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New Drug Application(NDA)

VsAbbreviated new drug application

(ANDA)

1

Name: B.Vamsikrishna Reddy

Year : M.Pharm (Pharmaceutics)

College : Manipal College of PharmaceuticalScieces(MCOPS), Manipal

Email id: [email protected]

Name: Sneya Priya

Year : M.Pharm( Pharmaceutics)

College: Manipal college of PharmaceuticalScieces(MCOPS), Manipal

Email id: [email protected]

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Contents

1.New Drug Application(NDA)a) Introduction.b) Goal of NDAc) Classification of NDA

d) New drug development reviewe) The NDA in CTD Format

2. Abbreviated new drug application(ANDA)a) Introduction

b) Goal of ANDAc )Patent certification condition

3. Conclusion.

4. References.2

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New Drug Application

y Introduction

Critical component for drug approval processwhich required to submit to USFDA before drugcommercialization.

The data gathered during the animal studies andhuman clinical trials of an Investigational New Drug(IND) become part of the NDA.

y Goal

The NDA provide enough information to permitFDA reviewer to reach safety, efficacy and quality for

pharmaceutical production 3

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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 switchin marketing status from prescription to OTC)

Already Marketed Drug Product - No Previously Approved NDA 4

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New Drug Development and Review Process

Steps from Test Tube to New Drug Application Review

5

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Phases of clinical testingPhase Number of

patients

Length Purpose Percent

successfully

completing

Phase1 20-100 Several months Mainly safety67

Phase2 Up to several

hundred

Several months

to two years

Some short-term

safety but mainly

effectiveness45

Phase3 Several hundred

to several

thousand

1-4 years Safety,

effectiveness,

dosage

5-10

6

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NDA Review Process

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NDA CONTENTS

y Section 1: Overall NDA index:-

The NDA index is a comprehensive table of contents thatenables the reviewers to find specific information in thismassive 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 theproposed 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 benefitsy 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 controlsy 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 thepharmacodynamic ED50 in dose- ranging studies and themechanism 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

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Section 6: Human Pharmacokinetics and bioavailability

y includes data from Phase I safety and tolerance studies inhealthy volunteers. Element in the section tabulatedsummary of studies showing all in vivo biopharmaceuticsstudies performed.

Summary of analytical method used in in vivo

biopharmaceutic study Pilot or background studies

Bioavailibility or bioequivalence studies

Pharmacokinetic studies

In vitro studies 13

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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 thedrug action on microbial physiology

The drugs antimicrobial spectrum

Describe any known mechanism of resistance to the drug

and provide information/data of any known epidemiologicstudies 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 overv iew of clinical investigations

Clinical pharmacology Controlled clinical trials

Uncontrolled clinical trials

Other studies and information

Integrated summar y of effecti veness data

Integrated summar y of safet y information

Drug abuse and overdose information

Integrated summar y of benef its and risks of drug 15

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Section 9: Saf ety 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 r eport tabulationy include complete tabulation for each patient from every

adequately are well controlled phase II and Phase IIIefficacy, clinical pharmacology study. It also tabulation of

safety data from all clinical studies.

Section 12: Case r eport forms

y include the complete CRF for each patient who diedduring a clinical study or adverse event, regardless of whether the AE is considered to be related to the studydrug, 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 formFDA-356h along with several other supporting items asappropriate

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 use18

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The NDA in CTD Format

Module 1 is not part of the CTD because it is not harmonizedCTD NDA: 314.50

Module 1 a) Application formc)2.1 Annotated text of proposed

labelinge)Samples and Labeling

h)Patent informationi) Patent certif ication j)Claimed exclusi v it y

Module 2 c)Summariesd)5.7 A buse potential

Module 3 d)1 CMCModule 4 d)2 Nonclinical pharm/tox

Module d)3 Human PKd)4Microbiology d)5 Clinical data d)6 Statistical section

f ) CRF and CRT 19

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ANDA

³ 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 Requir ements ar e:--

y Same active ingredient(s)

y Same route of administrationy Same dosage form

y Same strength

y Same conditions of use

y Inactive ingredients already approved in a similar NDA 20

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Goal of ANDA

y To reduce the price of the drug.

y To reduce the time development.

y

Increase the bioa v ailabilit y of the drug in comparisonto references list drug.

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ANDA Review process

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NDA vs. ANDA Review ProcessNDA 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

ANDADescribed in section 505(j)(2)(A)(vii) of the Act.

I Patent Not Submitted to FDA ±

Approval effective after OGD scientific determination II Patent Expir ed ±

Approval effective after OGD scientific determination

III Patent Expiration Date (honor ed) ±

Tentative approval after OGD scientific determination, finalapproval when patent expires

IV Patent Challenge ±

Tentative approval after OGD science determination, final

approval when challenge won 25

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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 aparagraph IV certification to each owner of the patent that

is the subject of the certification and to the holder of theapproved NDA to which the ANDA refers

And by Section 505(j)(5)(B)(iv)

y An incentive for generic manufacturers to file paragraph IVcertifications 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 completeapplication with patent challenge

Protection from other generic competition ± blocksapproval 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 y ears exclusi v it y

Granted on approv al of designated orphan drug

OGD works with the Off ice of Orphan Products

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ANDA approval status

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CONCLUSION

NDAANDA

Applicable for new drug Applicable for generic drug

Take longer time ( 12-15years)

Compare to NAD less timetaken(1-2 years)

More expenditure of money Comparatively less

Cost of drugs are more Cost of drugs are less

Nonclinical studies and clinical

investigations are essential

Nonclinical studies and clinical

investigations are nonessential

except bioavailability and

bioequivalence30

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REFERENCES

y Douglas J. Pisano, David S. Manlus ±FDA Regulatory Affairs, Aguide for Prescription Drugs, Medical Devices and Biologics-New drug Application ±Second edition-Marcel Dekker,inc- pageno 69-108.

y Richard A. Guarino- New Drug Approval process-1)The NewDrug Application, Content, Format 2) Abbreviated $Supplementary New Drug Application- Fourth edition-MarcelDekker,inc- page no 113-183.

y

Loyd V. Allen Jr, Nicholas G. Popovich, Howard C. Ansel¶sPharmaceutical Dosage Forms and delivers systems- NewDrug Development and Approval Process-8th edition- B.I.publication- Page no 25-65.

y http://www.fda.gov/cder/guidance/index.htm.31

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