1. Tutorial Guide : Dr. P P Lanjewar
Dr.Vishal H Gosavi
Transocean Offshore International Drilling Inc
19th AFIH Batch 2010-11
Roll no 09
CLI, Mumbai

2. Contents :
 Introduction
 Definitions
 Indian Scenario & Locations of Industry in India
 Categories of Pharma agents
 Pharmaceutical Industrial Process
 Pharmaceutical manufacturing of dosage-form products
 Physical Health Hazards
 Specific Health Hazards related to drugs and pharmaceuticals
 Studies : Mortality & Morbidity
 References

3. Introduction: General overview of Industry
 The Drugs and Pharmaceutical industry develops, produces, and
markets drugs licensed for use as medications.
 On the surface, the industry looks clean, the white lab coats worn
by workers add to the illusion of health & safety, appearances are
deceptive.
 Arguably the Second largest profit making industry in world
 A Global industry, Pharmaceutical companies can deal in generic
and/or brand medications. They are subject to a variety of laws and
regulations regarding the patenting, testing and marketing of drugs.

4. Introduction: General overview of Industry
 The production of medicinals demands a carefully maintained
and sterile working environment
 Producing drugs and other medicinals may involve exposure to
toxic industrial chemicals.
 As per Factory Act 1948, India - Schedule I ~ [Amendment 1987]
Drugs and Pharmaceutical (Narcotics) are classified as
Hazardous processes industry.
 Finished products may be lifesaving medications for sick people,
but they can be dangerous to healthy workers who are inhaling
or absorbing them during the production process.

5. Definitions
 Drugs are substances with active pharmacological properties in humans and animals.
 Biologics are bacterial and viral vaccines, antigens, antitoxins and analogous products,
serums, plasmas and other blood derivatives for therapeutically protecting or treating
humans and animals.
 Bulks are active drug substances used to manufacture dosage- form products, process
medicated animal feeds or compound prescription medications.
 Diagnostic agents assist the diagnosis of diseases and disorders in humans and animals.
 Ethical pharmaceuticals are biological and chemicals agents for preventing, diagnosing
or treating disease and disorders in humans or animals.

6. Definitions
 Excipients are inert ingredients which are combined with drug substances to create a
dosage form product.
 Over-the-counter pharmaceuticals are drug products sold in a retail store or
pharmacy which do not require a prescription or the approval of a medical, pharmacy or
veterinary professional.
 Pharmacy is the art and science of preparing and dispensing drugs for preventing,
diagnosing or treating diseases or disorders in humans and animals.
 Pharmacokinetics is the study of metabolic processes relating to the absorption,
distribution, biotransformation, and elimination of a drug in humans or animals.
 Pharmacodynamics is the study of drug action relating to its chemical structure, site of
action, and the biochemical and physiological consequences in humans and animals.

7. Indian Scenario

8. Indian Scenario
 In India since independence and post Globalization pharma & drugs
manufacturing has sprung up very fast and still continues to grow.
 It has provided a major boost and played a significant role in India’s goal of
growth, self reliance, revenue earnings, employment.

9. Indian Scenario : Economic Perspective
 The pharma industry generally grows at about 1.5-1.6 times the Gross Domestic
Product growth
 Globally, India ranks third in terms of manufacturing pharma products by volume
 The Indian pharmaceutical industry is expected to grow at a rate of 9.9 % till 2010
and after that 9.5 % till 2015
 In 2007-08, India exported drugs worth US$7.2 billion in to the US and Europe followed
by Central and Eastern Europe, Africa and Latin America
 The Indian vaccine market which was worth US$665 million in 2007-08 is growing at a
rate of more than 20%
 The retail pharmaceutical market in India is expected to cross US$ 12-13 billion by
2012
 The Indian drug and pharmaceuticals segment received foreign direct investment to the
tune of US$ 1.43 billion from April 2000 to December 2008

10. Major categories of pharmaceutical agents
Central nervous Renal and Gastrointestinal Anti-infectives Immune system Chemotherapy Blood and Endocrine
System cardiovascular System and blood-forming system
System target organs Organs
Analgesics Antidiabetics Gastrointestinal Systemic Analgesics Antineoplastic Blood modifiers Diagnostics
· Biguanides agents anti-infectives · Non-steroidal s · Anticoagulants · Adreno cortical
· Acetaminophen · Glycosidase · Antacids · AIDS therapies anti- · Adjunct · Antiplatelet steroids
· Salicylates inhibitors · Antiflatulents · Amebicides inflammatory therapy agents · Glucocorticoids
· Insulins · Antidiarrhoeals · Anthelmintics agents·(NSAIDs) · Alkylating · Colony · Gondotropins
Anaesthetics · Sulphotryforeas · Antiemetics · Antibiotics agents stimulating · Hypothalamic
· General and local · Antispasmodics · Antifungals Biological · Antibiotics factors dysfunction
Cardioprotectiv · Laxatives · Antimalarials response · · Haemantinics · Thyroid
Anticonvulsants e agents · Prostaglandins · Sulphonamides modifiers Antimetabolites · Haemostatics function
· Barbituates · Adrenergic · Cephalosporins, · Alpha proteinase · Hormones · Plasma test
· Benzodiazepine blockers penicillins, inhibitors · Immuno- fractions
· Stimulants tetracyclines, etc. · Antitoxins modulators Hormones
Migraine · Angiotensin · Immune serums Vasodilators · Adreneal
preparations inhibitors Respiratory · Toxoids · Cerebral· cortical
· Beta adrenergic · agents · Vaccines vasodilators steroid
blocking agents Antiarrhythmics · Antitussives inhibitors
· Serotonin receptor · Calcium · Bronchodilators Antifibrosis · Anabolic
antagonists channel · Decongestants therapy steroids
blockers · Expectorants · Androgens
Narcotics · Diuretics · Oestrogens
· Opiates · Vasodilators · Gonadotropins
· Vasodepressors · Growth
hormone
· Progesterone
· Somatostatin
Skin and mucous
membrane agents
Psychotherapeutics · Acne Immunodilators Prostaglandin
· Antianxiety agents preparations and immuno-
· Antidepressants · Allergans suppressives
· Anti-infectives
Sedatives and · Burn preparations Multiple
hypnotics · Emollients sclerosis
· Barbituates management
· Benzodiazepine Urinary tract
agents
· Anti-inflectives
· Antispasmodics
Vaginal
preparations
· Antifungals

11. Solvents Processes Solvents Processes
 Acetone C F B  Formaldehyde C F B
 Acetonitrile C F B  Formamide C
 Ammonia (aqueous) C F B  Furfural C
 n-Amyl acetate C F B  n-Heptane C F B
 Amyl alcohol C F B  n-Hexane C F B
 Aniline C
 Isobutyraldehyde C
 Benzene C
 2-Butanone (MEK) C
 Isopropanol C F B
 n-Butyl acetate C F  Isopropyl acetate C F B
 n-Butyl alcohol C F B  Isopropyl ether C B
 Chlorobenzene C  Methanol C F B
 Chloroform C F B  Methylamine C
 Chloromethene C  Methyl cellosolve C F
 Cyclohexane C  Methylene chloride C F B
 o-Dichlorobenzene (1,2- C  Methyl formate C
Dichlorobenzene)  Methyl isobutyl ketone (MIBK) C F B
 1,2-Dichloroethane C B  2-Methylpyridine C
 Diethylamine C B  Petroleum naphtha C F B
 Diethyl ether C B  Phenol C F B
 N,N-Dimethyl acetamide C
 Polyethylene glycol 600 C
 Dimethylamine C
 n-Propanol C B
 N,N-dimethylaniline C
 N,N-dimethylformamide C F B  Pyridine C B
 Dimethyl sulphoxide C B  Tetrahydrofuran C
 1,4-Dioxane C B  Toluene C F B
 Ethanol C F B  Trichlorofluoromethane C
 Ethyl acetate C F B  Triethylamine C F
 Ethylene glycol C B  Xylenes C
C = Chemical synthesis,
F = Fermentation,
B = Biological or Natural extraction.
Solvents used in the pharmaceutical industry

12. Pharmaceutical Industrial Process

13. Preparation of
Pharmaceutical Product

14. Pharmaceutical manufacturing
of dosage-form products

15. Occupational Hazards
General / PHYSICAL Hazards Specific health hazards

16. Physical Health Hazards
Hazards Sources of exposure Occupational Health Control
to hazard effects Measures
I. Dust Gets airborne during  Allergic reactions Use efficient
manufacturing respirator & ensure
they fit well
 Allergic dermatitis
II. Formaldehyde Used to ensure  Lung cancer  Avoid frequent
Sterility of products  Hodgkin's disease contact
 Prostate cancer  Use of PPE
 Pulmonary oedema
(Acute exposures)
 Pneumonia
III. Ultraviolet Used to maintain  Dry, inelastic wrinkled  Use of PPE
Lamps sterility in plants skin,
 Skin sores and
 Skin cancer

17. Physical Health Hazards
Hazards Sources of Occupational
exposure Health effects Control Measures
to hazard
IV. Ergonomics  Raw materials for  Repetitive Strain  Good Industrial
& Material bulk chemical Injuries to back engineering
handling mobilization
 Carpal tunnel  Facility Management
 Material-handling syndrome practices
devices
 Tendinitis  Ergonomic Design of
 Heavy manual tools
work
 Administrative Practices
(e.g. rotating workers, &
worker training)

18. Physical Health Hazards
Hazards Sources of exposure Occupational
to hazard Health effects Control Measures
V. Rotating  Unguarded moving  Crush  Interlocked guards
Machines machine parts Injuries
&  Control switches
Hazardous  Exposed “crush  Puncture &
Energy and nip points Penetrating  Emergency stop devices
Sources injuries
 Loose hair, long-  Appropriate PPE
sleeved clothing,  Caught
jewellery between  Operator training
injuries
 Routine inspection and
 Amputations periodic maintenance
 Mechanical / Electrical
Isolation procedures

19. Physical Health Hazards
Hazards Sources of exposure Occupational
to hazard Health effects Control Measures
VI. Noise  High sound levels  Irritability  Engineering methods :
Exposures (> 85 db) Identify, Modifying,
 Loss of job Enclosing & Dampening
Causes : concentration noise sources.
E.g :-
I. Compressed air  Temporary  Employee rotation
II. Vacuum sources Hearing loss program
III. Ventilation systems
IV. Packaging machines  Permanent  Hearing-protective
Hearing Loss devices ~ Noise mapping
(NIHL) (Earplugs/muffs/defenders)
 Enclosed design of
workplace  Noise monitoring &
medical surveillance
(i.e., audiometry)
 Train workers

20. Specific Health Hazards related to
drugs & pharmaceuticals
Hazards Sources of exposure Occupational Health effects
(Drug Exposures) to hazard
I. Hormones Chronic / Acute Exposure Male workers:
during manufacturing or
Packaging  Breast development (Gynaecomastia)
a) Estrogens & Female workers:
derivatives
 Menstrual disorders
 Abnormal endometrial growth
 Excessive Menopausal bleeding,
 Nausea,
 Headaches,
 Breast pain,
 Leucorrhoea
 Ankle oedema

21. Specific Health Hazards related to drugs & pharmaceuticals
Hazards Sources of exposure Occupational Health effects
(Drug Exposures) to hazard
I. Hormones (cont..) Chronic / Acute exposure Male workers:
during manufacturing or
Packaging  Lack of sexual drive
 Testicular pain.
b)Progesterone/Androgens
& its derivatives Female workers:
 Menstrual and ovarian function
disorders
 Diminished fertility
 Frequent spontaneous abortions
 Masculine symptoms

22. Specific Health Hazards related to drugs & pharmaceuticals
Hazards Occupational Health effects
(Drug Exposures)
II. Antibiotics 1. Allergic reactions: Anaphylactic Shock i. Asthma ii. Skin rashes
iii. Itching and redness of the eyes iv. Rhinitis
E.g.: -
Streptomycin, 2. Vitamin deficiency: e.g.: Tetracycline, Streptomycin
Tetracycline, Repeated occupational exposure to antibiotics destroy normal intestinal
Penicillin etc ... flora thus decreasing Vitamin absorption.
3. Fungal infections: Daily exposure to antibiotic dust can lead to
fungal infections of the skin & nails.
E.g.: black hairy tongue and rectal itch
Women workers may develop Vaginal yeast infections
4. Toxic effects: Exposure to certain antibiotics may lead to Toxicity
similar to that occur when that drug is given as medicine.

23. Specific Health Hazards related to drugs & pharmaceuticals
Hazards Occupational Health effects
(Drug Exposures)
III. Drugs for  Headaches may be accompanied by a rapid heart beat
Cardiac disease and a flushed face.
E.g.: Nitroglycerin  Nitrates dilate the blood vessels and make blood pressure
fall.
 Dizziness /Fainting
 Cardiac pain / Heart attacks
 Sudden death following "withdrawal" from exposure.

24. Specific Health Hazards related to drugs & pharmaceuticals
Hazards Occupational Health effects
(Drug Exposures)
IV. Tranquilizers  Habituating and Additive : In combination with alcohol
they may cause a person to loose consciousness.
E.g..
Diazepam etc..  In high doses, can lead to coma and death
 Workers may become drowsy as a result of exposure to
tranquilizers and barbiturates.

25. Specific Health Hazards related to drugs & pharmaceuticals
Hazards Occupational Health effects
(Drug Exposures)
V. Anti Depressants Mostly affects the heart leading to
E.g.  Irregular heartbeat (cardiac arrhythmias) precipitating
Amitriptyline heart conditions in production workers
Nortriptyline,
Imipramine

26. Standards for Exposure Prevention
NO OSHA standards regulating exposure to pharmaceuticals.
NO Threshold Limit Values (TLVs) for pharmacologically active substances
(except for acetylsalicylic acid -- a value of 5 mg/m3, 1979).
Now and then threshold limits are recommended for pharmaceuticals by research
workers, mostly in the former USSR.
The almost complete absence of official data shows that it is necessary to reduce
exposures to the lowest possible levels (ALARP)

27. Studies
Some researchers have concluded that it is difficult to evaluate causes of morbidity
in pharmaceutical workers because manufacturing processes and additives differ
between factories and exposures are to multiple chemicals.
Mortality
1. A 1988 study of 826 pharmaceutical workers (USA) found increased death risk
from cancer and suicide.
Men had elevated rates of CA Colon, Kidney & CNS.
Women had elevated rates of CA Breast.
Morbidity
Many workers develop allergic reactions to medicinals that involve
Bronchial sensitivity, Asthma & difficulty in breathing.
It is difficult to evaluate morbidity in pharmaceutical workers because of the wide
diversity of chemicals used in the manufacturing process.

28. Limitations of Studies :
1. Workers can be exposed to more than one drug at a time and the effects of
multiple exposures are not known.
2. The effects of short exposures to a variety of drugs may be very different from
the effects of longer exposures to only one or two drugs.
3. The routes of absorption are different. The respiratory system and skin are the
main routes of entry for pharmaceuticals in the workplace.
4. The gastrointestinal tract and other internal routes are the normal routes of entry
for pharmaceuticals in patients. Practically no research has been conducted on
the relationship between external dose, internal dose, and effects.

29. References :
 ILO Encyclopedia of Occupational Health and Safety (4th Edition)
Chapter 79 – Pharmaceutical Industry
 Wikipedia Web Dictionary : Occupational Health Hazards in Drugs &
Pharmaceuticals Industry.