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Revision# 0

Pfizer Global Engineering Guideline


Issued by:
R. Hansen
Publication Date:
January 09, 2007

1.

Room Differential Pressure Operating Levels


for Non-Aseptic Drug Product Manufacturing
Facilities

Review Date:
January 09, 2010
Supersedes:
None (new)

PURPOSE:
The purpose of this document is to provide guidance for establishing operating
levels for room differential pressure and associated alarms.

2.

SCOPE:
This guideline applies specifically to new and existing Drug Product
Manufacturing Facilities, producing non-aseptic products and materials,
classified as OEB-1 OEB-3.
This guidance does not apply to Aseptic Manufacturing Facilities, or to products
classified as OEB-4 or OEB-5. For Aseptic Manufacturing Facilities, refer to
Pfizer PQS FE2101, Air Handling Systems and Air Classifications for Aseptic
Operations.
This guideline documents good practice. It is not the intent of this guideline to
mandate modifications or alterations of existing facilities that comply with
product and process requirements and current regulatory expectations.
While no regulatory requirements currently exist for maintaining a specific
magnitude of differential pressure between rooms, expectations vary between
regulatory agencies and across different regions. Existing facilities should be
assessed for compliance with regulatory requirements and expectations for the
markets they serve.
Assessments may also consider actual operating differential pressures, degree
of criticality of differential pressure in controlling cross-contamination, presence
of airlocks (which may allow the use of lower pressures), etc., when evaluating
whether to make changes to meet the operating conditions suggested in this
guideline.
Note: Installations presently operating with room differential pressures that are
of greater magnitude than the values indicated herein do not need to reduce
their differential pressures to meet this guideline. However, doing so (possible
energy savings) may be acceptable if all issues are addressed and agreed
upon with appropriate stakeholders (e.g., the impact on previously qualified
environments will require assessment, and potential re-qualification).

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Revision# 0

Pfizer Global Engineering Guideline


Issued by:
R. Hansen
Publication Date:
January 09, 2007

3.

4.

Room Differential Pressure Operating Levels


for Non-Aseptic Drug Product Manufacturing
Facilities

Review Date:
January 09, 2010
Supersedes:
None (new)

DEFINITIONS:
Room Differential Pressure

The pressure directly measured between two


rooms (or room and corridor). Where
independent measurements are made
between individual rooms and a common
reference point, it is the difference between
the measured values for each pair of rooms.

Alarm (room pressure)

A visual or audible indication that a


differential pressure alarm limit has been
exceeded. Alarms can indicate deviation
from GMP-Critical limits (e.g., Action Level) or
deviation from the Non-GMP Critical normal
operating limits (e.g., Alert Level).

RESPONSIBILITIES:
Site Engineering Departments are responsible for ensuring that the guidance in
this document is followed where it has been determined that there is a need to
do so.

5.

GUIDELINE:
There is commonly a directional airflow between different manufacturing rooms,
manufacturing rooms and manufacturing corridors, etc. to limit the potential for
cross-contamination between rooms or areas.
Because it is easily measured, the differential pressure associated with the
directional airflow is the parameter that is commonly established during design
and operation.
The differential pressure should be of sufficient magnitude that it will;
result in a stable directional airflow (smoke test) that is not easily
disturbed by normal movement of personnel and equipment
be easily and accurately measured with standard instrumentation (e.g.,
Magnehelic gauge)
meet any applicable regulatory requirements

2 of 4

Revision# 0

Pfizer Global Engineering Guideline


Issued by:
R. Hansen
Publication Date:
January 09, 2007

5.1

Room Differential Pressure Operating Levels


for Non-Aseptic Drug Product Manufacturing
Facilities

Review Date:
January 09, 2010
Supersedes:
None (new)

OPERATING DIFFERENTIAL PRESSURE (door-closed values)

When pressure differential is used as an engineered control to minimize the


migration of airborne particulate between adjacent spaces, it is recommended
that the OPERATING differential pressure be greater than (or equal to) 0.02inches-water (5.0 Pa).
5.2

DIFFERENTIAL PRESSURE ALARMS

Alarms that indicate deviation from GMP-Critical differential pressure levels are
often installed.
GMP-alarms should remain active until manually acknowledged and reset
(latching type).
Criteria to consider when determining the alarm strategy (e.g., alarm limit and
time delay period) include, but are not limited to:
The normal operating differential pressure value (set-point or target)
The degree of criticality of differential pressure in controlling crosscontamination (e.g., degree of process closure, product type and
properties)
The normal functioning of the room (e.g., door usage)
The accuracy of the monitoring system/equipment
Non-aseptic manufacturing rooms are commonly connected directly to the
manufacturing-corridor (i.e., without airlock) by large doors that allow for the
passage of personnel and materials/equipment. This means that such rooms
are generally in one of two operating states:
door closed maintaining operating differential pressure
door open zero differential pressure
The alarm strategy should to address the way normal non-aseptic
manufacturing rooms function.
Alarms should incorporate a time-delay
between the time an alarm limit is exceeded and the time an alarm is initiated.
This delay should to be of sufficient time to allow for normal functioning of the
facility (e.g., opening and closing of doors, movement of people and material in
and out of rooms).

3 of 4

Revision# 0

Pfizer Global Engineering Guideline


Issued by:
R. Hansen
Publication Date:
January 09, 2007

Room Differential Pressure Operating Levels


for Non-Aseptic Drug Product Manufacturing
Facilities

Review Date:
January 09, 2010
Supersedes:
None (new)

Differential pressure GMP-Alarms are generally low-limits. High-limit differential


pressure alarms are not generally applied.
An example of a GMP-alarm strategy might be to alarm when the differential
pressure between two rooms is less than or equal to 0.001 inches-water (0.25
Pa) for 10.0 minutes or longer. Note that the actual alarm set-point of the
monitoring system/equipment might be a slightly greater value to account for
measurement system accuracy.
6.

REFERENCES:
PGE Pharmaceutical Drug Product Manufacturing And Packaging Module
Design/Construction Guidelines (differential pressure design values for new
facilities or significantly upgraded modules)

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