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

Contents a) Introduction. b) Goal of NDA c) Classification of NDA  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.  

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

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

New Drug Development and Review Process Steps from Test Tube to New Drug Application Review

Phases of clinical testing 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 effectiveness 45 Phase3 Several hundred to several thousand 1-4 years Safety, effectiveness, dosage 5-10

NDA Review Process

NDA CONTENTS 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. 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.

Section 3: Application summary Proposed annotated package insert Pharmacology class, scientific rational, intended use, and potential clinical benefits Foreign marketing history Chemistry, Manufacturing and control summary Nonclinical pharmacology and toxicology summary Human pharmacokinetics and bioavailability summary Microbiology summary Clinical data summary and results of statistical analysis Discussion of benefit/risk relationship

Section 4: Chemistry, manufacturing and controls Chemistry, manufacturing and control information Samples Methods validation package Section 5: Nonclinical pharmacology and toxicology Provide 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

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 studies Pharmacokinetic studies In vitro studies

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

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

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

Section 11: Case report tabulation 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 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.

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

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

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 administration Same dosage form Same strength Same conditions of use Inactive ingredients already approved in a similar NDA

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.

ANDA Review process

NDA vs. ANDA Review Process NDA Requirement ANDA Requirement

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

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 – 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

Paragraph IV certification According to section 505(j)(2)(B)(i), 2157 CFR 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) 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

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

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

ANDA approval status

CONCLUSION Applicable for new drug Applicable for generic drug 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

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.

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