This document provides an introduction to pharmaceutical technology and the history of drug development. It discusses key topics in 3 paragraphs: In the first paragraph, it defines pharmaceutical technology as the application of scientific knowledge and techniques used in manufacturing, preparing, testing, and storing drugs. It also discusses the related fields of pharmacology and toxicology. The second paragraph provides a detailed timeline of major discoveries and innovations in drug development from 5000 BC to the present. It covers milestones such as the isolation of active compounds from plants, development of vaccines and antibiotics, and creation of new drug classes. The third paragraph outlines the drug development process, noting it takes 9-17 years to bring a new drug to market. It also

1. INTRODUCTION TO PHARMACEUTICAL
TECHNOLOGY
By
A. Nandakumar, M.tech.,
AP/BT
KIT- CBE.

2. What is Pharmaceutical Technology?
 Pharmaceutical technology is application of scientific knowledge
or technology to pharmacy, pharmacology, and
thepharmaceutical industry.
 It includes methods, techniques, and instrumentation in the
manufacture, preparation, compounding, dispensing, packaging, and
storing of drugs and other preparations used in diagnostic and
determinative procedures andinthetreatment of patients.

3.  Pharmacology can be definedasthestudy of substances thatinteract with
living systems through chemical processes, especially by binding to
regulatorymoleculesand activatingor inhibitingnormalbody processes.
 Toxicology is the branch of pharmacology that deals with the undesirable
effects of chemicals on living systems, from individual cells to humans to
complexecosystems

4. Historical Outbreaks….
S. No. Period
Scientists/
Community
Product Purpose
1. 5000 BC Sumerians Opium
Hul Gil (Joy
Plants)
2. 3500 BC Egyptians Alcohol Rejoicing
3. 3000 BC China Use of Tea Refreshment
4. 2500 BC Swiz Eating of poppy seeds For joy
5. 450 BC - Cannabis
Psychoactive
drugs
6. 300 BC Americans Hallucinogenic drugs Sedatives
7. 4th century - Use of wine Neutral spirit
19th Century
8.
1803-1805 German
Botanical drugs
(Morphine & Quinine)
An analgesic
9. Opium
Sleep inducing
agent
10. 1809
François
Magendie
action of nux vomica (a
strychnine-containing
plant drug) on dogs
spinal cord was
the site of its
convulsant
action

5. Historical Outbreaks….
S. No. Period
Scientists/
Community
Product Purpose
11. 1841 Jacques Joseph Hashish
Treatment of Mental
patients
12. 1842 Claude Bernard
Arrow poison
curare
acts at the neuromuscular
junction to interrupt the
stimulation of muscle by
nerve impulses
13. 1844 Francis Rynd Hypodermic needle Surgery
14. 1856 British – France war - Opium war
15. 1859 - Cocaine Psychoanalysis
16. 1864 Adolf van Baeyer
Derivatives of
Barbituric acid
Sedatives
17.
1838–
1921
Oswald
Schmiedeberg
Studied the
pharmacology of
chloroform and
chloralhydrate
Founder of Modern
Pharmacalogy
18. 1869 Muscarine
Effect on the heart as
electrical stimulation of the
vagus nerve
19. 1885 Urethane Hypnotic

6. Historical Outbreaks….
S.
No.
Period
Scientists/
Community
Product Purpose
21. 1887 WW I & II Amphetamines Sedatives
22. 1885 Louis Pasteur Rabies vaccines Treatment for Rabies
23. 1890 - Adrenal Extracts
Mechanism of chemical
signaling
24. 1897
John Jacob Abel
Epinephrine
Acute treatment
of asthma attacks
25. 1919
Isolation of histamine
from pituitary extract
For immune responses
26. 1926
Preparation of pure
crystalline insulin
Diabetes
27. 1903
Hermann Emil
Fischer
and Joseph von
Mering
Diethylbarbituric acid Induces sleep
28. 1906 Reid Hunt
Acetylcholine in
adrenal extracts
Neurotransmitters
29.
1911
Paul Ehrlich and
Alfred Bertheim
Arsphenamine
First synthetic anti-infective
drug, syphilis

7. Historical Outbreaks….
S. No. Period
Scientists/
Community
Product Purpose
31. 1912 Bayer
Phenobarbital
(upto 2014)
Potent anti-epileptic activity
32. 1914
Diphtheria
vaccines
Treatment for diphtheria
33. 1923
Gaston Ramon
and Alexander
Glenny
Formaldehyde Treating diphtheria toxin
34. 1921 Frederick Banting
Induced pancreatic
extracts
Insulin therapy
35. 1928 Alexander Fleming Penicillin
Treatment of human
disease
36.
1937
-
Tricyclic
antidepressants
Common use for
depression
37.
S.E. Massengill
Company of
Tennessee
Elixir Sulfanilamide
A highly toxic solvent that
is now widely used as
antifreeze
38.
After
WWII
Eli Lilly, Merck &
Lederle Laboratories
Antibiotics
Against Bacterial
Pathogens
39. 1943 Merck Streptomycin Tuberculosis

8. Historical Outbreaks….
S. No. Period Scientists/ Community Product Purpose
42.
Mid
1950’s
Karl H. Beyer, James
M. Sprague, John E.
Baer, and Frederick
C. Novello of Merck
Chlorothiazide Antihypertensive drug
43.
1960
Merck Sharp &
Dohme
Identified SV40
virus
44.
Carl
Djerassi and Frank
Colton
Envoid First oral contraceptive
45.
William S. Merrell
Company of
Cincinnati
Thalidomide Sedative
46. 1962 John Franklin Enders Measles Vaccine Treating Measles
47. 1964
Hoechst
Pharmaceuticals –
ACE inhibitors
(Angiotensin
Converting enzyme)
Propranolol
(Inderal) was the
first specific β-
adrenergic receptor
blocking agent
Major therapy for angina
pectoris, cardiac
arrhythmias, hypertension,
and essential tremor
48. 1967 Hilleman, Merck Mumps Vaccine Treating Mumps
49. 1969 Hilleman, Merck Rubella Vaccine Treating Rubella

9. Historical Outbreaks….
S. No. Period
Scientists/
Community
Product Purpose
51. 1971 Akira Endo
Mevastatin from
Penicillium citrinum
Inhibitor of HMG-CoA
reductase
52. 1977 - Tagamet Ulcer medication
53.
1980’s
Minipress Prazosin
Blockers of the α-
adrenoreceptors
54. Hytrin Terazosin α1-blockers
55.
1987
Merck Lovastatin (Mevacor) Reduce cholesterol
Eli Lilly
Serotonin reuptake
inhibitor (SSRI),
Prozac
Revolutionizing mental
health practice56.
57. 1990’s -
Labetolol
(Normodyne) and
carvedilol (Coreg)
Exhibit selective α1 and non
selective β-blocking action
58. 1994 Merck Simvastatin
Treating high cholesterol
and heart disease
59. 2001 AstraZeneca
Nexium
(esomeprazole)
Proton pump inhibitor
Antihypertensive drugs

10. Historical Outbreaks….
S. No. Period Act/Law Purpose
1. 1902 Biologics Control Act
Premarket approval for every biological
drug and for the process and facility
producing such drugs
2. 1906
Pure Food and Drug
Act
Forbade the interstate distribution of
adulterated or misbranded foods and
drugs
3. 1938
The Federal Food,
Drug, and Cosmetic
Act
Pre-market demonstration of safety
before a drug could be sold, and
explicitly prohibited false therapeutic
claims.
4. 1959
Revisions of the
FD&C Act
Policy issues, including advertising
abuses, questionable efficacy of drugs,
and the need for greater regulation of
the industry
5. 1962
Kefauver-Harris
Amendment law
Regulate advertising of prescription
drugs and to establish good
manufacturing practices
6. 1964 Declaration of Helsinki Ethics on clinical research
7. 1984
The Hatch-Waxman
Act
Regularized generic production

12. DRUG CLASSIFICATION

13. Drugs
 Chemicals that are designed to prevent, diagnose, treat
or cure a disease.
 Simply medicines.
 They may have similar chemical structures, mechanism
and mode of action, ability to treat the diseases.
 Drugs can be categorized in a number of ways. In
pharmacology, a drug can be classified by its chemical
activity or by the condition that it treats.
 In general, drugs are classified based on
 Therapeutic classification
 Pharmacologic classification (based on mechanism of action
and mode of action)
 Chemical classification
 Amalgamated classification
 Legal classification (Controlled Substances, Drug Schedules,
and Teratogenic Risks)

14. Therapeutic classification
 Therapeutic classification is diffed as organizing
drugs is based on their therapeutic usefulness in
treating particular diseases.
 Analgesics
 Antibiotics
 Anticoagulant
 Antidepressant
 Anticancer
 Anti-epileptics
 Antipsychotics
 Antiviral
 Sedatives
 Anti-diabetics
 Cardiovascular

15. Pharmacologic classification
 A pharmacologic classification refers to the way a
drug works at the molecular, tissue, and body
system levels.
 The pharmacologic classification addresses a drug’s
mechanism of action, or how a drug produces its
physiological effect in the body.

16. Chemical classification
 Stimulants:
 Accelerate the activity of CNS (Makes to feel energetic,
focused and alert).
 Also to feel edgy, angry or paranoid.
 Increase respiration and heart rates, decreases appetite and
increases blood pressure.
 Addictive. Ex: Cocaine, amphetamine, nicotine.
 Depressants (Psychoactive drugs):
 Suppress or slow the activity of brain and nerves, act directly
on the CNS (To create clamming or sedating effect).
 Used to relieve anxiety, promotes sleep and manage seizure
activity.
 Ex: Barbiturates, benzodiazepines, alcohol and gamma
hydroxybutyrate.

17. Chemical classification
 Tranquilizers:
 Treat anxiety and problems with sleep.
 Depressing CNS, most prescribed psychoactive
medications.
 Direct effects on brain (Enhance the action of receptors).
 Hallucinogens (Antipsychotic drug):
 Psychedelic – drugs act on CNS to alter the perception of
reality, time and space.
 It may leaves to hear or see things that don’t exist or
imagine situations that are not real.
 Ex: Psilocybin (Magic Mushroom), LSD (Lysergic acid
diethylamide), peyote and dimethyltyptamine (DMT).

18. Chemical classification
 Inhalants:
 Exists in vapor form at RT.
 Mainly found in household items, frequently abused by
children's and adolescent's.
 Ex: Paints, glue, paint thinners, gasoline's, markers or pen
ink.
 Cannabis:
 Plant derived drug, acts through cannabinoid receptors in the
brain.
 Changes in perception and mood, short term physical and
neurological effects (Increased heart rate and LBP).
 Visual and auditory hallucinations, body temperature
fluctuations, paranoia, insatiable lungs, weight gain and
pscyhosis.
 Ex: Bhang, ganja, charas and hashish oil.

19. Chemical classification
 Opioids and opiates:
 Injected, snorted or smoked.
 Surge of euphoria with warm flushing of skin, dry mouth
and heavy extremities.
 Wakeful and drowsy state.
 Ex: Morphine, papaverine, heroin, oxycodone.
 New psychoactive substances:
 These drugs are designed to evade the existing drug
laws.
 Ex: synthetic cannabis, cannabinoids, synthetic
cathinones, ketamines, piperazines and plant based
drugs (Khat and Kratom).

20. Legal classification of drugs
 Controlled substances act, leads to five
classifications/schedules.

21. Drug development process
 The process by which a new pharmaceutical drug is emerging into
market, if the lead compound is identified by the process of drug
discovery.
Pre-clinical studies
Regulatoryapproval

24. Drug development process
 For a new drug to market from laboratory, it takes 9-17 years.
 After the development of new substances, it needsto be screenedfor its
lead molecules and then it is subjected to physiochemical properties
analysis.
 Later, preclinical studies are carried out.
 General toxicity research.
 Pharmacokinetic research.
 General pharmacological research.
 Pharmacodynamics research.
 Special toxicityresearch.

25. Drug development process
 Clinicalresearch:
 Phase I trials – for safety and dosing studies in healthy
individuals.
 PhaseII trials- test theefficacy of a drug or device.
 Phase III trials - involve randomized and blind testing in
several hundred toseveral thousandpatients.
 PhaseIV trials - Post MarketingSurveillanceTrials.
FDA approval
Marketing

27. Drug development process

28. Drug development process

29. Manufacturing
process in the
pharmaceutical
industry

30. Vaccine
development
process

31. Dosage forms
Dosage forms are the means (or the form) by which drug molecules are
delivered to sites of action within the body.
The need for dosage forms:
1-Accuratedose.
2-Protectione.g. coatedtablets,sealedampules.
3-Protectionfrom gastricjuice.
4-Maskingtasteandodour.
5-Placementofdrugswithinbodytissues.
6-Sustainedreleasemedication.
7-Controlledreleasemedication.
8-Optimaldrugaction.
9-Insertionofdrugsintobodycavities(rectal,vaginal)
10-Useofdesiredvehicleforinsolubledrugs.

32. Dosage forms
They are classified according to:
Route of Administration Physical forms
Oral (Tablets, Pills, Capsule, Lozenge, Pastilles, Dental
cones, Granules, powder)
Solid
Topical (Ointments, Creams, gels, Pastes, dusting powders,
Liniments, Lotions, Collodion, Paints, Aerosol sprayers)
Semi-Solid
Rectal (Suppository, Enema) Liquid (Oral solutions, emulsions,
suspensions and syrup, Elixir, oral
drops, mouthwashes, gargles)
Parental (Injection) Gaseous
Vaginal (Pessary)
Inhaled (Inhaler, Nebulizer)
Ophthalmic (Eye drops, Ophthalmic ointment and gels,)
Otic (Ear drops), Nasal (Nasal drops and sprays)

33. Therapeutic agents

34. Therapeutic agents
Therapeutic agents are used to the treatment of disease or disorders
by remedial agents.
Nature is an attractive source of new therapeutic agents as a
tremendous chemical diversity is found in millions of species of
plants, animals, marine organisms and microorganisms.
Natural products remain an important source of new drugs and
therapeutic agents.
Microorganisms have great potential as natural sources of drugs for the
treatment and prevention of diseases like cancer, anaemia, diarrhoea,
obesity, diabetes etc.,
Non recombinant organisms are also potential sources of natural
antioxidants, immuno-suppressants, enzyme inhibitors, vitamins,
enzymes.

35. Types of Therapeutic agents
Enzymes
Antimicrobial peptides
Proteins
Interferons
Immunosuppressors
Vitamins etc.,

36. Enzymes
Therapeutic enzymes have abroad variety of specific uses.
Oncolytics
Anticoagulants
Thrombolytics
Replacements for metabolic deficiencies
Digestive aids
Metabolic storage disorders, etc.,
Miscellaneous enzymes of diverse function

37. Enzymes

38. Enzymes
Enzymes Therapeutic Uses Basis
Prolactazyme Lactose intolerance It is proenzyme that produces lactase in
stomach
β-lactamase Penicillin allergy When penicillin is converted to
penicillioate
Aglucerase Gaucher’s disease type I Enzyme replacement therapy
Streptokinase Heart attacks (Myocardial
infraction)
Used as “clot blusters” to dissolve clots
in the arteries of heartwall.
Asparginase Acute childhood Leukemia Decreased level of serum asparginase
and inhibition of aspargine dependent
multiplication of tumor cells.
Collagenase Skin ulcers Causes collagen hydrolysis
DNase Cystic fibrosis DNase hydrolyses extracellular DNA
responsible for cystic fibrosis

39. Enzymes
Enzymes TherapeuticUses Basis
Trypsin Inflammation Causes protein hydrolysis
Uricase Gout Converts Urate to allantoin
Enzyme inhibitors To increasethe efficacy
of drugs
Against resistant bacteria’s
Lysozyme Antibiotic therapy Causes bacterial cell wall synthesis
Ribonuclease Antiviral therapy Causes RNA hydrolysis

40. Anti Inflammatory Agents
 Administration of some enzymes is shown to be effective in the
reduction of various inflammatory responses.
 Chymotrypsin: chymotrypsinogen (the zymogen form produced in
pancreas) is converted to active form in small intestine.
 Bromelains: plant proteases purified from the stem or the fruit of
pineapple.
 Their anti-inflammatory action is not known in detail. Probably their
abilityto degrade protein.
 Based inflammatory mediators play a role in their action.

41. Anti Inflammatory Agents
 Administration of some enzymes is shown to be effective in the
reduction of various inflammatory responses.
 Chymotrypsin: chymotrypsinogen (the zymogen form produced in
pancreas) is converted to active form in small intestine.
 Bromelains: plant proteases purified from the stem or the fruit of
pineapple.
 Their anti-inflammatory action is not known in detail. Probably their
abilityto degrade protein.
 Based inflammatory mediators play a role in their action.

42. Anti microbial peptides
 Antimicrobialpeptides-definedaspolypeptideantimicrobialsubstances.
 More than 100 of these peptides identified in fungi, insects, amphibians and
humans.
 Between12-50aminoacids;halftheresidueshydrophobic.
 Generallycationicandamphipathicmolecules.
 Aroleininnatedefensemechanismofmanyspecies.
 Majorclassesinclude:
(a)beta-sheetswithS-Sbonds
(b)linearalpha-helices
(c)extendedcoils
(d)loop structures
Predominant classisthe linear,amphipathic,α-helicalpeptide.

43. Anti microbial peptides
 Antimicrobialpeptidesparticipateintheinnateimmunesystem.
 Canprotecthostfrominvasivemicrobialinfections.
 New evidence views antimicrobial peptides as multifunctional molecules
thatlinkinnateimmuneresponsetoadaptiveimmunesystem.
 Mediate of cross-talk between 2 wings of immune system, achieved by
cytokineandchemokineproduction(immunomodulation).
 Alsobyfacilitatingimmuneandinflammatorycellmigration.
 α and β-defensins, and cathelicidin extend neutrophil lifespan(by
suppressionofneutrophilapoptosis).
 Inducesecretionofhistamineandprostaglandinsfrommastcells.
 InducecytokinereleasefromTcells

44. Nucleic acids as therapeutic agents
• Nucleicacids
• AntisenseRNA andoligonucleotides
• Ribozymes
• Aptamers
• InterferingRNAs orRNAi
• Genetherapy
• Conventionalmethods
• GenomeEditingwithCRISPR-Cas9
• Stemcellsandtherapeuticcloning

45. Proteins
 Our body naturally produces many of the proteins that are act as
therapeutics.
 Protein therapy is similar to gene therapy, but unlike gene therapy, protein
therapydeliversproteintothebodyinspecificamounts.
 It helpstissuerepair,illness,treatpainorremakestructures.
 Antibody based drugs, anticoagulants, blood factors, growth factors,
hormones, interferon, bone morphogenetic proteins, interleukins and
thrombolytic.
 Introduced in 1920’s Human insulin is considered to be the first therapeutic
protein.

46. Proteins
 Proteinshavebeenconsideredforthefollowingfacts:
 Diversityoffunctionalgroups:free thiols(oncysteineresidue)&amine(on
theN-terminusoronlysineresidue).
 Imitationsbysimplechemicalcompoundsare less.
 Lower side effects: due to high specificity there’s less potential for protein to
interruptthenormalbiologicalprocesses.
 Less likely for the body to evoke immune responses as the body naturally
producesmanyoftheproteins.
 Clinical development and FDA approval time are comparatively faster than
thatforsmallmoleculedrugs.

47. Proteins Classification
 Classificationbasedonpharmacologicalaction:
 GroupI: protein therapeutics with enzymatic or regulatory activity.
 a:Replacementofa proteinthatis deficient orabnormal:e.g. - Exubera,Increlex
 b:Augmentationofanexisting pathway:e.g. - Ovidrel ,Neupogen
 c:Providesanovel functionoractivity:e.g. - Myoblock6
 GroupII : protein therapeutics with specialtargeting activity
 a:Interferes witha moleculeor organism:e.g. - Avastin
 b:Delivers othercompoundsorproteins(such as radionuclie,cytotoxicdrug oreffector
protein):e.g. –Ontak
 GroupIII: Protein vaccines
 a:Protectingagainstadeleterious foreign agent:e.g. - Engerix
 b:Treatinganautoimmunedisease.: e.g. – Rophylac
 GroupIV : Protein diagnostics: e.g.–Geref.

48. Proteins Classification
 Classificationbased on moleculartypes:
 Antibody based drugs, Fc fusion proteins, anticoagulants, blood
factors, growth factors, hormones, interferon, bone morphogenetic
proteins, interleukins andthrombolytic.
 Classificationbased onmolecularmechanism:
 Binding non-covalently to target e.g. –mAbs
 Affecting covalent bonds e.g. – enzymes
 Exerting activity without specific interactions e.g. - serum albumin

49. Therapeutic Proteins
METHODSUSED TO PRODUCE RECOMBINANTPROTEINS:
(i) Production of recombinant proteins in microbial
bioreactors. Example: E.coli expression system,
Saccharomycescerevisiae.
(ii) Mammalian cell derived bioreactors. E.g. Chinese
Hamster Ovary cell(CHO) bioreactors.
(iii) Animal Bioreactors “Pharming” Production of
Recombinant Therapeutic Proteins in the Milk of Transgenic
Animals. Example:Cows, sheep, pigs etc.,.

50. Therapeutic Proteins
 Recombinant proteins is extensively used in biotechnology,
medicineand research.
 Hematopoieticgrowth factor.
 Product of blood cells in bone marrow of central axial skeleton is
referred to as medullary hematopoiesis.
 While the mechanism of early stages of lineage commitment by
bone marrow to particular type of blood cells remains elusive, the
later stages of this process is driven by hematopoietic growth
factor.

51. Therapeutic Proteins
 Recombinant technology is mostly used in production of
insulin,humangrowth hormone,vaccines,Interferons etc.,
 Recombinant proteins are used in medical applications,
particularly as medicationsand vaccines.
 Developmentof improved drug delivery system.
Product Usage
Thrombopoietin Thrombocytopenia
Erythropoietin Anaemia
Ancestim Blood cell transplantation
α-glucosidase Pompe’s disease

52. Therapeutic Proteins
Product Usage
HIV vaccine AIDS
Prostvac Prostate cancer
Neurex Cystic fibrosis
Human chronic gonadotropin Breast cancer
Leptin Diabetes mellitus
Thyroid stimulating hormone Recurrent thyroid cancer
IL-4 receptor Asthma
TNF receptor Rheumatoid arthritis
Vascular endothelial GF Cardiovascular disorders

53. Interferons
 Interferons are proteins secreted by immune cells that interfere with a
virus's abilityto reproduce andproliferate.
 The human body produces interferons as part of the immune response.
 The name comes from the fact that they literally interfere with virus
replication.
 Through recombinant DNA technology, various interferons have been
genetically engineered for use in the medical treatment of disease.
 These agents increase the cell-killing activity of the immune system,
making tumor cells more vulnerable to immune attack by increasing
antigens and blocking the formation of new blood vessels by tumors.
 They also slow tumor cell replication by inhibiting DNA and protein
synthesis.

54. Interferons
Types Uses
IFα-n3 (Alferon-N) Genital and perianal warts
IFβ-1b (Betaseron)
& β-1a (Avonex)
Multiple Sclerosis
IFγ-1B (Actimmune) Chronicgranulomatous
disease, malignant
osteopetrosis
IFα-2b Chronichepatitis C &B

55. Interleukins
 It is a group of bioactive proteins produced by leukocytes, monocytes,
and othercells that regulate the immune response.
 They act like messengers between the white blood cells of the immune
system.
 Interleukin-2 increases the activity of lymphocytes, especially killer T-
cells.
 Recombinant IL-2 is used for cancer therapy and continues to be
studied asa biological therapy agent for other diseases.

56. Vitamins
 The term vitamin is derived from the words VITAL & AMINE, because
vitamins are required for life & were originally thought to be amines.
 Importance of Vitaminsare:

57. Economics in Pharma
industries

58. Need for Economics
1. Thesupply side – R&D
2. Demandfor medicines
3. Thecost-effectiveness ‘4th hurdle’
4. Regulatingmedicineprices

59. Need for Economics - Structure
• NME - New medical entity
• HTA - Health technology assessment

60. Five global Challenges

61. Characteristics of Medicines Markets
Supply is R&D intensive,whichimplies:
Intellectualproperty rights (patents)
Long lead times
High risk
Dynamiccompetitionisas important as static
Genericcompetition after patent expiry
Demand is regulated – governments and social insurers are
major buyers of medicines
Prices are regulated

62. Supply Side – Main Characteristics
Patents are an incentive for dynamic efficiency – by promising
temporarymonopolyifsuccessful
Patents last 20 years; first 9-11 of which are spent getting the
medicinetomarket,i.e.research &development(R&D)
Commercial success in R&D-based companies has depended on
finding‘blockbusters’
R&Dcostofanew medicine
 Includes costs of failures
 Out of pocket costs ≈50%
 Opportunity cost of capital≈ 50%
 Only ≈ 30% of launched medicines earn revenues that exceed their
lifetime costs

63. Supply Side – Main Characteristics
R&D costs are sunk(global) joint costs
R&D costs ≈ 17% of pharmaceuticalsales p.a.
But ≈ 31% of costs onnet presentvalue basis
 (even long-run)marginalcost << average cost
Price discrimination (based on Ramsey rule) if non- linear
pricing is impractical
Paralleltrade

64. Demand for Medicine
• OTC’s–
Overthe
Counter
Medicines

65. National Institute for Health and Care Excellence
NICE established in 1999
Fasteraccesstomedicines
Address the‘postcodelottery’
Provideevidence-basedguidance tothe health system on new
technologies
Independentspecial healthauthority
Expanded remitto cover public health in 2005

66. NICE
• NHS –National Health Service

67. NICE approach
• ICER– Institutefor Clinical and Economic Review
• HRQoL –Health related quality of Life
• QALY –Quality –adjusted lifeyear

69. Regulating Market Price
 Public goods andthefree-rider problem (e.g.research)
 Externalities
 E.g.your vaccinationreduces myrisk ofcatching aninfection
 E.g.thecaring externality:I’mhappyifyou’re caredfor
 Incomplete or asymmetricinformation
 Moralhazard (= ‘hiddenaction’)
 Selectionproblem(= ‘hiddeninformation’)
 Principal/agentproblems
 Governmentprocurement

70. Regulatory aspects in
Pharma industries

71. Regulatory requirements
 In an ideal world, the need for analysis should be driven by the desire to
assurethequalityofa drugproduct.
 However, in the real world the need for pharmaceutical drug analysis is
drivenlargelybyregulatoryrequirements.
 A team consisting of R&D, QC, and QA unit members develops these quality
andcompliancesystems.
 It should be one of the highest priorities of top management and QA units to
develop and monitor these systems to comply with the cGMP and GLP
expectations.
 Compliance documents are needed, in addition to the regulatory and
researchdocuments,todemonstratetheintegrityofthedata.
 Compliance documents refer to those reports required by GMP and/or
utilizedduringthecourseofinspectionbyahealthauthority.

72. Regulatory requirements
 Key function of regulatory agencies
 Product registration (drug evaluation and authorization, and
monitoring of drug efficacyandsafety);
 Regulation of drug manufacturing, importation, anddistribution;
 Regulation & Control of drug promotion andinformation.
 Adverse drug reaction (ADR) monitoring.
 Licensing of premises, persons andpractices.
 Goal of regulatory agency
 Main goal of drug regulation is to guarantee the safety, efficacy and
quality of drugs availableto public.

73. Drug Regulation

74. Drug Regulatory System in India
 Drug regulatory system in India Drugs and Health is in concurrent list
of Indian Constitution. It is governed by both Centre and State
Governments under the Drugs & Cosmetics Act, 1940.
 MAIN BODIES:
 CentralDrugStandard Control Organization(CDSCO)
 MinistryOfHealth& FamilyWelfare(MHFW)
 Indian Council OfMedical Research (ICMR)
 Indian Pharmaceutical Association (IPA)
 DrugTechnical AdvisoryBoard(DTAB)
 CentralDrugTesting Laboratory(CDTL)
 Indian Pharmacopoeia Commission (IPC)
 National Pharmaceutical PricingAuthority(NPPA)

76. Types of Applications
 InvestigationalNew Drug Application
 NewDrug Application
 Abbreviated New Drug Application
 Biologic LicenseApplication
 Over-the-counter(OTC) drug application

78. IND
 The investigational new drug (IND) application is the result of a
successful preclinical development program. The IND is also the vehicle
through which a sponsor advances to the next stage of drug
development known asclinical trials (human trials).
 TYPES: Investigator IND: It is submitted by a physician who initiates
and conducts an investigation, and under whose immediate direction
the investigational drug is administered or dispensed. A physician
might submit a research IND to proposed studying an unapproved
drug, or an approved product for a new indication or in a new patient
population.

79. IND
 Emergency Use IND: This allow the FDA to authorize an experimental
drug in an emergency situation that does not allow for submission of
an IND in accordance with 21CFR, Sec. 312.23 0r Sec.312.20. It is also
used for patient who do not meet the criteria of an existing study
protocol, or if anapproved study protocol does not exist.
 Treatment IND: It is submitted for experimental drugs showing
promise in clinical testing for serious or immediately life-threatening
conditions while the final work is conducted and the FDA review takes
place.

81. NDA
 The New Drug Application (NDA) is the vehicle in the United States
through which drug sponsors formally propose that the FDA approve a
new pharmaceutical for sale andmarketing.
 The goals of the NDA are to provide enough information to permit FDA
reviewers to establishthe following:
 Is the drug safe and effective in its proposed use(s) when used as
directed, and do the benefits ofthe drug outweigh the risks?
 Is the drug’s proposed labeling (package insert) appropriate, and what
should itcontain?
 Are the methods used in manufacturing (Good Manufacturing Practice,
GMP) the drug and the controls used to maintain the drug’s quality
adequate to preserve the drug’s identity, strength, quality, and purity?

83. ANDA
 An Abbreviated New Drug Application (ANDA) contains data submitted
to FDA's Center for Drug Evaluation and Research, Office of Generic
Drugs, for review and ultimate approval of a generic drug product.
 Once ANDA is approved, an applicant may manufacture and market the
generic drug product to provide a safe, effective, low cost alternative to
the public.
 A generic drug product is the one that is comparable to an innovator drug
product in dosage form, strength, route of administration, quality,
performance characteristics and intended use. All approved products,
both innovator and generic, are listed in FDA's Approved Drug Products
withTherapeuticEquivalenceEvaluations(Orange Book).

85. FDA

86. How does ICH works?

87. Pharmacopoeia
 The word derives from the ancient Greek word pharmakon means drug & poeia-
to make.
 It is a legally binding collection, prepared by a national or regional authority&
contains list of medicinal substances, crude drug & formulas for making
preparation from them.
 Thepharmacopoeia contain:
 List of drug and other relatedsubstances
 Sources
 Description
 Tests
 Formulas for preparationactions
 Uses
 Doses
 Storage conditions

88. Indian Pharmacopoeia
 Indian Pharmacopoeia Commission (IPC) is an autonomous
institution of the Ministry of Health and Family Welfare which sets
standards for all drugs that are manufactured, sold and consumed in
India.
 The set of standards are published under the title Indian
Pharmacopoeia (IP).

89. Indian Pharmacopoeia - History

90. Indian Pharmacopoeia
 The Indian Pharmacopoeia 2010 is presented in three volumes.
 Volume I contains the Notices, Preface, the Structure of the IPC,
Acknowledgements, Introduction, andthe General Chapters.
 Volume II contains the General Notice, General Monographs on
Dosage Forms and Monographs on drug substances, dosage forms
and pharmaceutical aids (A to M).
 Volume III contains Monographs on drug substances, dosage forms
andpharmaceutical aids (N to Z).
 Followed by Monographs on Vaccines and Immunosera for Human
use, Herbs and Herbal products, Blood and blood- related products,
Biotechnology products andVeterinary products.

91. Indian Pharmacopoeia
 The scope of the Pharmacopoeia has been extended to include
products of biotechnology, indigenous herbs and herbal products,
veterinary vaccines and additional antiretroviral drugs and
formulations, inclusiveof commonly used fixed-dose combinations.
 Standards for new drugs and drugs used under National Health
Programmes are added and the drugs as well as their formulations not
in use now aday are omitted from this edition.

92. British Pharmacopoeia
 The British Pharmacopoeia (BP) is the national pharmacopoeia of the United
Kingdom.
 The British Pharmacopoeia is an important statutory component in the control of
medicines. Along with the British National Formulary (BNF), it defines the UK's
pharmaceutical standards.
History
 The first edition of the British Pharmacopoeia was published in 1864 and was one
of the first attempts to harmonize pharmaceutical standards.
 A Commission was first appointed by the General Medical Council (GMC) under
the Medical Act 1858 for producing a British Pharmacopoeia on a national basis.
 In 1907 the British Pharmacopoeia was supplemented by the British
Pharmaceutical Codex, which gave information on drugs and other pharmaceutical
substances not included in the BP, andprovided standards for these.

93. British Pharmacopoeia
Editions
 The current edition of the British Pharmacopoeia comprises six volumes which
contain nearly 3,000 monographs for drug substances, excipients and formulated
preparation.
 Items used exclusively in veterinary medicine in the UKareincluded in the BP.

94. EUROPEAN Pharmacopoeia
 The European Pharmacopoeia is a pharmacopoeia that aims to provide
common quality standards throughout Europe to control the quality of
medicines and the substancesused to manufacture them.
Editions
 The 8th Edition, published in July 2013 and is currently in force,
contains more than 2220 monographs and 340 general chapters.