New Drug Application(NDA) Vs Abbreviated new drug application (ANDA)

Name: B.Vamsikrishna Reddy Year : M.Pharm (Pharmaceutics) College : Manipal College of Pharmaceutical Scieces(MCOPS), Manipal Email id: vamsikrishnareddy57@gmail.com

Name: Sneya Priya Year : M.Pharm( Pharmaceutics) College: Manipal college of Pharmaceutical Scieces(MCOPS), Manipal Email id: snehpriya123@gmail.com
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Contents
1.New Drug Application(NDA) a) Introduction. b) Goal of NDA c) Classification of NDA d) New drug development review e) The NDA in CTD Format 2. Abbreviated new drug application(ANDA) a) Introduction b) Goal of ANDA c )Patent certification condition 3. Conclusion. 4. References.
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New Drug Application

y Introduction

Critical component for drug approval process which required to submit to USFDA before drug commercialization. The data gathered during the animal studies and human clinical trials of an Investigational New Drug (IND) become part of the NDA.
y Goal

The NDA provide enough information to permit FDA reviewer to reach safety, efficacy and quality for pharmaceutical production
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NDA Classifications
 New Molecular Entity  New Salt of Previously Approved Drug (not a new molecular entity)  New Formulation of Previously Approved Drug (not a new salt OR a

new molecular entity)

 New Combination of Two or More Drugs  Already Marketed Drug Product - Duplication (i.e., new

manufacturer)

 New Indication (claim) for Already Marketed Drug (includes switch

in marketing status from prescription to OTC)

 Already Marketed Drug Product - No Previously Approved NDA

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New Drug Development and Review Process

Steps from Test Tube to New Drug Application Review

Phases of clinical testing

Phase

Number of patients

Length

Purpose

Percent successfully completing

Phase1

20-100

Several months

Mainly safety 67

Phase2

Up to several hundred

Several months to two years

Some short-term safety but mainly 45 effectiveness

Phase3

Several hundred to several thousand

1-4 years

Safety, effectiveness, dosage

5-10
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NDA Review Process

NDA CONTENTS
y Section 1: Overall NDA index:-

The NDA index is a comprehensive table of contents that enables the reviewers to find specific information in this massive document quickly.
y Section 2: Labeling

It must include all draft labeling that is intended for use on the product container, cartons or packages, including the proposed package insert.

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Section 3: Application summary

y Proposed annotated package insert y Pharmacology class, scientific rational, intended use, and potential clinical benefits y Foreign marketing history y Chemistry, Manufacturing and control summary y Nonclinical pharmacology and toxicology summary y Human pharmacokinetics and bioavailability summary y Microbiology summary y Clinical data summary and results of statistical analysis y Discussion of benefit/risk relationship
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Section 4: Chemistry, manufacturing and controls y Chemistry, manufacturing and control information y Samples y Methods validation package Section 5: Nonclinical pharmacology and toxicology y Provide individual study reports, including pharmacology, toxicology, ADME studies. y Effects related to the therapeutic indication, such as the pharmacodynamic ED50 in dose- ranging studies and the mechanism of act ion (if know n) y Interactions with other drugs (or cross-reference the location of the information in any of the above subsection 12

Section 6: Human Pharmacokinetics and bioavailability

y includes data from Phase I safety and tolerance studies in

healthy volunteers. Element in the section tabulated summary of studies showing all in vivo biopharmaceutics studies performed.
 Summary of analytical method used in in vivo

biopharmaceutic study  Pilot or background studies  Bioavailibility or bioequivalence studies  Pharmacokinetic studies  In vitro studies

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Section 7: Microbiology Includes for anti infective drug products. requires the following technical information and data: A complete description of the biochemical basis of the

drug action on microbial physiology  The drugs antimicrobial spectrum  Describe any known mechanism of resistance to the drug and provide information/data of any known epidemiologic studies demonstrating prevalence to resistance factor  Clinical microbiology laboratory methods
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Section 8: Clinical data Includes.  List of investigators and list of INDs and NDAs  Background or overview of clinical investigations  Clinical pharmacology  Controlled clinical trials  Uncontrolled clinical trials  Other studies and information  Integrated summary of effectiveness data  Integrated summary of safety information  Drug abuse and overdose information  Integrated summary of benefits and risks of drug

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Section 9: Safety data  Statements in draft labeling  Contraindications  Warnings  Precautions  Adverse events Section 10: Statistical data  All controlled clinical trial reports  Integrated efficacy and safety summaries  Integrated summary of risks and benefits
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Section 11: Case report tabulation y include complete tabulation for each patient from every adequately are well controlled phase II and Phase III efficacy, clinical pharmacology study. It also tabulation of safety data from all clinical studies. Section 12: Case report forms y include the complete CRF for each patient who died during a clinical study or adverse event, regardless of whether the AE is considered to be related to the study drug, even if the patient was receiving a placebo or comparative drug.
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Application itself consists of a cover letter and a completed form FDA-356h along with several other supporting items as appropriate
 Item 13: Patent information  Item 14: Patent certification  Item 15: Establishment description  Item 16: Debarment certification  Item 17: Field copy certification  Item 18: User fee cover sheet (Form FDA-3397)  Item 19: Financial disclosure (Form FDA 3454, form FDA-3455)  Item 20: Other/pediatric use
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The NDA in CTD Format

Module 1 is not part of the CTD because it is not harmonized
CTD Module 1 NDA: 314.50 a) Application form c)2.1 Annotated text of proposed labeling e)Samples and Labeling h)Patent information i) Patent certification j)Claimed exclusivity c)Summaries d)5.7 Abuse potential d)1 CMC d)2 Nonclinical pharm/tox d)3 Human PK d)4 Microbiology d)5 Clinical data d)6 Statistical section f) CRF and CRT

Module 2 Module 3 Module 4 Module

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ANDA
A drug product that is comparable to a brand/reference listed

drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use It termed "abbreviated" because they generally not required to include preclinical (animal) and clinical (human) data to establish safety and effectiveness. Basic Generic Drug Requirements are:-y Same active ingredient(s) y Same route of administration y Same dosage form y Same strength y Same conditions of use 20 y Inactive ingredients already approved in a similar NDA

Goal of ANDA
y To reduce the price of the drug. y To reduce the time development. y Increase the bioavailability of the drug in comparison

to references list drug.

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ANDA Review process

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NDA vs. ANDA Review Process

NDA Requirement ANDA Requirement

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What is Bioequivalence?
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, or  The extent of absorption does not show a significant difference and any difference in rate is intentional or not medically significant

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Patent Certification condition for ANDA

Described in section 505(j)(2)(A)(vii) of the Act.
 I Patent Not Submitted to FDA

Approval effective after OGD scientific determination  II Patent Expired Approval effective after OGD scientific determination  III Patent Expiration Date (honored) Tentative approval after OGD scientific determination, final approval when patent expires  IV Patent Challenge Tentative approval after OGD science determination, final approval when challenge won
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Paragraph IV certification
According to section 505(j)(2)(B)(i), 2157 CFR y The ANDA applicant must provide appropriate notice of a paragraph IV certification to each owner of the patent that is the subject of the certification and to the holder of the approved NDA to which the ANDA refers And by Section 505(j)(5)(B)(iv) y An incentive for generic manufacturers to file paragraph IV certifications and to challenge listed patents as invalid, or not infringed, by providing for a 180-day period of marketing exclusivity
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Patent Challenge Successful Award of 180-Day Exclusivity Period

 Awarded to first ANDA holder to file a complete

application with patent challenge

 Protection from other generic competition blocks

approval of subsequent ANDAs

 Protection triggered by:

First commercial marketing Forfeiture provisions

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Orphan Drug Exclusivity (ODE)

 Orphan drug refers to a product that treats a rare disease -

affecting fewer than 200,000 Americans

 7 years exclusivity  Granted on approval of designated orphan drug  OGD works with the Office of Orphan Products

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ANDA approval status

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CONCLUSION
NDA ANDA

Applicable for new drug Take longer time ( 12-15 years) More expenditure of money Cost of drugs are more

Applicable for generic drug Compare to NAD less time taken(1-2 years) Comparatively less Cost of drugs are less

Nonclinical studies and clinical Nonclinical studies and clinical investigations are essential investigations are nonessential except bioavailability and bioequivalence
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REFERENCES
y Douglas J. Pisano, David S. Manlus FDA Regulatory Affairs, A guide for Prescription Drugs, Medical Devices and BiologicsNew drug Application Second edition-Marcel Dekker,inc- page no 69-108. y Richard A. Guarino- New Drug Approval process-1)The New Drug Application, Content, Format 2) Abbreviated $ Supplementary New Drug Application- Fourth edition-Marcel Dekker,inc- page no 113-183. y Loyd V. Allen Jr, Nicholas G. Popovich, Howard C. Ansels Pharmaceutical Dosage Forms and delivers systems- New Drug Development and Approval Process-8th edition- B.I. publication- Page no 25-65. y http://www.fda.gov/cder/guidance/index.htm.
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Thank u
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