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NDA ANDA IND by Anthony Crasto

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NDA ANDA IND by Anthony Crasto

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NDA ANDA IND by Anthony Crasto

  1. 1. BY DR ANTHONY CRASTO 1
  2. 2. He was only in first standard in school (dec2007) when I was Paralysed head to toe. His smiling face sees me through day in and day out. Vast readership from academia and industry motivates me, and keeps me going. I am helping millions with free websites and has 7 million hits on google Thanks for helping me to keep lionel smiling
  3. 3. 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. 4
  4. 4. *DRUG DEVELOPMENT Development of a new therapeutic drug is a complex, lengthy and expensive process costs nearly 900 million dollars and an average of 15 years.
  5. 5. Basic Biomedical Research Clinical Science and Knowledge Goal: Improved Health Translation from basic science to human studies Translation of new knowledge into clinical practice
  6. 6. DRUG DEVELOPMENT PROCESS
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  8. 8. 9 *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
  9. 9. 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) 10 Already Marketed Drug Product - No Previously Approved NDA
  10. 10. *The Federal Food, Drug, and Cosmetic Act is the basic food and drug law of the U.S The law is intended to assure consumers that foods are pure and wholesome, safe to eat, and produced under sanitary conditions; that drugs and devices are safe and effective for their intended uses; that cosmetics are safe and made from appropriate ingredients; and that all labeling and packaging is truthful, informative, and not deceptive.
  11. 11. * Code Of Federal Regulations (CFR) oThe final regulations published in the Federal Register (daily published record of proposed rules, final rules, meeting notices, etc.) are collected in the CFR. o The CFR is divided into 50 titles that represent broad areas subject to Federal regulations. o The FDA's portion of the CFR interprets the The Federal Food, Drug, and Cosmetic Act and related statutes. Section 21 of the CFR contains most regulations pertaining to food and drugs. 21CFR Part 312 Investigational New Drug Application 21CFR Part 314 INDA and NDA Applications for FDA Approval to Market a New Drug (New Drug Approval) 21CFR Part 316 Orphan Drugs 21CFR Part 58 Good Lab Practice for Nonclinical Laboratory [Animal] Studies 21CFR Part 50 Protection of Human Subjects 21CFR Part 56 Institutional Review Boards 21CFR Part 201 Drug Labeling 21CFR Part 54 Financial Disclosure by Clinical Investigators
  12. 12. *CDER's Manual of Policies and Procedures (MaPPs) MaPPS are approved instructions for internal practices and procedures followed by CDER staff to help standardize the new drug review process and other activities.
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  19. 19. 20 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 effectiveness 45 Phase3 Several hundred to several thousand 1-4 years Safety, effectiveness, dosage 5-10
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  28. 28. *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. 29
  29. 29. 30 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
  30. 30. 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 31
  31. 31. 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 32
  32. 32. 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 33
  33. 33. 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 34
  34. 34. 35 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
  35. 35. 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. 36
  36. 36. 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) 37 Item 20: Other/pediatric use
  37. 37. CTD NDA: 314.50 Module 1 a) Application form c)2.1 Annotated text of proposed labeling e)Samples and Labeling h)Patent information i) 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 38
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  40. 40. “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 41
  41. 41. *To reduce the price of the drug. *To reduce the time development. *Increase the bioavailability of the drug in comparison to references list drug 42
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  49. 49. 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 50
  50. 50. Described in section 505(j)(2)(A)(vii) of the Act. I Patent Not Submitted to FDA – Approval effective after OGD scientific determination 51 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
  51. 51. 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 52
  52. 52. 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 53
  53. 53. Orphan drug refers to a product that treats a rare disease - affecting fewer than 200,000 Americans 54 7 years exclusivity  Granted on approval of designated orphan drug  OGD works with the Office of Orphan Products
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  55. 55. NDA ANDA Applicable for new drug Applicable for generic drug Take longer time ( 12-15 Compare to NAD less time years) 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 56
  56. 56. *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. 57
  57. 57. Something about IND 58
  58. 58. IND (Investigational New Drug Application)  FDA's role in the development of a new drug begins when the drug's sponsor has screened the new molecule for pharmacological activity and acute toxicity potential in animals, wants to test its diagnostic or therapeutic potential in humans  The molecule changes in legal status under the Federal Food, Drug, and Cosmetic Act and becomes a new drug subject to specific requirements of the drug regulatory system  Drug is to be the subjected to an approved marketing application before it is transported or distributed across state lines  IND- notice of claimed investigational exemption for a new drug must be filed with regulatory body
  59. 59. CCLLAASSSSIIFFIICCAATTIIOONN OOFF IINNDD Commercial o Permits sponsor to collect data on clinical safety and effectiveness needed for application for marketing in the form of NDA Research (non-commercial) o Permits the sponsor to use drug in research to obtain advanced scientific knowledge of new drug oNo plan to market the product
  60. 60. In three broad areas: Animal Pharmacology and Toxicology Studies – oAn assessment as to whether the product is reasonably safe for initial testing in humans oAny previous experience with the drug in humans Manufacturing Information ocomposition, manufacturer, stability, and controls used for manufacturing the drug Clinical Protocols and Investigator Information oCommitments to obtain informed consent from the research subjects, to obtain review of the study by an institutional review board (IRB), and to adhere to the investigational new drug regulations.
  61. 61. Once the IND is submitted, the sponsor must wait 3300 ddaayyss before initiating any clinical trials. During this time, FDA has an opportunity to review the IND for safety to assure that research subjects will not be subjected to unreasonable risk 63
  62. 62. Safety Reporting Requirements for INDs and BE/BA Studies CGMP for Phase 1 Investigational Drugs Exploratory IND Studies Content and Format of Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including Well Characterized, Therapeutic, Biotechnology-Derived Products Q & A - Content and Format of INDs for Phase 1 Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-Derived Products Bioavailability and Bioequivalence Studies for Orally Administered Drug Products IND Exemptions for Studies of Lawfully Marketed Drug or Biological Products for the Treatment of Cancer Guideline for Drug Master Files A Drug Master File (DMF) is a submission to the Food and Drug Administration (FDA) that may be used to provide confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more human drugs. Required Specifications for FDA's IND, NDA, and ANDA Drug Master File Binders Immunotoxicology Evaluation of Investigational New Drugs
  63. 63. To take full advantage of Chemical Web content, it is essential to use several Software:Winzip,Chemscape Chime, Shockwave, Adobe Acrobat, Cosmo Player, Web Lab Viewer, Paint Shop Pro, Rasmol, ChemOffice, Quick Time,etc
  64. 64. DR ANTHONY CRASTO amcrasto@gmail.com http://newdrugapprovals.org/

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