Biowaiver is Simplified approval for IR generic solid oral products. It is a document or process which demonstrates the BE by in vitro instead of in vivo PK Studies.
Criteria for biowaiver
- Highly soluble: Highest dose soluble in 250 ml in pH 1.2 – 6.8
- Highly permeable: extent of absorption greater than 85%
- Rapidly dissolving: 85% or greater by basket method 100 rpm or paddle method 50 rpm in 900 ml in pH 1.2, 4.5 and 6.8
- For a waiver of BE, T and R products should exhibit similar dissolution profile (f2 > 50)
Auriga Research Ltd (ARL) is assisting clients in identifying the right drug candidate applicable for biowaiver. With the availability of analytical and clinical capabilities, ARL prepares a complete bio waiver reports as per international regulatory requirements. ARL also provides clarity on the below subject points for a biowaiver application.
- Defining of BCS class of pharmaceutical products
- Optimal support &Clarification of regulatory requirements and harmonised use of the BCS-based biowaiver approach
- Discuss ‘risk of bioinequivalence’.
- Defining dose to be investigated in terms of solubility
- Discuss whether BCS-based biowaiver may be acceptable within a restricted dose
- Range due to solubility limitations, i.e., biowaiver for lower strengths and in vivo BE study for higher dose strengths.
- Defining permeability and/or absorption requirements.
- Discuss/clarify acceptance or exclusion of biowaiver extensions, e.g., BCS based biowaiver for BCS class II and/or III drugs.
- Drug product considerations
- Comprehensive description of in vitro dissolution requirements
- Experimental setting; method validation.
- Evaluation of absence of product differences (or product ‘similarity’).
- Delimitation from in vitro/in vivo correlations and quality control.
- Specify number of batches to be investigated.
- Specify evaluation of excipients.
- Clarification regarding fixed dose combinations and pro-drugs.
The content of final report is prepared meeting harmonized regulatory requirement as mentioned below.
Content of Biowaiver Report:
Title
Abbreviations
Abstract
It basically covers literature (and experimental) data relevant to the decision to allow a waiver of in vivo bioequivalence testing for the approval of immediate release (IR) solid oral dosage forms
Introduction
Briefly, the aim is to evaluate all pertinent data available from literature sources, to assess the risk of such a biowaiver (risk being defined as both the chance of arriving at an incorrect biowaiver decision, and an assessment of the likely impact of such an incorrect biowaiver decision on public health and individual patient risks) and recommend whether a biowaiver can be recommended or not.
Therapeutic indication
Chemical Properties
Solubility
In water, in aqueous buffers, dose: solubility ratio for WHO dose at pH 1.2 pH 4.5, pH 6.8
Polymorphism
Partition coefficient
pKa
Available dose/tablet
PHARMACOKINETIC PROPERTIES
DOSAGE FORM PERFORMANCE
Excipients
Excipients present in registered innovator drug product or market leader in studied market(s)
Dissolution
- USP dissolution methodology
- Comparative studies of different formulations in vitro
DISCUSSION
Conclusion about classification with respect to permeability, where possible, according to the current BCS criteria
CONCLUSION
Biowaiver conclusion for products of BCS class I and class III on basis of dissolution testing, which is a surrogate for bioequivalence testing.
ARL also offers summarized literature information in the form of Expert Reports of pharmaceuticals products Clinical, Pharmacological and Toxico-Pharmacological as per regulatory requirements.