert Der Schwerpunkt liegt dabei auf der Darstellung der aktuellen Entwicklungen und nicht auf dem systematischen Vergleich der Verfahren Es werden die Rolle der Coordination Group for Mutual Recognition and Decentralised Procedures-Human [CMD(h)] und die Prozesse der Entscheidungsfindung in beiden Verfahren zueinander in Bezug gesetzt

Marketing of medicinal products in the European Community. The Mutual Recognition and Decentralised Procedures

Purpose: The Biopharmaceutics Classification System (BCS) based biowaiver is a scientific model which enables the substitution of in vivo bioequivalence studies with in vitro data as evidence of therapeutic equivalence subject to certain conditions. Despite being based on the same principles, BCS-based biowaivers are interpreted and regulated differently among international regulatory agencies. In this survey, the Bioequivalence Working Group (BEWG) of the International Generic Drug Regulators Programme (IGDRP) compared the criteria for BCS-based biowaivers applied by the participating regulators and organisations. Methods: Differences and similarities regarding solubility, permeability, dissolution, excipients and fixed-dose combination products, were identified and compared in a detailed survey of each participant’s criteria for BCS-based biowaivers. These criteria were determined based upon the participants’ respective regulatory guidance documents, policies and practices. Results: This review has, with the exception of two participants who do not accept BCS-based biowaivers, revealed that most IGDRP participants interpret the BCS principles and conditions similarly but notable differences exist in the application of these principles.  Conclusion : Although many similarities exist, this review identifies several opportunities for greater convergence of regulatory requirements amongst the surveyed jurisdictions. This article is open to POST-PUBLICATION REVIEW . Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page

/pdf/a-survey-of-the-regulatory-requirements-for-bcs-based-2glnvs60iu.pdf

A Survey of the Regulatory Requirements for BCS-Based Biowaivers for Solid Oral Dosage Forms by Participating Regulators and Organisations of the International Generic Drug Regulators Programme

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Peter Bachmann

Author Tools

Chat about Author

Papers

Marketing of medicinal products in the European Community. The Mutual Recognition and Decentralised Procedures

A Survey of the Regulatory Requirements for BCS-Based Biowaivers for Solid Oral Dosage Forms by Participating Regulators and Organisations of the International Generic Drug Regulators Programme