scholarly journals 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

2018 ◽  
Vol 21 (1) ◽  
pp. 27 ◽  
Author(s):  
Joy Elizabeth Van Oudtshoorn ◽  
Alfredo García-Arieta ◽  
Gustavo Mendes Lima Santos ◽  
Christopher Crane ◽  
Clare Rodrigues ◽  
...  
Keyword(s):  
Generic Drug ◽  
Oral Dosage ◽  
Fixed Dose ◽  
Scientific Model ◽  
Regulatory Requirements ◽  
Regulatory Guidance ◽  
Dose Combination ◽  
Oral Dosage Forms

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

scholarly journals Development, Characterization and In Vivo Pharmacokinetic Assessment of Rectal Suppositories Containing Combination Antiretroviral Drugs for HIV Prevention

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1110
Author(s):  
Kunal Jhunjhunwala ◽  
Charles W. Dobard ◽  
Sunita Sharma ◽  
Natalia Makarova ◽  
Angela Holder ◽  
...  
Keyword(s):  
Hiv Prevention ◽  
Antiretroviral Drugs ◽  
Water Soluble ◽  
Fixed Dose ◽  
Receptive Anal Intercourse ◽  
On Demand ◽  
Dose Combination ◽  
Rectal Suppositories

Receptive anal intercourse (RAI) contributes significantly to HIV acquisition underscoring the need to develop HIV prevention options for populations engaging in RAI practices. We explored the feasibility of formulating rectal suppositories with potent antiviral drugs for on-demand use. A fixed-dose combination of tenofovir (TFV) and elvitegravir (EVG) (40 mg each) was co-formulated in six different suppository bases (three fat- and three water-soluble). Fat-soluble witepsol H15 and water-soluble polyethylene glycol (PEG) based suppositories demonstrated favorable in vitro release and were advanced to assess in vivo pharmacokinetics following rectal administration in macaques. In vivo drug release profiles were similar for both suppository bases. Median concentrations of TFV and EVG detected in rectal fluids at 2 h were 1- and 2-logs higher than the in vitro IC50, respectively; TFV-diphosphate levels in rectal tissues met or exceeded those associated with high efficacy against rectal simian HIV (SHIV) exposure in macaques. Leveraging on these findings, a PEG-based suppository with a lower dose combination of tenofovir alafenamide (TAF) and EVG (8 mg each) was developed and found to achieve similar rectal drug exposures in macaques. This study establishes the utility of rectal suppositories as a promising on-demand strategy for HIV PrEP and supports their clinical development.

scholarly journals FDA Guidance for Industry 1 Extended Release Solid Oral Dosage forms: Development, Evaluation, and Application of In Vitro/In Vivo Correlations

1997 ◽  
Vol 4 (4) ◽  
pp. 23-32 ◽  
Author(s):  
Henry Malinowski ◽  
Patrick Marroum ◽  
Venkata Ramana Uppoor ◽  
William Gillespie ◽  
Hae-Young Ahn ◽  
...  
Keyword(s):  
Extended Release ◽  
Dosage Forms ◽  
Oral Dosage ◽  
Fda Guidance ◽  
Solid Oral Dosage Forms ◽  
Development Evaluation ◽  
Oral Dosage Forms

scholarly journals Requirements for Additional Strength Biowaivers for Modified Release Solid Oral Dosage Forms in International Pharmaceutical Regulators Programme Participating Regulators and Organisations: Differences and Commonalities

2021 ◽  
Vol 24 ◽  
pp. 548-562
Author(s):  
Matthias Shona Roost ◽  
Henrike Potthast ◽  
Chantal Walther ◽  
Alfredo García-Arieta ◽  
Ivana Abalos ◽  
...  
Keyword(s):  
Immediate Release ◽  
Dosage Forms ◽  
Oral Dosage ◽  
In Vitro Dissolution ◽  
Quantitative Composition ◽  
Modified Release ◽  
Solid Oral Dosage Forms ◽  
Oral Dosage Forms

This article describes an overview of waivers of in vivo bioequivalence studies for additional strengths in the context of the registration of modified release generic products and is a follow-up to the recent publication for the immediate release solid oral dosage forms. The current paper is based on a survey among the participating members of the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Program (IPRP) regarding this topic. Most jurisdictions consider the extrapolation of bioequivalence results obtained with one (most sensitive) strength of a product series as less straightforward for modified release products than for immediate release products. There is consensus that modified release products should demonstrate bioequivalence not only in the fasted state but also in the fed state, but differences exist regarding the necessity of additional multiple dose studies. Fundamental differences between jurisdictions are revealed regarding requirements on the quantitative composition of different strengths and the differentiation of single and multiple unit dosage forms. Differences in terms of in vitro dissolution requirements are obvious, though these are mostly related to possible additional comparative investigations rather than regarding the need for product-specific methods. As with the requirements for immediate release products, harmonization of the various regulations for modified release products is highly desirable to conduct the appropriate studies from a scientific point of view, thus ensuring therapeutic equivalence.

scholarly journals Tailored on demand anti-coagulant dosing: An in vitro and in vivo evaluation of 3D printed purpose-designed oral dosage forms

2018 ◽  
Vol 128 ◽  
pp. 282-289 ◽  
Author(s):  
Basel Arafat ◽  
Nidal Qinna ◽  
Milena Cieszynska ◽  
Robert T. Forbes ◽  
Mohamed A. Alhnan
Keyword(s):  
Dosage Forms ◽  
Oral Dosage ◽  
In Vivo Evaluation ◽  
On Demand ◽  
3D Printed ◽  
Oral Dosage Forms

Postmarketing In Vitro/In Vivo Assessment of Fixed Dose Combination Products of First Line Antiretrovirals

2010 ◽  
Vol 99 (6) ◽  
pp. 2655-2663 ◽  
Author(s):  
A. Joshi ◽  
F. Esseku ◽  
L. Silva ◽  
C. Igwilo ◽  
D. Oqua ◽  
...  
Keyword(s):  
Fixed Dose Combination ◽  
Fixed Dose ◽  
First Line ◽  
Dose Combination ◽  
In Vivo Assessment

scholarly journals A Survey of the Regulatory Requirements for the Waiver of In Vivo Bioequivalence Studies of Generic Products in Certain Dosage Forms by Participating Regulators and Organisations of the International Pharmaceutical Regulators Programme

2021 ◽  
Vol 24 ◽  
pp. 113-126
Author(s):  
Alfredo Garcia Arieta ◽  
Craig Simon ◽  
Andrew Tam ◽  
Gustavo Mendes Lima Santos ◽  
Eduardo Agostinho Freitas Fernandes ◽  
...  
Keyword(s):  
Immediate Release ◽  
Dosage Forms ◽  
Oral Dosage ◽  
Regulatory Requirements ◽  
Intravenous Injections ◽  
Soft Gelatin Capsules ◽  
Solid Oral Dosage Forms ◽  
Oral Dosage Forms ◽  
Regulatory Convergence

The requirements to waive in vivo bioequivalence studies for immediate release solid oral dosage forms based on the Biopharmaceutics Classifications System (BCS) are well known, and biowaivers[1] for other types of oral dosage forms based on pre-defined criteria may also be acceptable. Similarly, biowaivers for dosage forms such as injectable products may also be allowed if certain criteria are met. The current paper summarises the biowaiver requirements for oral solutions and suspensions, soft gelatin capsules and injectable products (intravenous injections, subcutaneous and intramuscular injections, emulsions for injection and micellar solutions for injection) among the participants of the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Programme (IPRP). A review of the requirements indicated that there was a trend towards convergence when the dosage form became less complex; however, the most common approach used by each of the jurisdictions was a case-by-case approach given that most jurisdictions do not have well defined guidelines to support all possible scenarios. Even in the simplest case of intravenous solutions, the acceptability of qualitative changes in excipients differ between the IPRP members.  Notwithstanding the differences, the dissemination of the information is a first step towards regulatory convergence regarding biowaivers for certain dosage forms and should be useful for pharmaceutical companies currently developing generic medicinal products for IPRP jurisdictions.  

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