Waivers 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.
In 2011 this blog was listed as one of the top 10 blog in pharma technical information it is popular amongst the pharmacists and pharma industry professionals. We have published very important and very useful information for pharma industry professionals.
Subscribe to:
Post Comments (Atom)
What is 21 CFR Part 11, US FDA guidelines requirements of FDA compliance and CFR 21 Part 11.
What is a Site Master file of a pharmaceutical company
What is Generic Drug
What is Reference Listed Drug ? ( RLD )
What is Pharmaceutical Equivalents
What is Pharmaceutical Alternatives
What is Therapeutic Equivalents
What are Post Market studies
Why a drug is bound to protein, What is protein binding? What is drug absorption , distribution ?
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 Resistance and Antibiotic resistance mechanism
Antioxidants food supplements
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
Clean Room Classification
Time limitations in sterile pharmaceuticals processing
Aspects of validation of manufacturing process in sterile pharmaceuticals
Clinical Trials
Requirements of US FDA Inspections of Clinical Investigators of Clinical Trials
PROCEDURE OF AN INSPECTIONS OF CLINICAL TRIAL INVESTIGATOR BY US FDA HOW ARE CLINICAL INVESTIGATOR INSPECTIONS CONDUCTED?
US FDA INSPECTION OF CLINICAL INVESTIGATORS OUT OF UNITED STATES OF AMERICA
REPORTS AFTER AN INSPECTION OF A INVESTIGAOTR OF 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 , detailed 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
No comments:
Post a Comment