Drug discovery and Development by vinay gupta

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Drug discovery and Development by vinay gupta

  1. 1. July 17, 2013 vinay-pharmacology 1 Clinical Presentation at UP RIMS & R, Saifai, Etawah On 23rd June 2011 Vinay Gupta (Lecturer) Department of Pharmacology UP RIMS & R Drug Discovery & Development
  2. 2. July 17, 2013 vinay-pharmacology 2 Drug Discovery & Development Process Ref: Bennett & Brown: clinical pharmacology Clinical StudyClinical StudyClinical StudyClinical StudyClinical StudyClinical Study
  3. 3. July 17, 2013 vinay-pharmacology 3 Clinical Development of Drug Clinical trials in the different countries are approved & monitored by different regulatory agencies-  1) In India- DCGI (Drug Controller General of India) Under CDSCO (Central Drug Standard Control Organization).  2) In UK- MHRA (Medicine & Healthcare Products Regulatory Agency), advised by CSM (Committee on Safety of Medicine).  3) In USA- FDA (Food & Drug Administration) & CDER (Center for Drug Evaluation & Research).
  4. 4. July 17, 2013 vinay-pharmacology 4 Techniques of Drug Discovery Older Approaches-  Natural Products (Phytochemical & Pharmacological Evaluation)-  Traditional Medicines-  Modification of the Structure of known drugs-  New uses of drug already in general use-
  5. 5. July 17, 2013 vinay-pharmacology 5 Natural Product Screening- PHARMACOLOGICAL BIOLOGICAL SCREENING Extracts Purify Rejected Positive Negative Establish Structure To Serve as Lead Compound
  6. 6. July 17, 2013 vinay-pharmacology 6 Pri-clinical Studies Discovery & Development Cycle Establishment of Test in Animals LEAD COMPOUND DESIRED ACTIVITY Crude Extract Comp. Of Known Structure Targeted Disease of Interest In vitro Activity In vivo Activity Clinical Activity Purification & Characterisation Establishment of Target Organ Establishment of Molecular Target
  7. 7. July 17, 2013 vinay-pharmacology 7 Newer Approaches-  Molecular Modeling-  Biotechnology & Recombinant DNA Technology-  Positron Emission Tomography (PET)-  Combinatorial Chemistry- Techniques of Drug Discovery
  8. 8. July 17, 2013 vinay-pharmacology 8 Combinatorial Chemistry- The objective of combinatorial chemistry is the generation of huge numbers of compounds very quickly. THERAPEUTIC TARGET LEAD DISCOVERY LEAD OPTIMIZATION DEVELOPMENT CANDIDATE DRUG Combinatorial Chemistry Impacts Here
  9. 9. July 17, 2013 vinay-pharmacology 9 Approaches to Drug discovery Target Selection-  Molecular Targets (genetic information ).  Selection Of Lead Compound.  Validation of Lead Compound.
  10. 10. July 17, 2013 vinay-pharmacology 10 Many targets are most often Proteins, but Nucleic Acids may also be an attractive target. TARGET MECHANISM  Enzyme Inhibitor- reversible or irreversible  Receptor agonist or antagonist  Nucleic acid binder, modifier (alkylating agent) or substrate  Ion channels blockers or openers  Transporters uptake inhibitors
  11. 11. July 17, 2013 vinay-pharmacology 11 Pre-clinical Studies in Animals At the Pre-clinical stage, the regulatory bodies generally ask about- Pharmacological Testing To determine the Acute Toxicity of the drug in at least two species of animals. To develop a Pharmacological profile of Drug. Toxicological Testing To conduct Pharmacokinetic studies from 2 weeks to 3 months. Pharmacokinetic Testing Pharmacological Testing To develop a Pharmacological profile of Drug.Pharmacological Testing To develop a Pharmacological profile of Drug. Toxicological Testing To conduct Pharmacokinetic studies from 2 weeks to 3 months. Pharmacokinetic Testing
  12. 12. July 17, 2013 vinay-pharmacology 12 Pharmacological Testing- Animal Model of Human Disease May Occur-  1) Naturally- eg. squirrel monkeys develop dementia in old age which is behaviorally & histologically similar to AD (Alzheimer's Disease) in human with about same pathophysiology.  2) By introduction of genetic defect into the germ cells of an animal strain so that its reproduction produces offspring with the disease of interest.  3) Using drugs/ chemicals to alter or produce disease of Interest in animal model. Pre-clinical Studies in Animals…
  13. 13. July 17, 2013 vinay-pharmacology 13 Toxicological Studies- Toxicity studies are done to calculate-  1) Maximum Tolerated Dose. (MTD)  2) Gross Pathology to Indicate Target Disease.  3) Satisfactory Therapeutic Ratio ( Efficacy & Toxicity). Pre-clinical Studies in Animals…
  14. 14. July 17, 2013 vinay-pharmacology 14 Toxicity studies Required for Complete Pre-clinical development- Acute Toxicity 2 weeks studies in 3-4 species to determine maximum tolerated dose (MTD). Sub-Acute Toxicity 6 month studies in 2 species. Chronic Toxicity  Up to 12 month studies in rodents & non-rodent to determine if adverse effects occur with repeated daily dosing. Oncology studies for at least 18 months in mice & for 24 months in rat. Reproductive Up to 9 month studies in 2 species to determine effects of drug on fertility & reproduction & expose any teratogenic effects. Pre-clinical Studies in Animals…
  15. 15. July 17, 2013 vinay-pharmacology 15 ‘First do no harm It is good remedy some times to use nothing.’ Hippocrates (460-355 BC)
  16. 16. July 17, 2013 vinay-pharmacology 16 ‘That medicine is a right one and pure one which cures a disease –physical, mental, spiritual- and does not give rise to adverse reactions and does not create other disease.’ Charak Samhita
  17. 17. July 17, 2013 vinay-pharmacology 17 ‘All things are poisons and there is nothing that is harmless, the dose alone decides that something is not poison.’ Paracelsus(1493-1541)
  18. 18. July 17, 2013 vinay-pharmacology 18 Pharmacokinetic Testing  Physio-chemical properties.  Designing Dosage forms. Product Stability  Shelf life.  Drug Expiry. Pre-clinical Studies…
  19. 19. July 17, 2013 vinay-pharmacology 19 Investigational New Drug Application (INDA) IND application is a result of a successful pre-clinical development program & with this a researcher advances to the clinical trials with following results & information- 1) Animal Pharmacological & Toxicological studies with an assessment that the product is reasonably safe for initial testing in human beings. 2) Information pertaining to the composition, stability & control use for manufacturing the drug substances. This information is assessed to ensure that the manufacturing company can adequately produce & supply consistent batches of drug.
  20. 20. July 17, 2013 vinay-pharmacology 20 INDA Cont… 3) Detailed protocols of proposed clinical studies to assess whether the initial phase trials will expose subject to unnecessary risks & details of Clinical investigators (usually Physicians/concerned branch Specialist) who oversee the administration & monitoring of the subject for experimental compound. The IND is not an application for marketing approval but it is an approval for further proceedings of clinical trials in human beings.
  21. 21. July 17, 2013 vinay-pharmacology 21 Phases of Clinical Development Phase I: Human Pharmacology (20 to 50 subjects)  Healthy volunteers or volunteer patients according to class of drug & its safety & initial introduction of experimental drug to humans.  Deals with pharmacokinetics (ADME) &  Pharmacodynamics with tolerability, safety & efficacy parameters. Time Period: 1-2 Years
  22. 22. July 17, 2013 vinay-pharmacology 22 Phase 1 Trial Address:  How rapidly the drug is absorbed.  Where is the drug distributed in the body.  Which organ/system are involved in metabolism of the drug.  Drug elimination rate in the body. Phase 1 Trial Address:  How rapidly the drug is absorbed.  Where is the drug distributed in the body.  Which organ/system are involved in metabolism of the drug.  Drug elimination rate in the body. Phase I Trial Address:  How rapidly the drug is absorbed.  Where is the drug distributed in the body.  Which organ/system are involved in metabolism of the drug.  Drug elimination rate in the body.
  23. 23. July 17, 2013 vinay-pharmacology 23 Phase II: Therapeutic Exploration (50 to 300 subjects)  Volunteer patients.  The study helps to determine common short term side effects & risks associated with the experimental drug.  Establishment of Pharmacokinetic & Pharmacodynamics Dose ranging, in carefully controlled studies for efficacy & safety.  The study may be conducted with test & placebo drugs as- • Open non blind trial. • Single blind trial. • Double blind trial. Time Period: 2-3 Years
  24. 24. July 17, 2013 vinay-pharmacology 24 Phase II Trial Address:  What is the minimum effective dose ?  What is the max. tolerated effective dose ?  Is the drug effective in mild, moderate & severe case of disease/condition.  Is the drug effective for all expected indications.
  25. 25. July 17, 2013 vinay-pharmacology 25 Phase III: Therapeutic Confirmation (250 to 1,000+)  Phase 3 studies are expanded as controlled & uncontrolled trials.  The aim of this phase is to verify the drug’s effectiveness & possibility of any adverse reaction in a large group of patients over a longer period of exposure, to establish safety & efficacy of experimental drug & comparison with existing drug.  In b/w all Phases, the regulatory bodies can impose a clinical hold if the study is unsafe or if the protocol design is deficient in meeting its stated objectives. Once the phase 3 clinical trial has been completed satisfactorily, the organization can apply for marketing application to the regulatory authorities to market the drug by filing NDA (takes 12 months for approval). Time Period: 3-5 Years
  26. 26. July 17, 2013 vinay-pharmacology 26 The value of toxicity testing is illustrated by experience with triparanol a cholesterol lowering drug marketed in the USA in 1959. Three years later a team from FDA made a surprise visit that revealed falsification of toxicological data, demonstrating cataracts in rats & dogs, the drug was withdrawn but some patients who had been taking it for a year or more also developed cataract.
  27. 27. July 17, 2013 vinay-pharmacology 27 Phase III Trial Address:  Overall Risk-benefit relationship.  Adverse Reactions in large group of patients over a longer period of exposure .  The ideal dosage regimen. Should the drug is allowed to be marketed.
  28. 28. July 17, 2013 vinay-pharmacology 28 New Drug Application (NDA) It is an application submitted to regulatory agency (DCGI) for permission to market a new drug product. The sponsor have to submit the pre-clinical & clinical test data, analysis, drug information & description of manufacturing procedure. After a NDA is received, it undergoes a technical screening generally referred as Completeness review for a period of 12 months.  After approval, the license is issued to the sponsor for the exclusive marketing rights for a limited period which is further renewable with satisfactory drug response.
  29. 29. July 17, 2013 vinay-pharmacology 29 Phase 4 (Post Marketing Surveillance) Some times ADR only come to light after drug has been in the market for a while & has been used by a large population. Post Marketing Surveillance identifies such problems. Withdrawal of a drug from the market is not an uncommon occurrences eg. Drug Name Withdrawn Remarks Thalidomide 1950-60 Teratogenicity (Phocomelia). Phenacetin 1983 Risk of cancer & Kidney Problems Chlormezanone 1996 Toxic epidermal necrolysis Cisapride 2000 Risk of Cardiac Arrhythmias Roficoxib 2004 Risk of MI Tegaserod 2007 Imbalance of cardiovascular ischemic events Sibutramine 2010 Europe, US & Australia (Cardiovascular Risk)
  30. 30. July 17, 2013 vinay-pharmacology 30 Surveillance System: Pharmacovigilance The term Pharmacovigilance refers to the process of identifying & responding to issues of drug safety through detection in the community of adverse drug effects. ADR monitoring in India: Central Drugs Standard Control Organization( CDSCO) under ministry of health and family welfare launched the National Pharmacovigilance Programme (NPP) in Nov.2004. Under this programme, the whole country is divided into zones and regions for operational efficiency. The reports from periphery is sent to higher centre and then to WHO center (Uppsala Medical Centre, Sweden).
  31. 31. July 17, 2013 vinay-pharmacology 31 CDSCO (Central Drug Standard Control Organization), Nirman Bhawan, New Delhi is at the top of the hierarchy followed by two zonal centers viz. Seth GS Med. College, Mumbai and AIIMS, New Delhi. Five regional pharmacovigilance centers are- Kolkata (IPGMR-SSKM Hospital) Mumbai (TN Med.College) Nagpur (Indira Gandhi Med.College) New Delhi (Lady Hardinge Med.College) Pondicherry (JIPMER) ADR monitoring in India:
  32. 32. July 17, 2013 vinay-pharmacology 32 A Tale to Remember The Thalidomide Disaster Seal Extremities Phocomelia CONTERGAN
  33. 33. July 17, 2013 vinay-pharmacology 33 Research & Development Time Scale Pre-Clinical (Synthesis) IND Clinical Study NDA Phase IV (Launch) Patent Expiry 1992 1996 2002 2003 2004 (10-12 year) 2012 Discovery Research Clinical Development Regulatory Review Development & Post Marketing 2000-6000 compounds 1 Drug RATE OF ATTRITION Cost about 500 million Dollar
  34. 34. July 17, 2013 vinay-pharmacology 34 Essential Clinical Trial Documentation 1) Protocol- A document that states Objectives, Design, Methodology & Statistical consideration of study. 2) Informed Consent Document (ICD)- A document for voluntary written consent of a subject’s willingness to participate in the particular study. 3) Investigator’s Brochure (IB)- A collection of data including justification for the proposed study, the nature, scale & duration of the proposed trial & to evaluate the potential safety. 4) Case/Clinical Record Form (CRF)- Recorded data & other information on each trial subject on a prescribed format.
  35. 35. July 17, 2013 vinay-pharmacology 35 5) Source Document (SD)- may include Subject’s file, recordings from automated instruments, tracings, X ray & other investigational documents. 6) Regulatory Approval- a document to grant permission to conduct a trial from Investigator’s site. The approval must be obtained prior to initiating the clinical trial & the duration of approval. 7) ERB/IRB/IEC Approval- The approval must be obtained prior to initiating any clinical trial & the duration of approval. 8) Financial Agreement- Financial aspect of the trial b/w investigator (institute) & the sponsor. Essential Clinical Trial Documentation
  36. 36. July 17, 2013 vinay-pharmacology 36 9) Curriculum Vitae (CV)- A document to provide qualification & eligibility of investigator(s) prior to initiate the trial. 10) Investigational Product Accountability- A document to provide complete accountability of investigational product including receipt, dispensing & storage condition of the test drug etc. 11) Certificates of Analysis (COA)- A document to provide identity, purity & strength in term of assay of investigational product. 12) Clinical Study Report (CSR)- A report prepared at the end of the trial including results & interpretation for submission to regulatory bodies. Essential Clinical Trial Documentation
  37. 37. July 17, 2013 vinay-pharmacology 37 Statistical Approaches In Clinical Trials Requirement of Statistics- “Making wise decision in the face of uncertainty.”  To find the action of a drug – the response produced is due to the drug or independent of it.  To compare the safety & efficacy of a particular drug or two different drugs.  To find out the relative potency of a new drug with respect to the standard drug.  To find out an association between two attributes.  Clinical trial design based on the primary & secondary objectives.
  38. 38. July 17, 2013 vinay-pharmacology 38 Power and sample size. Bias & Confounding. Randomization. Stratification. Blinding. Intent-to-Treat. Randomized controlled designs-  Parallel Design  Multi arm parallel Design  Factorial Design  Cross-over Design  Two stage Design  Adaptive Design  Equivalence Design & non inferiority Design Statistical Approaches In Clinical Trials
  39. 39. July 17, 2013 vinay-pharmacology 39 Statistical Errors in Clinical Trials  Type 1 Error  Type 2 Error Statistical Analysis Methods- 1) Parametric Tests  ANOVA  t-Test  One Sample t-Test  Two Sample t-Test  Paired t-Test 2) Non Parametric Tests  Mann-Whitney U Test  Wilcox on Test  Krushall-Wallis Test  Friedman’s Test Statistical Approaches In Clinical Trials
  40. 40. July 17, 2013 vinay-pharmacology 40 Drug Regulatory Act & Schedules Schedule C - biological & other special products eg. Vaccines, Insulin, Sera & Antibiotics. Schedule F - Specification of standard Ophthalmic preparations. Schedule G - with a label that states “caution” dangerous to use except under medical supervision. Schedule H- Prescription Drug. Schedule J- HIV & Atherosclerosis. Schedule X- drugs having dependence liability, the supply of these drugs has to be maintained & recorded in a register. Schedule Y- Clinical trials in India. Schedule W- drugs marketed under Generic names.
  41. 41. July 17, 2013 vinay-pharmacology 41 Ethical Review Board (ERB) ERB is also known as-  IRB - Institutional Review Board.  IEC - Independent Ethics Committee.  EC - Ethics Committee. Composition of ERB- (As per ICMR-2000 & Indian GCP- 2001)  Minimum of 5 Memb. (max. up to 15)  Includes 1 non-scientific memb.  Includes 1 memb. Independent from Institute/ trial site.  1 legal expert.  Rest may be clinicians & scientists.
  42. 42. July 17, 2013 vinay-pharmacology 42 CPCSEA (Committee for the Purpose of Control & Supervision of Experiments on Animals) Provisions of the prevention of the cruelty to animals Act,1960 & the rules under the Act of 1998 & 2001. The concerned research institute are required to get themselves registered with CPCSEA before commencing the research. The main activities are-  Registration of institute for breeding of animals.  Registration of establishment for experiments on animals.  Approval of animal house facilities.  Permission of committee (IAEC) for conducting experiments.  IAEC Composition- 1 Veterinarian, a non-scientific socially aware member, a representative of CPCSEA, Scientist in-charge of animals facility of the institute & other scientist.
  43. 43. July 17, 2013 vinay-pharmacology 43 Indian Patent Office & Duration Patent Duration : Term of every patent in India is 20 years from the date of filling of patent application, irrespective of whether it is filled with provisional or complete specification. Administrated by the office of the CGPDTM (Controller General of Patents, Design & Trade Marks) Mumbai. Headquarter – Kolkata  Branch Office – 1) New Delhi 2) Mumbai & 3) Chennai.
  44. 44. July 17, 2013 vinay-pharmacology 44 DISEASE WISE CLINICAL TRIALS DONE IN INDIA
  45. 45. July 17, 2013 vinay-pharmacology 45 CDSCOOverall Global Clinical Trials India 3rd most preferred destination Notes: Higher scores indicate higher levels of attractiveness. The 15 countries analyzed were selected based on size, diversity & geographical distribution. Czec. Rep. U.K. China Russia Brazil Argentina Poland Hungary Germany Taiwan Israel Singapore Ireland South Africa 6.10 5.58 5.55 5.26 5.00 5.00 4.90 4.84 4.81 4.69 4.46 4.28 4.27 3.86 4.56 United USA 6.88 Patient pool Cost efficiency Regulatory conditions Relevant expertise Infrastructure & environment Scale : 1-10 INDIA
  46. 46. July 17, 2013 vinay-pharmacology 46 Study Average US cost (in millions) Indian cost Phase I 40 50% less than the average cost in US Phase II 100 60%less than the average cost in US Phase III 160 60%less than the average cost in US Cost of Clinical trials in USA / India
  47. 47. July 17, 2013 vinay-pharmacology 47 Growth of Indian Clinical Trial Industry in India Growth of Indian Clinical Trial Industry 35 120 160 300 1000 0 200 400 600 800 1000 1200 2002 - 03 2005 - 06 2006 - 07 2007 - 08 2009 - 2010 Year USD(Million)  As per FICCI - Ernst & Young Survey Report, India can attract between 5 - 10% of the global contract research outsourced market . (all services including chemistry, toxicology and clinical research) over next 5 years.
  48. 48. July 17, 2013 vinay-pharmacology 48 Clinical Trials from India (www.clinicaltrials.gov) 1 10 100 1000 10000 100000 Phase of trial No.Trials(Logtransformed) India 32 165 394 63 USA 6324 11305 5683 2474 All 8540 16878 11662 6142 Phase-1 Phase-2 Phase-3 Phase-4
  49. 49. July 17, 2013 vinay-pharmacology 49 Country All Studies % Industry Sponsored Australia 1572 62.72 Chinese Taipei 903 45.29 Japan 732 67.76 Korea 674 72.26 China 643 53.50 India 582 72.16 Singapore 335 68.36 Thailand 327 69.42 Chinese Hong Kong 250 82.00 Philippines 206 93.20 Malaysia 180 93.33 CLINICAL TRIAL ACTIVITIES IN ASIA ALL STUDIES www.clinicaltrials.gov-Snapshot: 7 Feb 2008 Countries with more than 100 studies listed
  50. 50. July 17, 2013 vinay-pharmacology 50 Sr. No. Company Clinical Trial in India CLINICAL Trial in China 1 Astra Zeneca 10 10 2 BMS 17 6 3 Eli Lilly 17 12 4 GSK 22 14 5 J&J 20 13 6 Merck 8 5 7 Novartis 9 6 8 Pfizer 16 5 9 Roche 5 14 10 Sanofi Aventis 15 13 Total 139 98 GLOBAL CLINICAL TRIALS COMPARISON INDIA : CHINA
  51. 51. July 17, 2013 vinay-pharmacology 51 INDIA BUILDING A TRACK RECORD Clinical Trial Data From India to Achieve an FDA NDA Drug Company Compound Researched Indication US Launch Canagene Hepagam Hepatitis B Jan 06 Eli Lilly Alimta Cancer Feb-04 Eli Lilly Cialis Erectile dysfunction Nov-3 Jannsen Risperidal Psychosis Oct-03 Wyeth Flumist Influenza May-03 Alcon Vigamox Ophthalmic Infections Jan-03 Glaxo Lamictal Epilepsy Jan-03 Novrtis Zelcorm Irritable Bowel Syndrome Jul-02 Pfizer Vfend Fungal Infection May-02 Eli Lilly Xigris Septicemia Nov-01 Santen Quixin Ophthalmic Infections Oct-00
  52. 52. July 17, 2013 vinay-pharmacology 52 Evolution of Drug Regulation 1) Virus Toxin Act of 1902. 2) Federal Food & Drugs Act of 1906. 3) The Sherley Amendment of 1912. 4) The Food, Drug & Cosmetic Act of 1938. 5) The Federal Insecticide, Fungicide & Rodenticide Act of 1947. 6) The Durham Humphery Amendment of 1951. 7) Insulin & Antibiotic Certification Amendments 1952. 8) Comprehensive Drug Abuse Prevention & Control Act of 1970. 9) Orphan Drug Act of 1983. 10) Drug Price Competition & Patent Term Restoration Act 1984. 11) Generic Drug Act of 1990. 12) FDA Modernizations Act of 1997. 13) Paediatric Exclusively Act of 1998. 14) Prescription Drug User Fee Act of 1994-2003.
  53. 53. THANKS Dedicated to those poor animals whose life were sacrificed for our future
  54. 54. July 17, 2013 vinay-pharmacology 54
  55. 55. July 17, 2013 vinay-pharmacology 55 INDIA BUILDING A TRACK RECORD Clinical Trial Data From India to Achieve an FDA NDA Drug Company Compound Researched Indication Launch Canagene Hepagam Hepatitis B Jan 06 Eli Lilly Alimta Cancer Feb-04 Eli Lilly Cialis Erectile dysfunction Nov-3 Jannsen Risperidal Psychosis Oct-03 Wyeth Flumist Influenza May-03 Alcon Vigamox Ophthalmic Infections Jan-03 Glaxo Lamictal Epilepsy Jan-03 Novrtis Zelcorm Irritable Bowel Syndrome Jul-02 Pfizer Vfend Fungal Infection May-02 Eli Lilly Xigris Septicemia Nov-01 Santen Quixin Ophthalmic Infections Oct-00
  56. 56. July 17, 2013 vinay-pharmacology 56 Ethical Review Board (ERB) ERB is also known as-  IRB - Institutional Review Board.  IEC - Independent Ethics Committee.  EC - Ethics Committee. Composition of ERB- (As per ICMR-2000 & Indian GCP- 2001)  Minimum of 5 Memb. (max. up to 15)  Includes 1 non-scientific memb.  Includes 1 memb. Independent from Institute/ trial site.  1 legal expert.  Rest may be clinicians & scientists.
  57. 57. July 17, 2013 vinay-pharmacology 57 CPCSEA (Committee for the Purpose of Control & Supervision of Experiments on Animals) Provisions of the prevention of the cruelty to animals Act,1960 & the rules under the Act of 1998 & 2001. The concerned research institute are required to get themselves registered with CPCSEA before commencing the research. The main activities are-  Registration of institute for breeding of animals.  Registration of establishment for experiments on animals.  Approval of animal house facilities.  Permission of committee (IAEC) for conducting experiments.  IAEC Composition- 1 Veterinarian, a non-scientific socially aware member, a representative of CPCSEA, Scientist in-charge of animals facility of the institute & other scientist.
  58. 58. July 17, 2013 vinay-pharmacology 58 Indian Patent Office & Duration Patent Duration : Term of every patent in India is 20 years from the date of filling of patent application, irrespective of whether it is filled with provisional or complete specification. Administrated by the office of the CGPDTM (Controller General of Patents, Design & Trade Marks) Mumbai. Headquarter – Kolkata  Branch Office – 1) New Delhi 2) Mumbai & 3) Chennai.
  59. 59. July 17, 2013 vinay-pharmacology 59 Drug Regulatory Act & Schedules Schedule C - biological & other special products eg. Vaccines, Insulin, Sera & Antibiotics. Schedule F - Specification of standard Ophthalmic preparations. Schedule G - with a label that states “caution” dangerous to use except under medical supervision. Schedule H- Prescription Drug. Schedule J- HIV & Atherosclerosis. Schedule X- drugs having dependence liability, the supply of these drugs has to be maintained & recorded in a register. Schedule Y- Clinical trials in India. Schedule W- drugs marketed under Generic names.
  60. 60. July 17, 2013 vinay-pharmacology 60 Important Results in Drug Research Since 1806 & onwards 1806 1875 1884 1888 1899 1903 1909 1921 1922 1928 1928 1935 1944 1945 1952 1956 1960 Morphine Salicylic acid Cocaine Phenacetin Acetylsalicylic acid Barbiturates Arsphenamine Procaine Insulin Estrone Penicillin Sulphachrysoidine Streptomycin Chloroquine Chlorpromazine Tolbutamide Chlordiazepoxide Hypnotic Antiinflammatory Stimulant, local anesthetic Analgesic and antipyretic Analgesic and antipyretic Sedatives Antisyphilitic Local anesthetic Antidiabetic Female sex hormone Antibiotic Bacteriostatics Antibiotics Antimalarials Neuroleptic agent Oral antidiabetics Tranquillizer 1962 1963 1964 1971 1975 1976 1981 1981 1983 1984 1985 1986 1987 1987 1988 1990 1991 1993 Verapamil Propranolol Furosemide L-Dopa Nifedipine Cimetidine Captopril Ranitidine Cyclosporin A Enalapril Mefloquine Fluoxetine Artemisinin Lovastatin Omeprazole Ondansetron Sumatriptan Risperidon Calcium channel blocker Antihypertensive agent (beta-blocker) Diuretic agent Anti-Parkinson agent Calcium channel blocker Anti-ulcus agent (H2 blocker) Antihypertensive (ACE inhibitor) Anti-ulcus agent (H2 blocker) Immunosuppressant Antihypertensive (ACE inhibitor) Antimalaria agent Antidepressant (5-HT transporter) Antimalaria agent Cholesterol biosynthesis inhibitor Anti-ulcus agent Antiemetic agent (5-HT3 blocker) Anti-migraine agent (5-HT1 blocker) Antipsychotic agent
  61. 61. July 17, 2013 vinay-pharmacology 61 1994 1995 1995 1996 1996 1996 1997 1997 1997 1998 1998 1999 1999 1999 2001 2001 Famciclovir Losartan Dorzolamide Meloxicam Nevirapin Indinavir, Ritonavir, Saquinavir Nelfinavir Finasteride Sibutramine Orlistat Sildenafil Celecoxib, Rofecoxib Amprenavir Zanamivir, Oseltamivir Fondaparinux Imatinib Anti-herpes (DNA polymerase inhibitor) Antihypertensive agent (A II antagonist) Glaucoma (Carbonic anhydrase inhib.) Anti-arthritis agent (COX 2 inhibitor) HIV reverse transcriptase inhibitor HIV protease inhibitors HIV protease inhibitor Hair loss Adipositas (uptake blocker) Adipositas (lipase inhibitor) Erectile dysfunction (PDE inhibition) Anti-arthritis agents (COX-2 inhibitors) HIV protease inhibitor Influenza (neuraminidase inhibitors) Thrombosis (synthetic LMWH) CML (specific abl-TK inhibitor)

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