ANDA - Abbreviated New Drug Application

BY N.NARESH KUMAR m.pharm(cology)

Definition of ANDA:

AN “abbreviated new drug application” (ANDA) is an application for a US generic drug approval for an existing licensed medication or approved drug.

Definition of generic drug :

A generic drug product is one that is comparable to an innovator drug product in dosage form, strength, route of administration, quality, performance characteristics and intended use.

All approved products, both innovator and generic, are listed in FDA's Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book).

Advent of generic drug competition:

-Genetic drugs always been available in US market DESI: drug efficacy study implementation.

When the desi program was in progress, the agency estimated that there were between 5-13 products without NDA”s that were identical and similar to each of the 13,000 products that held NDA”s under the 1938 act

These products contain same active ingredients in the same amount and dosage form, often though they claim some unique characteristics i.e: a different salt or ester, different amount, a different dosage form or an extra added ingredients.

Evolution of ANDA:

CHF patients who had been treated carefully with a specific dose of digoxin, went out of control upon getting prescriptions refilled

Investigations revealed that digoxin, never subject to an NDA, varied from manufacturer to manufacturer not in quantity of actual drug per tablet , but in the amount of drug released from the tablet into the body

The consequences could be life threatening

the agency responded with an order that each manufacturer submit an ANDA that included bioavailability studies showing the rate and extent of absorption into the body

The ANDA process and bioequivalence studies permitted the individual generic products to be therapeutically equivalent to approved brand drug

ANDA Generics:

An ANDA contains data which when submitted to FDA’s centre for drug evaluation and research , office of of generic drugs, provides for the review and ultimate approval of a generic drug product

Once approved an applicant may mfg and market the generic drug product drug to provide a safe, efficant, low cost alt to the American public

A generic drug product is one that is Comparable to an innovator drug product in dosage form, strength, route of administration, quality and performance characteristics

Generic applicants must scientifically demonstrate that their product is bioequivalance

One way to demonstrate bioequivalance is to measure the time it takes the generic drug to reach the blood stream in 24 to 36 hrs In a healthy volunteer

This gives the rate of absorption or bioavailability of generic drug which they can compare to the innovator drug

Why it is abbreviated ?

the term abbreviated is used in generic drug applications because these applications does not require preclinical and clinical data to establish safety and efficacy

Scientific demonstration of the bioequivalance is important and must

Necessary items of ANDA

The composition of drug stating the name and amount of each ingredient whether active or not, contained in a stated quantity of the drug

Identify the place where the drug is manufactured, processed, packaged, Labeled and the name of the supplier of the active ingredient

Identify any person other than the applicant who performs a part of those operations

include certifications from the applicant and the methods used in the process and the facilities and controls used for mfg, processing, packing, labeling in conformity with the current GMP

assure that the drug dosage form and components comply with the specifications and tests described in an official compendium

if the drug differs from the compendium drug, the specifications and tests applied to the drug and its components are adequate to assure their identity, strength, quality and quantity

Outline the methods used in and the facility and control used for mfg, processing, and packaging of the drug

If the drug require only an ANDA also specifies that there must be included adequate data to assure the bioavailability of the drug

goal of ANDA:

to reduce the price of the drug

to reduce the time development

increase the bioavailability of the drug in comparison to reference list drug

WAXMAN- HATCH ACT:

using the bioequivalance as the basis for approving generic copies of products was established by the “drug price commission and patent term restoration act of 1984”, is known as Waxman - hatch act

this act expedites the availability of less costly generic drugs by permitting FDA to approve application to market generic versions of brand – names without conduct costly clinical trials

Also it provides mechanism to grant drug companies upto 5 years additional patent protection to compensate the patent life lost as a result of the time consumed during test required by FDA

Conditions which must be fulfilled in order to ask an extension are :

Patent must not have expired at the time of filing the request for extension

The product must have been subjected to examination by FDA

The request for extension must have been filed within 60 days of the granting of FDA

the request for extension must have been filed at the latest during the last three months of the life of the patent

A fee of $750 is paid

NDA vs ANDA review process:

NDA requirements ANDA requirements1.Labelling 1. Labelling2.Pharm/tox 2.Pharm/tox 3.Chemistry 3.Chemistry4.Manufacturing 4.Manufacturing 5.Controls 5.Controls 6.Microbiology 6.Microbiology7.Inspection 7.Inspection8.Testing 8.Testing9.Animal studies10.Clinical studies 9.bioequivalence 11.bioavailability

Labelling:

o Same information as brand name labelling

o May differ in excipients and product description (color, shapes)

Pharm/tox:

o All inactive ingredients must be approved in either the reference list or similar NDA in same or higher levels

Chemistry, manufacturing and controls:

o Components and compositiono Mfg and controlso Batch formulation and recordso Description of facilitieso Packagingo Stability

Microbiology:

o Includes for anti infective drug compoundso A complete description of the biochemical basis of

drug action on microbial physiiology

o Clinical microbiology laboratory methods

o Assure the sterility of products especially with injectibles

Inspection/testing :

o Assure mfg facilities are in compliance with current GMP’S

o assure bioequivalance sites are in compliance with good clinical practices (cGCP’S)

Bioequivalance: A generic drug is considered to be bioequivalent to

the brand name drug if:

-The rate and extent of absorption do not show a significant difference from listed drug