PHARMACEUTICAL INDUSTRY Prepared by A.Erenşah Kaya Hande Kartal Merve Maçin Züleyha Atlay.
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Transcript of PHARMACEUTICAL INDUSTRY Prepared by A.Erenşah Kaya Hande Kartal Merve Maçin Züleyha Atlay.
PHARMACEUTICAL INDUSTRY
Prepared by
A.Erenşah KayaHande KartalMerve MaçinZüleyha Atlay
OUTLINE
Description of Pharmaceutical Industry
- Hıstory of Pharmaceutical Industry in Turkey
- Acts and Standards
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.
Description of Industry
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
The Major Manufactured Groups
The products are available as :
tablets capsules liquids ointments aerosols
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
History of Pharmaceutical Industry In Turkey
1928-1950: Production of Pharmaceutical preparations done at laboratories
1952: The start of fabrication period of the Turkish Pharmaceuticals industry
1984-1990: 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.
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)
History of Pharmaceutical Industry In Turkey
Turkish Manufacturers:
EIS Eczacıbaşı Abdi İbrahim Fako İlsan İltaş Mustafa Nevzat İbrahim Ethem Bilim
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
Additional Product Preparation
Steps are:
Granulation Drying Tablet pressing Printing Coating Filling and packaging
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.
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 ( 04.09.1998)
ACTS & STANDARDS
The Control of Water Pollution Management
Discharge Standards For Pharmaceutical
TABLES FROM EPA
Processes In Pharmaceutical Industry
Goods Receiving Laboratory Preparation Formulation Finishing Packaging Warehouse & Distrubituon
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.
Goods receiving
Laboratory
laboratory management means proven solutions for access control,
building automation, and risk management to ensure constant and secure environmental conditions in lab.
Laboratory
Research & Development
Including several fields;
chemical research, microbiological research, pharmacological research
Produces different waste types
Preparation
The production process, for example, depends on being able to process the correct
amounts of the right raw materials at the right time
Preparation
Chemical Synthesis
Most drugs production
Chemical synthesis process
manufacturing pharmaceuticals using
organic and inorganic chemical reactions
Typical manufacturing plant,
one or more batch reactor vessels series of reaction,
separation and purification steps desired end product
In drug manufacturing plant,
reaction vessels Equipments arranged into separate
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.
Some solvents also control the reaction temperature.
common practice in a batch-type synthesis
Natural Product Extraction
Many materials as pharmaceuticals derived from such natural sources; the roots, leaves of plants, animal glands, and parasitic fungi
numerous and diverse pharmaceutical applications, ranging from
Tranquilizers and allergy-relief medications Insulin and Morphine Blood fractionation plasma and its
derivatives.
Despite diversity, all extractive pharmaceuticals common
characteristic: Too complex to synthesize commercially either very large molecules to synthesize
Extraction expensive manufacturing process
requires collecting and processing large volumes of specialized plant animal matter to produce small quantities of products.
Fermentation
Most antibiotics ,steroids and vitamin B fermentation process,
two major steps: inoculum and seed preparation fermentation, followed by crude product
recovery and purification
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.
For further propagation, the cells are then transferred to
Seed tanklike 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.
Formulation
Formulation
Pharmaceutical formulation is the preparation of dosage forms such as
Tablets Capsules Liquids Parenterals Creams Ointments
Finishing
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.
Packaging
Warehouse & Distribution
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.
Typical Waste Streams
The pharmaceutical industry is also highly diverse.
With this diversity of processes comes a similarly diverse set of waste streams.
spent fermentation broths, process liquors, solvents, equipment washwaters, spilled materials, off-spec products, used processing aids.
Potential Environmental Issues
Air emissions Wastewater Solid and hazardous wastes
Air emissions
Volatile organic compounds(VOCs) Acid gases Particulates Greenhouse gas emissions (Combustion
Source Emissions) Odors
emitted during manufacturing facilities
Volatile Organic Compounds
significant emissions of VOCs come from
1) Mostly in chemical synthesis and extraction phases
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.
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.
How can we control the VOCs emissions?
1) Venting of emissions from sterilization chambers into control devices such as
carbon adsorption
OR
catalytic converters;
2) Condensation and distillation of solvents emitted from reactors or distillation units.
Possible installation of cryogenic condensersthat can reduce the gas stream temperaturebelow dew point to achieve higher VOC recovery efficiencies. Cryogenic condensers have higher removalefficiency (up to 99 percent) but they have higher energy requirements.
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 inorder 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.
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.
Recommended particulate matter management :
Collection of particulates through air filtration units, typicallybaghouse / 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, especiallyafter combustion / thermal oxidation treatments.
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.
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 withpractices as described in the regulations. Use of wet scrubbers to remove odors with a high
affinity to water;
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
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.
Treatment of solid wastes
Contaminated solid wastes are generally incinerated,and the flue gases are scrubbed.
Combustion devices should be operated at temperaturesabove 1,000° C, with a residence time of at least 1 second,to achieve acceptable destruction efficiency(over 99.99%) of toxics.
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.
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.
WastewaterIndustrial 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.
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.
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
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,
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
biological nutrient removal for reduction in nitrogen and phosphorus
using clarifiers; biological treatment, typically aerobic treatment for reduction of soluble organic matter (BOD)
biological nutrient removal for reduction in nitrogen and phosphorus
chlorination of effluent when disinfection is required
dewatering and disposal of residuals in designated hazardous waste landfills.
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
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),
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.
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,
Recirculate cooling water, Use dedicated dust collectors to recycle
recovered materials, Vent equipment through a vapor recovery
system, Use loss-free vacuum pumps,
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,
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.
References
http://www.cygm.gov.tr/mevzuat/yonetmelik/DKYD5.doc http://www.epa.gov/waterscience/guide/pharm/techdev/
ch5.pdf http://209.85.129.132/search?
q=cache:oY_mrWym7BUJ:en.wikipedia.org/wiki/Validation_(drug_manufacture)+drug+production+process&cd=4&hl=tr&ct=clnk&gl=tr
http://www.automation.siemens.com/pharma/html_76/process/pro_manu_07.htm
http://www.ifc.org/ifcext/enviro.nsf/AttachmentsByTitle/gui_pharmmfg_WB/$FILE/pharma_PPAH.pdf