ISO 12370:2025

International
Standard
ISO 12370
First edition
Guidelines for treatment and
2025-01
reuse of fermentation-based
pharmaceutical wastewater
Lignes directrices pour le traitement et la réutilisation des eaux
usées pharmaceutiques issues de la fermentation
Reference number
© ISO 2025
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ii
Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms, definitions and abbreviated terms . 1
3.1 Terms and definitions .1
3.2 Abbreviated terms .2
4 Pollution loading . 2
4.1 Classification of wastewater .2
4.2 Wastewater volume .3
4.3 Quality of produced wastewater .4
5 General principles . 4
6 Wastewater treatment processes . 5
6.1 Pretreatment process .5
6.2 Biological treatment process .6
6.2.1 General .6
6.2.2 Hydrolysis acidification reactor .6
6.2.3 UASB reactor .7
6.2.4 Activated sludge process.7
6.2.5 IFAS process .7
7 Reclamation treatment processes . 8
7.1 General .8
7.2 Denitrification .8
7.3 Activated carbon adsorption .8
7.4 Coagulation precipitation .8
7.5 Membrane separation .9
7.6 High-efficiency sedimentation tank .9
7.7 Ion exchange .9
7.8 MBR.10
7.9 Fenton oxidation .10
7.10 Ozone catalytic oxidation.10
7.11 Ultraviolet disinfection .10
8 Example processes for wastewater treatment and reclamation .10
Annex A (informative) Pharmaceutical wastewater quality .11
Annex B (informative) Influent quality for membrane separation .13
Annex C (informative) Examples of treatment and reclamation processes for fermentation-
based pharmaceutical wastewater . 14
Bibliography . 17

iii
Foreword
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This document was prepared by Technical Committee ISO/TC 282, Water reuse, Subcommittee SC 4,
Industrial water reuse.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www.iso.org/members.html.

iv
Introduction
With the development of the social economy and the improvement of people's living standards, the
public's demand for drugs to improve the quality of life and prolong lifespan is continually increasing.
Pharmaceutical manufacturing ranks among the top five industries in the global economy. Fermentation-
based pharmaceuticals, such as analgesics, anti-inflammatory drugs, antibiotics, lipid regulators, receptor
blockers and X-ray contrast agents, have been widely used in health treatment. At the same time, the impact
of drug pollution and pharmaceutical wastewater discharge has become a global hot topic of concern for
environmental protection. At present, traces of drugs have been detected in sewage wastewater, drinking
water and rivers in many different places, including the United States, China, Australia, Europe and Africa,
and research shows that one of the reasons is the discharge of pharmaceutical wastewater.
Pharmaceutical manufacturing is generally divided into two categories: biopharmaceutical production
and chemical pharmaceutical production. Fermentation-based pharmaceutical production is one kind of
biopharmaceutical production with a long history of development, relatively advanced technology and wide
application. Fermentation-based drugs include antibiotics, vitamins, amino acids and other types of drugs.
The fermentation pharmaceutical production process not only requires a stable supply of pure water, but
also produces a large amount of wastewater. Studies have found that such wastewater usually contains
high levels of waste solvent, refractory organic matter, residual drugs and salt. Meanwhile, for different
production processes, such as bacteria screening, refining and purification, drying, packaging and other
steps, the concentration of pollutants in organic wastewaters varies greatly. The chemical oxygen demand
(COD ) can reach 4 410 mg/l to 40 000 mg/l.
Cr
The rapid development of the fermentation-based pharmaceutical production industry also poses challenges
to the treatment and discharge of wastewater, as well as the management of water resources. If wastewater
is released into the environment without effective treatment, pharmaceutical pollutants will cause water-
quality risks, thus adversely affecting the aquatic ecosystem and public health. In recent years, many
countries have put forward new requirements for the reclamation treatment of industrial wastewater and
introduced many laws and regulations on the reuse of the treated wastewater, requiring treated wastewater
to be reused in various applications, such as in-plant production, greening and irrigation. However, there is
still a lack of reasonable technical specifications for the reclamation treatment and reuse of fermentation
pharmaceutical industry wastewater in terms of how to select the most suitable treatment technology for
each type of wastewater and how to efficiently recycle or reuse the wastewater.
This document is intended to help solve the current technical problems regarding the treatment and
reuse of fermentation-based pharmaceutical wastewater. In view of the particularity of the production
processes generating fermentation-based pharmaceutical wastewater, this document puts forward the
general recommendations of the process flow and technology selection for reuse of wastewater after
treatment under different pollution loads. At the same time, according to the different reuse scenarios of
treated wastewater, different reuse water treatment technologies are recommended to meet the reuse
requirements in each scenario. This document can provide theoretical support and technical guidance for
the treatment and reuse of fermentation-based pharmaceutical wastewater. At the same time, it can be
conducive to promoting technology advancement, product upgrading, energy conservation and emission
reduction of fermentation-based pharmaceutical enterprises. Moreover, it can promote the standardized
and the high-quality development of fermentation-based pharmaceutical wastewater treatment and reuse
projects, improve water efficiency and thus promote a more sustainable and high-quality development of
the whole industry.
v
International Standard ISO 12370:2025(en)
Guidelines for treatment and reuse of fermentation-based
pharmaceutical wastewater
1 Scope
This document provides technical guidance for fermentation-based pharmaceutical wastewater treatment
and reclamation for different reuse purposes.
This document contains information on pollution loading, general principles and applicable wastewater
treatment and reclamation treatment. In addition, example processes for wastewater treatment and
reclamation are listed to support different treatment conditions and reuse purposes.
2 Normative references
The following documents, in whole or in part, are normatively referenced in this document and are
indispensable for its application. For dated references, only the edition cited applies. For undated references,
the latest edition of the referenced document (including any amendments) applies.
ISO 20670:2023, Water reuse — Vocabulary
3 Terms, definitions and abbreviated terms
For the purposes of this document, the terms and definitions given in ISO 20670:2023 and the following apply.
ISO and IEC maintain terminology databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
— IEC Electropedia: available at https:// www .electropedia .org/
3.1 Terms and definitions
3.1.1
denitrification
reduction of nitrate and nitrite to the end product nitrogen (in the form of gas) by the action of bacteria
[SOURCE: ISO 11733:2004, 3.6]
3.1.2
fermentation-based pharmaceutical wastewater
process and non-process wastewater generated in the production operations of fermentation pharmaceutical
enterprises
Note 1 to entry: Process wastewater refers to the in-situ residual mother liquor and wastewater produced in the
process of fermentation-based pharmaceutical production (3.1.3). Non-process wastewater refers to wastewater
produced by cooling or cleaning equipment and from washing ground surfaces.
3.1.3
fermentation-based pharmaceutical production
process of producing antibiotics or other active pharmaceutical ingredients by fermentation and producing
drugs through separation, purification, refining and other processes
Note 1 to entry: The types of drugs can be divided into antibiotics, vitamins, amino acids and other categories.

3.1.4
hydraulic retention time
theoretical average period of time that influent wastewater remains in the biological reactor
Note 1 to entry: The hydraulic retention time (HRT) is calculated as net biological reactor volume (m ) divided by the
daily influent wastewater flow (m /d).
3.1.5
kettle liquid
liquid left at the bottom after distillation in a distillation column
3.1.6
basic on-site domestic wastewater
water that contains only human body waste and human liquid waste, and can contain grey water from
washing, but does not contain commercial or industrial discharges
[SOURCE: ISO 24513:2019, 3.2.2.2.1]
3.2 Abbreviated terms
B/C ratio ratio of BOD /COD
5 Cr
BOD five-day biochemical oxygen demand
COD chemical oxygen demand by dichromate method
Cr
IFAS integrated fixed-film activated sludge
MBR membrane bioreactor
MLSS mixed liquor suspended solids
MLVSS mixed liquor volatile suspended solids
NH -N ammonia-nitrogen
NO -N nitrate-nitrogen
NTU nephelometric turbidity unit
SS suspended solids
TN total nitrogen
TP total phosphorus
UASB upflow anaerobic sludge blanket
4 Pollution loading
4.1 Classification of wastewater
The typical process configuration for fermentation-based pharmaceutical production and the main
wastewater generation links are shown in Figure 1.

Figure 1 — Typical processes and wastewater generation links for fermentation-based
pharmaceutical production
Fermentation-based pharmaceutical wastewater is classified as follows:
a) Process wastewater: residual mother liquor and wastewater generated in the process of fermentation-
based pharmaceutical production, such as extraction residual mother liquor, refining residual mother
liquor or resin regeneration wastewater.
b) Non-process wastewater: production flushing drainage (e.g. equipment flushing water, ground flushing
water), dynamic system drainage (e.g. drainage from recirculating cooling water system and once-
through cooling water), etc.
4.2 Wastewater volume
Measured data should be used for quantifying the amount of wastewater generated in the fermentation-
based pharmaceutical production process. The total amount of wastewater discharge should be measured
and determined at the point of final discharge from the factory, and the process wastewater discharged
from each production process should be measured individually.
When there is no actual measurement data available, analogous survey data can be used. The amount of
wastewater can be determined by analogy with the emission data of existing fermentation pharmaceutical
enterprises with the same production scale, similar raw materials and products and similar production
processes. Annex A provides further information about pharmaceutical wastewater quality. See Table A.1
for representative generation of wastewater from fermentation-based pharmaceutical production.
If there is no measured or analogous data, this can be estimated using Formulae (1) and (2):
QQ=∑ (1)
yi
QQ=⋅αβ⋅+T (2)
ii
where
Q is the total wastewater production (m /d);
y
Q is the wastewater generation rate of each production process (m /d);
i
α is the reduction factor for generated wastewater calculated according to the water supply, which
is determined according to factors such as the production process of the enterprise and the level of
water supply and drainage facilities, generally taking 70 % to 90 %;
β is the percentage of sub-item water supply for process water that can be determined according to
actual material accounting;
Q is the production water consumption (m /d), which can be determined according to production
water quota;
T is the amount of water transferred in or out (m /d) for this process; the transfer-in is positive and
i
the transfer-out is negative.
4.3 Quality of produced wastewater
The main pollutants in fermentation-based pharmaceutical wastewater are fermentation residues,
intermediate products, various organic solvents and inorganic salts residual in the extraction and refining
process. Wastewater usually is characterized by complex composition, many kinds of organic pollutants,
high COD and BOD values, high NH -N concentration, high toxicity and high concentration of SS.
Cr 5 3
The determination of wastewater quality should be based on the actual monitoring data, and the wastewater
generated by each production process should be sampled and analysed individually.
When the wastewater quality does not meet the detection conditions, it can be determined by analogy with
the emission data of existing fermentation pharmaceutical enterprises with the same production scale,
similar raw materials and products and similar production processes.
In the absence of measured and analogous data, refer to Table A.2 and Table A.3 for typical wastewater
quality generated during production.
5 General principles
Before the process design, the water quality and quantity should be comprehensively investigated, and
necessary monitoring and analysis should be carried out. In addition, the process design should be based
on the water quality characteristics of wastewater and the destination after treatment; the appropriate
process flow should be selected after considering reliability and economy.
Wastewater containing hydrocarbons should be equipped with level monitoring equipment for leak
detection. Wastewater containing antibiotic active ingredients with biological toxicity or ecological risks
should be pretreated separately to eliminate potential biological toxicity and ecological risks before flow
into the wastewater plant for overall wastewater treatment and reuse. Furthermore, the environmental
risk prevention system should be improved and relevant environmental risk prevention facilities such as
accident pools should be set up to ensure that the wastewater can be fully collected and effectively treated
under the accident condition and all effluent should meet discharge standards. In addition, measures such as
oxidation and disinfection should be adopted to prevent secondary pollution before discharge.
Wastewater generated in each process of fermentation-based pharmaceutical production should be
pretreated by quality classification, mixed and discharged as comprehensive and concentrated wastewater
for anaerobic biological treatment to improve the biodegradability of wastewater, and then mixed with low-
concentration wastewater for aerobic biological treatment. Basic on-site domestic wastewater contains
numerous biodegradable organics, which can meet the basic demands of the microorganisms in activated
sludge. It also provides sufficient carbon sources and nutrients for microbial growth. At this stage, the
pretreated basic on-site domestic wastewater can also be added according to the quality of wastewater to
increase the B/C ratio. Reclamation treatment of secondary treated effluent can be conducted to further
remove contaminants. The overall treatment flow chart of fermentation-based pharmaceutical wastewater
is shown in Figure 2.
Key
pretreated by enterprises process wastewater
wastewater treatment non-process wastewater
sludge treatment basic on-site domestic wastewater
odor treatment
Figure 2 — Flow chart of fermentation-based pharmaceutical wastewater treatment
6 Wastewater treatment processes
6.1 Pretreatment process
The pretreatment system should consist of one-stage or multi-stage pretreatment measures for special
wastewater containing high salt and high NH -N in pharmaceutical wastewater, according to the water
quality characteristics, to ensure that the water quality meets the requirements of the downstream
biological treatment system. Wastewater with good biotreatabi
...