1. PHARMACEUTICAL INDUSTRY
Prepared by
A.Erenşah Kaya
Hande Kartal
Merve Maçin
Züleyha Atlay

2. OUTLINE Description of Pharmaceutical Industry
- Hıstory of Pharmaceutical Industry in Turkey
- Acts and Standards

3. Description of Industry
The Pharmaceutical Industry provides medicines to
be used as medications for humans and animals.
The Pharmaceutical Industry includes:
Manufacture
Extraction
Processing
Purification
Packaging of chemicals to be used as medications.

4. Description of Industry

5. The Main Pharmeceutical Groups
The main groups that are manufactured are:
Proprietary ethical products ( prescription-only medicines POM)
General ethical products
Over-the counter (OTC) products

6. The Major Manufactured Groups
The products are available as :
tablets
capsules
liquids
ointments
aerosols

7. The Major Manufactured Groups
The groups include:
Antibiotics such as penicillin
Other synthetic drugs
Vitamins
Synthetic hormons
Glandular products
Vaccines and sera
Drugs of vegatable origin

8. History of Pharmaceutical Industry In Turkey
: Production of Pharmaceutical preparations done at laboratories
1952: The start of fabrication period of the Turkish Pharmaceuticals industry
: Investments of foreign capital companies increased. Foreign Capitals entered into Turkish Market
Today: There are 300 entities operating in Turkey. 43 manufacturing facilities, 14 of them are multinational firms.

9. History of Pharmaceutical Industry In Turkey
The most important international pharmaceutical companies are:
Bayer (Germany)
GlaxoSmithKline (UK)
Aventis (US)
Roche(Switzerland)
Sanofi (France)
Novartis( Switzerland)

10. History of Pharmaceutical Industry In Turkey
Turkish Manufacturers:
EIS Eczacıbaşı
Abdi İbrahim
Fako
İlsan İltaş
Mustafa Nevzat
İbrahim Ethem
Bilim

11. The Principal Manufacturing Step
Steps are:
Preparation of process intermediates
Introduction of functional groups
Coupling and esterification
Seperation processes such as washing and stripping
Purifications of the final product

12. Additional Product Preparation
Steps are:
Granulation
Drying
Tablet pressing
Printing
Coating
Filling and packaging

13. Industrial Pollution
According to manufacturing steps, air emissions, liquid effluents ( wastewater) and solid wastes may be generated.
To reduce the wastes, we should reuse and recycle. Remaning wastes should be treated according to characteristic.

14. ACTS & STANDARDS
The Production and marketing of medicines must be authorized by The Health Ministry.
Treated wastewater should be discharged; According to The Control of Water Pollution Management ( )

15. ACTS & STANDARDS The Control of Water Pollution Management
Discharge Standards For Pharmaceutical

17. TABLES FROM EPA

21. Processes In Pharmaceutical Industry
Goods Receiving
Laboratory
Preparation
Formulation
Finishing
Packaging
Warehouse & Distrubituon

22. Goods receiving pharmaceuticals are stored,
either in the form of raw materials or packaging.
It’s vital to optimally manage these materials, protect them from end to end,
and systematically document them.

23. Goods receiving

24. Laboratory
laboratory management means proven solutions for access control,
building automation,
and risk management to ensure constant
and secure environmental conditions in lab.

25. Laboratory

26. Research & Development
Including several fields;
chemical research,
microbiological research,
pharmacological research
Produces different waste types

27. Preparation The production process, for example,
depends on being able to process the correct amounts of the right raw materials at the right time

28. Preparation

29. Chemical Synthesis Most drugs production Chemical synthesis process
manufacturing pharmaceuticals using
organic and
inorganic chemical reactions

30. Typical manufacturing plant,
one or more batch reactor vessels series of reaction,
separation and purification steps desired end product

31. In drug manufacturing plant,
reaction vessels
Equipments arranged into separate

32. Solvents to dissolve
Gaseous
Solid
Viscous reactants
To bring all the reactants close molecular
also serve to transmit heat to or from the reacting molecules.

33. Some solvents also  control the reaction temperature.
common practice in a batch-type synthesis

34. Natural Product Extraction
Many materials as pharmaceuticals
derived from such natural sources;
the roots,
leaves of plants,
animal glands,
and parasitic fungi

35. numerous and diverse pharmaceutical applications, ranging from
Tranquilizers and allergy-relief medications
Insulin and
Morphine
Blood fractionation plasma and its derivatives.

36. Despite diversity,
all extractive pharmaceuticals  common characteristic:
Too complex to synthesize commercially
either very large molecules to synthesize

37. Extraction  expensive manufacturing process
requires collecting and processing large
volumes of specialized plant
animal matter
to produce small quantities of products.

38. Fermentation
Most antibiotics ,steroids and vitamin B fermentation process,
two major steps:
inoculum and seed preparation
fermentation, followed by crude product recovery and purification

39. Sterile inoculum preparation begins
in the lab with
carefully maintained population of a microbial strain.
A few cells this culture matured into a dense suspension through a series of test tubes, agar slants, and shaker flasks.

40. For further propagation, the cells are then transferred to
Seed tanklike a full scale fermenter and is
Designed for maximum cell growth
Final seed tank volume occupies
from 1 to 20% of the volume used in full scale production.

41. Formulation

42. Formulation
Pharmaceutical formulation is the preparation of dosage forms such as
Tablets
Capsules
Liquids
Parenterals
Creams
Ointments

45. Finishing

46. Finishing The best way to reliably drug finishing efficiency,
quality and transparency
is through consistent,
end-to-end automation solutions
can seamlessly integrate
components from a wide range of manufacturers.

47. Packaging

48. Warehouse & Distribution

49. Warehouse & Distribution
They’re efficient way stations on the road from manufacturer to consumer,
using the most precise and
up-to-date climate control,
automation, and
building security.

50. Typical Waste Streams
The pharmaceutical industry is also highly diverse.
With this diversity of processes comes a similarly diverse set of waste streams.

51. spent fermentation broths,
process liquors,
solvents,
equipment washwaters,
spilled materials,
off-spec products,
used processing aids.

52. Potential Environmental Issues
Air emissions
Wastewater
Solid and hazardous wastes

53. Air emissions Volatile organic compounds(VOCs) Acid gases Particulates
Greenhouse gas emissions (Combustion Source Emissions)
Odors
emitted during manufacturing facilities

54. Volatile Organic Compounds
significant emissions of VOCs come from
1) Mostly in chemical synthesis and extraction phases

55. 2) In primary pharmaceutical manufacturing ;
reactor vents
filtering systems in the separation process
Solvent vapors from purification tanks and dryers (including loading and unloading operations)
fugitive emissions from valves, tanks, pumps, and other equipment
prefermentation and fermentation solvents
wastewater collection and treatment units.

56. 3) In secondary pharmaceutical manufacturing;
mixing, compounding, granulation, and formulation
operations involving the use of solvents (e.g. granulation)
alcoholic solutions (e.g. tablet coating)
aerosol manufacturing processes.

57. How can we control the VOCs emissions?
1) Venting of emissions from sterilization chambers into control devices such as
carbon adsorption OR
catalytic converters;

58. 2) Condensation and distillation of solvents emitted from reactors or distillation units.
Possible installation of cryogenic condensers
that can reduce the gas stream temperature
below dew point to achieve higher VOC
recovery efficiencies.
Cryogenic condensers have higher removal
efficiency (up to 99 percent) but they have
higher energy requirements.

59. 3) Installation of wet scrubbers (or gas absorbers), which may remove VOCs as well as other gaseous pollutants from a gas stream.
Also, addition of hypochlorite to the scrubber in
order to reduce emissions of nuisance odors;
WHAT IS SCRUBBER?
Water, caustic, and acidic scrubbers are widely used for organic and inorganic gas emission reduction. Acid gas emissions are controlled through water and caustic scrubbing systems (often several scrubbersin series). Scrubbers create a wastewater stream requiring further treatment.

60. Particulate Matter
Particulates consisting of manufactured or in-process product can be emitted from
bulk (e.g. fermentation)
secondary manufacturing.
The most common sources of particulates
include milling, mixing,compounding,formulation,
tableting, and packaging.

61. Recommended particulate matter management :
Collection of particulates through air filtration units, typically
baghouse / fabric filters.
Depending on the volume of emissions and size of particulate matter,
additional particulate emissions control methods should be considered,
such as
Wet scrubbing and wet electrostatic precipitators, especially
after combustion / thermal oxidation treatments.

62. Combustion Source Emissions
Exhaust gas emissions produced by the
combustion of gas or diesel in turbines, boilers, compressors, pumps and other engines for power and heat generation, are a significant source of air emissions from pharmaceuticals manufacturing facilities.

63. Odors
The main source of odor emissions is typically associated with fermentation activities.
Recommended odor management strategies include:
Post-combustion of venting gases;
Use of exhaust stack heights that are consistent with
practices as described in the regulations.
Use of wet scrubbers to remove odors with a high affinity to water;

64. Solid and Hazardous Wastes
The principal solid wastes of concern include
process and effluent treatment sludges,
raw materials packaging waste
container residues
used air filter media
Offspec and expired products
laboratory wastes

65. Approximately 200 kg wastes per ton of
product of waste are generated.
Hazardous and non-hazardous industrial wastes should be stored, transported, and managed as described in the regulations.

66. Treatment of solid wastes
Contaminated solid wastes are generally incinerated,
and the flue gases are scrubbed.
Combustion devices should be operated at temperatures
above 1,000° C, with a residence time of at least 1 second,
to achieve acceptable destruction efficiency
(over 99.99%) of toxics.

67. Water Supply
Water is generally needed both for the process (e.g., dilution) and for other uses including cooling water, deionized water, equipment and piping cleaning water, etc.
Water for injection is used for manufacture of injectable products and in any process where sterile conditions are needed.

68. Water purity is obtained by deionized water distillation or by double reverse osmosis.
The storage tank is blanketed with pure nitrogen or air.
Piping and storage are maintained at a temperature higher than 80°C, and water is continuously recycled to avoid contamination.

69. Wastewater Industrial Process Wastewater
Wastewater streams in pharmaceuticals
manufacturing come from;
chemical reactions streams
product wash water
spent acid and caustic streams
condensed steam from sterilization and strippers
air pollution control scrubber release
equipment and facility wash water
clean-in-place wastewater.

70. The main pollutants of concern in these wastewater streams from
primary manufacturing (e.g.fermentation, chemical synthesis,
crystallization, purification, and biological / natural extraction)
parameters are
biochemical oxygen demand (BOD)
chemical oxygen demand(COD)
total suspended solids (TSS)
Ammonia
Toxicity
Biodegradability
pH.

71. Typical Wastewater Characteristic
Typical amounts released with the wastewater are:
25 kg/t (BOD)
50 kg/t (COD)
3 kg/t (TSS)
0.8 kg/t phenol

72. Wastewaters produced from pharmaceutical industry may contain :
mercury, in a range of 0.1–4 (mg/l),
cadmium (10–600 mg/l),
isomers of hexachlorocyclohexane,
1,2-dichloroethane,

73. Typical wastewater treatment steps
grease traps, skimmers, dissolved air floatation or oil water separators for separation of oils and floatable solids;
filtration for separation of filterable solids;
flow and load equalization;
sedimentation for suspended solids reduction
using clarifiers; biological treatment, typically aerobic treatment for reduction of soluble organic matter (BOD)
biological nutrient removal for reduction in nitrogen and phosphorus

74. biological nutrient removal for reduction in nitrogen and phosphorus
using clarifiers; biological treatment, typically aerobic treatment for reduction of soluble organic matter (BOD)
chlorination of effluent when disinfection is required
dewatering and disposal of residuals in designated hazardous waste landfills.

75. Additional engineering controls may be required for
advanced metals removal using membrane filtration or other physical/chemical treatment technologies
removal of recalcitrant organics and active ingredients using activated carbon or advanced chemical oxidation
residual color removal using adsorption or chemical oxidation
reduction in effluent toxicity using appropriate technology (such as reverse osmosis, ion exchange, activated carbon, etc.)
reduction in TDS in the effluent using reverse osmosis or evaporation

76. Pollution Prevention and Control
Recommended pollution prevention and control measures include:
Waste reduction by material substitution (e.g. use of water based solvents),
Process modifications (e.g. continuous rather than batch operations to reduce spillage and other material losses),

77. Spent solvent recycling and reuse, through distillation,evaporation, decantation, centrifugation and filtration,
Potentially pathogenic waste from biotechnology manufacturing should be inactivated through sterilization or chemical treatment before final disposal.

78. Use automated filling to minimize spillage,
Use “closed” feed systems into batch reactors,
Use equipment washdown waters and other process waters (such as leakages from pump seals) as makeup solutions for subsequent batches,

79. Recirculate cooling water,
Use dedicated dust collectors to recycle recovered materials,
Vent equipment through a vapor recovery
system,
Use loss-free vacuum pumps,

80. Return toxic materials packaging to the supplier for reuse, or incinerate it in an environmentally acceptable manner,
Minimize storage time of off-specification products through regular reprocessing,
Find productive uses for off-specification products to avoid disposal problems,

81. Use high-pressure hoses for equipment cleaning to reduce wastewater,
Provide stormwater drainage and avoid contamination of stormwater from process areas,
Label and store toxic and hazardous materials in secure, bunded areas. Spillage should be collected and reused.

82. References http://www.cygm.gov.tr/mevzuat/yonetmelik/DKYD5.doc