Insights into the

Pharmaceutical
Effluent
Treatment A Key to Check
Plant Antibiotic Pollution

NOVEMBER 2021
Research Team

Supervised by

Piyush Mohapatra ([email protected])

Report and Study by

Dr. Omkar Gaonkar ([email protected])

About Toxics Link

Set up in 1996, Toxics Link is an Indian environmental research and advocacy

organization engaged in disseminating information to help strengthen the campaign
against toxics pollution, provide cleaner alternatives and bring together groups
and people affected by the problem. Toxics Link’s Mission Statement is: “Working
together for environmental justice and freedom from toxics.”

We have taken upon ourselves to collect and share both information about the
sources and the dangers of toxins in our environment and bodies, and information
about clean and sustainable alternatives for India and the rest of the world. The
unique expertise of organization lies in the areas of hazardous, medical and
municipal waste, international waste trade, and the emerging issues of pesticides,
Persistent Organic Pollutants (POPs), hazardous heavy metal contamination etc. from
the environment and public health point of view. We have successfully implemented
various best practices and have brought in policy changes in the aforementioned
areas apart from creating awareness among several stakeholder groups.

Copyright @ Toxics Link, 2021

All rights reserved

For further information

Toxics Link
H2 (Ground Floor), Jungpura Extension
New Delhi-110014, India
Phone: +91-11-24328006, 24320711
Fax: +91-11-24321747
www.toxicslink.org
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

Contents
1. Introduction 1
1.1 What is Effluent Treatment Plant (ETP)? 2
1.2 Need for Effluent Treatment Plant (ETP) 2
1.3 Effluent Treatment Plant (ETP) vs Sewage Treatment Plant (STP) 2
1.4 Design of ETP 3

2. Treatment levels & Mechanisms of ETP 5

3. Pharmaceutical industry and Effluent Treatment Process 7

3.1 Challenges associated with treatment of pharmaceutical effluents 9
3.2 Why conventional ETPs are not successful at treating drug residues? 9
3.3 Zero Liquid Discharge in Pharmaceutical Industries 11

4. Emerging technologies for treatment of pharmaceutical wastewater 13

4.1 Membrane separation processes 13
4.2 Advanced oxidation processes 13
4.3 Hybrid Technologies 14

5. Pharmaceutical wastewater treatment for removal of APIs: International case-studies 15

6. Recommendations for pharmaceutical effluent treatment and reducing pharma pollution 17

Suggested Resources 17
Annexure 18

III
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

IV
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

01 Introduction

Water is an essential component of multiple processes

in different manufacturing industries. Water is used
as a coolant, solvent or in many industrial chemical or
biological reactions. After the manufacturing process
is completed, wastewater is produced as a
byproduct. This wastewater contains various toxic
materials, depending on the type of wastewater.

The adoption of the Further depending upon the type of industry

stringent Water and the manufacturing process, the toxicity of
(Prevention and wastewater varies accordingly. Therefore, it
Control of Pollution) cannot be directly disposed to the environment
Act, 1974 by the Govt
and has to be treated to remove the harmful
of India has put
materials from it. The adoption of the stringent
a mandate on the
Water (Prevention and Control of Pollution) Act,
industries to install
1974 by the Govt of India has put a mandate on
Effluent Treatment
the industries to install Effluent Treatment Plant
Plant (ETP).
(ETP).

1
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

1.1 About Effluent Treatment Plant (ETP)

ETP is defined as a process design for treating the industrial wastewater

for its reuse or safe disposal to the environment. The untreated wastewater
entering the ETP or wastewater treatment plant is known as influent and
the treated wastewater is known as effluent. Different industries have
varying wastewater composition and require different ETP designs to
treat their effluents. Apart from the industries, there are growing
requirements of ETPs in non-industrial processes including hotels,
housing society and hospitals, etc.

1.2 Need for Effluent Treatment Plant (ETP)

ETP
Influent Effluent

01 Treatment (or cleaning) of industrial effluent and recycling it for further use

02 Reduction in the usage of fresh or potable water in industries

03 Reduction in expenditure on water procurement

04 Complying with the standards for discharge of environmental pollutants from

various industries set by the government

05 Safeguarding environment against pollution and contributing to sustainable

development
The Ministry of Environment,
1.3 Design of ETP Forest and Climate Change
(MoEF & CC), Government of
The design and size of any ETP depends on the quantity and quality of India has launched the centrally
discharge effluents from the industries. It also depends on the land and sponsored scheme, namely,
fund availability for construction, design and maintenance. Common Effluent Treatment
Plant (CETP) in order to make
a cooperative movement of
Generally, small-scale industrial facilities face problems in setting
pollution control especially, to
up individual ETPs due to lack of space, resources, capital cost, and
treat the effluent, emanating
specialized manpower for operation and maintenance. In such cases,
from the clusters of compatible
Common Effluent Treatment Plant (CETP) is preferred over ETP. CETP are
small-scale industries.
treatment systems specifically designed for collective treatment of effluent
generated from small-scale industrial facilities in an industrial cluster.1 CETP
helps small scale units in terms of land conservation, better treatment,

1. Padalkar A V., Kumar R. Common effluent treatment plant (CETP): Reliability analysis and
performance evaluation. Water Sci Eng. 2018;11(3):205-213. doi:10.1016/J.WSE.2018.10.002

2
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

easy operation and maintenance, and shared expenses. The Ministry of

Environment, Forest and Climate Change (MoEF & CC), Government of
India has launched the centrally sponsored scheme, namely, Common
Effluent Treatment Plant (CETP) in order to make a cooperative movement
of pollution control especially, to treat the effluent, emanating from the
clusters of compatible small-scale industries.2

1.4 Difference between Effluent Treatment Plant (ETP) and

Sewage Treatment Plant (STP)

There is an inherent confusion between Effluent Treatment Plant (ETP) and

Sewage Treatment Plant (STP). Therefore, it is important to understand that
there are two broad categories of wastewater treatment processes based
on their usages in different settings. Sewage is wastewater generated
from residential areas like community whereas industrial effluent is waste
water generated from various industries. The process treating industrial
effluents is known as ETP, while that employed for sewage treatment is
known as STP.

The major differences between ETP and STP are highlighted below

Effluent Treatment Plant (ETP) Sewage Treatment Plant (STP)

ETP is the process of removal of toxic and non-toxic STP is the process of removal of contaminants from
chemicals from industrial wastewater wastewater and household sewage, both runoff
(effluents) and domestic

It uses primary, secondary and tertiary treatment It includes physical, chemical, and biological process-
technologies such as oil and grease chamber, floccula- es to remove physical, chemical and biological
tion and biological methodologies contaminants

Requires specialized staff for operations and mainte- Easy to operate

nance

ETP is also a preferred technology for pharmaceuticals, STP is generally preferred in case of household
chemicals, textiles and even hospitals because of the wastewater discharge and utilized in societies and
hazardous nature of wastewater apartments

2. Mondal P. Types of Wastewater Treatment Process: ETP, STP and CETP. Accessed
October 29, 2021. https://www.yourarticlelibrary.com/water/types-of-wastewater-treatment-
process-etp-stp-and-cetp/27418

3
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

4
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

02 Treatment levels &

Mechanisms of ETP
Treatment levels

An ETP is designed to treat physical, chemical and biological substances

present in the wastewater. The flowchart of a typical ETP is shown in Figure
1. Depending on the level of treatment required, an ETP is divided into four
different levels, each designed to remove a certain type of material in the
effluent as briefly discussed below:

• Preliminary treatment

Removal of physical waste (gross solids and materials that can be easily
collected) from the wastewater

Involves physical separation techniques (e.g., sedimentation, filtration,

etc.)

• Primary treatment
Removal of floating and settable materials, such as oil and grease and
organic matter

Involves both physical (same as preliminary level) and chemical processes

(e.g., chemical coagulation, flocculation, etc.)

• Secondary treatment
Removal of biodegradable organic materials and suspended matter

Involves both chemical (same as primary level) and biological processes

(e.g. suspended-growth and the attached-growth/fixed film processes)

• Tertiary treatment/Advance treatment

Final treatment (or polishing) to improve the wastewater quality before it
is reused, recycled or disposed to the environment

Removal of remaining organic and inorganic compounds using the

physical, chemical and biological processes (as summarized in the
previous levels) utilized together

Adds additional cost to the treatment process but produces high

quality effluent which can be reuse further for commercial and industrial
purposes

5
6
Figure 1. Flow chart of a typical ETP

Preliminary Primary Secondary Tertiary

Treatment Treatment Treatment Treatment

Air

Wasterwater Preliminary Primary Aeration Secondary Final

Disinfection
Influent Treatment Clarifier Tank Clarifier Effluent

Recycling of Activated Sludge

Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

Primary Sludge

Waste Activated Sludge

To Sludge Treatment and

Disposal
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

03 Pharmaceutical
industry and
effluents
The pharmaceutical industry manufactures thousands of drugs or active
pharmaceutical ingredients (APIs) for a range of treatment applications
including cancer therapy, antidepressants, steroids, antibiotics, etc.
Increase in global demand for drugs has made pharmaceutical industry
one of the major 26 polluters of solid wastes and effluent into the
environment.3 While the extent of the impact of pharmaceutical pollution
on humans, animals, and the environment is the topic of ongoing research,
antibiotic APIs have been linked to the growing problem of antimicrobial
resistance (AMR) and the rise of antibiotic-resistant superbugs.

Pharmaceutical industry can be divided into two

stages as per their manufacturing activity:

Active Pharmaceutical Ingredients (bulk active drugs)

A typical bulk drug manufacturing unit involves a series of reactions, separa-

tion and purification steps to make the desired end product. The bulk drug or
active pharmaceutical ingredient (API) then goes for formulation.

Finished Dosage Forms (Formulation)

Formulation means a medicine in the forms of tablets, capsules, liquids,

ointments processed out of or containing one or more bulk drugs.

3. Kumari V, Tripathi AK. Characterization of pharmaceuticals industrial effluent using GC–

MS and FT-IR analyses and defining its toxicity. Appl Water Sci 2019 98. 2019;9(8):1-8.
doi:10.1007/S13201-019-1064-Z

7
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

Pharmaceutical wastewater contains a high level of pollutants

because of the presence of non-biodegradable organic matter
such as antibiotics, other prescription drugs, non-prescription
drugs, animal and plant steroids, reproductive hormones,
betalactamides, anti-inflammatories, analgesics, lipid
regulators, anti-depressants, cytostatic agents, personal care
products, detergent metabolites, flame retardants, product
of oil use and combustion, and other broadly used chemicals,
i.e., spent solvents, reaction residues, used filter media, heavy
metals (such as lead, mercury, cadmium, nickel, and chromium),
and other pollutants.4 5 ,

4. Babaahmadi F, Dobaradaran S, Pazira A, Sajjad Eghbali S, Khorsand M, Keshtkar M. Data on metal levels in the inlet and outlet waste-
water treatment plant of hospitals in Bushehr province, Iran. Data Br. 2017;10:1-5. doi:10.1016/j.dib.2016.11.054
5. Singh A, Ramola B. Heavy Metal Concentrations in Pharmaceutical Effluents of Industrial Area of Dehradun (Uttarakhand), India. India J
Env Anal Toxicol. 2013;3(3):173. doi:10.4172/2161-0525.1000173

8
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

Pharmaceutical sector falls within the category of high polluting industries.

This sector generates strong wastewater having high chemical oxygen
demand (COD) which require proper disposal. Moreover, it also produces
hazardous waste which require effective treatment. As purity of the final
product is very important, pharmaceutical industry requires very high-
grade purity water apart from other raw materials for its manufacturing
process. The rejects (both unreacted and converted portion of raw
materials) contribute to major pollution load to pharmaceutical ETP.

A typical pharmaceutical industry involves several batch reactors to get

the required product and each reaction yields different kinds of pollutants
depending on particular reactants and processes. There are number of
streams with different characteristics from different sections of the plant
which may require segregation and corresponding treatment instead
of conventional end of pipe treatment system for combined effluent
(Annexure)
According to The Environmental
(Protection) Rules, 1986, the
3.1 Challenges associated with treatment of pharmaceutical
general standards for discharge effluents
of effluents from industries
are focused only on COD,
■ Highly diverse nature of pharmaceutical wastewater as the
Biochemical oxygen demand composition of raw materials varies widely for one class of
(BOD), suspended solids, products to another
heavy metals, etc. Most of the
pharmaceutical industries ■ Many pharmaceutical companies do not reveal the quantity
comply with these standards. and nature of toxic substances under a false impression of
However, there are no standards confidentiality of composition to escape from stringent pollution
for APIs in pharmaceutical control norms. Thus, without completely revealing the magnitude
of toxic substances, they continue to release pharmaceutical
effluents and therefore, the
wastes into the environment
industries do not monitor
or reveal these compounds. ■ Often, illogical mixing of industrial effluents and domestic sewage
Recently, MoEF&CC proposed in industries results in very complex wastewater which makes
standards for antibiotic residues treatment difficult
in the treated effluents, but the
draft is still to be notified.
3.2 Why conventional ETPs are not successful at treating
drug residues?

APIs are challenging to treat with conventional wastewater technologies

because they are chemically stable, often recalcitrant and non-
biodegradable. In many cases, conventional on-site pharmaceutical
ETPs are either ineffective at treating APIs or unable to treat APIs to the
levels required to minimize environmental impacts. There is a significant
concentration of antibiotics and other drugs which can kill microorganisms
involved in the biological treatment; therefore, biological treatment is
not effective in the removal of APIs from pharmaceutical wastewater.
Following are some important points to be taken into account in context
of conventional ETPs.

9
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

■ In line with current regulations, the existing ETPs are designed

to meet the requirements for BOD, COD and TDS but there is
no specific consideration with regards to API content or antibiotic
residues. Therefore, it is difficult to determine the removal
efficiency of APIs in the existing treatment technologies as there
are no standards yet and these compounds are not regularly
monitored

■ In some cases, it has also been observed that traces of

pharmaceutical products reappear in the treated water samples
from WWTP. This points to the failure of existing facilities in
complete removal of APIs.6

■ The existing treatment strategies are not only ineffective to treat

APIs completely but can also introduce other problems such as
formation of unknown pharmaceutical metabolites and resistant
bacteria

A few studies conducted till now have pointed out that the existing
technologies are not capable of treating API residues. A Toxics Link
study found Ciprofloxacin at 296 µg/L in the sample collected from secret
outlet discharging effluent to the river in the Baddi-Nalagarh industrial
zone, Himachal Pradesh.7 In the recent case of “Veterans Forum for
Transparency in Public Life v/s State of Himachal Pradesh & Ors”, the
inspection and compliance report submitted to the Hon’ble National
Green Tribunal clearly highlighted the inefficiency of CETP at Baddi in the
removal of APIs.8

The pharmaceutical industries in India have adopted various treatment

options i.e., Anaerobic Digesters, Activated Sludge Process (ASP), Electro-
coagulation followed by ASP, and tertiary treatment i.e., Multiple-effect
Evaporator (MEE) and Reverse osmosis (RO).9

ETPs are mandated in every Health

Care Facility to treat the wastewater
generated from the hospital in order
to comply with the effluent standards
prescribed under the Biomedical Waste
6. Hedgespeth M, Sapozhnikova Y, Pennington P, Clum A, Fairey A, Wirth E. Pharmaceuticals
and personal care products (PPCPs) in treated wastewater discharges into Charleston Har-
bor, South Carolina. Sci Total Environ. 2012;437:1-9. doi:10.1016/J.SCITOTENV.2012.07.076
7. Toxics Link. Pharmaceutical Pollution in India: An Emerging Concern.; 2020. Accessed
October 29, 2021. http://toxicslink.org/docs/Pharmaceutical pollution in India An emerging
concern.pdf
8. https://greentribunal.gov.in/sites/default/files/news_updates/Report%20of%20the%20
Joint%20Committee%20in%20OA%20No.%20136%20of%202020%20(Veteran%20
Forum%20for%20Transparency%20in%20Public%20Life%20Vs%20State%20of%20
HP%20&%20Ors.).pdf
9. https://cpcb.nic.in/openpdffile.php?id=UmVwb3J0RmlsZXMvMzAxXzE0NzEzNDM5ODJ-
fUGhhcm1hY2V1dGljYWxzIENlbnRyYWwgWm9uZS5wZGY=

10
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

Management (BMW) Rules, 2016.

Sources of wastewater in the hospital
are wards, laboratories, disinfectants,
floor washing, washing of patient area,
hand washing, laundry, discharge
of accidental spillage, firefighting,
bathroom/toilet, etc.10 The hospital
effluents may also contain drug
residues; however, the BMW Rules do
not focus on complete neutralization
of drug residues from hospital
wastewater before discharging.

3.3 Zero Liquid Discharge in Pharmaceutical Industries

Many pharmaceutical companies, especially in India, are considering

ways to minimize their liquid discharge. Therefore, some have adopted
a zero-liquid-discharge (ZLD) program for their facilities. ZLD is a closed-
loop cycle that minimizes or eliminates discharge of any liquid effluent
by recycling and treating all wastewater. With a ZLD system not initially
designed to fully deactivate antibiotic residues in the waste streams, as
well as lack of regular monitoring data, the effectiveness of the deployed
treatment technologies to eliminate APIs is not fully established.

Figure 2. A typical Effluent Treatment Plant with Zero Liquid Discharge

Stripper

High COD
MEE AFTD

Process
RO Reject

Low COD

ETP RO RO Permate

COD : Chemical Oxyegn Demand MEE : Multiple-effect Evaporator RO : Reverse Osmosis AFTD : Agitated Thin Film Dryer

10. Implementation Guidelines for Management of Healthcare Waste in Health Care Facilities,
MOEFCC

11
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

It should be noted that the requirement of high-quality standards in most

of the pharmaceutical industries are limiting the sector to do only partial
ZLD.11 Moreover, despite widespread awareness and National Green
Tribunal guidelines for adoption of ZLD, its use has been limited to units of
major multi-national companies.12

Although, a typical ETP with ZLD (as depicted in Figure 2), implies no liquids
are discharged from the manufacturing units, that does not mean the
pharmaceutical residues do not enter the environment. While one could
justify it by saying that since the manufacturing units are not discharging
any liquid waste, there is no possibility of any discharge of antibiotics
into the environment. However, there is no evidence to substantiate this
conclusion. Apart from the direct discharge of treated wastewater with
active ingredients into the environment, there are other possible sources
contributing to the problem, such as:

■ Discharge of API-rich wastewater during plant shutdowns

■ Discharge of APIs into the environment through storm water

drainage

■ Improper disposal of solid wastes into the environment

■ Re-use of treated wastewater within the premises of the

manufacturing facilities for horticulture

■ Accidental spills of concentrated waste streams within the

manufacturing facilities

11. http://sustainabilityoutlook.in/content/market/zero-liquid-discharge-outlook-indian-indus-
try-755079
12. https://www.downtoearth.org.in/blog/waste/zeroing-in-on-discharge-76089

12
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

04 Emerging
technologies
for treatment of
pharmaceutical
wastewater
4.1 Membrane separation processes

■ Promising technology for treatment of wastewater containing

APIs since it is able to produce a high quality permeate without
increasing its toxicity

■ Can be scalable, and applied to a broad range of contaminants

■ Nanofiltration is the most recently developed pressure driven

membrane separation process, and has been widely used in
aqueous systems such as the concentration of antibiotic aqueous
solutions

■ Other examples of relatively new and robust membrane

separation processes are forward osmosis, membrane distillation

4.2 Advanced oxidation processes

Advanced oxidation processes (AOPs), on the other hand, are found to

be most effective treatment technology for completely mineralizing the
pollutants to inorganic compounds, CO2 and water.13 AOPs are low cost,
easy to operate and effective options for treatment of pharmaceutical
wastewater and can also be coupled with biological or conventional
physico-chemical processes for designing cost effective solutions. These
processes are based on the generation of highly reactive hydroxyl
radicals which can rapidly oxidize the target pollutants non-selectively.14

13. Poyatos JM, Muñio MM, Almecija MC, Torres JC, Hontoria E, Osorio F. Advanced Oxidation
Processes for Wastewater Treatment: State of the Art. Water, Air, Soil Pollut 2009 2051.
2009;205(1):187-204. doi:10.1007/S11270-009-0065-1
14. Chelliapan S, Sallis P. Removal of organic compound from pharmaceutical wastewater
using advanced oxidation processes. J Sci Ind Res. Published online 2013. Accessed
October 29, 2021. https://www.semanticscholar.org/paper/Removal-of-organic-com-
pound-from-pharmaceutical-Chelliapan-Sallis/271af2d1d0beeec344d23a81bfb-
658b401a8f0b6

13
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

It has also been reported that the combinations of AOPs are more efficient
in removal of organic compounds than individual techniques.15

Some of the advanced oxidation processes that have the potential to

degrade APIs are:

■ Photocatalysis
■ UV or solar irradiation
■ Electrooxidation
■ Fenton and photo-Fenton processes
■ Wet air oxidation
■ Ultrasound irradiation and
■ Microwave treatment

4.3 Hybrid Technologies Most widely accepted way of

determining the presence of
Hybrid technologies involve combinations of one or more conventional/
pharmaceuticals, including
advanced treatment technologies for the complete eradication of
antibiotics, is based on
pharmaceutical contaminants.16 As none of the single treatment
technologies can remove all the target compounds, the use of hybrid
laboratory testing methods
technologies can help overcome this problem. The technology basically that involve physical separation
uses the conventional filtration step to remove any solid matrix and the and mass chromatography
sludge is removed for incineration. The clear wastewater is then treated techniques. USEPA Method 1694
by the different combination of processes. determines pharmaceuticals
in environmental samples
Some examples of hybrid technologies by high performance liquid
■ Two-phase anaerobic digestion (TPAD) system and a chromatography combined with
subsequential MBR mass spectrometry (HPLC/MS/
■ Ozonation (pretreatment) coupled with biological activated MS)
sludge treatment

15. Chelliapan S, Sallis P. Removal of organic compound from pharmaceutical wastewater using
advanced oxidation processes. J Sci Ind Res. Published online 2013. Accessed October 29,
2021. https://www.semanticscholar.org/paper/Removal-of-organic-compound-from-pharma-
ceutical-Chelliapan-Sallis/271af2d1d0beeec344d23a81bfb658b401a8f0b6
16. Patel S, Mondal S, Majumder SK, Das P, Ghosh P. Treatment of a Pharmaceutical Industrial
Effluent by a Hybrid Process of Advanced Oxidation and Adsorption. ACS Omega.
2020;5(50):32305-32317. doi:10.1021/ACSOMEGA.0C04139

14
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

05 Pharmaceutical
wastewater
treatment for
removal of APIs:
International case-
studies

Haupt Pharma (Germany)

Haupt Pharma in Germany is the biggest site for formulation of high

potential sexual hormones in Europe. In 8 formulation lines all types of
sexual hormones like 17α-ethynylestradiol (EE2) are formulated and
packed for final application. The wastewater from this industry is treated
by Advanced Oxidation Process developed by Belmar technologies,
UK (https://www.belmartechnologies.co.uk) to remove all hormones in a
proper way to release clear and clean water into the municipal sewer. The
treatment system was able to remove sexual hormones like EE2 from inlet
concentration of 10 to 100 mg/L to less than 0.01 mg/L in the outlet.

GSK (Singapore)

Amoxicillin manufacturing site of GSK in Singapore (https://www.gsk.com/

en-gb/contact-us/worldwide/singapore/) is one of the biggest sites for
production of antibiotics worldwide. It is a well-known fact that biological
treatment plants are not very capable of treating the strong wastewater from
antibiotic manufacturing lines which resulted in incineration of the waste
by GSK. The manufacturing site was in search for a more suitable process
to be applied for removal of target compounds from the contaminated
wastewater. A photo-oxidation pre-treatment system has been installed
based on the UV process at GSK for elimination of residual amoxicillin and
non-bio-available organics from the strong process wastewater. Due to
pre-treatment by photo-oxidation, the existing biological system at GSK is
also able to handle this wastewater.

15
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

Merck (Switzerland)

The pharmaceutical manufacturing site of Merck & Cie in Altdorf

Switzerland (https://www.merckgroup.com/ch-en) is producing an
antihypertensive containing a phenolic structure. The wastewater
generated in the facility was initially collected and sent to incineration for
significant costs. Later a process was successfully developed for treating
this wastewater by elimination of all aromatic structures, all solvents and
increasing bioavailability of the remaining organics. A recuperation system
was integrated into the UV-plant for achieving oxidation with highest
efficiency. Toxicity was found to be completely removed. Moreover,
installation of this unit was significant improvement for Merck combined
with huge cost saving.

Pharma Action (Germany)

The GMP compliant heparin processing plant of Pharma Action (Toennies

Group) (https://www.cphi-online.com/pharma-action-gmbh-comp245280.
html) has achieved a supply chain, in which the entire process: starting from
animal slaughter, extraction of prime raw material to the final refinement
into API occurs within a single company. The process wastewater is
treated with UV oxidation to break down the organic substances. With
this method, the treated water can be recovered and reused in the same
process.

Some other case studies

■ Axine’s (https://axinewater.com/industries/) electrochemical

advanced oxidation process (EAOP) technology is commercially
proven and capable of treating a diverse range of complex APIs
and/or organic pollutants to achieve the most stringent Predicted
No-Effect Concentration (PNEC) levels through multiple oxidation
mechanisms. This technology has been installed at many US
pharmaceutical manufacturing plants
■ Arvia’s Nyex™ Treatment Systems (https://arviatechnology.com/
pharmaceutical-residues/) have already successfully treated
challenging wastewaters containing pharmaceutical residues in
the UK, Europe and China from different sources

16
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

Recommendations for pharmaceutical

effluent treatment and reducing
pharma pollution
■ Use of hybrid technologies has been shown to successfully remove APIs. Therefore, a comprehensive
policy is necessary for upgradation of ETPs and CETPs to evaluate and adopt these technologies. Some
of the sustainable and effective technologies in operation in developed countries can be adopted. In
addition, various Indian research institutions can also be funded to develop indigenous treatment systems
■ A regulatory framework should be developed to frequently monitor effluents from pharmaceutical
industries and discharge bodies for API concentrations
■ The proposed standards for antibiotic residues in the treated effluents of the pharmaceutical industries
under the Environment (Protection) Amendment Rules, 2019 should be notified; following which, India will
become the first country in the world to have legally enforceable discharge limits for antibiotics in waste
from the pharmaceutical industry
■ Environment (Protection) Amendment Rules should also include discharge standards for other API
residues in addition to limits for antibiotic residues. Apart from antibiotic residues, the regulatory body
should also come up with discharge standards for other API residues. The discharge standards can be
formulated based on the PNEC values for these compounds

Suggested Resources

1. Gadipelly C, Pérez-González A, Yadav GD, et al. Pharmaceutical Industry Wastewater: Review of the
Technologies for Water Treatment and Reuse. Ind Eng Chem Res. 2014;53(29):11571-11592. doi:10.1021/
IE501210J
2. United States Environment Protection Agency (US EPA). Economic Analysis of Final Effluent Guidelines
and Standards for Pharmaceutical Manufacturing Category - 1998.; 1998. Accessed October 29, 2021.
https://19january2017snapshot.epa.gov/sites/production/files/2015-11/documents/pharmaceutical-
manufacturing_economic-analysis_1998.pdf
3. Organisation for Economic Co-operation and Development (OECD). Pharmaceutical Residues in
Freshwater: Hazards and Policy Responses. OECD; 2019. doi:10.1787/C936F42D-EN
4. Caldwell DJ, Mertens B, Kappler K, et al. A risk-based approach to managing active pharmaceutical
ingredients in manufacturing effluent. Environ Toxicol Chem. 2016;35(4):813-822. doi:10.1002/ETC.3163
5. Nyagah DM, Njagi A, Nyaga MN. Pharmaceutical waste: overview, management and impact of improper
disposal. J PeerScientist. 2020;3(2). Accessed October 29, 2021. https://www.peerscientist.com/volume3/
issue2/e1000028/pharmaceutical-waste-overview-management-and-impact-of-improper-disposal.pdf?_
ga=2.99485021.2124854435.1635485271-426220115.1635485271
6. Pal P. Treatment and Disposal of Pharmaceutical Wastewater: Toward the Sustainable Strategy.
2017;47(3):179-198. doi:10.1080/15422119.2017.1354888
7. Kosek K, Luczkiewicz A, Fudala-Książek S, et al. Implementation of advanced micropollutants removal
technologies in wastewater treatment plants (WWTPs) - Examples and challenges based on selected EU
countries. Environ Sci Policy. 2020;112:213-226. doi:10.1016/J.ENVSCI.2020.06.011
8. Martínez F, Molina R, Rodríguez I, Pariente MI, Segura Y, Melero JA. Techno-economical assessment of

17
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

coupling Fenton/biological processes for the treatment of a pharmaceutical wastewater. J Environ Chem
Eng. 2018;6(1):485-494. doi:10.1016/J.JECE.2017.12.008
9. Angeles LF, Mullen RA, Huang IJ, et al. Assessing pharmaceutical removal and reduction in toxicity provided
by advanced wastewater treatment systems. Environ Sci Water Res Technol. 2019;6(1):62-77. doi:10.1039/
C9EW00559E

Annexure: Different processes and wastewater generated in each process of the pharmaceutical industry

Process Inputs in the processes Wastewater

Reaction Solvents, catalysts, reactants, Process wastewaters (high
(e.g. benzene, chloroform, di- BOD, COD and TSS) with spent
chloromethane, toluene, meth- solvents, catalyst, reactants
anol, ethylene glycol, xylenes
and hydrochloric acid)

Separation Separation and extraction Spills, leaks, spent solvents

solvents (e.g. methanol, toluene,
acetone and hexanes)

Purification Purification of solvents (e.g. Spills, leaks, spent solvents

methanol, toluene, acetone and
hexanes)

Drying Finished active drug and inter- Spills, leaks, spent solvents
mediates

Natural product extraction Plant roots, animal tissues, ex- Equipment cleaning, spills,
traction solvents (e.g. ammonia, leaks, spent solvents (low BOD,
chloroform and phenol) COD and TSS)

Fermentation Inoculum, sugar, starches, Spent fermentation broth,

nutrient, phosphates, fermenta- wastewater containing sugar,
tion solvents (e.g. ethanol, amyl nutrients, etc. High BOD, COD
alcohol, methanol, acetone, etc.) and pH 4–8

Formulations Active drug, binders, sugar Equipment cleaning, spills,

syrups, etc. leaks, spent solvents (low BOD,
COD and TSS)

18
Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

19
 Insights into the Pharmaceutical Effluent Treatment Plant: A Key to Check Antibiotic Pollution

H2 (Ground Floor),
Jungpura Extension,
New Delhi - 110014
India
Tel: 91-11-24328006, 24320711
Fax: 91-11-24321747

https://www.instagram.com/toxics_link/

https://www.facebook.com/toxicslink

https://twitter.com/toxicslink

https://www.youtube.com/user/toxicslink2012

www.toxicslink.org

20