PRESENTED BY
Sneh Priya Roll no-080603011 M Pharm part-1 Dept of Pharmaceutics
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Contents: 1.New Drug Application a) Introduction. b) Goal of NDA c) Classification of NDA d) New drug development review e) NDA content f) NDA review process flow chart g) The NDA in CTD Format
2. Abbreviated new drug application a) Introduction b) Goal of ANDA c) ANDA contents d) ANDA review process flow chart e)Patent certification condition
3. Conclusion. 4. References.
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New Drug Application
IntroductionCritical 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 NDA
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New Drug Development and Review ProcessSteps from Test Tube to New Drug Application Review
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Phases of clinical testingPhase Number of
patientsLength Purpose Percent
successfully completing
Phase1 20-100 Several months Mainly safety
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Phase2 Up to several hundred
Several months to two years
Some short-term safety but mainly effectiveness
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Phase3 Several hundred to several thousand
1-4 years Safety, effectiveness, dosage
5-10
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NDA Review Process
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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: LabelingIt 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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CONTD....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
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CONTD....…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
CONTD....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
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CONTD....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 methods14
CONTD....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
CONTD....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
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CONTD....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
Contd…..Application itself consists of a cover letter and a
completed form FDA-356h along with several other supporting items as appropriate
Item 13: Patent informationItem 14: Patent certificationItem 15: Establishment descriptionItem 16: Debarment certificationItem 17: Field copy certificationItem 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 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
Abbreviated New Drug Application (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”
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 NDA20
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.
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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 ANDA
Described in section 505(j)(2)(A)(vii) of the Act.I Patent Not Submitted to FDA – approval effective after OGD scientific determinationII Patent Expired – approval effective after OGD scientific determinationIII Patent Expiration Date (honored) – tentative approval after OGD scientific
determination, final approval when patent expiresIV 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 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
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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 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
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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-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.
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THANK YOU
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