Waste generation in pharmaceutical manufacturing industry
1. WASTE GENERATION IN
PHARMACEUTICAL MANUFACTURING
INDUSTRY
by
Vishal Duggal
Alliance Engineers
7812/5, Passi Road, PATIALA (Punjab).
Ph.: 98 140 059 33
email: visduggal@gmail.com; mailto@allianceers.com
for
CESE, IITB
Powai, Mumbai (MS)
2. PHARMACEUTICAL INDUSTRY
Medications/therapeutic products for humans and
animals
Manufacture, extraction, processing, purification and
packaging of chemical materials (may include
following);
Medicinal chemicals and botanical products
Pharmaceutical active ingredients – resulting from
fermentation, biological and natural extraction, chemical
synthesis, and formulation products
Biological (and micro-biological) products
Multiple end-use products – components of formulations,
intermediates, final products
Cosmetic preparations – containing pharmaceutically active
ingredients (typically intended for treatment of some skin
condition)
3. PHARMACEUTICAL INDUSTRY
Products or activities specifically excluded from
pharmaceutical manufacturing category are;
Surgical and medical instruments and apparatus
Orthopaedic, prosthetic, and surgical appliances and supplies
Dental equipment and supplies
Medical/dental laboratory services
Diagnostic devices
Food and beverage products fortified with vitamins or other
pharmaceutical active ingredients
5. Pharmaceutical Processes
(Fermentation)
Manufacturing of most antibiotics, steroids, enzymes,
hormones, vitamins, etc.
Three basic steps
Inoculum and seed preparation
Fermentation (including mycelia filteration)
Product recovery
Fermentation is a large scale batch process
Usually begins with a water wash and steam
sterilisation of fermenter vessel
Usually an exothermic process and needs temperature
control
Product recovery – solvent extraction, direct
precipitation, ion exchange, adsorption
Sterilisation – steam is major medium, chemical also
6. Pharmaceutical Processes
(Fermentation) ..
Fermentation waste off-gases – CO2 and odiferous
substances (e.g., oxides of N and S)
Scrubbing water from APCE – absorbed chemicals, soluble
organic compounds, insoluble organic oils and waxes
Solvents used – recovered and reused
Small fraction of solvents left in aquous phase
Direct precipitation – Cu and Zn are commonly used
priority pollutant metals
Occassional infestation of fermentation batch by “phage” –
large amount of wastewaters in very short time (very high
nutrient concentration)
Spent fermentation broth – sugars, starches, proteins, N,
phosphates
Sterilizing/cleaning rejects
8. Pharmaceutical Processes
(Biological and Natural Extraction)
Products derived from natural sources – roots/leaves of
plants, animal glands, parasitic fungi, etc.
Also include blood fractionation – production of plasma
and its derivatives
These are too complex to synthesize commerically
Usually requires collection and processing of large
quantities of specialised plant or animal matter to produce
small quantities of products
Active ingredients extracted are generally present in raw
materials at very low levels
Series of steps – volume of material in process reduces
significantly after almost every step
Mostly, a unique assembly-line, small-scale batch
processing
9. Pharmaceutical Processes
(Biological and Natural Extraction)…
Residual wastes mostly equal to weight of raw materials
Solid wastes are greatest source of pollutant load
Use of solvents in processing steps (sometimes used to
decontaminate material)
Detergents and disinfectants used in equipment cleaning –
wastewater – use of phenols is prevalent
Metals (Pb, Zn, etc.) used as precipitating agents
Some extraction processes use ammonia where pH control
is necessary
Principal sources of waste include;
Spent raw material
Chemical wastes
Equipment and floor cleaning
Cleanup of spills
11. Pharmaceutical Processes
(Chemical Synthesis)
Use organic and inorganic chemical reactions
Most of the active ingredients marketed/sold as drugs
Conventional batch reaction vessel
Reaction vessels may be fitted with different attachments –
depending on process needs
Common modifications for additional uses;
Heating/refrigeration medium
Reflux condensation equipment
Vacuum
Perform solvent extraction/crystallization operations
Common attachments – filter, centrifuge, solvent recovery
header, etc.
Usually product is manufactured in a “campaign”
Same equipment can be utilized for manufacturing
different products
13. Pharmaceutical Processes
(Chemical Synthesis) …
Most of the industries have solvent recovery units
SRU operation result in aqueous wastes fully or partially
saturated with residual solvent
Wastewater is generally produced with each chemical
modification – requiring filling and emptying of reactors
Wastewaters contain – unreacted raw materials, some
solvents, along with number of compounds
The pollutants vary w.r.t. toxicity and biodegradability
Principal sources of waste include;
Process wastes – spent solvents, filtrates, concentrates, etc.
Pump seal water
Equipment and floor cleaning
Spills
APCE blowdown
15. Pharmaceutical Processes
(Mixing, Compounding & Formulating)
Converting pharmaceutical active ingredients (produced
in bulk) to dosage (usable) form for consumer use – tablets,
capsules, liquids, and ointments
Tablets – need blending with filler and binder (lubricants
also sometimes). Some tablets use solvent based coatings
Capsules use hard gelatine shell
Liquid preparations are formulated for injection or oral use
Need sterilization sometimes
Principal sources of waste include;
Equipment and floor cleaning
Spills and breakage
Broken tablets – reused in granulation
Improper capsules – remelted and reused or sold for glue
manufacture
16. Pharmaceutical Manufacturing Process
Variability
Waste generation (quantitatively and qualitatively) can be
highly variable
Factors contributing to variability
Campaigning
Batch processing
Waste commingling
17. Utilities in Pharmaceutical
Manufacturing
Water treatment – RO, DM, EDI, etc.
Compressed air
Process heating – steam generation/distribution, thermic
fluid heater
Process cooling – cooling water, chiller, brine-water
Work environment conditioning
Cleaning – including CIP
Air pollution control equipment
Vacuum system
Solvent recovery
Effluent treatment
Thermal destruction – incineration, MEE, drier
18. Water Use and Wastewater generation
in Pharmaceutical Manufacturing
As product – becomes a part of final product
Water of reaction – water formed during chemical reaction
Process solvent – used to transport or support chemicals
involved in reaction process
Water is usually removed – centrifugation, decanting, filtration,
drying, stripping, etc.
Process stream wash
Product wash
Spent acid/caustic
Condensed steam
APCE blow-down
Process cleaning, washing and housekeeping
Pump seal water
Non-contact cooling blow-down
19. Wastewater Characterization
Mixing, compounding and formulation
May contain carbohydrates and inert formulating material
Low to moderate in BOD
Low TSS
Around neutral pH
Fermentation
~2-10 m5/kg of final product
Mycellium cake – wet cake has 40-70 g/l of BOD and 30-50 g/l
of TSS
BOD – 2500-1000 mg/l
pH – 4-8
Vaccination, microbial suspension, antitoxin preparation
Wastes contain very high BOD/COD and bad odours
Antiseptic and anti-bacterial agents contribute to toxicity
20. Wastewater Characterization …
Chemical synthesis
General process liquor
High strength process liquor
Acidic and alkaline effluent
Emulsified effluent
Toxic effluent
21. Composition of Pharmaceutical Process
Wastes
Waste Description Process Origin Composition
Process liquors Chemical synthesis Contaminated solvents
Spent fermentation
broth
Fermentation processes Contaminated waters
Spent natural product,
raw materials
Natural product,
extraction processes
Plant residues, tissues
Spent aqueous solutions Solvent extraction
processes
Contaminated water
Leftover raw material,
containers
Unloading of materials
into process equipment
Bags/drums (fibre,
plastic, metal), plastic
bottles
Scrubber water from
APCE
Dust or hazardous
vapour generation
process
Contaminated water
22. Composition of Pharmaceutical Process
Wastes …
Waste Description Process Origin Composition
Volatile organic
compounds
Chemical storage tanks,
drums
Solvents
Off-spec or out-dated
products
Manufacturing
operations
Miscellaneous
chemicals
Spillages Manufacturing and
laboratory operations
Miscellaneous
chemicals and heavy
metals
Wastewater Equipment cleaning,
extraction residues
Contaminated water,
phenol based
Spent solvents Solvent extraction or
wash practices
Contaminated solvents
Used production
materials
Manufacturing
operations
Filters, tubing,
diatomaceous earth
23. Composition of Pharmaceutical Process
Wastes …
Waste Description Process Origin Composition
Used chemical reagents R&D activities Miscellaneous
chemicals, solvents,
acid/alkaline wastes,
radio-isotopes,
formaldehyde
Spent ethylene oxide Sterilization operations Ethylene oxide
Miscellaneous wastes Maintenance operations Waste lube oils,
vacuum pump oils,
cleaning solvents, paint
stripping wastes,
leftover paints and
accessories, spent
flourescent lamps, trash
24. Composition of Pharmaceutical Process
Wastes …
Waste Description Process Origin Composition
Used packaging
material
Packaging operations Plastic, wood,
cardboard, foam
products
Infectious/medical
wastes
R&D, manufacturing
operations, off-spec
products
Vials, biomass, blood
products, human/animal
specimens
Incinerator exhaust On-site incinerators Metals, oxides
Combustion products Boilers, thermic fluid
heater
Carbon compounds,
oxides of N & S, boiler
blow-down, cooling
tower sludges, and
sediments
25. Conventional approach;
Waste collection
Treatment for compliance (and to make the waste
compatible for disposal)
Dispose
Alternative thoughts;
Cheapest available solution just avoiding prosecution
Best available solution not entailing excessive cost
Waste Management
Spend resources or face penalty
26. Source Reduction
Material substitution
Process modification
Good operating practices
Waste Management
(Waste Minimization)
27. Waste Management
(Waste Minimization) …
Waste Waste Minimization Option
Containers Return empties to suppliers
Thoroughly empty and triple rinse with minimal water
Use containers with recyclable liners
Segregate solid waste
Collect and reuse plastic from in-house molding
Air
emissions
Control bulk storage air emissions
Use dedicated dust collectors & rework dust back into product
Optimize fossil fuel combustion
Use dedicated vent condensers & return condensate to source,
where possible
Maintain N2 purge rates at minimum through vapour space of
agitated reactors
28. Waste Management
(Waste Minimization) …
Waste Waste Minimization Option
Equipment
cleaning
wastes
Maximize number of campaigns to reduce cleaning frequency
Use final rinse as pre-rinse on next cleaning cycle
Use wiper blades & squeezes and rework remainders into
products
Use low volume, high efficiency cleaning (e.g., spray heads)
Spills and
area
washdown
Use dedicated vacuum systems
Use dry-cleaning methods
Use recycled water
Off-spec
products
Rework off-spec material
Use automated processing systems
29. Waste Management
(Waste Minimization) …
Waste Waste Minimization Option
Solvents Substitute with aqueous systems where possible
Reduce quantity of solvent used
Regenerate/recover spent solvent
Production
materials
Validate cleaning and reuse
30. Waste Management
(Good Operating Practices)
Plant Management Waste Management Material handling
Management incentives Waste/environmental
audits
Material tracking &
inventory control
Employee training Waste stream
segregation
Spill prevention
Closer supervision Waste handling and
storage procedures
Material handling &
storage procedures
Production scheduling Preventive maintenance
Additional
documentation