INERTING AS A BASIS OF SAFETY

Version: 1.3 Prepared by: Francisco Lorente Oct 2018

 COURSE OBJECTIVES

SCOPE:
What are the basic principles of Inerting
How different methods available of inertization can be used
Critical elements to obtain a reliable inertization method.
TARGET AUDIENCE:
All personnel involved in activities inerting is applied. From design
phase to inerting execution. For instance: Production, Engineering &
Maintenance, EHS, etc …
INDEX:
• KEY ELEMENTS ON INERTING
• METHODS OF INERTING
• MAINTAINING INERT CONDITIONS & RELIABILITY
• ASPHYXIATION HAZARD
REQUIREMENTS FOR AN EXPLOSION
 DEFINITIONS
OXIDANT A substance which supports combustion. Any Gaseous material that can react with a fuel
(either gas, dust, mist or hybrid) to produce combustion. Most widely recognized oxidant
is Air which contains 20.9% O2. Other examples are Halogens such as Chlorine or
Fluorine, Nitrous Oxide, Nitric Acid, etc.

FUEL Liquid (vapor or mist), gas or solid, capable of being oxidized. Combustion always occurs
in the vapor phase; liquids are volatized and solids are decomposed into vapor prior to
combustion

IGNITION An energy source capable of initiating a combustion reaction. Ignition sources can be
SOURCE generated in a multitude of applications and come in a variety of forms. Some examples
include smoldering or burning dust, open flames, hot surfaces, heat from mechanical
impact and electrical discharges.

CONFINED An enclosed structure surrounding the suspended dust cloud must exist in order to
AREA achieve the pressure rise characteristic of a dust explosion. In the absence of a confined
area, flash fires are still a hazard but explosions typically are not..

DISPERSION The explosive dust being processed must be entrained in a cloud of sufficient
concentration. Fine solid particles (500mm or less), which may be suspended in air, may
burn and may form explosive mixture with air at atmospheric pressure and normal
Temperature
 DEFINITIONS
FLAMMABLE The minimum (LFL-Lower Explosion (Flammable) Limit: applicable to gases, it is a concentration
LIMITS volume per volume) and maximum (UFL-Upper Explosion Flammable Limits: applicable to gases
and it is a concentration volume per volume) concentrations of a combustible material in a
homogeneous mixture. Below the LFL the fuel-oxidant mixture is too lean in the fuel
concentration to burn and above the UFL, the fuel-oxidant mixture is too rich in the
fuel concentration or the oxygen concentration is not enough

LOC Limiting Oxygen Content (also called MOC – Minimum Oxygen Content), below which
ignition will not occur and flame will not propagate

MAOC Maximum Allowable Oxygen Concentration: Oxygen concentration which should not
be exceeded in the system that has to be protected, even with anticipated upsets or
operating errors. It is set using a margin below the limiting oxygen concentration,
safety factor. This margin Should consider variations in process conditions which might
deviate from the experimental conditions.

MEC Minimum Explosion Concentration. Dust Concentration in terms of weight per volume,
below which fire will not occur

MIE Minimum Ignition Energy that is needed to ignite a flammable material a its optimum
mixture with air that will cause flame propagation
 DEFINITIONS
INERT GAS A gas that is non combustible and non reactive

PURGE GAS An inert or a combustible gas that is continuously or intermittently added to a

system to render the atmosphere non ignitable

BLANKETING The technique of maintaining an atmosphere that is either inert or fuel enriched
in the vapor space of a container or vessel. Also known ad Padding.

INERTING A technique by which a combustible mixture is rendered non-ignitable by

reducing the oxidant concentration below a level that will no longer support
combustion through the addition of an inert gas or a non combustible dust to the
vessel where the flammable/combustible atmosphere exist. Inerting can be
required to:
- Prevent Explosions
- Eliminate Undesired Reaction
- Keep Moisture away from products, etc…
 FLAMMABILITY DIAGRAM
Flammability diagrams show the control of flammability in mixtures of fuel, oxygen and
an inert gas, typically nitrogen.
Mixture of the three gases are usually depicted in a triangular diagram known as a
TERNARY PLOT
FLAMMABILITY DIAGRAM
TYPE OF INERT GASES
These are the most popular gases in Pharmaceutical
industry. Specially Nitrogen
 TYPE OF INERT GASES
Estimated Reference Cost of N2 depends on its source and Place of Origin:

Liquid N2 as a Source for inerting Gas

Europe: 0.13 – 0.28 US$ per Normal m3 of N2 Gas
Israel: 0.25 – 0.36 US$ per Normal m3 of N2 Gas

On-Site Generation of N2 Gas Rented Units

Hungary: 0.20 US$ per Normal m3 of N2 Gas
Puerto Rico: 0.12 US$ per Normal m3 of N2 Gas
Israel: 0.15 US$ per Normal m3 of N2 Gas

On-Site Generation of N2 Gas – Purchased units

Sicor De Mexico: 0.06 US$ per Normal m3 of N2 Gas

Israel: 0.06 US$ per Normal m3 of N2 Gas (not yet operational)
India : 0.05 US$ per Normal m3 of N2 Gas

Pay Back period of a Purchased On-Site N2 Generator is less than 1 year,

when compared to Liquid Nitrogen source.
 FEW CONSIDERATION ABOUT N2
Cost will be determine by the source of the N2

The type of source will determine the factors that will affect the
availability.

N2 Gas Cylinders Liquid N2 Station On site N2 generation

 FEW CONSIDERATION ABOUT N2
N2 will become a critical element for some manufacturing
steps, so the proper reliability study should be conducted:
Supplier, Pipes, maintenance, etc..

On site N2 generation

Location of Gas Cylinders on Safe Location

Supply and Gas Cylinders management and alarms.

N2 Gas Cylinders Liquid N2 Station

Compressed Air reliability.
PED requirements.
Pipes and instruments involved on distribution.

Liquid N2 supply and maintenance on the station.

Pipes and instruments involved on distribution.
PED requirements
 APPLICABLE CODES & STANDARDS
NFPA 69 : Standard on Explosion Prevention
CEN/TC - European Standard: Guidance for Inerting for Explosions Prevention
CEN-TR-305: Guidance on Inerting for the prevention of explosions
Local Laws and Regulations

Normative References

EN 1127-1 "Explosive atmospheres - Explosion prevention and protection - Part 1:Basic concepts and methodology"
EN 1839 "Determination of explosion limits of gases and vapours"
EN 14034-4 "Determination of the explosion characteristics of dust clouds - Part 4: Determination of the limiting oxygen concentration of dust clouds”
per EN 14756 "Determination of the limiting oxygen concentration (LOC) for gases and vapours"
EN 50104 "Electrical apparatus for the detection and measurement of oxygen - Performance requirements and test methods"
IEC 61508 "Functional safety of electrical/electronic/programmable electronic safety-related systems", Parts 1, 2, and 3.
IEC 61511 "Functional safety - Safety instrumented systems for the process industry sector“ CLC/TR 50404 "Electrostatics - Code of practice
for the avoidance of hazards due to static electricity"
EN ISO 4126-6 "Safety devices for protection against excessive pressure. Application, selection and installation of bursting disc safety devices"

Basic Requirements in all standards: Risk Assessment

 RISK ASSESSMENT

• Type of operation and potential risk (Centrifuge type, Reactor, Storage tank)
• Definition of intended use (substances, temperature, pressures)
• Control over modifications or changes to the equipment or process
• Detailed records of the original design, modifications, process changes and calibrations

• Characteristics of the product handled (MIE, Kst, Pmax, MIT, LIT, etc …)
• Control and maintenance to ensure tightness of the system, grounding & bonding, etc …
• Consider all activities performed: loading & unloading, cleaning, sampling, etc …
• Consider all the potential ignition sources associated to all activities and situations

• Frequency of the tasks & severity analysis of a potential incident, available PPE, …
• Probability of failure, determination of effectiveness of Safety Critical Elements Risk evaluation
EN1127:1
• Risk quantification: for instance IR= P x Z + (I x G)/M as per EN 1127:1
RISK ASSESSMENT
 Impact on ATEX Hazardous Area Classification
The definition of the demands for safety critical equipment involves the following steps:

• Definition of basis of safety for the inerted equipment. This may involve the use of
inerting to modify the probability of the occurrence of flammable atmospheres;

• Identification of safety critical equipment distinguished from process control equipment

as defined in IEC 61508-1 to IEC 61508-3;

• The safety critical equipment should comply with requirements of European Directive
94/9 and should be covered by a conformity assessment;

• A risk assessment shall be carried out in accordance with IEC 61508-1 to IEC 61508-3 or
with an equivalent or higher safety standard, and safety critical equipment shall comply
with IEC 61511-1 to IEC 61511-3 or with an equivalent or higher safety standard.
The direct oxygen measurement reliability is determined by the standards
relevant to oxygen measurement systems (EN 50104). Annex A of CEN-TR 305
includes also information about O2 monitoring technology.

For the inferential methods, as they are not always based upon oxygen analysis, reliability
depends upon several factors which should be considered .
A risk assessment should be undertaken, as this defines the hazards of the system and the
choice of inerting method that will be applied.
CORP- 0864Global Engineering EHS by Design Guideline: Inertization and Blanketing
FILTER DRYER EXAMPLE
The theoretical oxygen content, after a given number of Pressure (or Vacuum) swing
cycles, can be calculated by this the equation:
Examples n
 P1 
C n  C i  (C 0  C i )  Pressure method: (assume Ci = 1% and P2 = 1.5 barg)
 P2 
Cn = 1% + (21% - 1%) (1 bara / 2.5 bara)2 = 4.2 %
Two cycles are required.
NFPA allows Pressure Swings One cycle will give only 9%, which is definitely not
sufficient.
without Direct Oxygen Analysis

From NFPA 69 – 2008 edition

Example of HSM in Ulm with a retrofit to Inerting capabilities with continuous O2 monitoring.
This method is suitable for a system that cannot withstand significant Vacuum or Pressure,
OR when the system is not Gas Tight and can not hold any pressure.
Gas feeding point should be as far as practical from venting (to avoid shortcut)
 The safety factor F has to be used in equation unless the
actual oxygen content at various points in the system is
measured. As a minimum, the calculated time should be
multiplied by a safety factor of between 2 and 5.

For non-branched pipe-work, it is likely that plug flow will

occur, so the safety factor can be taken as unity. For a vessel
with no branches, a safety factor of 2 would be applicable
where the inlet and outlet are diametrically opposite, and
for vessels where the inlet and outlet are not diametrically
opposite, a safety factor of 5 would be used.

In systems where the inert gas is injected at high velocity

(typically in excess of 10 m s-1), the jet mixing which occurs
will allow a reduced safety factor to be used.

It is recommended that the oxygen of the exhausted gas is monitored during the first few purges of a
system to confirm the adequacy of the purging and determine a suitable safety factor

As an example, a large hopper of 80 m3 purged with nitrogen injected at 170 m3 hr-1 at the bottom,
took 75 minutes to reduce the oxygen to 2 % v/v in the gas vented from the top, compared with a
theoretical time of 66 minutes, giving a safety factor F of 1,14.
For calculating the concentration of oxygen after a given purge time at a
given purge rate the reverse solution is used:

and similarly, for calculating the flow required to purge in a given time, a
different reverse solution is used:

EXAMPLE C.1 EXAMPLE C.2

A vessel of 3 m3 is to be purged with oxygen-free nitrogen
to reduce the oxygen content to less than 5 % v/v.
The flow rate is 10 m3 hr-1 and the gas is injected through
a 25 mm bore pipe.
The injection velocity is 5,6 m s-1, so mixing will be good.
Therefore a factor of 2 is suitable for F.
How long will the purge take?
The same vessel as in Example C.1 is to be purged
using inert gas containing 2 % v/v oxygen.
What flow of inert gas is required to reduce the
oxygen from 21 % v/v to 5 % v/v, assuming the
same time for purging?

Substituting in equation gives:

Calculation flow and pressure
Example from Ulm
about N2 flow
calculation for a vessel.
Verification of theoretical time
Example from Ulm
about N2 flow
calculation for a vessel.
We can also adapt an open vessel with stand alone stirrer to be inerted. Ideally the vessel should be gas
tight, but we can make it fit for our purpose.
All the places with potential leak should be observed: N2 and flammable vapors. Local Extraction would be
recommended. This would affect the HAC zoning according ATEX.

Lid to adjust to
shaft of stirrer

Solvents inlet facing the

Venting and N2 income
wall to minimize energy.
as far as possible to
avoid “short cut”.
Usually considered for bigger storage tanks. The nature of the flammable vapors should be evaluated in
order to select the inert gas and the location of the vent.
 RELIABILITY OF INERTING PROCESS
In the CEN TR 305 Guideline, there are different methods of determining whether a system is inert.
There is direct measurement, where the actual oxygen concentration is measured using an oxygen
sensor, and inferential methods where there is no direct measurement.
• Continuous oxygen measurement
• Inferential methods:
• Periodic oxygen measurement
• Sequential oxygen measurement
• Pressure control (with/without cycles)
• Flow control (with/without time)

Direct Measurement Method Inferential Methods

It is necessary to measure the oxygen concentration at a
point or several points that are representative of the
system to be inerted.
The advantages of continuous oxygen measurement are:
• Direct measurement of the safety critical parameter and ability to control;
• Minimizes inert gas consumption as gas is only used as required;
• Detects leaks and process upsets.
The disadvantages of continuous oxygen measurement :
• The safety integrity level (SIL) of oxygen sensors may be inadequate on its
own to ensure safety and additional control methods may be required.
• Sensors can be contaminated with process materials
The application of indirect methods requires
a thorough analysis of the process /plant
including process upsets to ensure that
adequate inerting is achieved at all times as
there is no direct measurement of the
oxygen level.
There are several methods of achieving the
inferential methods, each of which has its
own limitations.
 RELIABILITY OF INERTING PROCESS
From the CEN TR 305 Guideline: Inferential methods:
• Periodic oxygen measurement
• Sequential oxygen measurement
• Pressure control (with/without cycles)
• Flow control (with/without time)

Pressure Control Method Flow Control Method

Once inert conditions have been achieved, the

This method operates by controlling the Pressure / inert atmosphere can be sustained by
Vacuum at each cycle and the number of cycles. It maintaining minimum flow rate. It needs to be
may be manual on simple installations. monitored and maintained throughout the
More complex systems may need an automatic entire time that the atmosphere is being
counter and interlocks, and may require venting at inertized
more than one point.
European guide requires confirmation by a periodic
oxygen measurement .
Once inert conditions have been achieved, the inert
atmosphere can be sustained by maintaining an
overpressure providing that air is not introduced
during the process operation.
 RELIABILITY OF INERTING PROCESS
Inferential Method
Once the flow have been calculated, you can define the
procedure and train the personnel.
• Ensure N2 flow is always present (at least a rotameter)
• Ensure N2 pressure is well set and fixed
• Time control should be necessary
• Several practical test should be done to confirm
• Test should include some check inside of vessels
• Automatic will allow interlocks, so safer approach
• Manual will rely on operator

Direct O2 Measurement Method

Once the flow have been calculated to select flow and
pressure of N2
• Oxygen measurer can be placed in the venting
• Several practical test should be done to confirm
• Test should include some check inside of vessels
• Automatic will allow interlock with O2 sensor
• Manual will rely on operator as per O2 indication.
• Ensure N2 flow is always present (at least a rotameter)
• Ensure N2 pressure is well set and fixed
We may find dust clouds in several of the common
pharmaceutical technology: High Shear Mixer, Fluid
Bed Dryer, Biconic blender, Dust Collectors.
Example: HSM solids charging

Source CEN TR 305

We may find hybrid mixtures in several of the
common pharmaceutical technology: solution
preparation vessel, High Shear Mixer, Fluid Bed
Dryer.
Example: Fluidized Bed Dryer
We may find mists in a Coating Pan process or during cleaning activities: CIP, WIP or
manual cleaning
We should not forget cleaning activities in our explosion risk analysis
Example: Mist of spray of solvent that is used for washing purposes in a vessel.
 Reference NFPA 69

If LOC in unknown you can assume

temporarily 5%, but we should do the
proper arrangements for testing LOC.
In CEN TR 305 we can find the following table related to specification of safe limits
• Trip point (TP), at which the process controller initiates a shut-down trip
• Set point (SP), at which the process controller maintains the oxygen concentration
 MAINTAINING INERT CONDITIONS
POWDERS ADDING
We should ensure that the inert conditions (below MPOC) are maintained all the time
inside of the equipment meanwhile flammable vapors/dust are present.
Several ways can be considered for powders dosing in a closed manner.
Even though a closed manner is considered, usually 50% of added powder is air. So the
proper steady purge should be considered. Calculation method available in EN Standards

le valve
u s h) Doub
N2 fl
p lus
PTS (

w ith y valve
e r r
Hopp p lid Rota
to
MAINTAINING INERT CONDITIONS
POWDERS ADDING
Example from Ulm
 MAINTAINING INERT CONDITIONS
POWDERS ADDING
Example from Ulm

This PTS system can be used for powders loading in several equipment: HSM, FBD,
Vessels, Blender, Sieving systems, etc…
MAINTAINING INERT CONDITIONS
POWDERS ADDING

This Product Transfer Concept system can be used for powders loading in several equipment:
HSM, FBD, Vessels, Blender, Sieving systems, etc…
Some limitations should be observed in the MIE, flow and Ex certification of the equipment
MAINTAINING INERT CONDITIONS
LIQUIDS ADDING
We should ensure that the inert conditions (below MPOC) are maintained all the time
inside of the equipment meanwhile flammable vapors/dust are present.
Several ways can be considered for liquids dosing in a closed manner.
Even though a closed manner is considered, usually 50% of added powder is air. So the
proper steady purge should be considered. Calculation method available in EN Standards

ing from froma

y feed er ping
it
Grav contain Pu m
nta iner
co
MAINTAINING INERT CONDITIONS
STEADY PURGE
• We should ensure that the inert conditions (below MPOC) are maintained all the time
inside of the equipment meanwhile flammable vapors/dust are present.
• It will be necessary to have a steady purge of inert gas to keep oxygen out, during all
the operations and until flammable vapors/dust have disappeared.

Usually this purge is done at a lower pressure but this is

should be carefully calculated and monitored.
Monitoring can be done in different ways:
• Flow of inert gas: Flowmeter or simple Rotameter
• Direct continuous measuring of O2 in the venting

This steady purge is specially required when:

• During liquids and powders adding (previous slides)
• Vessel/container “breaths” due to liquid unloading. Usually pumping
from solution preparation vessel to the next equipment (FBD, HSM,
Coater, …)
• As much as physically feasible all manufacturing
steps should be done in a closed manner, if not
possible the proper minimization measures
should be considered:
• Minimize the size of ports, time of the
operation, allow recovery time for inert
conditions, etc …
• It should be carefully evaluated activities, due to
N2 and flammable vapors release, such as:
• Sampling
• Liquids addition
• Powders addition
• Materials extraction (solution or blended
powders)
• Breakdowns that will required open closed
equipment
• It should be carefully review potential leaks:
• Inspection ports, charge holes, loose covers,
damaged gaskets, etc …
• The proper control should be in place like
local extraction of N2 and flammable vapor.
 18.5% is usually the
lowest limit
considered for
triggering stoppage.
Usually above this
value a warning alarm
should be set.

https://www.youtube.com/watch?v=jNsKGx94_KE
• All manufacturing steps should be done in a closed manner.
• It should be carefully evaluated activities such as:
• Sampling
• Liquids addition
• Powders addition
• Materials extraction (solution or blended powders)
• Breakdowns that will required open closed equipment
 • 2 TEVA SPC are available within TEVA EHSMS Chemical Management and Hazard Communication:
• TEVAEHS-GDE-05-311.02 & TEVAEHS-GDE-05-312.02

• Recommended to use an excess flow valve in the Nitrogen line and minimize the pressure.
(Do not rely “only” on this device, as even low flow of toxics/flammable can be still high enough to
cause a major incident.
• Reliable flexible hoses for the gas and pressure handled. Proper maintenance in place.
• Conduct venting from equipment under inert conditions to the exhaust.
• Oxygen measurement in the room and alarm in place in case of HVAC system failure
• Exhaust and LEV should be assessed for environmental concerns due to solvents vapors emissions
and Ex rating considerations.
BEYOND MANUFACTURING ROOM…
• VOC from solvents vapors should be considered in the exhaust and local extraction system.
• Proper equipment of monitoring and control should be considered accordingly: Scrubbers,
Filters, RTO, etc…
• TEVA ESHS STDS and GDE are available in EHS portal related to this topic

• Ex rating of the equipment involved in exhaust or venting should be observed.

• HAC zoning assessment should be extended beyond manufacturing room.
• Several PHA scenarios need adequate review when inerting is in place. Overpressure of N2 due
to high flow or regulator failure, N2 leak into room, low N2 flow/inadequate inerting.
• All the controls mentioned should be considered EHS critical equipment: the rotometers for N2, O2
sensors, Pressure regulators and any associated interlocks. As such they need to be identified and
included on the Maintenance program to assure reliability.
• SOPs need appropriate steps to assure N2 flowing and that O2 levels are reached and that both are
maintained with proper ignition pre operational verifications in the batch record/operator log and
periodic checks during the batch.
 Arigatou

ANY QUESTIONS ?
Send pending questions to email address: francisco.lorente@tevaes.com

Some slides based on SIGMA EHS presentation :

“Understanding Inerting as a Basis of Safety”