M. Pharm. Syllabus (Draft) updated on 28 March 2012 (5.

30 pm)
Structure of M.Pharm (Quality Assurance) Semester I Subject Theory/ week (hr) 4 hr Practical/we ek (hr) 6 hr Total Period ic Test hours 1/3 (Th/Pr ) 1 Periodi c Marks 20 Universi ty Exam hours 3/6 (Th/Pr) Universi ty Exam Marks 80

Common Paper I (Modern Pharmaceuti cal Analysis) Common Paper II (Research Methodology, Statistics & Computer Applications) Specializatio nI (Product Development ) Specializatio n II (Advanced QA Technology) Semester II Subject

10 hr

4 hr

4 hr

20

80

4 hr

6 hr

10 hr

1/3

20

3/6

80

4 hr

4 hr

20

80

28 hr Theor y/ week (hr) 4 hr Practical/we ek (hr) 6 hr Total Periodi c Test hours 1/3 (Th/Pr) 1 Periodi c Marks 20 Universi ty Exam hours 3/6 (Th/Pr) 3 Universit y Exam Marks 80

Specialization III (Biological Evaluation) Common Paper III (Regulatory Affairs & IPR) Specialization IV (Product Development & Packaging)

10 hr

4 hr

4 hr

20

80

4 hr

6 hr

10 hr

1/3

20

3/6

80

Specialization V

4 hr

4 hr 28 hr

20

80

General Structure of M.Pharm (Sem- I and Sem II) Semester I Subject Theory/ week (hr) Practical/we ek (hr) 6 hr Total Period ic Test hours 1/3 (Th/Pr ) 1 Periodi c Marks 20 Universi ty Exam hours 3/6 (Th/Pr) Universi ty Exam Marks 80

Common 4 hr Paper I (Modern Pharmaceuti cal Analysis) Common 4 hr Paper II (Research Methodology, Statistics & Computer Applications) Specializatio 4 hr nI Specializatio n II Semester II Subject Theory / week (hr) 4 hr 4 hr 4 hr

10 hr

4 hr

20

80

6 hr -

10 hr 4 hr 28 hr

1/3 1

20 20

3/6 3

80 80

Practical/we ek (hr) 6 hr -

Total

Period ic Test hours 1/3 (Th/Pr ) 1

Periodi c Marks 20 20

Specializatio n III Common Paper III (Regulatory Affairs & IPR) Specializatio n IV Specializatio nV

10 hr 4 hr

Universi ty Exam hours 3/6 (Th/Pr) 3

Universi ty Exam Marks 80 80

4 hr 4 hr

6 hr -

10 hr 4 hr 28

1/3 1

20 20

3/6 3

80 80

hr

Modern Pharmaceutical Analysis (Common Paper I) No I 1 Topics Separation Techniques: Classification of chromatographic methods based on mechanism of separation & their basic principles including Ion exchange and separation of chiral compounds. Gas Chromatography: Instrumentation, column efficiency parameters, derivatisation methods, application in pharmaceutical analysis, validation of analytical method Liquid Chromatography: Instrumentation in HPLC, UPLC, Comparison of GC & HPLC, phase packing materials, column selection, mobile phase selection, efficiency parameters, application in pharmaceutical analysis including validation of analytical method. HPTLC: Instrumentation & pharmaceutical applications of HPTLC Advanced techniques: Flash chromatography, Supercritical Fluid chromatography, Capillary Electrophoresis (CE) Spectroscopic Methods: UV- Visible spectroscopy: Introduction, Basic principles, Applications; Absorption spectra of organic compounds & complexes illustrating the phenomenon & its utilization in qualitative & quantitative studies of drugs; calculation of absorption maximum of unsaturated hydrocarbonsWoodwards-Fieser Rule, Derivative spectroscopy, Derivation of equation for Simultaneous determination and Absorbance Ratio methods, Application of Chemometrics. IR Spectroscopy: Interaction of infrared radiation with organic molecules & its effect on bonds; Sample handling, detailed interpretation of ir spectra, Pharmacopoeial Importance of ir spectra. Instrumentation in Brief, Dispersive IR spectrophotometer compared with FTIR and ATR NMR Spectroscopy: Fundamental principles of NMR, Concept of Chemical shift, Spin-spin coupling, Decoupling techniques and their importance, shielding & deshielding; solvents in pmr and 13C-NMR;

72 hr Duration 3

3 4

II 1

5 1 10

Detailed interpretation studies of pmr spectra; Introduction & application of 13 C-NMR spectra and 2D NMR. Instrumentation in Brief, FTNMR. 4 Mass Spectroscopy: Basic principles Ionization techniques, mass spectrum & its characteristics - molecular ion, metastable ion, fragment ions, isotope ions; fragmentation process and rules & characteristic fragmentation patterns, fragment characteristics in relation to parent structure & functional groups; relative abundance of isotopes & their contribution to characteristic peaks. Mass spectroscopy in Metabolomics Instrumentation- Mass spectrometers, Tandem mass spectrometers Hyphenated instruments LCMS, GCMS Other Techniques: Thermal Analysis: Theory, instrumentation & applications of Thermogravimetric analysis,differential thermal analysis, differential scanning calorimeter. Immunochemical Techniques: Immuno-electrophoresis, Immunoprecipitation, ELISA, Radioimmunoassay. Powder X-ray Diffraction: Braggs law and its applications, Instrumentation and pharmaceutical applications.

2 7

III 1 2 3

6 4 4

References: 1. Skoog, DA, Holler, FJ, Crouch, SR. Principles of instrumental analysis. 6thed., Baba Barkha Nath printers, Haryana, 2007 2. Silverstein, RM, Webstar, FX. Spectrometric identification of organic compounds. 6 thed., John Wiley & Sons (Asia) Pvt. Ltd., Singapore, 2005 3. William Kemp. Organic spectroscopy, 3rded., Palgrave, New York, 2006 4. Jag Mohan, Organic spectroscopy: Principles and Applications, 2nded., Narosa publishing house Pvt Ltd., New Delhi, 2005 5. Conners KA. A Text book of pharmaceutical analysis, 3rd ed., John Wiley & Sons, Singapore, 2004 6. Willard HH, Merritt LL, Dean JA, Settle FA. Instrumental methods of analysis, 7th ed., CBS Publishers & Distributors, New Delhi, 1986 7. Pavia DL, Lampman GM, Kriz GS, Vyvyan JA. Introduction to spectroscopy. 4th ed., Brookescole publishers, California, 2008 8. Sharma BK. Instrumental methods of chemical analysis, 25th Ed., Goel Publishing house, Meerut, 2006 9. Beckett, AH, Stenlake, JB. Practical pharmaceutical chemistry, Part I & II, 4th ed., CBS Publishers & distributors, New Delhi, 2004 10. Ewing, GW. Instrumental methods of chemical analysis, 5thed., McGraw Hill Book Company, New York, 1985 11. Schirmer, RE. Modem methods of pharmaceutical analysis, Vol. I & II, 2nded., CRC Press, Florida, 2000 12. Moffat, AC, Osselton, MC, Widdop, B. Clarke's analysis of drugs and poisons, Vol. I & II, 3rd ed., K.M. Varghese Company, Mumbai, 2004

Modern Pharmaceutical Analysis (Practicals) *A minimum of 18 Practicals (Exercises on both Quantitaive, Qualitative analysis to be elaborated) shall be conducted from the following. Practical-1 UV/Visible spectrum scanning of a few organic compounds for UV- absorption and correlations of structures and isosbestic point in case of mixtures. Practical-2 to 3 Effect of solvents and pH on UV spectrum of drugs Determination of Rate constant by UV spectroscopy Practical-4 to 8 Estimation of multi component formulation by UV- Spectrophotometer in formulations (Simultaneous equation Method, Absorbance Ratio Method) Practical-8 to 9 Experiments based on the application of derivative spectroscopy. Practical-10 to 11 Experiments based on HPLC (Isocratic and Gradient elution) techniques. - Single and multiple component analysis - Calculation of System Suitability Parameters Practical-12 to 14 Interpretation of drugs by IR spectra Use pharmacopoeial spectra (atleast 10) for correlation of structural features Practical- 15 to 19 Workshop of spectroscopy: (UV, IR, NMR, Mass) structural elucidation of atleast 10 compounds with UV, IR, NMR and Mass spectral data. Practical-20 Separation of protein drug substances by electrophoresis

Research Methodology, Statistics & Computer Applications (Common Paper II) No I 1 Topics Research Methodology Introduction: Meaning & Objectives of research, types of research, approaches to research; Research methods, research process; Criteria for good research, common problems, qualitative & quantitative research methods. Research Topic: Selection of research problem, research design; meaning, concept & features of research design, experimental design, plan of research work. Data Collection: Primary & secondary data collection method, design of questionnaires for data collection, identification of sources of information, searching and classifying information; compilation, processing & analyzing of data & information. Interpretation of Results and Presentation: Meaning of interpretation, techniques of interpretation; scientific writing & report preparation, fundamentals of scientific writing, report preparation, types & layout of report, precautions in writing research report; statistical aspects of research output. Principles of validity & reliability of research work, ethical aspects of research methodology. Developing research proposals: Format of research proposals, Individual & Institutional research proposals. Statistics and Computer Applications Introduction, Concept of Statistics in Quality Control (SQC), its role and uses. Collection, organization, graphic & pictorial representation of data, measurement of central tendencies & dispersion; degree of freedom, standard deviation, standard error, Coefficient of variation, Probability, Sample and Sampling method Estimation and Hypothesis testing: Null Hypothesis, confidence level, Point & interval estimation, concept of hypothesis testing & types of error, Student t test, Chi-Square test. Linear regression and Correlation: Analysis of variance (one way & two way), Factorial design Brief review of non parametric tests, experimental design in clinical trials, statistical test for bioequivalence, Dose-Response study, statistical quality control; validation, optimization techniques & screening design, significance of coefficient of correlation, non-linear regression, 8 4 Duration

2 3

6 10

5 6 II 1

6 6

2 3 4

8 4 12

Application of software for statistical calculations. Validation and security measures for electronic data and computer assisted process.

References: (1) Research in education John W. Best Jems V. Kahn (2) Research methodology C. R. Kothari (3) Methodology and techniques of social research Willkinson and Bhandarkar (4) Presentation skills Michel Halton Indian society for institute education (5) Practical introduction to copyrights Gavin Mofariane (6) Thesis projects in sciences and engineering Richard M. Devis (7) Scientist in legal system Ann Labor Science (8) Thesis and assessment writing Janolthon Anderson (9) Writing a technical paper Donald Manzel (10)Effective business report writing Lel and Brown (11)Protection of industrial property rights Purshottam Das and Gokul Das (12)Spelling for millions Edna Furmess (13)Preparation for publications King Edwards hospital foundation for London (14)How to write and publish a scientific paper Robert A. Day Cambridge University Press 4th Edition, 1994 (15)Introduction to Statistical Methods- C. B. Gupta (16)A first course in Mathematical Statistics- C. E. Weatherborn (17)Introduction to Biostatistics-Mahajan (18)Experimental Pharmacology by S K Kulkarni. (19)Fundamentals of Science & Technology Communication N R Rajagopal, NISCAIR (CSIR)

Drug Regulatory Affairs & Intellectual Property Rights (Common Paper III) No I 1 Topic Regulatory Affairs: Historical perspectives, organization structure, activities and responsibilities of drug regulatory agencies in India, US, EU, Australia, Africa Concepts of total quality management, Good laboratory practices and ISO; Quality assurance & quality control for APIs and other intermediates in process & finished products. GMP for bulkdrugs & formulations, Good clinical practice guidelines. US Regulatory practices, ICH guidelines. Validation of process, equipments, procedures, validation master plan. Documentation like master records, batch records, regulatory compliance records, distribution records, drug recall registers, management review records. Regulatory Acts: Drugs & Cosmetic act-1940 & rules 1945 with special relevance to schedule M, Y, U; latest drug price control order & latest drug policy Pollution & environmental control act. Intellectual Property Rights: Introduction: Scope, Objectives & IPR in pharmacy, Indian legal system & its role in IPR; importance for pharma industry. Concept of property with respect to intellectual creativity; Tangible & Intangible property, concept of IPR, scope & nature of patents, copyrights, trade mark, geographical limitations. Patent and its Practical aspects: Indian Patent Act 1970, Patenting in India & abroad, role of international organization WTO, WIPO, EPO in patent act; practical aspects of patent filing, components of a patent application in India, PCT filing, patent infringement & litigation therein, commercialization & licensing 4 6 4 Duration

6 4 4 2 2 4 8

6 4

II 1 2

10

Ethics in IPR: Positive & negative aspects, drug related controversies, traditional knowledge, current strategies & solutions.

References: 1. Drugs & Cosmetics Act 1940 and rules there under. 2. Drugs Laws by Hussain. 3. Indian Patent Act. 4. Quality assurance & GLP by Y. Anjaneyulu. 5. Quality control & Application by Bentrand L. Hanser. 6. Quality assurance in Analytical chemistry by Werner Funk.. 7. Guidelines of various countries like MCA, TGA, ICH. 8. GLP regulation by Alen Hirsch Vol 38 Marcel Decker series 9. GMP for pharmaceuticals forth edition by S. Willing, J. Stocker Marcel Decker series 1997. 10. I.P., B.P., U.S.P. International Pharmacopoeia

Product Development & Formulation (Quality Assurance - Specialization I) No. 1 Topic Pre-Formulation: A consideration of physio-chemical characteristics of medicinal agents in their dosage form. Physical characteristics: Particle size, polymorphism, crystal form, solubility, Interfacial tension, Salt formation, wetting of solids, flow characteristics, compressibility, Rheology, Partition coefficient. Chemical Characteristics: Degradation-Hydrolytic, oxidative, reductive, photolytic. Biopharmaceutical Characteristics: Liquid solubility, dissociation constant, dissolution rate, bulk solubility and diffusibility in diffusion layer, drug stability in G.I.track, complexation. Quality Control- Process & Dosage forms: Sources of variations, control of variation-material control and manufacturing control. Statistical quality control- sampling, testing programme and methods. Pilot Plant Scale-up Techniques: Evaluation of formula, equipments, raw materials, process, stability, uniformity. Techniques related to tablets including coating, capsules, liquid dosage forms & semi-solid dosage forms. Antioxidants, Preservatives, Colorants and flavourants Product Development Approach for the following Dosage Forms: Tablets, Capsules, Sustained release Medication, Injectables Ointments. Packaging of Pharmaceutical Dosage forms Types, QC tests Pharmaceutical Stability Studies- Stability aspects: Basic concept and objectives of stability study. Regulatory requirement for stability studies: A very brief introduction to FDA and WHO guidelines. Detail study of ICH guidelines [Q1A (R2), Q1B, Q1C, Q1D, Q1E, Q1F, Q5C]. Kinetic principles applied for stability evaluation and their applications in predicting shelf life and half life of pharmaceutical formulations. Importance of accelerated stability study. Duration 10

4 5 6 7

6 12 8 10

Degradation pathways (Degradation by hydrolytic, oxidative, reductive, photolytic, etc) and stabilization methods for formulation. Stability indicating assays and its importance Stability testing and dating of solid and liquid dosage forms: Different approaches for stability testing of solid and liquids, kinetic principles, physical and chemical stability testing of pharmaceutical dosage forms and packages. Product life-cycle management Product liability and compensation Stability issues related to proteins and insulin type formulations Stability issues related to herbal formulations, extracts, fractions and natural products/isolated compounds. Stability issues for vaccines and biological products 10

REFERENCES: 1. Drug Stability, J.T. Carstensen, Marcel Dekker, New York. 2. Chemical Stability of Pharmaceuticals-A Handbook for Pharmacists, Kenneth Connors, John Wiley and Sons, Inc. 3. Good Drug Regulatory Practices: a Regulatory Affairs Quality Manual (Good Drug Development Series) Helene I. Dumit 4. United States Pharmacopoeia-27(NF-22), United State of Pharmacoppeal convention, INC, 12601 Twinbrook Parkway, Rockville, MD 20852. 5. The International Pharmacopoeia Vol. 1,2,3,4, General methods of analysis and quality specifications for pharmaceutical substances, excipients, dosage forms. 6. Phytochemical Methods, J.B.Harborne, Chapman and Hall, London and New York. 7. Pharmacopoeal standards for Ayurvedic Formulation (Council of Research in Indian Medicine and Homeopathy).

Product Development & Formulation (Quality Assurance - Specialization I) Practicals No. of experiments : Minimum 18 experiments should be covered and relevant documentation to be carried out in consultation with QA/ QC laboratory of pharmaceutical manufacturing company:1. Preparation and evaluation of Riboflavin/Ibuprofen tablets I .P. to characterize and evaluate the effect of different concentrations of binders and disintegrant. 2. Optimization of tablet formulation of poorly water-soluble drugs. 3. Design and fabrication of theophylline sustained release formulation and comparison of its release profile with the conventional dosage form. 4. Formulation and evaluation of micronized disperse system for parenteral delivery of drugs including test for pyrogens and sterility testing etc. 5. Preparation of solid dispersions of poorly water soluble drugs using different carriers and to study the release profile and compare with conventional dosage forms. 6. Preparation and evaluation of a hydrodynamically balanced drug delivery system of a drug having absorption problem 7. Disintegration and dissolution of per oral tablets 8. Influence of vehicle on drug availability from topical dosage forms in-vitro 9. Determination of Pharmacokinetic parameters and determination and evaluation of bioavailability of a drug administered I.V., I.M. and P.O. 10. Design and preparation of a suspension and its evaluation. 11. Development of moisture resistant coating formulation for Amoxycillin tablets/ Ranitidine tablets 12. Quality control of paper, Plastic and glass container 13. Quality control of closure 14. Quality control of labels and label adhesives. 15. Microbial limit test in oral products 16. Sterility testing of parenteral products 17. Validation of sterilization equipments e.g. Hot air oven, Autoclave. 18. Validation of Analytical procedure 19. Preformulation studies of a model Drug. 20. Accelerated stability testing and shelf life determination. 21. Biological evaluation of equipments and materials used in sterile or non-sterile working area. 22. Biological evaluation of sterile and non sterile working area.

Quality Assurance Techniques (Quality Assurance Specialization II) No. 1 Topic Quality and Concepts Quality: Concept of quality, nature of product quality, study of various approaches for quality like Deming, Juran, Crosby, Feigenbaum, Shikaw. Quality Assurance Approach and Improvement - Quality improvement process, Quality in research and development, Quality income and cost. Relevance of TQM Quality benchmarking, details of international standards (ISO, GMP, GLP, TGM, VAN and ISI), its need and fact sheet evaluation (statistics of industries implemented these standards with those which have not implemented these) Role of quality audit and quality circle in quality assurance. Quality assurance and GLP, implementing of GLP in analytical laboratory. Process management, project management, strategic development and product development. Measurement of quality, information and decision making or utilization of data. Quality operations, its inspection and test used for it. Human resource and training for quality. Market survey, customer demand and marketing in addition to supplier and customer relationships. Quality, society and national culture. Computerized system- software development, computer applications and quality system. Requirements of product registration, in India and other countries (USA, UK, Japan and Europe etc). II Organization & functions of the Federal Food & Drug Administration of USA. Federal trade commission Act. The Environmental Pollution Control Act, Laws related to pharmacy - Tort law, Contract law. FDA Guidelines on i) Dissolution testing of immediate release Solid Oral Dosage forms ii) Extended Release Oral Dosage forms: Development, Evaluation, and Applications of In Vitro/In Vivo Correlations Duration 16

12

iii) Waiver of In Vivo Bioavailability and bioequivalence Studies for immediate release solid oral dosage forms Based on Biopharmaceutics Classification system iv) PAC-ALTS: Post approval changes Analytical Testing Laboratory Site v) SUPAC IR Immediate release solid oral dosage forms: Scale up and approval changes: Chemistry Manufacturing and controls In Vitro dissolution testing, and In Vivo bioequivalence documentation vi) Drug Metabolism / Drug Interaction Process in drug development process: Studies In Vitro vii) In Viva Metabolism or drug interaction studies Study design, Data analysis and recommendations for Dosing and Labeling III A detailed study of Food & Drug Laws affecting drug products design, manufacture and distribution in USA. The Federal Food. Drugs & Cosmetics Act 1938. Druham Humphrey Amendment 1951. Kefauver Harris Amendment 1962. The Drug Listing Act 1972 Prescription Drug Marketing Act 1987. Concept and historical development of pharmaceutical product registration. Effect of GATT and WTO on commerce of pharmaceuticals. Introduction to Intellectual Property Rights. Globalization of drug industries, Export Import Policy of drugs, WHO certification, Trademarks and copyrights. Regulation & licensing of drugs & cosmetics recent amendments and other relevant rules. Consumer protection Act Factory Act Loan license Standard institutes, certification agencies, Other prominent drug regulatory agencies like ISI, BSS, ASTM, SO, WHO, US-FDA, UKMHRA, TGA, MCA Quality control laboratory responsibilities and laboratory practices. Routine controls on instruments, reagents, sampling plans, standard test procedures and protocols, control on animal house, data generation and storage, quality control documentation and audits of QC facilities. 6

IV

V VI

6 6

VII

10

VIII

10

REFERENCES: 1. Jurans Quality Handbook, 5th Ed, by J M Juran, A B Godfrey, McGrawHill International Edition 2. Total Quality Management- Guiding Principle for Application, J. P. Peker, ASTM manual series, Philadelphia. 3. Total Quality Management The Key to Business Improvement, Champman and Hall, Londan. 4. Quality Assurance Guide by Organisation of Pharmaceutical products of India. 5. ISO 9000 and Total Quality Management Sadhank. G. Ghosh. 6. Project Management, Clifford F. Gray and Erik W., Larson Publisher: McGraw Hill Company. 7. Quality Assurance of Pharmaceuticals: A Compendium of Guidelines and Related Materials (v. 1) by WHO. 8. FDA Regulatory Affairs: A Guide for Prescription Drugs, Medical Devices and Good Drug Regulatory Practices: a Regulatory Affairs Quality Manual (Good Drug Development Series) Helene I. Dumitriu 9. ISO 9000 Quality Systems Handbook - updated for the ISO 9001:2008 standard, Sixth Edition: Using the standards as a framework for business improvement by David Hoyle (Paperback - July 10, 2009). 10. Total quality management: strategies and techniques proven at today's most successful companies (Portable Mba Series) by Stephen George and Arnold Weimerskirch (Hardcover - Feb. 1998).

Biological Evaluation and GLP - (Quality Assurance Specialization III) Sl. No 1 2 Topics Biological Evaluation and Standardization Need for biological models and methodologies Laboratory Animals a) Commonly used laboratory, transgenic and other genetically prone animal models (viz. nude mice SH rats etc.) b) Techniques of blood collection, anesthesia & euthanasia of experiment animals. c) Maintenance & breeding of laboratory animals. d) Regulation and ethics requirements. e) Guidelines & regulatory agencies CPCSEA, OECD, FDA ICH, FHSA, EPA, EEC, WHO, etc. f) Importance of alternative experimental models, its advantages & disadvantages. Principles of Biological Standardization a) Methods of biological assay, principles of biological assays with examples as per IP and BP. b) Development of new bioassay methods. Immunoassay a) General principles of immunoassay, Theoretical basis, Optimization of immunoassay, Heterogenous immunoassay system, Homogenous immune system. b) Production of immunoassay reagent: Introduction, receptors or binders, unlabelled ligands Calibrators, Labelled ligands and receptor, Separation technique, buffers. c) Immunoassay Methods Evaluation: Protocol outline, objective & preparation, evaluation of precision, standard tracer, sensitivity, evaluation of accuracy, antibody characteristics, monitoring, reaction conditions, clinical evaluation. Organization of screening for the Pharmacological activity of new substances with emphasis on evaluation using in-vivo, invitro and other possible animal alternative models. a) General Principles & safety pharmacology procedure. b) CVS Pharmacology Antihypertensive, Anti arrhythmics, Duration 2 8

10

12

Vasodilators, disentail. c) CNS Pharmacology behavioral & muscle co-ordination, CNS stimulants, antiepileptics, Nootropics. d) Drugs for Neurodegenerative diseases, like parkinsonism, Alzheimers, multiple sclerosis. e) Drugs acting on ANS. f) Respiratory Pharmacology Anti-asthmatics, COPD, Antiallergic & Mucoactives. g) Reproductive Pharmacology Aphrodisiacs & antifertility agents. h) Analgesics, anti-inflammatory & antipyretics. i) G.I.T. Anti-ulcer, anti-emetics, anti-diarrhoeal & laxatives. j) Anti-cancer agents. k) Metabolic disorders like anti-diabetics, anti-hyperlipidemic, anti-obesity, hepatoprotective. l) Models in drug absorption & metabolism. m) Immuno Pharmacology specific (cell & hormonal mediated) & non-specific methods. n) Screening of free radical scavenging activity. o) Acute, Sub-acute & Chronic toxicity test. 6 7 Clinical pharmacology and pharmacodynamics: clinical study design, documentation, presentation and interpretation Clinical trials: definition, phase I IV studies, design documentation, presentation and interpretation, statistical analysis of clinical data, factorial design, guidelines as per Indian and other regulatory authorities. Documentation related to New application : NDA and ANDA requirements, Data presentation pertaining to safety of drug as per FDA requirements Good Laboratory Practices (GLP)Regulations , biological evaluation, microbiological limit tests, sterility tests for effectiveness of antimicrobial preservative , LD 50, ED 50 teratogenicity , mutagenecity , clinical trials , Bioassays, pyrogens and pyrogen testing safely testing presentation of related data and supporting raw data. Related quality systems : ISO, WHO etc, and their applications in pharmaceutical industry. 8 8

10

RECOMMENDED BOOKS 1. S. Weinberg, Good laboratory practice Regulations, Marcel and Dekker. 2. J. Swarbrick Boylan, encyclopedia of pharmaceutical technology, Marcel and Dekker. 3. J.R. Berry and R.A. Nash, Pharmaceutical process validation. Marcel and Dekker. 4. S.H. Will and J.R. Stoker, good manufacturing Practices for Pharmaceutics Marcel Dekker. 5. R.F. Brewer, Design of experiments for process improvement and quality Assurance Narrosa. 6. B. Othery. ISO 14000 and ISO 9000 Gower. 7. D.H. Stamatis, Understanding ISO 9000 and implementing the basics to quality; Marcel Dekker. 8. Biological standardization by J.H. Burn, D.J. Finney & L.G. Goodwin. 9. I.P. & B.P. 10. Screening Methods in Pharmacology by R.A. Turner. Vol. I & II Academic Press, New York and London. 11. Evaluation of drug activities by Laurence & Bacherce. 12. Methods in Pharmacology by Arnold Schwartz. 13. Selected topics on Experiment Pharmacology by Issha G. Kamat, Dadkar, N.K. & Seth, UK. 14. Fundamental of Experimental Pharmacology, by M..N. Ghosh. Scientific Book Agency, Calcutta. 15. Pharmacological Experiment on intact preparation by Churchill Livingstone 16. Drug Discovery and evaluation by H.G. Vogel & W.H. Vogel. Springer Verlag, Berlin Heideleberg. 17. Animal Model in Toxicology by Shayne Cox Gad & Christopher P, Chengelis. 18. Principles & Methods of Toxicology by Hays. 19. CRC Handbook of Toxicology by Derelako & Hollinger. 20. Handbook of Experimental Pharmacology by S.S. Kulkarni. Vallabh Prakashen, Delhi. 21. Pharmacological Experiments on Intact and Isolated preparations, Edinburgh University Pharmacology Staff, Livingstone. 22. Goodman and Gilmans The Pharmacological basis of Therapeutics Ninth edition, Editors. A. G. Gilman, J. G. Hardman, L. E. Limbiod, P. B. Melineff, R. W. Rudder, Macmillan Publishing Co. Inc. Latest edition. 23. Clinical Pharmacotherapecutics, edited by Kamalesh Kohli, Elsevier Publication

Biological Evaluation and GLP - (Quality Assurance Specialization III) - PRACTICALS (6 HOURS/WEEK) EXPERIMENTS BASED ON FOLLOWING 1. Sterility testing of medical devices. LVP antibiotics, ophthalmic preparation. 2. Pyrogen testing. 3. Microbiological limit test of starch, acacia and antacid preparation. 4. LD 50 and ED 50 determination. 5. Eye irritation and Patch test. 6. Bioassays of some drugs. RECOMMENDED BOOKS 1. S. Weinberg, Good laboratory practice Regulations, Marcel and Dekker. 2. J. Swarbrick Boylan, encyclopedia of pharmaceutical technology, Marcel and Dekker. 3. J.R. Berry and R.A. Nash, Pharmaceutical process validation. Marcel and Dekker. 4. S.H. Will and J.R. Stoker, good manufacturing Practices for Pharmaceutics Marcel Dekker. 5. R.F. Brewer, Design of experiments for process improvement and quality Assurance Narrosa. 6. B. Othery. ISO 14000 and ISO 9000 Gower. 7. D.H. Stamatis, Understanding ISO 9000 and implementing the basics to quality; Marcel Dekker.

Pharmaceutical Method Development and Validation - (Quality Assurance Specialization IV) Sl. No. 1 Topics Introduction to pharmaceutical validation: definition, manufacturing process model, scope of validation, advantage of validation, organization for validation, validation of master plan, types of process validation, design qualification, installation qualification, operational qualification and performance qualification of facilities. Process validation: prospective, concurrent, retrospective and revalidation, Process validation of formulations like tablets, capsules, ointment/creams, liquid orals, sterile dosage form which should include following aspects of Personnel and organization o Raw materials o Equipments (e.g. Dry powder mixers, fluid bed and tray dryers, tablet compression machine, capsule filling machines etc) o Area, premises and environment including storage of raw materials to finished products o Water (validation of pharmaceutical water system and pure steam), o Packaging and labeling controls and its validation o Cleaning validation: cleaning of equipment, cleaning of facilities o Validation of Integrated lines by media fill test. o Validation of HVAC system Vendor Certification. Validation of compressed air, validation of water and air handling systems Validation of existing equipment and utilities validation Computer system validation including installed softwares Pharmaceutical development of drug substance and drug product, formulations, manufacture and supply of materials, labeling and presentation, stability and storage, purity, compatibility, disposal. Method Development and Validation Application of process analytical technology (PAT) in quality assurance Qualification validation and calibration of equipment. Analytical and Bioanalytical method validation Calibration and validation of various instruments used for drug analysis such as UV Visible Spectrophotometer, IR spectrophotometer, spectrofluorimeter, HPLC, HPTLC and GC. Regulatory requirement in pharmaceutical analysis US-FDA, ICH, PAC-ALTS: Post approval changes analytical testing laboratory site etc. Duration 10

18

12

5 6

Analysis of drug from biological fluids Application of analytical methods to product obtained through genetic engineering, Amino acid sequence analysis, tryptic mapping, ion exchange amino acid analysis, isoelectric focusing etc. Application of analytical methods to product obtained from natural sources (extracts, herbal formulations, isolated compounds, modern herbal formulations) (Compendial methods for evaluation of crude drug and herbal formulation) Dosage form impurity profile and its validation

6 10

REFERENCES: 1. Pharmaceutical Process Validation, B. T. Loftus and R. A. Nash, Drugs and Pharm Sci. Series, Vol. 129, Marcel Dekker Inc., New York. 2. Pharmaceutical Packaging Technology, Dean, D. A. Evans, E. R. and Hall, J. H., Taylor and Francis, London. 3. Validation of Aseptic Pharmaceutical Processes, Carleton and Agalloco, Marcel Dekker Inc., New York. 4. Cleaning Validation Manual: A Comprehensive Guide for the Pharmaceutical and Biotechnology Industries by Syed Imtiaz Haider and Erfan Syed Asif 5. Pharmaceutical Computer Systems Validation: Quality Assurance, Risk Management and Regulatory Compliance, Second Edition by Guy Wingate 6. Pharmaceutical Process Scale-Up, Michael Levin, Drugs and Pharm. Sci. Series, Vol. 157, Marcel Dekker Inc., New York. 7. Pharmaceutical Packaging Technology, Dean, D. A. Evans, E. R. and Hall, J. H., Taylor and Francis, London. 8. Pharmaceutical Analysis Modern Methods Part A, Part B, J. W. Munson, Marcel Dekker, NY. 9. Spectroscopic identification of organic compounds. John Dyer, Willy, NY. 10. Organic Spectroscopy W. Kemp, NY. 11. NMR spectroscopy (Basic Principles, concepts and application in Chemistry) Herald Gunther, (John Wiley and Sons), NY. 12. Spectroscopic identification of organic compounds. R.M. Silverstein, G.C. Bassler, T.C. Morrill, Pub: John Wiley and Sons, NY. 13. Quality control of herbal drugs: an approach to evaluation of botanicals, Pulok K. Mukherjee, 2002, Business horizons. 14. Encyclopedia of Pharmaceutical Technology Vol.1-3, Swarbric, J and Bolyln, J. C., Marcel Dekker, Inc., New York. 15. United States Pharmacopoeia-27(NF-22), 2004, United State of Pharmacoppeal convention, INC, 12601 Twinbrook Parkway, Rockville, MD 20852. 16. The International Pharmacopoeia Vol. 1,2,3,4, General methods of analysis and quality specifications for pharmaceutical substances, excipients, dosage forms. 17. Phytochemical Methods, J.B.Harborne, Chapman and Hall, London and New York. 18. Pharmacopoeal standards for Ayurvedic Formulation (Council of Research in Indian Medicine and Homeopathy)

Pharmaceutical Method Development and Validation - (Quality Assurance Specialization IV) - Practicals *A minimum of 18 Practicals shall be conducted. Practical 1: Prerequisite (01) Basics of instrumentation, validation documentation Practical 2: (06) 1) Quantitative estimation by UV, HPLC 2) Acquaintance with working or principles of major spectroscopic and chromatographic techniques (IR, NMR, MS, AAS, GC, HPTLC and HPLC etc Practical 3: (02) 1. Method development and validation using UV, HPLC and HPTLC Practical 4: (03) 1. Quantization of different phytoconstituents from extracts and herbal formulation by Spectroscopic, HPLC and HPTLC method Practical 5: (02) 1. Stability indicating assay methods Practical 6: (02) 1. Impurity profile (AIP, formulations) 2. Quantitative estimation of drugs in biological fluids Practical 7: (04) 1. Validation of following equipment: Autoclave, hot air oven, powder mixer (dry), tablet compression machine and equipments required for formulations 2. Validation of a processing area. 3. Cleaning validation of equipment. 4. Validation of tablet, capsule, liquid (oral, topical etc) manufacturing facilities 5. Evaluation equipments validation Practical 8: (01) 1. Preparation of calibration master plan Practical 9: (02) 1. Evaluation and validation of packaging materials & facilities. 2. Test of packaging materials, cartons, aluminum foils, strip packing, blister packing, ampoules, vials, etc. 23 Practical 10: (01) 1. Software, computer system validation. Practical 11: (01) Documentation involved in above process REFERENCES: 1. Practical Pharmaceutical Chemistry (part II) by Beckett and Stenlake 2. Interpretation of Mass Spectra of organic compounds-B. Kienicz, C. Djerassi 3. Cleaning Validation Manual: A Comprehensive Guide for the Pharmaceutical and 4. Biotechnology Industries by Syed Imtiaz Haider and Erfan Syed Asif

5. Pharmaceutical Process Validation Robert A. Nash, Alfred H. Wachter. 6. Pharmaceutical Analysis Modern Methods Part A, Part B, J. W. Munson, Marcel Dekker, NY. 7. United States Pharmacopoeia-27(NF-22), 2004, United State of Pharmacopeial convention, INC, 12601 Twinbrook Parkway, Rockville, MD 20852. 8. British Pharmacopoeia, 2004, The British Pharmacopoeia commission office, Market Tower, Nine Elms Lane, London. 9. Indian Pharmacopoeia-2007, Indian pharmacopoeia commission, Sector-23, Raj Nagar, Ghaziabad. 10. Chromatographic Analysis of Pharmaceuticals, A. John, Adamovics, Cytogan Corporation, Princeton, NJ. 11. Clinical Pharmacotherapecutics, edited by Kamalesh Kohli, Elsevier Publication. 12. Biological standardization by J.H. Burn, D.J. Finney and L.G. Goodwin. 13. Pharmaceutics of Solids and Solid dosage form by Cartensens. 14. Advance in Pharm. Sciences by Bean and Beckett. 15. Quality Assurance of Pharmaceuticals: A Compendium of Guidelines and Related Materials (v. 1) by WHO. 16. Good Drug Regulatory Practices: a Regulatory Affairs Quality Manual (Good Drug Development Series) Helene I. Dumitriu. 17. Pharmaceutical Computer Systems Validation: Quality Assurance, Risk Management and Regulatory Compliance, Second Edition by Guy Wingate. 18. Relevant articles from journals. 19. Quality control of herbal drugs: an approach to evaluation of botanicals, Pulok K. Mukherjee, 2002, Business horizons. 20. Pharmaceutical Packaging Technology, Dean, D. A. Evans, E. R. and Hall, j. H., Taylor and Francis, London. 21. Packaging of Pharmaceutical and Healthcare products, H. Lockhart, F. A. Paine, Champman and Hall, London. 22. Packaging of Pharmaceuticals, C.F. Ross. 23. Drug Stability, J.T. Carstensen, Marcel Dekker, New York. 24. Chemical Stability of Pharmaceuticals-A Handbook for Pharmacists, Kenneth Connors, John Wiley and Sons, Inc.

Pharmaceutical Quality Assurance and Management (Quality Assurance Specialization V)

Sl. No. 1 Topics Study of following concepts with related documentation PERSONNEL Introduction,Qualification Experience and Training, Responsibilities and Key Personnel, Personal hygiene and clothing, Legal Aspects and Consultants Introduction, Principal Area, Plumbing and Drainage system, Lighting, Sewage, Refuge and Disposal of Water, Washing and Toilet Facilities, Sanitation, Maintenance
SURROUNDING, BUILDING AND FACILITIES EQUIPMENT Introduction, Design, size, location and

Duration 6

Construction of Equipment, Equipment Identification, Equipment log, Cleaning and Maintenance of Equipment, Automatic, Mechanical and Electronic Equipment 4
MATERIALS MANAGEMENT Introduction, Purchasing, Raw

Materials, Packaging Materials, Intermediate and Bulk Products, Finished Products, Rejected and Recovered Materials, Recalled Products, Returned goods, Reagents and Culture Media, Waste Materials, Reference standards and Miscellaneous Materials 5
QUALITY MANAGEMENT Introduction, Quality Assurance,

Components of Q.A., Good Manufacturing Practice, Quality Control 6

MANUFACTURING OPERATIONS AND CONTROL Introduction,

10

Sanitation of Manufacturing Premises, Mix-ups and Cross Contamination, Processing of Intermediates and Bulk product, Packaging Operations, I.P.Q.C., Release of Finished Product, Process Deviations, Charge-in of Components, Time Limitations on Production, Drug product Inspection, Expiration Dating, Calculation of Yields, Production Record Review 7
DOCUMENTATION AND RECORDS Introduction,

Specifications, Master Production and Control Record, Batch Production and Control Record, Important SOPs and Record, Change Control and Site Master File 8
OUTSOURCING Introduction, Manufacturing and

Packaging Outsourcing, Analytical Outsourcing, Other Services- Outsourcing

POST OPERATIONAL ACTIVITIES Introduction, Distribution,

Recall Products, Returned Products, Complaints and Adverse Effects, Drug Product Salvaging 10
SITE AND PLANT SECURITY Introduction, Security

Personnel, Entry to Site, Entry to Plant Buildings, Internal Security and Current Issues 11

SAFETY AND ENVIROMENTAL PROTECTION Introduction, Safety and Environmental Protection and Procedures STERILE PHARMACEUTICAL PRODUCTS Introduction, Personnel, Building and Premises, HVAC system, Water and Steam System, Equipment, Processes, Sterilization, Quality Control, Sanitation, Finishing of Sterile Products, Documentation and Document Formats PHARMACEUTICAL QUALITY AUDITS - Plant Level documentation, Plant Level Department wise Quaternaries and Principle of Quality Audit

12

13

Recommended Books: 1. Pharmaceutical Quality Assurance, M.A. Potdar, Nirali Prakashan, Pune. 2. Current Good Manufacturing Practices, M.A. Potdar, Pharma-Med Press, Hyderabad. 3. GMP for Pharmaceuticals, 5th Edition, Sidney H. Willing, Marcel Decker Series 4. Regulatory guidelines related to GMP by a. Australian code of GMP for medicinal products, 16th Aug. 2002. b. 21 Code of Federal Regulation, parts 210, 211 & 58. (USFDA guidelines) c. MHRA, UK Guidelines on GMP d. GMP Guidelines by Medicines Control Council of South Africa e. Schedule M of D & C Act