New Drug Application(NDA) Vs

Abbreviated new drug application (ANDA)

1

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

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.  2

New Drug Application

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.

Goal

The NDA provide enough information to permit FDA reviewer to reach safety, efficacy and quality for pharmaceutical production

3

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 NDA4

New Drug Development and Review ProcessSteps from Test Tube to New Drug Application Review

5

Phases of clinical testingPhase Number of

patientsLength 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 effectiveness

45

Phase3 Several hundred to several thousand

1-4 years Safety, effectiveness, dosage

5-10

6

7

8

NDA Review Process

9

NDA CONTENTSSection 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.

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.

10

Section 3: Application summary

Proposed annotated package insertPharmacology class, scientific rational, intended use, and

potential clinical benefitsForeign marketing historyChemistry, Manufacturing and control summaryNonclinical pharmacology and toxicology summary Human pharmacokinetics and bioavailability summaryMicrobiology summaryClinical data summary and results of statistical analysisDiscussion of benefit/risk relationship

11

Section 4: Chemistry, manufacturing and controlsChemistry, manufacturing and control informationSamplesMethods validation package

Section 5: Nonclinical pharmacology and toxicologyProvide individual study reports, including pharmacology,

toxicology, ADME studies.Effects related to the therapeutic indication, such as the

pharmacodynamic ED50 in dose- ranging studies and the mechanism of act ion (if know n)

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

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 studiesPharmacokinetic studiesIn vitro studies

13

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 spectrumDescribe 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

14

Section 8: Clinical dataIncludes.List of investigators and list of INDs and NDAsBackground or overview of clinical investigationsClinical pharmacologyControlled clinical trialsUncontrolled clinical trialsOther studies and informationIntegrated summary of effectiveness dataIntegrated summary of safety informationDrug abuse and overdose informationIntegrated summary of benefits and risks of drug15

Section 9: Safety dataStatements in draft labelingContraindicationsWarningsPrecautionsAdverse events

Section 10: Statistical dataAll controlled clinical trial reportsIntegrated efficacy and safety summariesIntegrated summary of risks and benefits

16

Section 11: Case report tabulationinclude 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 formsinclude 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.

17

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

18

The NDA in CTD FormatModule 1 is not part of the CTD because it is not harmonized

CTD NDA: 314.50

Module 1 a) Application formc)2.1 Annotated text of

proposed labelinge)Samples and Labelingh)Patent informationi) Patent certificationj)Claimed exclusivity

Module 2 c)Summariesd)5.7 Abuse potential

Module 3 d)1 CMC

Module 4 d)2 Nonclinical pharm/tox

Module d)3 Human PKd)4 Microbiologyd)5 Clinical data d)6 Statistical sectionf) CRF and CRT 19

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:--Same active ingredient(s)Same route of administrationSame dosage formSame strengthSame conditions of useInactive ingredients already approved in a similar NDA 20

Goal of ANDA

To reduce the price of the drug.

To reduce the time development.

Increase the bioavailability of the drug in comparison to references list drug.

21

ANDA Review process

22

NDA vs. ANDA Review ProcessNDA Requirement ANDA Requirement

23

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

24

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

25

Paragraph IV certificationAccording to section 505(j)(2)(B)(i), 2157 CFRThe 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)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

26

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

27

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

28

ANDA approval status

29

CONCLUSION

NDA ANDA

Applicable for new drug Applicable for generic drug

Take longer time ( 12-15 years)

Compare to NAD less time taken(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 bioequivalence

30

REFERENCES Douglas J. Pisano, David S. Manlus –FDA Regulatory Affairs, A guide

for Prescription Drugs, Medical Devices and Biologics-New drug Application –Second edition-Marcel Dekker,inc- page no 69-108.

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.

Loyd V. Allen Jr, Nicholas G. Popovich, Howard C. Ansel’s Pharmaceutical Dosage Forms and delivers systems- New Drug Development and Approval Process-8th edition- B.I. publication- Page no 25-65.

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

31

32

Thank u