Summary

Invensys offers
proven Environmental
Monitoring System (EMS)
solutionsfrom Entry up
to High Availabilityto
help customers meet
the particular challenges
of the Life Sciences
Industry.

Business Value
The FDA, EMEA and
other Life Sciences
regulatory bodies
require monitoring
environmental critical
process parameters that
affect product quality
and patient health.

Environmental Monitoring
System (EMS) At A Glance
Monitoring environmental parameters might seem as easy as simply recording
some low frequency data. This is not the case. Life Sciences regulatory bodies
call significant attention to environmental critical process parameters. If a
pharmaceutical company is not able to show a proper audit trail for relevant
data, a medicine cannot be released. Hence, secure data management and
storage are vitally important.
Proper reporting, alarm management and sensor calibration are each
relevant and contribute to simple, effective solutions. Ease of expansion
and integration with HVAC or building management systems help minimize
life-cycle costs. Modular, incremental validation based on proven code
fragments and functions maximizes process availability when changes
are introduced. Invensys EMS Industry Solution Blueprint provides a
structured environment designed to promote rapid innovation and to avoid
reinventing the wheel by learning from past experiences and leveraging
the contribution of all involved parties to help deliver a risk-free, on-time
and on-budget EMS solution.

RULES TO BE APPLIED

Where environmental conditions could reasonably be expected to

have an adverse effect on product quality, the manufacturer shall
establish and maintain procedures to adequately control these
environmental conditions. Environmental control system (s) shall be
periodically inspected to verify that the system, including necessary
equipment, is adequate and functioning properly. These activities
shall be documented and reviewed. - FDA 21 CFR Part 820.70
Production and Process Controls, section c.
EMS criticality is dictated by the impact of the process parameters
being monitored on product purity, safety, quality, and efficacy (21
CFR Part 211), not the functionality of the EMS itself.
Control and monitoring of storage and production environments
have become an important issue in the Pharmaceutical Industry.
The FDA, EMEA and other regulatory bodies require accurate
measurement and storage of critical process parameters (CPPs),
and, in the U.S. if the storage medium is electronic, the methods
used must comply with 21 CFR Part 11.
The FDA also states in its 21 CFR Part 203.32a that:
Manufacturers; authorized distributors of record and their
representatives shall store and handle all drug samples under
conditions that will maintain their stability, integrity and
effectiveness and ensure that the drug samples are free of
contamination, deterioration, and adulteration.

Some regulatory
rules in place:
21 CFR Part 203, 211, 600
and 820

USP31 General Notices

FDA GuideSterile Drugs
FDA GuideCGMP for
Phase1 Drugs

EU Guide to GMPPart I & II

and Annex 1 Revision

FDA Compliance - Chapter 56

PIC/S PE005, PE009, PI005,
PI007, PI012

FDA Guide to Inspections

FDA Biotechnology
Inspection Guide

ICH Q7A

There is virtually no pharmaceutical production where the monitoring of environmental parameters

is not required.

GUIDANCES AND REFERENCES

The International Society for Pharmaceutical Engineering (ISPE)

Baseline Guides provide detailed information and recommend
practices for implementation of EMS and HVAC systems in
pharmaceutical facilities. Often EMS is mixed/embedded within
HVAC or BMS (Building Management System)/BAS (Building
Automation Systems) control systems. Over the last five years, it
has been common practice to consider BMS/BAS systems as the
sum of a validated EMS plus a GEP HVAC (with Access and Fire
controls considered as options). The latest information can be
obtained by joining the ISPE HVAC Community of Practice (CoP).
It is common practice to qualify monitoring systems (sensors,
transmitters, indicators, recorders, alarms, etc.) for those parameters defined as critical and to use GEP to ensure the development
and maintenance of a robust control system A-1.6.17
It may be possible to monitor, record, and alarm with portable
or other instrumentation which is not a part of the HVAC control
system in order to avoid validating control system vendors
proprietary software B-6.8

Some reference guides:

A. ISPE Good Practice Guide
Heating, Ventilation, and
Air Conditioning (HVAC)
Sep 2009
B. ISPE Baseline Guide
Volume 1: Bulk
Pharmaceuticals Chemical
2nd Ed. Jun 2007
C. ISPE Baseline Guide
Volume 2: Oral Solid
Dosage Forms 2nd Ed.
Nov 2009
D. ISPE Baseline Guide
Volume 3: Sterile
Manufacturing Facilities
1st Ed. Jan 1999

It is possible to monitor, record, and/or alarm with portable or other instrumentation, which is not
part of the HVAC control system C-7.4.2
It may be preferable that the monitoring and documenting of these GMP Critical Parameters
should be isolated from any HVAC (Building Management System: BMS) control systems, to avoid
qualification complications D-5.8.2
When specifying systems to control HVAC, the following should be considered:
HVACs industrial nature in cleanroom applications may not justify use of PLC- or DCS-based solutions
pharmaceutical HVAC can be controlled satisfactorily using HVAC industry control systems
Other factors that may support use of PLC- or DCS-based systems; however, these are unlikely to offer
baseline solutions. D-8.7.1

APPROACH - FIT TO ADOPT

Independent Integrated Monitoring Systems

GMP and non-GMP EMS/BMS are often monitored independently
through segregated solutions and then integrated later.
Integrating independent EMS, BMS and CEM systems results in:
a sizable decrease in validation efforts
elimination of sensor duplication and wiring
integrated diagnostic and alarm management
energy and maintenance optimization
A reasonable approach is to employ an independent system for
alarming and managing critical process parameters. The BMS
(BAS, HVAC) control system is limited to control and maintenance
information required to manage a facility.1

The most scalable, reliable,

innovative, fault tolerant and
cost effective EMS system
Collaborative approach
leveraging Open Connectivity,
Active Intelligence and
Advanced Graphics
Fast DeploymentFast Results
Engineering effort reduced
by 50% including GAMP
documentation
Comprehensive Invensys
Global Ecosystem

It is a common practice to validate (qualify) an environmental

monitoring system (EMS) for those parameters defined as process
critical and to use good engineering practices (GEP) to ensure the
developments and maintenance of a robust control system (BMS, BAS, HVAC).2

The implementation of independent monitoring systems also may bring the added benefit in terms of
minimizing the risk of simultaneous failure of control and monitoring functions.3
Adopting Invensys unique software marshaling results in avoiding sensor duplication for ease of
maintenance, increased precision and quality data to the BMS, while maintaining the EMS and BMS
systems segregated for ease of validation compliance.

________________________________________
ISPE GPG - HVAC - Page 180 (8.5.1).
ISPE GPG HVAC - Page 188 (8.5.6).
3
ISPE PE Use of BMSs and EMSs in Regulated Environments (Vol. 25, No. 5) Page 13, 1st sentence.
1
2

CRITICAL PROCESS PARAMETERS

Critical process parameters should be managed by an EMS

integrated with, but separated from, a BMS (BAS, HVAC).
This approach provides the quality unit with a record from
a validated system of room conditions during process
operations, without the need for a formal change control
process for the HVAC control system (an engineering charge
control is still required, which typically is more manageable
and less extensive in its scope, e.g. it may include only
some set points and some hardware in the system).
According to the product impact on patient safety each of
the parameters listed above could be classified as critical
4, 5, 6, and 7
(CPPs related to CQAs) requiring to be managed
under a GMP qualified framework. Critical parameters are
part of direct impact systems as defined in the ISPE Guide
Volume 5: Commissioning & Qualification.8
Usual Critical Process Parameters:
Temperature (T)
Relative humidity (RH)
Differential pressure (DP)
Airborne particles (AP)
Air changes (AC)
Terminal HEPA filters status

Critical Process Parameters

(CPPs) as those that have a
high probability of affecting
product quality attributes if
they deviate from stated limits
for a defined period of time.
CPPs are derived from the
relevant Critical Quality
Attributes (CQAs).8
CPPs should be identified as
early as the writing of the User
Requirements Specification
(URS).

Additional parameters:
Door status
External temperature
AHU(s) status
AHU(s) operating mode
Room occupancy

________________________________________
ISPE GPG - HVAC (2.2.1), (8.5.6.1)
ISPE Guide Volume 1: Bulk Pharmaceuticals Chemicals 1st Ed. Jun 1996 (6.4, Table 6-1), (6.8)
6
ISPE Guide Volume 2: OSD Forms 2nd Ed. Nov 2009 - (3.1.1), (3.1.2.3), (3.1.2), (6.3.6), (7.1), (7.4.1)
7
ISPE Guide Volume 3: Sterile Manufacturing Facilities 1st Ed. Jan 1999 (5.4.2), (5.8.1), (5.8.2), (8.2.1), (12.1.2), (12.2), (12.2.1)
8
ISPE GPG HVAC - Page 35 (2.3.1).
4
5

REQUIREMENTS AND FUNCTIONS

Also known as Scope of Supply. Requirements should be

described in the User Requirements and Quality Plan documents.
Main factors to consider when specifying sensors and devices for
CPP monitoring (GMP relevant):
Accuracy, repeatability, stability and failure modes
Alarm requirements
Design point and tolerance (Hi-Lo range)
Operation thresholds and validated acceptance criteria
Maintenance and calibration requirements
Required system functions need to be addressed as well:
Sensor operating modes and failure detection
Alarm management
Local displays, operator practices, site or company standards
Security (redundancy, time stamping, data archiving)
Reporting, Electronic Batch Records, Records requirements
Back-up and recovery
Calibration
Most of these come from existing procedures, equipment in
place, site best practices, corporate guidance, and regulatory
predicate rules.

Risk assessment is used as a

process to evaluate the impact
of systems or components on
product quality. Cost to the
business has to be considered
as well.
For a complex, centralized
system, there may be several
users including engineering,
system and data owners,
subject matter experts,
and quality assurance. It is
important that the needs of
all stakeholders are captured
and aligned in the URS.
An effective approach
when conducting the risk
assessment is to assess each
component (e.g., room,
laboratory, utility area),
equipment, and functions
(e.g., alarm annunciation
and reporting, data historian,
network).

SOLUTION ARCHITECTURES

The Invensys Environmental Monitoring System is designed to satisfy

the requirements of prominent regulatory bodies (e.g., U.S. FDA and
its 21 CFR Part 11). The EMS offers:
Scalability, from a single room to a plant-wide solution
Simplified validation using flexible and modular standard code
fragments functions based on a dedicated EMS object
Centralized and/or remote monitoring of facilities and equipment
Intelligent alarm capability for early warning of process deviations
Secure management and storage of environmental data and audit
trails
Facilitated enhancement and expansion
Predictive maintenance planning
Integrated with Invensys Facilities Management System application
Integrated with Invensys Corporate Energy Management
application

From new plant to

refurbishment:

Perform a risk assessment

Identify new/existing CPPs
Select the best fit
architecture

Expand/maintain leveraging
the compliance oriented
area-room based code
fragments made available
by Invensys EMS blueprint.

Four different template architectures are available:

Entry: designed around Eurotherm recorder proven functionalities. One or more recorders (paper or
paperless) can be networked providing local visualization and tamperproof data logging. Sized for
one or more rooms, equipment and cold stores.
Simplex: looking for a cost-effective Microsoft Windows-based operator station with a few
distributed I/O devices and web reports, easily expanded and validated? If so, this is the solution.
Ideal for warehouses, laboratories and climatic chambers.
Redundant: unique fully hot redundant solution, with built-in store & forward and Wonderware SQL
Historian. Designed for manufacturing, sterile facilities, and large facilities.
High Availability: large, object-based, hardware agnostic, fully redundant, time proof, and state-ofthe-art solution. For all critical applications.

DOCUMENTATION

A key requirement for EMS solutions is validation. Where environmental conditions (e.g. temperature,
humidity, differential pressure, air flow, sterility, containment) have a direct impact on product purity,
safety, quality or efficacy, they need to be monitored against predetermined limits and logged. In this
case, the BMS/EMS system used for collecting and logging the data needs to be validated.
Each EMS project will require the following sets of documentation:
Project Planning Documents: AF&IDs, Design Basis, Air Balance, Critical Instruments Specification,
Health & Safety Procedures. Many of these docs are Critical master documents and to be provided
as as-build versions.
GEP and Validation Documents: Risk Assessment, Traceability Matrix, User Requirements, Project
Plan, Quality Plan, Design Specification, Test Protocols, IQP, OQP, PQP, and Thermal Mapping
Other GEP Documents: Drawings Package, Bill of Material, Calibration SOP, Handover Checklist,
Operator Manuals, Contractual Ts&Cs, Sub-contractors Quality Systems, Expediting-InspectingDelivery Control Procedures
Commissioning & Qualification Documents: Test Protocols and Test Results, Acceptance Criteria
Most of these documents will be part of the EMS Blueprint. Invensys Compliance Services Team is
available during project planning and execution.
For additional information, refer to Heating, Ventilation, and Air Conditioning (HVAC), Section 6,
Documentation Requirements, ISPE Good Practice Guide, September 2009.

Initial Risk
Assessment

Iteration as
required

Functional Risk
Assessment

User Req.
Specification

Requirements
Testing

Functional
Specification

User Testing of
Controls & Procedures

Functional
Testing

Configuration
Specification

Configuration
Testing

Module (Unit)
Specification

Testing of System
Controls

Module (Unit)
Testing

Code Modules

Invensys Operations Management 5601 Granite Parkway III, #1000, Plano, TX 75024 Tel: (469) 365-6400 Fax: (469) 365-6401 iom.invensys.com
Invensys, the Invensys logo, ArchestrA, Avantis, Eurotherm, Foxboro, IMServ, InFusion, SimSci-Esscor, Skelta, Triconex, and Wonderware are trademarks of Invensys plc, its subsidiaries or affiliates.
All other brands and product names may be the trademarks or service marks of their representative owners.
2011 Invensys Systems, Inc. All rights reserved. No part of the material protected by this copyright may be reproduced or utilized in any form or by any means, electronic or mechanical, including
photocopying, recording, broadcasting, or by any information storage and retrieval system, without permission in writing from Invensys Systems, Inc.

Rel. 08/11

PN I-LS-0104