Waivers of In Vivo BE Studies (Biowaivers) INDs, NDAs, and ANDAs: Preapproval

Waivers of In Vivo Bioequivalence Studies (Biowaivers) in INDs, NDAs, and ANDAs: Preapproval.

When the drug product is in the same dosage form, but in a different strength, and is proportionally similar in its active and inactive ingredients to the strength on which BA or BE ( bioequivalence ) testing has been conducted, an in vivo BE demonstration of one or more lower strengths can be waived based on dissolution tests and an in vivo study on the highest strength.(This recommendation modifies a prior policy of allowing biowaivers for only three lower strengths on ANDAs.)

For an NDA, biowaivers of a higher strength will be determined to be appropriate based on
(1) clinical safety and/or efficacy studies including data on the dose and the desirability of the higher strength, (2) linear elimination kinetics over the therapeutic dose range,
(3) the higher strength being proportionally similar to the lower strength, and
(4) the same dissolution procedures being used for both strengths and similar dissolution results obtained.

FDA recommend that a dissolution profile be generated for all strengths. If an appropriate dissolution method has been established , and the dissolution results indicate that  the dissolution characteristics of the product are not dependent on the product strength, then dissolution profiles in one medium are usually sufficient to support waivers of in vivo testing. Otherwise, dissolution data in three media (pH 1.2, 4.5, and 6.8) are recommended. FDA recommend that the f2 test be used to compare profiles from the different strengths of the product. An f2 value greater than or equal to  50 indicates a sufficiently similar
dissolution profile such that further in vivo studies are not needed. For an f2 value greater than or equal to 50, (21 CFR 320.22(d)(2)(ii)). The f2 approach is not suitable for rapidly dissolving drug products (e.g., greater than or equal to  85% dissolved in 15 minutes or less).

For an ANDA.

Conducting an in vivo study on a strength that is not the highest may be appropriate for reasons of safety, subject to approval by the FDA, and provided that the following conditions are met:

* Linear elimination kinetics has been shown over the therapeutic dose range.

* The higher strengths of the test and reference products are proportionally similar to their corresponding lower strength.

* Comparative dissolution testing on the higher strength of the test and reference products is submitted and found to be appropriate.

NDAs and ANDAs:
Postapproval Information on the types of in vitro dissolution and in vivo BE studies for immediate-release drug products approved as either NDAs or ANDAs in the presence of specified postapproval changes are provided in an US FDA's guideline SUPAC-IR: Immediate Release Solid Oral Dosage Forms Scale-Up and Post-Approval Changes: Chemistry, Manufacturing, and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation. For postapproval changes, FDA recommend that the in vitro comparison be made between the prechange and postchange products. In instances where dissolution profile comparisons are suggested, FDA also recommend an f2 test be used. An f2 value greater than or equal to 50 suggests a sufficiently similar dissolution profile and no further in vivo studies are needed. When in vivo BE studies are called for, FDA recommend that the comparison be made for NDAs between the prechange and postchange products, and for ANDAs between the postchange and reference listed drug products.
=====================================================================================================
Do you know now this website has become a most popular and most referred website in pharmaceutical industry and pharmaceutical companies and pharmaceutical manufacturers from all over the world ,for almost all topics related to Pharmaceutical Manufacturing , Pharmaceutical Regulatory Affairs and Good Manufacturing Practice for Pharmaceutical Manufacturing (c GMP guidelines ) and latest news and new drugs developments.

=====================================================================================================
You may also like following articles

Whar is Referance Listed Drug  ? ( RLD )

What is Pharmaceutical Equivalents

What is Pharmaceutical Alternatives

What is Therapeutic Equivalents


Do Physical properties contribute to drug activity.

What is drug receptor , How a drug resistance occurs

Mechanism of drug resistance

What is drug interaction

Drug interaction, and its examples

What is first pass metabolism of a drug

What is What is 510(k) Clearances ?

What is 510(k) Clearances,

Premarket Notification for medical devices - PMN or 510(k)

What is a drug interaction

Examples of drug interactions


Antibiotic Definition and classification


Antibiotic resitance and Antibiotic resistance mechanism

Antioxidants food suppliments

Vitamin D Details on FDA cautions on accurate dosage of Vitamin D


What is an antibody? what is monoclonal and polyclonal antibodies?

Terminologies In vaccine Production

Multi stage testing of Virus vaccine production

Testing of vaccines at different stages of production

TESTING FOR ADVENTITIOUS AGENTS CELL PROPERTIES IN VIRAL VACCINE PRODUCTION

Enzyme linked immunosorbent assay ELISA

Raido Immuno assay

http://whoguideline.blogspot.com/2010/04/terminalogy-and-their-explanations.html

Pharmaceutical Aseptic Manufacturing Process Terms , Terminology and Definitions.

http://whoguideline.blogspot.com/2010/02/pharmaceutical-aseptic-manufacturing.html

Here are some articles which will be useful for you in further understanding of aspects of sterile dosage form manufacturing and regulatory affairs and good manufacturing practice in

pharmaceutical industry

Pharmaceutical Validation

Types of validations in pharmaceutical manufacturing

Requirements of documents for validation of sterilisation process

How to investigate OOS out of specification results

Determination of Phenol coefficient of a disinfectant

Sterility testing

Cleen Room Classification

Time limitations in sterile pharmaceuticals processing

Aspects of validation of manufacturing process in sterile pharmaceuticals

Clinical Trials

Controlling Pyrogens in injectable dosage forms

Media fill run process simulation aspects Validation of Aseptic Process and Sterilisation

New Drug Application (NDA) how to make a New Drug Application (NDA) to US FDA

Abbreviated New Drug Application (ANDA) What is ANDA , detaied information about ANDA preparation and submission to US FDA

How to make Investigational New Drug (IND) Application to US FDA

Drug applications submission to us fda Over the counter Drugs OTC drugs

BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS

Electronic record in pharmaceutical manufacturing industry

Good manufacturing practice in pharmaceutical industry

Pharmaceutical industry pharmaceutical companies and FDA latest updates

Here is an interesting article on world wide pharmaceutical industry and making a carrier in one of pharmaceutical companies article on Pharmaceutical Industry pharmaceutical industry

Find a Job in Pharmaceutical Company
To Find Pharmaceutical jobs and make a Pharmaceutical careers see here pharmaceutical companies
Here are some interesting articles on Quality assurance systems for pharmaceutical company

1.Quality assurance in pharma industry

2.Quality by designe concept for pharmaceutical industry

3.Quality by designe concept in pharmaceutical industryan explanation