Challenges in ANDA Filling in Clinical Trials.

INTRODUCTION

       ANDA->> Abbreviated New Drug Application

• It contains DATA that is submitted for the review and ultimate approval of generic drug products to the FDA’s Centre for drug evaluation and research (CDER), Office of Generic drugs.

• Generic drugs are copies of innovator drugs or brand-name prescription drugs.

• Once the DATA has been approved an applicant may manufacture and market the generic drug.

• Generic drug application is termed as “Abbreviated” because it is not required to include preclinical (animal) and clinical (human) data to establish safety and effectiveness.

• A generic drug applicant must scientifically prove that their product is implemented in the same manner as the innovator drug by measuring the time it takes to reach the blood circulation in healthy volunteers.

• This demonstration of Bioequivalence gives the rate of absorption or bioavailability of the generic drug which can be then compared to the innovator drug.

• All approved drugs both innovator and generic are listed in FDA’s approved drug products with therapeutic equivalence evaluation (ORANGE BOOK).

Generic drug vs branded drug

HATCH-WAXMAN ACT

  The "Drug Price Competition and Patent Restoration Act" also known as the Hatch-Waxman Act.

• Act amended by FEDERAL FOOD, DRUG AND COSMETIC ACT (FD&C).

• Hatch Waxman act encourages the manufacture of generic drug by the pharmaceutical industry and established the modern system of government generic drug regulation.

DRUG DEVELOPMENT PROCESS OF NDA/ANDA.

Patented drug	Generic drug
Companies apply for the patent during the discovery phase	It takes about years to develop the drug and  years for regulatory approval
Patent are generated for 20 years. It takes 10-12 years to bring the drug to the market.	Company does have to conduct the clinical trials, they have to prove bioequivalence.
Companies are left with 8 years to market the drug and recoup research and development costs	Company only has to recoup manufacturing and marketing costs

PATENT CERTIFICATION FOR FILLING OF ANDA:

When an applicant submits an ANDA to the FDA, the applicant must certify one of four things under Section 505(j)(2)(a)(vii):

            

• Paragraph I Certification indicates that the Orange Book lists no patents relevant to the ANDA.

• Paragraph II Certification indicates that the listed patents have expired.

• Paragraph III Certification indicates that the generic manufacturer will stay off the market until the patents expire.

• Paragraph IV Certification indicates that the generic manufacturer believes that the listed patents are either invalid or would not be infringed by the generic compositions.

 NDA & ANDA FILING REQUIREMENT

Brand name drug	Generic drug
Chemistry Manufacturing Controls Labeling Testing Animal studies Clinical studies Bioavailability	Chemistry Manufacturing Controls Labeling Testing bioequivalence

Generic drug applications submitted to FDA for approval must show that:

• The generic drug is "pharmaceutically equivalent" to the brand.

• The manufacturer is capable of making the drug correctly.

• The manufacturer is capable of making the drug consistently.

• The "active ingredient" is the same as that of the brand.

• The right amount of the active ingredient gets to the place in the body where it has an effect.

• The "inactive" ingredients of the drug are safe.

• The drug does not break down over time.

• The container in which the drug will be shipped and sold is appropriate.

• The label is the same as the brand-name drug's label.

• Relevant patents or legal exclusivities are expired.

EXAMPLES OF SOME DRUGS:

• AMOXIL (NDA applicant DR.REDDY'S) generic drug Manufacturer AUROBINDO PHARMA approved on NOV 9th 2005

• ULTRACET (NDA Applicant JANSSEN PHARMS) Generic Drug Manufacturer MYLAN LABS Approved On September 26th, 2008.

• ACCUPRIL (NDA Applicant PFIZER) Generic Drug Manufacturer AUROBINDO PHARMA Approved on April 29th, 2013.

• EXELON (NDA Applicant NOVARTIS) Generic Drug Manufacturer DR.REDDY'S APPROVED On October 31, 2007.

CONCLUSION: 

• An ANDA is a request to the Food and Drug Administration (FDA) to manufacture and market a generic drug in the United States.

• The ANDA does not require the applicant to conduct clinical trials.

• An ANDA-approved drug must be bioequivalent to the brand-name drug.

• If an ANDA is approved, it is listed in the Orange Book as an FDA-approved medicine.

REFERENCES

1. https://www.fda.gov/drugs/generic-drugs/what-approval-process-generic-drugs
2. https://youtu.be/f_1i9pPYs6c
3. https://www.fda.gov/drugs/types-applications/abbreviated-new-drug-application-anda -:~:text=An%20abbreviated%20new%20drug%20application,brand%2Dname%20drug%20it%20references
4. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/abbreviated-new-drug-application-anda-forms-and-submission-requirements

Written by: Noor us Sabah 

Pharm D

ClinoSol ID: 175/1022