Pure Steam System

in Pharmaceutical Industry

by
Eugene Liu
Email : eugene.liu@century-water.com
Mobile : (+65) 9112 0380
 Grade of Steam

Generation

Distribution

Sterilization

Purity & Quality

Regulation
Grades of Steam
Plant Steam
Plant Steam
• Known as Plant Steam, Industrial Steam, Black Steam
• Generated from fired water, either fire-tube and water-tube boiler
• No standards governing the quality of plant steam

What’s the problem with plant steam…….

Nothing for most industrial applications

Depending on application unacceptable due to:
• Boiler feedwater chemicals/soft water (to protect boilers and
pipework),
• Pipeline scale
• Rust / Corrosion particulates
• No defined endotoxin removal
• Changes in feedwater supply
• Recontamination through condensate loop
• Poor chemical purity of condensate
Plant steam
Plant steam quality is dependant upon many different factors:
• Raw water quality - Water softening equipment

• Water treatment management - Boiler management

• Boiler loading - Steam system design

• Steam trap management - Cross contamination

Water treatment
• Water treatment for boilers must be operated in accordance with
a specification to control corrosion, scale, foaming, fouling, etc.
• Food approved chemicals must always be used when using
steam in contact with the process or product!
• Approval is given by FDA or local equivalent.
• Even though the boiler water treatment chemicals are food
approved they should only come in contact with the
product/process in a VAPOUR form and even then there are FDA
limits!
Boiler carryover
Priming: The sudden draw off of boiler water into
the steam off-take is generally due to one or
more of the following:
• Incorrect selection, installation, maintenance of raw water
pre-treatment plant.

• Operating the boiler with an excessively high water level.

• Operating the boiler below its design pressure,

increasing the volume and the velocity of the steam
released from the water surface.

• Sudden, excessive steam demand.

FDA Standard: Controls the chemical limits on steam.

Priming is not steam and will therefore contain very high
concentrations of chemicals!
Boiler carryover
Foaming: This is the formation of foam in the space between
the water surface and the steam off-take and is generally due to
one or more of the following:
• High levels of Total Dissolved Solids (TDS) in the boiler.

• Excess water treatment chemicals, i.e. non adherence to a water treatment

programme.

• High alkalinity (>1 000 ppm).

Corrective action
Priming Foaming:
Boiler Operation: • Water Treatment: The control of
• Modulating boiler water level controls if chemical dosage into the boiler
on / off boiler controls are currently should be in line with a boiler water
fitted. treatment programme e.g. BS2486:
• Correct installation/maintenance of
1997 and BS EN 12953 – 10 2003.
water treatment plant
• Control of TDS: TDS control limits
• Operate boiler at the correct ‘design
pressure’ should be kept in line with water
treatment guideline
• Ensure water level is set correctly recommendations.
Automatic TDS controls on the
• ‘Surplusing controls’ boiler will maintain the boiler at
optimum TDS levels:
• Steam accumulator.

• Boiler sequencing.
Scale & Corrosion
• Scale deposits:
• Build up of calcium carbonate on boiler tubes,
Scale deposits
steam distribution system, plate heat
exchangers, etc.
• Potential particle contamination in
process/product.
• Reduce efficiency
Corrective Action:
• Adherence to an approved water treatment programme.

• Oxygen corrosion in the steam and

condensate pipe.
• Potential particle contamination in
process/product.
• Potential product failure, e.g. heat exchangers
Corrective Action:
• Adherence to an approved water treatment programme.
Cross Contamination - CIP

Most F&B manufacturers should return a high % of their

condensate. Some may not return condensate due to the risk of
cross contamination from:
• Cleaning in place (CIP)
• Process, Oil & fats, etc. Stress corrosion or pin hole
failures will cause cross
contamination!
Cross contamination
View inside a boiler at orange juice manufacturer
Process contamination often leads to foaming and more
carryover!

Top of boiler

Water line
Corrective Action

• Condensate contamination detection (CCD) systems can be

installed to monitor the condensate being returned to the boiler, to
prevent contamination.
• Detecting contamination enables customers to:
Save energy/water + prevent process contamination!

A turbidity/conductivity meter
will detect many contaminants,
such as oil/fat, TDS, etc
Filtered (culinary) Steam
Filtered steam
• ‘Filtered steam', is plant steam that has passed
through a fine stainless steel filter, (typically 5
microns).

• A 5 micron filter element is designed to remove

95% of all particles.

• 3-A Accepted Practices for a Method of

Producing Culinary Steam, Number 609 – 3, is a
standard developed in the US that establishes the
'minimum' sanitary (hygienic) requirements for
the method of producing culinary steam.

• It is important to note that the section on boiler

operation within the 3-A standard, stipulates that
boilers should be 'operated in such a manner as
to prevent foaming, priming, carryover, and
excessive entrainment of boiler water into the
steam'.
 Filtered steam

Steam inlet
Flow
Filtered
Steam

Extract from 3-A culinary steam standard 609-03

Steam filters
Steam filters
• Removes particulates only
• Does not effect steam / condensate ‘chemistry’
• Not designed to remove moisture!
• 1, 5 or 25 µm element
• Nominal ratings so only remove a percentage
of particles: 95-98%
• Sintered elements for finer particles
• Specialist cleaning required for sintered units
• Condensate trap to be present on housing

A 5 micron filter will remove particulates larger than 2 microns, but is not
designed to remove water or chemicals from the steam e.g. carryover.
Filtered Steam – Case Study

Location: Dairy Plant

Application: Steam was directly

injected into UHT milk

Issue: Customer had no filter

installed at all!

Solution: Filter installed. After one month operation the filter

was inspected with above results!

Results: Solution improved relationship with the customer

Filtered steam

m
i
c
r
o
n
Filtered steam
Filtered steam quality is still dependant upon many other factors:
• Raw water quality - Water softening equipment

• Water treatment management - Boiler management

• Boiler loading - Steam system design

• Steam trap management - Cross contamination

Direct Steam Contact Process
Guidelines and legislation

Very few guidelines/standards relating to

the quality of steam in contact with the
product/process:

USA: FDA: Code of Federal Regulation,

Title 21, Volume 3, Section 173.310

UK/Europe: EC No. 852/2004

‘Steam used directly in contact with food is
not to contain any substance that presents a
hazard to health or is likely to contaminate
the food’

Some companies have their own

standards e.g. Nestlé
Guidelines & legislation

USA: FDA: Code of Federal Regulation, Title 21, Volume 3,

Section 173.310:
(Food approved) ‘Boiler water additives may be safely used in the
preparation of steam that will contact food, under the following conditions:
(a) The amount of additive is not in excess of that required for its functional
purpose, and the amount of steam in contact with food does not exceed
that required to produce the intended effect in or on the food.…...‘
Indonesia : The National Agency of
Drug and Food Control

1. Undang-Undang No. 18 Tahun 2012 tentang Pangan :

Keamanan Pangan adalah kondisi dan upaya yang diperlukan untuk mencegah Pangan
dari kemungkinan cemaran biologis, kimia, dan benda lain yang dapat mengganggu,
merugikan, dan membahayakan kesehatan manusia serta tidak bertentangan dengan agama,
keyakinan, dan budaya masyarakat sehingga aman untuk dikonsumsi.

2 .Peraturan Kepala Badan Pengawas Obat dan Makanan

No. HK.03.1.23.04.12.2206 TAHUN 2012 tentang “Cara Produksi Pangan Yang Baik Untuk
Industri Rumah Tangga”, Persyaratan air :
(c) Air, es dan uap panas (steam) harus dijaga jangan sampai tercemar oleh bahan-bahan dari
luar;
(d) Uap panas (steam) yang kontak langsung dengan bahan pangan atau mesin / peralatan
harus tidak mengandung bahan-bahan yang berbahaya bagi keamanan pangan.
Clean Steam
 Clean steam
The potential risk of contamination
from particulates, boiler chemicals
and cross-contamination is
eliminated with the use of clean
steam, due to:

• The high quality of feed water used.

• Removal of water treatment

chemicals.

• Production of steam in a secondary

generator.

• System materials of construction.

Will the steam or condensate contact the product?
Consider the water quality in the process?
Clean steam generation
Water supply usually:
• Reverse Osmosis (RO)

• Demineralised/deionised (DI)

No standards governing clean

steam quality in food and drink
but allows full compliance with
3A / FDA requirements.

Component design standards

for hygienic processes:

www.3-a.org www.ehedg.org www.fda.gov

Clean Steam

Clean Steam is defined in Europe through:

HTM:2010
HTM:2031

EN:285
Filtered Steam v Clean Steam
Controlled Hazards Filtered (Culinary) Steam Clean Steam
Limited by filter System materials of
Particulates rating construction

Limited removal High level of

Chemicals of chemicals held feedwater purity:
in steam RO or DI
Steam raised No return of
Cross Contamination from returned condensate to
condensate Clean Steam Gen.
Controlled by High level of
Condensate Purity boiler water feedwater purity:
treatment RO or DI

Filtered steam requires control of

risks
Clean steam offers guaranteed
removal of risks
 Where is clean steam application?

Hospital
Food & Beverage
Pharmaceuticals
& Personal
Care/Cosmetics
Hospital Application
Every day steam sterilisers are
preparing medical devices for patient
use around the world
Repeatability is needed day in, day out

Steam is essential and its purity

and quality needs to be assured
day in, day out; even hour to hour
Clean Steam Quality

The key to success is

97% dryness
Food & Beverage Applications

Plant steam generator

Clean steam generator

Pharmaceutical Applications

Clean Steam Applications in Natural Herbal Production

Pure Steam
Clean Steam Generator (CSG)
Pure Steam Generator (PSG)

Pure Steam

Separator

Plant Steam

Feedwater

Plant Condensate

Blow Down
Multi-Effect Distillation

1st Effect 3rd Effect

Pre-Heaters Condenser

Evaporator / Separation Column 4th Effect Conductivity

2nd Effect
Multi-Effect Distillation

Multi-Effect, but only single phase change!

Feed
Water

Pure
Steam Cooling
Water

Plant
Steam
WFI

Condensate
Drain
CSG v PSG
CSG v PSG – general points
Typically clean steam generators will produce steam of the
same quality as the feed water if no additional separation
techniques are employed
• Generation orientation is vertical vs horizontal for CSG
• Complete segregation of heating medium and product
• Increased fabrication control – material traceability,
surface finish etc
• Multiple separation stages for complete removal of
endotoxins and other impurities
Where pure steam is not required an economic alternative
may be to utilise clean steam from a clean steam
generator.
Clean Steam v Pure Steam

PURE STEAM CLEAN STEAM

Complies with USP Complies with HTM or EN:285

Condensate complies with WFI or similar standard

Steam Quality determined by

process – norm covers EN:285

Important difference is conductivity of condensate - purity:

EN:285 <35µS/cm @ 25°C
WFI (USP) <1.3 µS/cm @ 25°C
Pharmaceutical Waters
Purified Water Water For Injection

USP EP USP EP
Bacterial
N/A N/A <0.25 EU/ml(1) <0.25 IU/ml (1)
Endotoxins
pH 5-7 N/A 5-7 N/A

Conductivity <1.1 µS/cm (20°C) <4.3 µS/cm (20°C) <1.1 µS/cm (20°C) <1.1 µS/cm (20°C)

Total Organic
<0.5 mg/l <0.5 mg/l <0.5 mg/l <0.5 mg/l
Carbon
<10 cfu per
Micro-organisms N/A(2) <100 cfu per 1ml(3) N/A(2)
100ml(3)
Nitrate N/A <2 ppm N/A <2 ppm

Heavy Metals N/A <0.1 ppm N/A <0.1 ppm

Aluminium N/A <10 µg/l N/A <10 µg/l

(1) 1 USP Endotoxin Unit (EU) = 1 EU (& WHO) International Unit of Endotoxin (IU)
(2) USP monographs for PW and WFI does not state micro-organism limit. <1231> Water For Pharmaceutical Purposes
gives guidance for an upper limit of 100 cfu per 1ml (PW) and 10 cfu per 100ml (WFI)
(3) cfu: Colony Forming Unit
Pure Steam Distribution
Distribution Design

Steam
Quality Test
Point

PI PI PI

Autoclave SIP
Clean/
Pure Sample
Steam Cooler

Generator

• Line Sizing • Condensate Removal

• Drainability • Air venting
• Adequate support • Sampling
• Take off points • Maintenance
Sterilisation

Sterilization can be defined as:

any process that effectively kills or

eliminates transmissible agents (such as
fungi, bacteria, viruses and prions) from a
surface, equipment, foods, medications,
or biological culture medium.

In practice sterility is achieved by exposure of the

object to be sterilized to chemical or physical agent
for a specified time.
SIP (Sterilize In Place)

SIP (Sterilize In Place) is a timed sterilization of the process piping and vessels
with pure steam.

Every square inch of all process piping and vessels that comes in direct, or
indirect contact with the process is sterilized to insure that there is no
microbiological activity in the system.

Steam typically is circulated through all the process tubing during this stage,
and enters large vessels through spray balls (engineered nozzles) imbedded in
the vessel ceiling.

Temperature Validation: The minimum regimen requires the injection of pure

steam into all piping and vessels for a minimum of ½ hour after the vessels
reach a minimum temperature of 121°C.
SIP Cycle

121°C

SIP time & temperature recording

Temperature °C

commences

Heat Up Sterilisation Phase >121°C

Phase Temperature hold
(minimum time 30 minutes)

Time
Time and temperature graph showing phases of sterilization
SIP Cycle
If the SIP temperature validation fails (if recorded temperature falls below
121°C), the sterilization time may be extended, but only if the temperature
fault can be determined and fixed.

Failed Sterilization cycle showing temperature faults

If not, the problem must be corrected, and the cycle repeated.

Extended processing – TIME, ENERGY, MONEY!
SIP Cycle
Majority of steam trap applications in Biopharma is vessel SIP

SIP Characteristics
Vessels: 10L to 50,000L
Steam pressure: 1-2 barg
Flow rates/loads
• up to 1500 kg/hr for start-up loads
• <15 kg/hr for maintenance loads

Where is the trap?

Inherently at the lowest point
Think about the validation sensors?
Remember issues with condensate in pure steam?
Air Removal

Steam
• Start-up of system vessel/space is full of
air
• Air needs to be removed rapidly and
completely
• Failure of air removal can delay or
prevent reaching operating/ sterilisation
temperatures
• For some cases air venting may be
necessary…

BUT the steam trap is the primary point of air removal

Steam
Trap
SIP – Vessel

Steam

Liquid
Product

Temperature & Trap

Condensate Monitoring
SIP Cycle - Temperature Validation

Validation sensors (RTD’s, Themocouple’s or

Thermister’s) are placed at the condensate
outlets of process equipment to make sure that
the sterilization temperature meets the specific
design requirements for the process system.

Measurements are made from sensors placed in

thermowells or tubing tees located 12 to 18
inches above the point where the condensate
exits the piping or vessel, at the steam trap.

Recorded data is stored in a PLC, Distributed

Control System (DCS), or standalone database.
SIP – Liquid Filter

Steam

Liquid Liquid
Product Product

Temperature
& Trap
Condensate Monitoring
SIP – Liquid Filter

Temperature Temperature
& Trap & Trap
Monitoring Monitoring
Steam Trap Selection & Monitoring

Float
Most traps retain some condensate to
(Mechanic)
allow operation

WATER
Thermodynamic RETENTION

Inverted
Bucket
(Mechanic)
Balanced
Bimetallic Pressure
(Thermostatic) (Thermostatic)
Steam Traps
Mechanical Thermodynamic Thermostatic

Principle density velocity Temperature

Blockage
resistance

Cleanability OK

Drainability /
Water Retention

Air venting

Failure Mode closed open open

• Thermodynamic traps should not be used on equipment SIP because of their

small passage promotes product retention / blockage
• High air velocity at start-up may also cause thermodynamic discs to close
Steam Trap Operation

Liquid Fill
Element

• During start-up air passes over the trap

• The trap is cold and fully open so allowing air to be removed
• The air will be followed by cold condensate
Steam Trap Operation

• The condensate temperature shall rise heat is trans

• Heat is transmitted to the element and the liquid inside
Steam Trap Operation

• Temperature continues to increase causing the liquid fill to boil

• The boiling creates pressure inside the element
• The pressure expands the element pushing the ball on to the seat
• The trap is sealed
Steam Trap Operation
Whilst closed the condensate shall cool.
The liquid fill shall condense.
The element shall retract allowing the seat to open
and condensate to flow.

• Whilst closed the condensate shall cool

• The liquid fill shall condense
• The element shall retract allowing the seat to open and condensate to flow
Steam Purity & Quality
Steam purity is a quantitative measure of dissolved solids, volatiles,
microbial or other particles (contamination)
Steam quality commonly refers only to the amount of water in the
steam:

Dryness fraction = Mass of Steam

Mass of steam + Entrained water

Dryness: >0.9 for porous loads

>0.95 for metal loads
Non-Condensables: <3.5ml of gas/100ml of condensate
Superheat: <25°C
Steam Purity & Quality
Steam impacts both the process and
contamination

QUALITY PURITY

Impacts the effectiveness of the Can lead to contamination of the

sterilization process sterilized articles
 Wet Loads

• It is a problem
• Load should be dry before the
sterilizer door is opened
• The presence of water will
compromise the sterility of the
product.

• As soon as the door opens air will rush

in
• Normally sterilised packages are
electrostatic charged so attracting dust
and particles
• Wet points, no matter how small can
lead to recontamination
• Reprocessing incurs – time, energy,
cost and delays
Autoclave/Sterilizer

Steam Quality Test Pressure Control

Pure Steam
Intake

Autoclave

Steam Separator

Sample Cooler
Steam Quality (EN:285)
Dryness
• Clean and pure steam is generated with
dryness value >0.95
• Excess moisture, where droplets are present
may cause:
- damp loads in porous materials
- uneven temperature distribution in non-
porous materials
• Can be maintained by:
Reducing the pressure just prior to
point of use - false
The use of an inline moisture
separator before control valves,
autoclaves and freeze dryers
Non-Condensable Gases
• NCGs are gases which cannot be liquefied by
compression under normal sterilisation conditions.
• Typically Air and Carbon Dioxide
• They have no latent heat, so even if they have the same
temperature of steam, they provide no heating effect.
• They can collect as a film on surfaces, and act as an
insulator inhibiting the flow of heat from the steam.
• They lower the steam temperature
Degree of Superheat
Prevention of superheat
• Not usually a concern in clean/pure
steam distribution systems as low
operating pressures
• Commonly occurs during pressure
reduction
• Superheated steam will not give up its
heat until the temperature has reduced to
saturation temp – ineffective for
sterilisation
• Rule of thumb should not reduce
pressure more than 50%
• Carefully consider distribution operational
pressure
Dryness (EN:285)
Non-condensables (EN:285)

Non condensable gasses

The following information will be taken during the test and recorded 3 times.
Vg = volume of gasses
Vc = volume of condensate
Formula:
NCG = Vg x 100 Example = 1.0 x 100 = 0.66%
Vc 150

Less than 3.5 to pass

Superheat (EN:285)
Measuring the Superheat consists of taking a reading of the steam line temperature
and the expansion tube temperature.

Temperature of expansion tube – Boiler point of water at local atmospheric pressure

Steam Quality Testing
Quality & Purity Testing

T2

T1 T1 T2
PI PI PI

Autoclave SIP
Clean/
Pure Sample
Steam Cooler

Generator

T1 Quality & Purity Testing

Purity Testing, intermittent quality

T2 testing application/site specific
Regulation
ISPE USP

- International Society of Pharmaceutical - United States Pharmacopoeia is

Engineer the official public standard setting
authority

ASME BPE HTM2031 and HTM2010

- American Society of Mechanical - European standards dictating the

Engineers Bioprocessing Equipment quality and purity of steam used in
autoclave sterilisation.

FDA and cGMP PIC/S

- Regulation body controlling the - Pharmaceutical Inspection

production and sale of pharmaceutical, Convention (PIC) &
food and cosmetics. Pharmaceutical Inspection Co-
operation Scheme (PIC/S)
Thank You