A Deep Dive Into MES Integration For Enhanced Biopharmaceutical Manufacturing

MES OF THE FUTURE
Unlocking efficiency:
a deep dive into MES
integration for enhanced
biopharmaceutical
manufacturing
Contents
1.0 Introduction . ...................................................................................................................................................................................... 6
2.0 Problem statement ........................................................................................................................................................................... 7
3.0 Benefit statements . .......................................................................................................................................................................... 8
4.0 General points to consider for interfaces ................................................................................................................................. 10
5.0 Scope ................................................................................................................................................................................................ 12
6.0 Interface considerations and guidance . .................................................................................................................................... 13
7.0 ERP (material management) ......................................................................................................................................................... 15
8.0 ERP (batch management) . ............................................................................................................................................................ 18
9.0 ERP (order management) .............................................................................................................................................................. 21
10.0 ERP (inventory management) ...................................................................................................................................................... 24
11.0 Electronic document management system (EDMS) ................................................................................................................ 26
12.0 Laboratory information management system (LIMS) ............................................................................................................. 28
13.0 Data Historian . ............................................................................................................................................................................... 32
14.0 Autonomous mobile robots and guided vehicles (AGV, AMR) ............................................................................................. 35
15.0 Batch execution (BE) application ................................................................................................................................................ 37
16.0 Computerized maintenance management system (CMMS) .................................................................................................. 40
17.0 Quality management systems (QMS) . ....................................................................................................................................... 43
18.0 Learning management systems (LMS) ....................................................................................................................................... 45
19.0 Product lifecycle management (PLM) ........................................................................................................................................ 47
20.0 Conclusion ....................................................................................................................................................................................... 52
Glossary . .......................................................................................................................................................................................... 54
References ....................................................................................................................................................................................... 55
List of figures
Figure 1: Adaptation of the ISA 95 automation functional model/pyramid with example system solutions assigned3 ..................................................................................7
Figure 2: System integration flow diagram ...................................................................................................................................................................................................................... 14
Figure 3: ISA S88 Hierarchy Model ................................................................................................................................................................................................................................... 42
List of tables
Table 1: In-scope interfaces ................................................................................................................................................................................................................................................ 12
Table 2: In-scope interfaces and proposed order of priority ...................................................................................................................................................................................... 13
Unlocking efficiency: a deep dive into MES integration

©BioPhorum Operations Group Ltd | March 2024 2
for enhanced biopharmaceutical manufacturing
About BioPhorum
BioPhorum’s mission is to create environments
where the global biopharmaceutical and device
industry can collaborate and accelerate its rate
of progress, for the benefit of all.
Since its inception in 2004, BioPhorum has become the
open and trusted environment where senior leaders of the
biopharmaceutical industry come together to openly share and
discuss the emerging trends and challenges facing their industry.
Growing from an end-user group in 2008, BioPhorum’s membership now

comprises top leaders and subject matter experts from global biopharmaceutical
manufacturers and suppliers, working in both long-established and new Phorums.
They articulate the industry’s technology roadmap, define the supply partner
practices of the future, and develop and adopt best practices in drug substance,
fill finish, process development and manufacturing IT.
In each of these Phorums, BioPhorum facilitators bring leaders together to create

future visions, mobilize teams of experts on the opportunities, create partnerships
that enable change and provide the quickest route to implementation, so that the
industry shares, learns and builds the best solutions together.
BioPhorum IT: MES of the Future

The MES of the Future workstream is a collaboration between leading
biopharmaceutical manufacturers and software vendors working together
to bring about a shared vision for digital technology which will form the
basis of the MES of the future.
For more information on the MES of the Future workstream mission and membership, go to
www.biophorum.com/MES-of-the-future

Authors
Apprentice.io Merck
Younge Qu Frank Krüger
Dassault Systèmes Takeda
Clément Glace Amina Didouche
Eli Lilly Vertex Pharmaceuticals Incorporated
Francisco Gonzalez Rob Gamber
Lonza
Bernard Corcoran
Contributors
AbbVie Emerson
Chris Jasensky Dewan Afzal
Roberto Liotino Christian Berg
Apprentice.io Johnson & Johnson Innovative Medicine
Emilee Cook Stephen Fleming
AstraZeneca Lonza
Marian Cebula Robert Lutskus
Krystal Hinderliter
Merck
Bayer Braj Nandan Thakur
Bianca Brenner
Novo Nordisk
Bristol Myers Squibb (BMS) Rebecca Julie Nørgaard
Nirav Patel
Rockwell Automation
Catalent Thomas Jacobsen
Chuck Mina Matt Weaver
Dassault Systèmes Takeda
Kim Wilson Elton Ramos
Eli Lilly BioPhorum
Floyd Springer Ciéra Clayton
This publication has been created through the combined efforts of companies and their representatives of
the BioPhorum MES of the Future strategic program.
Contributions from the team ranged from direct and significant involvement, engagement, and participation
through to fulfilling a monitoring role.

Executive summary
In the current biopharmaceutical manufacturing landscape, efficient

orchestration of end-to-end production processes is critical for success.
Manufacturing execution systems (MES) have evolved from basic
data collection tools into sophisticated systems that drive operational
excellence. However, their full potential is only unlocked when
integrated seamlessly with other software solutions.
This white paper outlines the significance of MES integration with systems such as enterprise
resource planning (ERP), quality management systems (QMS) and laboratory information
management systems (LIMS). A lack of standardized processes in the industry has led to
complexity, hindering implementation and scalability. These integration challenges result in
manual data entry, increased deviations, longer release times and higher costs.
Specific integrations highlighted in this paper through use-cases can streamline operations,
enhance efficiency, reduce costs and offer real-time visibility across departments and
business units. Clear guidelines and recommendations for integrating MES provide a shared
understanding of the value proposition and offer insights into the ‘why’ and ‘what’ of MES
integration for both manufacturers and supply partners.
Understanding the synergy between MES and other biopharmaceutical manufacturing
systems can empower companies to plan strategically, optimize production processes and
advance toward higher digital plant maturity. During implementation, it is crucial to consider
factors such as quality impact, automated interfaces, business continuity, security and data
governance for successful deployment.
In summary, MES integration is critical for enhancing biopharmaceutical manufacturing
operations and achieving digital maturity. By following these guidelines and recommendations,
this paper facilitates alignment between companies and vendors, enabling them to realize the
benefits of a comprehensive and efficient manufacturing ecosystem.

1.0
Introduction
In today’s manufacturing environment, it is essential to have an efficient and effective end-to-end workflow
to manage production processes, from the planning stages to the final delivery of goods. MES play a crucial
role in achieving this goal. MES have evolved significantly over the years, from simple data collection tools
to sophisticated systems that can provide a wide range of capabilities. They have become an integral part
of modern manufacturing operations, enabling companies to streamline production processes and optimize
performance. However, an MES cannot operate in isolation; it must be integrated with other systems to
provide a comprehensive view of the entire manufacturing process.
“Unlocking the full potential of manufacturing operations is akin to

lowering drawbridges from the MES, transforming the once-isolated
‘castles’ of data into interconnected hubs. Interfacing can act as the
key, enabling seamless communication in and out, and heralding
a new era of possibilities for enhanced efficiency and innovation
across the manufacturing landscape.”
Stephen Fleming, MES Product Line Leader
Johnson & Johnson Innovative Medicine
The integration of MES with other biomanufacturing In this white paper, the authors provide an overview
software solutions has become increasingly important of common biopharmaceutical industry systems and
in recent years. Integrating these systems enables their relationship with MES, including related integrated
manufacturers to streamline their operations, improve processes such as materials management, sample
efficiency, improve data quality and reduce costs. management, training and others (see Section 5).
Defining the integrations in a systematic manner will allow We discuss the key considerations when identifying
manufacturing execution to occur in the most effective way. the functional integrations needed with those systems
Additionally, integration provides real-time visibility into supporting the inter-related processes. Whether
manufacturing operations, enabling companies to manage you are a manufacturer looking to optimize your
production processes, monitor equipment and control production processes or an IT professional tasked
quality. Showing a holistic view of the entire manufacturing with implementing MES integration, this white paper
process allows for better decision-making and improved provides you with valuable insights and guidance on
collaboration across different departments. Regarding Digital how to envision an ecosystem and workflow for a
Plant Maturity Model 3.01, to achieve a level 4 or level 5 holistic manufacturing process.
plant maturity, your organization would be required to
interface the MES with the appropriate solutions.

2.0
Problem statement
Integrating MES with other systems has become increasingly complex and challenging. The integration of MES
with other solutions is critical for providing an effective way of executing the entire manufacturing process to
improve efficiencies within data transfer. This will reduce the need for manual entry (and minimize human error),
therefore reducing time and cost to manufacture.
The current integration process is complex and not user-friendly, leading to difficulties in set-up and configuration
for biomanufacturers. The systems detailed in Figure 1 are at different levels of integration maturity, which can result
in a misalignment in the capability to connect with different functionalities across the levels. Vendor lock-in is also a
common problem, limiting pathways for custom integrations and increasing reliance on vendor support.
Figure 1: Adaptation of the ISA 95 automation functional model/pyramid with example system solutions assigned3
Level 4:
Business
Management level and logistics ERP, EDMS, CMMS, QMS, LMS, PLM
Level 3:
Planning level Manufacturing MES, LIMS, Data Historian
operation planning
Level 2:
Supervisory level SCADA, DCS
Monitoring and supervising
Level 1:
Control level Sensing and manipulating PLC, AGVs, AMRs
the production process
Level 0: Machinery,
Field level
Physical production process sensors, etc.
These complexities often discourage customers from integrating their systems, which limits the system’s functionality
and scalability. In cases where legacy equipment is incompatible, upgrading the equipment and the plant to make it
compatible is costly and can outweigh the expected benefits. Without properly considered integrations, end-users must
rely on manual data entry, leading to increased deviations, longer release times and a more resource-intensive process,
ultimately increasing the total cost of ownership.
This white paper addresses the challenges of MES integration with other solutions relating to manufacturing and
proposes a guideline for vendors and biomanufacturers to support interface integrations with MES.

Sub Team 2
“We see more and more Pharmaceutical Organizations
3.0 investigating PLM solutions and how they can integrate
with MES. This is a great way for organizations to improve
data integrity and overall manufacturing agility to meet
Benefit statements
evolving demand needs.”
The goal of this white paper is to provide recommendations for a well-integrated MES in a clear IT
environment.
Clément It is intended to support biomanufacturers to make the right business choices and help supply
Glace
partners consider these needs in their roadmaps.
Life Sciences & Healthcare Solution Consultant, Dassault Systèmes
“For us, deciding on the priority for implementation of interfaces is

“For us, deciding on the priority for implementation of
one of the crucial elements of designing successful MES projects.
interfaces is one of the crucial elements of designing
Independent of the technical standards and realization, it is essential
successful
to know which MES projects.
information must beIndependent of the
exchanged with the MES.technical
standards
For and
that purpose, werealization, it is essential
cherish the exchange with other to know which
information must be exchanged with the MES. For that
biomanufacturers and suppliers in BioPhorum.”
Frank Krüger, Digital
purpose, Business Processes
we cherish Specialist, Global
the exchange withCMCother
Development
Merck
biomanufacturers and suppliers in BioPhorum.”
Frank Krüger
Digital Business Processes Specialist, Global CMC Development, Merck
Benefits to biomanufacturers Benefits to MES supply partners

• Improved understanding of the value • Identification of industry-specific needs, challenges
proposition, challenges, and best practice for and trends regarding MES integration and potential
MES integration in the biopharmaceutical solutions to help biomanufacturers
industry through several use-cases • Improved ability to tailor messaging, product
• Increased awareness of the importance and potential offerings and sales strategies to address
of MES integration leading to increased adoption biomanufacturer needs more effectively
• Practical guidance and clear recommendations on • Practical guidance to identify gaps and areas for
how to successfully integrate MES in a given IT improvement, best practices and industry guidelines
ecosystem, which can enable the prevention of for successful MES integration to provide the insights
common mistakes, optimizing the implementation into solutions and product development
process and achieving other desired outcomes • A way to collaborate and share knowledge inside the
• A way to collaborate and share knowledge inside company and with biomanufacturers
the company and with MES supply partners • Alignment with industry standards and guidelines
• Alignment with industry standards and guidelines related to MES integration that are adopted across
related to MES integration that are adopted across the biopharmaceutical industry.
the biopharmaceutical industry.

How it will influence the industry
If the recommendations in this white paper are followed, • Improved product quality, reduced waste
biomanufacturers could achieve: and more informed decisions
• Optimized production costs and manufacturing • Fewer errors, less training and reduced
efficiency by improving best practices, organizational change time by minimizing
streamlining processes and enhancing seamless manual transcription between systems
data flows between MES and other systems • Increased speed to market through dynamic and
• Enhanced data integrity, traceability and agile integrations
compliance with regulatory requirements to • Faster implementation of the MES solution and
meet regulatory expectations and navigate its associated interfaces leading to accelerated
audits more effectively digital maturity of your manufacturing.

4.0
General points to consider for interfaces
While the interfaces described in this paper are generally considered mainstream and deliver both data quality
and productivity benefits, any interfacing deployments should be undertaken with a thorough understanding of
some key points that usually apply across all interfaces:
• Quality impact—any system deployment should be • Risk of interfaces being unavailable—
undertaken with a solid understanding of potential MES themselves are typically architected to
impact on the patient’s needs. Product quality, patient be highly available. This is not always the case
safety and data integrity should be considered when for systems that require an interface with MES
integrating the MES external system. All interface systems interface. It is best practice to consider
deployments should include a risk assessment of the effects when external systems are offline.
potential risk to overall product quality and the One strategy is to create interfaces that are not
control mechanisms that should be put in place to highly coupled. Data buffering can be leveraged
mitigate any identified risks such that real-time connections are not needed
• Automated interfaces—while automated to start or continue manufacturing. In the
interfaces boost productivity by eliminating absence of buffering capabilities, a high degree
the need for manual data transfer, they should of consideration should be given to robust
not be left to operate unchecked. Monitoring business continuity plans that can be deployed
solutions should identify any failed transactions easily and quickly should critical connections
and inconsistent heartbeats/exception-based become unavailable
communications results and alert appropriate
personnel to act. All automated interfaces should
impose positive confirmation logic that only
proceeds when a positive response is received
and not the reverse
“Integration is key
“Integration to creating
is key a connected
to creating enterprise
a connected
and raising our digital maturity; increasing productivity
enterprise and raising our digital maturity;
and improving data integrity.”
increasing
Robert Gamber, productivity andPrincipal
Business Systems improving
Analystdata
integrity”
Vertex Pharmaceuticals Incorporated
Robert Gamber
Business Systems Principal Analyst, Vertex Pharmaceuticals Incorporated

• Security—major concerns with interfaces that language. Once the master data sources are
write data into MES, are around the security identified, it is imperative that governance
of those external systems and how data are processes are established to maintain the
transferred from one system to another. This can master data elements. Therefore, if something
include user authentication and authorization, is changed in one system, the impact of that
data encryption and network security. Security change needs to be understood by all systems
assessments should be conducted to ensure the consuming that information. For example, when
interfacing systems have appropriate control to rules around defining product shelf life are
ensure that only authorized users can access the changed, it is important to assess how the rules
data to be interfaced. Secure socket layers and are used to calculate an expiration date. It is
transport layer security are generally considered recommended that your organization complete
industry standards for securing data transfers a full assessment for the needs of the interfaces
between systems. While the purpose of this and the requirements and content of the data
white paper is not to provide design direction, being exchanged, as a common tendency is to
companies should ensure that mechanisms are in overpopulate the data
place for data in transit • Verification signals—an area of consideration
• Data governance—when embarking on an when implementing interfaces is the inclusion
interface strategy, it is critical to identify the of verification signals from the target to the
appropriate systems of a record for all critical source system. Including these signals provides
master data. Having a single version of the a level of confidence that all data transfer is
truth for data elements improves data quality successfully taking place as expected (especially
and ensures all systems are talking the same where real-time data is being transferred).

5.0
Scope
In scope
Table 1 lists the interfaces that are in scope of this white paper.
Table 1: In-scope interfaces
Interface
Enterprise Resource Planning (ERP) (material management)
Enterprise Resource Planning (ERP) (batch management)
Enterprise Resource Planning (ERP) (order management)
Enterprise Resource Planning (ERP) (inventory management)
Electronic Document Management System (EDMS)
Laboratory Information Management System (LIMS)
Data Historian (DH)
Autonomous Mobile Robots and Guided Vehicles (AMR, AGV)
Batch Execution application (BE)
Computerized Maintenance Management System (CMMS)
Quality Management Systems (QMS)
Learning Management Systems (LMS)
Product Lifecycle Management (PLM)
These topics are in scope for each of the Out of scope

interfaces in Table 1:
This paper does not focus on:
• Use-case
• Technical details or data standards within
• Benefits (value proposition) these interfaces
• Data exchange (inputs and outputs) • Risk and business continuity management; however,
• Challenges/limitations. it is recognized that this is an important business
consideration when integrating new systems
• How to integrate these systems in terms of business
changes and decisions
• How to utilize the data housed within these systems.

6.0
Interface considerations and guidance
Interface integrations with MES can bring numerous benefits, however, when integrating MES with
different interfaces, an organization is unlikely to have the capability to integrate with all available interfaces
simultaneously. The time, cost and resource requirements for interface integration with MES vary depending on
several factors, including the complexity of the integration, the existing infrastructure, the number of systems
involved and the expertise of the implementation team. Therefore, it is likely an organization will complete
various integration projects separately over time.
To decide which interface is best to integrate first, it is important to know what the interfaces provide from an MES
perspective. In this white paper we propose an order of priority for integration with several common interfaces (Table 2),
with number 1 being of the highest value. This list is not exhaustive and includes only 11 interfaces for integration.
Table 2: In-scope interfaces and proposed order of priority
Interface Priority
Enterprise Resource Planning (ERP) (material management) 1
Enterprise Resource Planning (ERP) (batch management) 1
Enterprise Resource Planning (ERP) (order management) 1
Enterprise Resource Planning (ERP) (inventory management) 1
Electronic Document Management System (EDMS) 2
Laboratory Information Management System (LIMS) 3
Data Historian (DH) 4
Autonomous Mobile Robots and Guided Vehicles (AMR, AGV) 4
Batch Execution application (BE) 4
Computerized Maintenance Management System (CMMS) 5
Quality Management Systems (QMS) 6
Learning Management Systems (LMS) 7
Product Lifecycle Management (PLM) 8

It is important to note that the prioritization of interfaces may differ based on the specific needs and priorities of
each organization. It is recommended to involve a cross-functional team, including representatives from different
departments, to collectively assess and prioritize the interfaces for integration with MES. This collaborative approach
helps ensure a comprehensive and well-informed decision-making process. The framework in this white paper for each
interface may be utilized to map your own company-specific interfaces, if not listed in Figure 2.
Figure 2: System integration flow diagram
STAGE ONE
ERP - Batch ERP - Order

Management Management
ERP - Material
ERP - Inventory
Management Management
T
ST
IGH
AG
EE
ET
STAG
WO
PLM EDMS
MES
E SEVEN
STAGE THR
LMS LIMS
STAG
EE
Autonomous robots
QMS and guided vehicles
(AMR, AGV)
ST
AG
E
SI
CMMS Batch Execution

X
application (BE)
Data
ST Historian
R
AG OU
EF
IVE GEF
STA
Note: arrows show direction of information flow (uni- or bidirectional)

7.0
ERP (material management)
Use-case
A critical process in a pharmaceutical environment is the application and maintenance of material master data,
ensuring consistency of master data across ERP and MES. An important interface to be considered enables the
material master data to be sent from the ERP system to the MES application upon creation or change of the
relevant master data. The interface used to drive this information exchange is the material master message
between the ERP and MES.
It is the role of the ERP system in this interface to supply the relevant material master data information to the
MES. Integration between ERP and MES for the material master is unidirectional (outbound from ERP and inbound
to MES) and ensures MES-relevant material known in ERP is also known in MES.
The role of the MES in this data transfer is to receive the relevant material data, to ensure alignment with ERP and
enable manufacturing within the MES environment. The material master interface is a crucial integration between
ERP and MES, and enables the full utilization of the MES.
Master data admin | ERP Master data admin | ERP Quality | ERP/MES
Creation of material Receive and Verify master data

master data acknowledge new and alignment across ERP
updated master data and MES
Editing/updating
master data

“From
“From what
what we hear,
we hear, biopharmaceutical
biopharmaceutical manufacturers manufacturers
struggle to
look for a sound, standard, single solution towards deploying a holistic
struggle to look for a sound, standard, single solution
digital manufacturing system. Although an interface between MES
towards
and deploying
ERP is one a common
of the most holisticanddigital manufacturing
first to system.
deploy, suppliers are
Although
frantic an interface
in finding between
alignment across MES
partners, andmodalities
multiple ERP is one of the
and manufacturing complexity in the industry.”
most common and first to deploy, suppliers are frantic in
Younge Qu, Product Manager
finding alignment across partners, multiple modalities,
Apprentice.io
Younge Qu and manufacturing complexity in the industry.”
Product Manager, Apprentice.io
Benefits Productivity benefits:
A material master message integrated between MES • Enables the ability to implement electronic batch
and ERP would provide data consistency and accuracy records, therefore removing dependency on
alongside operational efficiency. paper batch records
Data quality benefits: “Having BioPhorum to establish

• Enhances operational efficiency by reducing
an aligned set of
manual entry related to materials
•
interfaces, with ERP and •beyond,
Ensures accuracy and integrity of data
where manufacturers
Eliminates manual verification of material data
• Enables proper utilization of batches within the
and suppliers can all collaborate
manufacturing process and MES
and
• Eliminates work
secondary together
reviews of materialwill
data.
•
allow us to drive towards a healthy ecosystem for MES of
Provides a complete record of all MES-relevant
materials across thethe future.” process.
full manufacturing
Data exchange
The following data exchanges are required to create
a fully integrated MES/ERP system:
Younge Qu
Type Direction Minimal information Timing
Material master FROM ERP Material master message from ERP Upon initial creation or update of the material
includes: master in ERP
• Material group
Subteam 2 • Material type

• Unit of measure
• Material description
• Plant
• Alternative unit of measure
• Subject to quality control
• Requiring batch handling
• Deletion flag
• Material total shelf life (optional)
• Storage conditions (optional)*.
*Note: storage condition details (exposure to various conditions, temperature ranges, etc.) are not currently offered in the marketplace. Products manufactured
now are more complex than ever before. These parameters need to be able to be passed automatically from node to node in the supply chain, which could be
managed by the ERP systems to help reduce the impact of potential human error.

Challenges and limitations This verification should be undertaken with the
assumption that ERP is the source system of truth for
Interfacing ERP and MES is a priority to ensure the
material master data.
MES is utilized to reach its maximum potential. There
are some challenges implementing a material master To prevent misalignment, clear and consistent data
interface. Any material master interface between ERP governance processes are essential. These processes
and MES should consider the following in more detail: should define the roles and responsibilities of each
system, as well as the protocols for data exchange
• Material master header details
between them. It is important to establish data
• Material characteristics standards that are consistently applied across
• Alternative unit of measurement (UoM) both systems. In addition, automated notifications
and verification processes can help to identify
• Mandatory versus optional requirements.
discrepancies as soon as they occur, allowing for
Material master data is critical in the manufacturing prompt resolution of any issues.
process, as it defines the product and material related to
By following these best practices, manufacturers can
each batch. When the data is initially interfaced between
ensure that their material master data remains accurate
ERP and MES, verification/validation is required to ensure
and aligned across systems, minimizing errors and
the data has been transferred completely and correctly
improving overall efficiency.
and no disparity has arisen due to application limitations
(e.g. special characters available in ERP that are not
available in MES).
“From awhat
“Having spacewe hear, biopharmaceutical
in BioPhorum manufacturers
to establish an aligned set of
interfaces, with ERP and beyond, where manufacturers and
struggle to look for a sound, standard, single solution
suppliers can all collaborate and work together allows us to
towards
drive deploying
towards a holisticfor
a healthy ecosystem digital
MES of manufacturing
the future.” system.
Although
Younge an interface
Qu, Product Managerbetween MES and ERP is one of the
Apprentice.io
most common and first to deploy, suppliers are frantic in
finding alignment across partners, multiple modalities,
Younge Qu and manufacturing complexity in the industry.”
“Having BioPhorum to establish an aligned set of

interfaces, with ERP and beyond, where manufacturers
and suppliers can all collaborate and work together will
allow us to drive towards a healthy ecosystem for MES of
the future.”
Younge Qu
8.0
ERP (batch management)
Use-case
A critical process in biopharmaceutical manufacturing is management of the batch master to ensure product
quality through traceability of materials during production. Therefore, it is essential to ensure that batches
between systems are aligned. The key interface to track and align this information is the batch master message
between ERP and MES.
The role of an ERP system in this context is to receive and Integrating batch master data between ERP and MES
create batches related to inventory. Integration between is crucial for efficient material and batch management.
ERP and MES for the batch master involves ensuring that The absence of batch master integration can prevent
the batch data for the inventory is aligned so that the correct full utilization of MES material and batch management
batches are identified, used and recorded. Any additional capabilities. This can lead to misalignment between ERP
attributes or characteristics of a batch, such as expiry date and MES batches, resulting in unnecessary manufacturing
or potency that are relevant to manufacturing, must also be and operational disruptions. Without the integration
identified to support the manufacturing process. to ERP the MES would be treated as a paper-on-glass
The role of the MES in this context is to receive the batches execution system to execute the order, but verification
and use the correct data. However, there are some use- of materials and batches would be manual. Data must be
cases where the manufacturing process can create batches manually entered and updated in the ERP. Manufacturing
of products and update the batch data. In those cases, the operators can execute batch steps in the MES, but
MES would also need to be able to update existing batch material inventory and related tracking still needs to be
data and create new batches. These data would need to be manually updated in ERP, as ERP is the batch master.
interfaced with an ERP to ensure alignment. The batch master interface is a priority interface for
implementation for any ERP and MES deployment.
Warehouse/Planner | ERP Manufacturing operator | MES Quality | ERP/MES
Creation of batch for Create and/or update Review and update

material inventory receipt batches according batch information
to manufacturing
Creation of batch for order execution Ensure quality alignment
manufacturing order across departments

A batch master message integrated between MES and • Enhances operational efficiency by reducing
ERP would provide data consistency and accuracy manual entry related to batches
alongside operational efficiency. • Eliminates manual verification of batch data
Data quality benefits: • Eliminates secondary reviews of batch data.
• Ensures authenticity and integrity of data
• Improves traceability and compliance of batches
Data exchange
The following data exchanges are required to create a
• Provides a complete record of the batch across
fully integrated MES/ERP system:
the full manufacturing process.
Batch master FROM ERP Batch master message from ERP includes: Prior to material inventory or
• Product number manufacturing run
• Batch number
• Batch status
• Expiration date
• Batch characteristics, such as potency, output quantity
• Recipe ID.
Batch master TO ERP Batch master message to ERP includes: During manufacturing run
• Product number
• Batch number
• Batch status
• Expiration date
• Manufactured date
• Batch characteristics, such as potency.

Challenges and limitations It is also important to establish data standards that are
consistently applied across both systems. In addition,
Interfacing ERP and MES is always a priority for
automated notifications and verification processes
integrations and is generally well accepted. However,
can help to identify discrepancies as soon as they
there are some challenges and limitations with the
occur, allowing for prompt resolution of any issues.
batch master interface during its implementation. Any
batch master interface between ERP and MES should By following these best practices, manufacturers can
consider the following in more detail: ensure that their batch master data remains accurate
and aligned throughout the production process,
• Batch master
minimizing errors and improving overall efficiency.
• Batch status alignment.
Batch status alignment:
Batch master:
While biopharmaceutical companies generally call
Batch master data is critical in manufacturing processes, the names of the batch statuses to be not reviewed,
as it defines the characteristics and properties of blocked and approved, the naming of the statuses
each batch. When the data are interfaced between between two different vendor and supplier systems
ERP and MES, there is a possibility for misalignment are usually not aligned or standardized. To address
and a thorough investigation must be undertaken this, a mapping procedure or specification is needed
to determine the root cause of the issue. This to align the statuses between ERP and MES. This
investigation should focus on identifying which system approach is necessary not only from a technical
is the source of truth for the batch master data. It is integration perspective but also from a business
recommended that ERP should be treated as the master terminology perspective.
system for batch data, as it typically contains the most
Therefore, it is recommended that biopharmaceutical
comprehensive and up-to-date information.
companies have a standard mapping procedure in place
To prevent misalignment, it is important to establish to facilitate batch status alignment. This procedure
clear and consistent data governance processes. will allow the different systems to handle data in a
These processes should define the roles and standardized manner. It will also provide a common
responsibilities of each system, as well as the business terminology that avoids confusion and
protocols for data exchange between them. promotes efficient communication.

9.0
ERP (order management)
Use-case
In the biopharmaceutical industry, management of manufacturing orders is a critical process that requires
seamless integration between ERP and MES to ensure order accuracy, timely execution and compliance with
regulatory requirements.
One of the most important interfaces is the transmission message is triggered from ERP to MES, it is critical to note
of orders, or the campaign of orders (if used), from ERP to that data and information between the two systems must
MES for order execution. This interface ensures that the be in sync. In addition, triggers for the actual order
manufacturing orders are sent to the MES, where they are execution information are also sent (MES to ERP), such as
executed on time and in compliance with standard the actual start and end dates, the order status and the
operating procedures (SOPs). operations status.
Integrating manufacturing orders between ERP and MES is Integration of manufacturing orders between ERP and
a multi-step process that involves several data exchange MES has significant benefits, including reduced cycle
points. It begins with the creation of a manufacturing times, improved efficiency and better quality control. It
order in ERP, which is then transmitted to MES for eliminates the need for manual data entry, reduces the
execution. The ERP system pushes the manufacturing risk of errors and provides real-time visibility into order
order to the MES and then a corresponding order is status and progress.
created for the shop floor operators.
In conclusion, ensuring seamless integration between
When triggering the manufacturing order from ERP to ERP and MES is vital for successful order execution in
MES, triggers that send the interface message include, but biopharmaceutical manufacturing. The integration of
are not limited to, setting the manufacturing order to a manufacturing orders requires careful attention to data
planned state, changing the planned start and end times, exchange points, procedures and SOPs for accurate and
and adjusting the allocations or quantities of the bill of timely execution.
materials. Once the order has started in MES, the
ownership of the order is done by the MES. The triggers Benefits
from ERP would no longer be received by MES.
An order management message integrated between MES
Once the work order is in the MES, it triggers the and ERP would provide data consistency and accuracy
necessary actions required for order execution, such as alongside planning and scheduling efficiency.
scheduling, material availability checks, quality checks and
Data quality benefits:
production tracking. The MES collects data throughout the
• Provides near real-time data and date synchronization
process, such as the time spent on each operation and
operation status. In addition, execution of material • Reduces the risk of errors and data inconsistencies
consumptions, reversals, yields and inventory related to • Ensures accurate order details, such as operations,
the order is typically captured as well. Any time material is materials and quantities.
processed in an order, it should also trigger a related order
Operational benefits:
material interface message to ERP to align inventory.
• Eliminates the need for manual data and status
When triggering the manufacturing order from MES to entry for order management
ERP, triggers that send the interface message include,
• Speeds order processing leading to reduced lead
but are not limited to, updating the planned start and
times and improved efficiency
end times or adjusting the allocations and quantities of
the bill of materials. While it appears the interface • Facilitates decision-making based on planned
production schedule data.

“When you integrate your systems with MES, it suddenly requires
“Integration
data to andandfrom
correctness, robustness MESusage.
harmonized is key totake
It can ensuring flawless
andsome
away paperless production
flexibility, but processes.
the benefit of connecting The technical
your MES
system with ERP, for example, is that it ensures and requires
possibilities
high arereduces
quality of data and endless,
manualand establishing a set of
errors.”
preferred
Rebecca interface
Julie Nørgaard, Systemmethods
Architect and defined responsibilities
Novo Nordisk
has been an important framework for us”.”
Rebecca Julie Nørgaard

System
DataArchitect,
exchange Novo Nordisk
The following data exchanges are required to create a fully integrated MES/ERP system:
Order management
“WhenOrder
FROM ERP
you integrate your systems with
management message from ERP includes:
MES, it suddenly
On release of order
from ERP
• Order number • Operation
requires datanumber
• Product correctness, — Number robustness and harmonized
— Planned start time
usage. •ItBatch
can take away—some
• Product quantity
number
Planned end flexibility,
time but the benefit of
— Resource/Work center
connecting
• Campaignyour
numberMES system with eg. ERP is that it
• Bill of materials
• Order status
ensures• Order
andplanned
requires
start time high quality
— Bill of material ID
— Material ID of data and reduces
manual• Order
errors.”
planned end time — Batch allocations
— Quantity
— Unit of measure
Rebecca Julie Nørgaard • Order characteristics.
System Architect, Novo

Order execution
(header)
NordiskOrder management message to ERP includes:
TO ERP On completion of order
in MES
• Order number • Order actual end time
• Product number • Operation
• Batch number — Number
• Order status — Status
— Planned start time
• Order planned start time
— Planned end time
• Order planned end time
— Actual start time
• Order actual start time — Actual end time.
Order execution TO ERP Order management material message to ERP includes: On consumption of
(materials) materials in MES
• Order number • Material batch ID
• Operation number • Material container ID
• Material transaction type • Quantity (reversed)
• Bill of material ID • Unit of measure
• Material ID • Location.

Challenges and limitations
The biggest challenge and limitation for the ERP/MES order management is that the integration is complex when
mapping functionality and fields against vendor capability. Each vendor has different technical fields for the integration,
and the data need to be mapped to ensure accuracy between systems. Best practice is to have a mapping in place to
ensure that the data are accurately aligned and in sync.
A typical process to support business continuity is to have a manual process in place to continue manufacturing
during system downtimes. MES can support this process by maintaining continuity if ERP is unavailable. The order
management interface is needed so that orders are available in MES if ERP is not available. Best practice shows
planned orders available for manufacturing interfaced from ERP to MES, so that MES can execute in the event ERP
is unavailable. If an enterprise warehouse management system or related components are used, there is not an
option to maintain continuity, due to real-time inventory transactions that need to occur.

10.0
ERP (inventory management)
Use-case
The efficient management of material inventory is crucial for ensuring smooth operations in a biopharmaceutical
manufacturing plant. When both ERP and MES are in place, it is critical to ensure that accurate management of
material inventory is in sync. Any discrepancies in tracking and reconciling inventory levels should be avoided, to
ensure that inventory transactions between warehouse and operations are aligned.
ERP systems have long been utilized in the Benefits
biopharmaceutical manufacturing industry to store,
A material inventory message integrated between ERP
organize and be the master of material-related
and MES would provide data consistency and accuracy
information such as material master and stock quantity.
alongside operational efficiency.
As ERP is generally the system used by warehouse to
initially receive inventory, all materials would typically Data quality benefits:
start with ERP as the source. When the MES-specific • Provides near real-time data and
materials are transferred to manufacturing operations, date synchronization
the MES would need to receive the material inventory
• Reduces the risk of errors and
and quantity for processing. MES would then help
data inconsistencies
track and trace the materials as they move through the
manufacturing operations cycle, providing visibility into • Ensures accurate material inventory between
material and order usage, alongside material yield and systems and overall site inventory accuracy.
new stock generated, before the material is moved back Operational benefits:
to warehouse for storage, scrap or disposition.
• Departmental users only need access
Integration of material inventory and stock quantity to one system: ERP for warehouse and
between ERP and MES will improve efficiency and MES for manufacturing
productivity, and increase collaboration between
• Eliminates need for manual data entry
warehouse and manufacturing.
between systems
• Facilitates real-time material resource planning
and procurement decision-making based on
material deduction (and material generation)
from manufacturing.

Data exchange
The following data exchanges are required to create a fully integrated MES/ERP system:
Material inventory FROM ERP Material inventory message from ERP includes: On update in ERP
• Material ID
• Material batch ID
• Material pallet ID (optional)
• Material container ID (optional)
• Quantity
• Unit of measure
• Source location
• Destination location
• Plant/organization ID.
Material inventory TO ERP Material inventory message to ERP includes: On update in MES
• Material ID
• Material batch ID
• Material pallet ID (optional)
• Material container ID (optional)
• Quantity
• Unit of measure
• Source location
• Destination location
• Plant/organization ID.
Challenges and limitations container level, and different containers of the same
material batch will have a unique label and container
While ERP is generally considered the material and
ID. The way the material stock is physically tracked
inventory master, this interface between ERP and MES
and labeled may not be aligned with how the ERP
is intended to put material inventory and stock in sync.
and MES are configured, causing challenges for the
Therefore it is important to identify the ownership
systems in conjunction with how the interface should
of the inventory and at which locations, so that the
be implemented. Consideration of which ERP/MES
initial source of the interface message transaction can locations are batch managed, and which are container
originate correctly. If both systems have the capability managed can help alleviate this challenge.
to adjust inventory at similar times, then the inventory
If using MES, it is possible that material inventory and
quantities have the potential to be incorrect, which
stock transactions may be performed additionally using
may require physical inventory reconciliation and cycle
pallets or other groupings, to transact multiple sets of
count to ensure accuracy.
materials, batches, containers and quantities at once.
Some biopharmaceutical companies track stock Note that the pallet ID in the data exchange section of
quantity at the material batch level, and different this document is optional. Aggregation and serialization
physical containers of the same material batch have the of material inventory are also considered out of scope
same label attached. Others will track quantity at the for this interface message and use-case.

11.0
Electronic document
management system (EDMS)
Use-case
Use of SOPs during production is a critical requirement in the biopharmaceutical environment. Along with the
master batch records (MBRs), SOPs provide necessary policies, processes, step-by-step instructions and, when
required, visual aids which guide operators through their tasks.
With the deployment of MES, paper MBRs are Benefits
digitalized and guide shop floor operators for batch
Quality benefits:
record execution by providing critical step instructions
while access to the SOPs allows the operator to access • Ensures that the right SOP is used for the right
detailed step instructions. product and at the right step of the process
Establishing an interface between MES and EDMS • Ensures that only the currently effective version
should therefore be considered to improve operational of a specific SOP is used on the shop floor.
and recipe design efficiencies. With such an interface, Productivity benefits:
operators do not have to use EDMS to pull the SOP
• Improves user experience
they need to execute their tasks; SOPs can be opened
via hyperlinks directly from MES during batch record • Eliminates need to interact with EDMS and hence
execution. This interface also supports compliance maintains paper access to SOP/work instruction
requirements by ensuring that the right SOP is used at relevant for batch record executed in MES
the right step of the process and that only the currently • Speeds access to SOPs, leading to improved
effective versions are used on the shop floor. operational and design efficiencies
Indirectly, the EDMS interface helps in reducing the • Helps reduce instructions to critical steps requiring
size of the MBRs by limiting instructions to those that signoff within MBR and hence effort for MBR design,
are critical, notably requiring signoffs, as the detailed verification and release to production
instructions, part of the SOPs, become more easily
• Reduces the need to revise MBRs when changes
accessible to the operators.
to operational instructions are required
• Operational and design efficiencies, e.g. you can
reference an EDMS once rather than a specific
procedural document system. This saves time
and effort for recipe lifestyle management with
dynamic linkages.

Data exchange
The following data exchanges are required to integrate MES/EDMS systems.
DocRequest TO EDMS • Document ID (or hyperlink) On demand
DocRetrieval FROM EDMS • Content of last effective version On request

The main challenge when deploying an interface to EDMS resides in the capability of the system itself. EDMS should
provide a way to capture the currently effective version of a document by using a unique hyperlink or allow for
configuration for a singular link to be provided with the most recent valid SOP. However, when the EDMS does not
allow this, a middleware may be required to cover that requirement.
Performance is also an important factor to consider in the design of the interface, so the processing time to generate
PDF renditions of the requested document is limited as much as possible. Similarly, design of the interface should
account for the EDMS planned/unplanned shutdown and maintenance.
It is important to consider that the EDMS is to be maintained on the shop floor for operations that are not yet, or not
planned to be, covered by the MES.

12.0
Laboratory information
management system (LIMS)
Use-case
A key interface to be considered in expanding the integration of MES is that of a laboratory information
management system (LIMS). The role of the LIMS in an information management architecture is to execute a
sample plan and record analytical results derived from execution of analytical assays. Integration of MES and LIMS
typically involves guiding manufacturing operators pulling in batch-based, in-process samples that are required
for testing in an analytical laboratory, labeling these samples with required identification information, and labeling
samples for further processing. Raw material samples are considered out of scope for this use-case as this is
typically done in the warehouse and handled by the ERP.
Once the samples are pulled and tested, analytical when pulling samples on the shop floor, and the
data can be leveraged by the MES for downstream transmittal of these to manufacturing for execution.
processing that requires analytical test results (e.g. Manufacturing operators are then required to
protein concentrations, cell counts, viability). The value document the relevant chain of custody related to
of integrating MES and LIMS is typically derived from the who, what, when and where the samples were pulled
effort involved and quality of data that often accompanies before transferring the samples back to the laboratory
manual actions associated with these processes. for processing. Typically, these required data are
Without integration, LIMS users are required to transcribed and reviewed in both the sample plan that
generate a sample plan for required samples to be is returned to LIMS and the manufacturing batch record
collected, the associated sample labels to be applied that needs this information for downstream processing.
LIMS user Manufacturing operator Lab analyst
Generates sample plan Receives sample package Receives sample package

Pulls samples Logs sample
Prints labels Applies labels
Executes analytical assays
Documents samples in
Transmits package batch record Records and approves
to manufacturing analytical results in LIMS
Documents samples on
sample plan
Transmits package back
to lab

When data are needed in subsequent manufacturing steps to perform actions like determining the amount of material
to be added during a process step or calculating the amount of protein loaded onto a purification column, data must
be pulled from LIMS through a series of manual steps before performing the required calculation. A manufacturing
operator is required to:
Look up the Query LIMS for Document the

Access LIMS sample ID that was the associated result in MES and
previously pulled analytical result have it reviewed
Manufacturing operator Lab analyst Manufacturing operator
Pulls samples as defined in Receives samples with data Executes EBR steps to
the EBR transmitted from MES retrieve analytical results
from LIMS
Generates and applies Executes analytical assays
sample labels printed Records and approves
from MES analytical results in LIMS
Delivers samples to lab

An integrated MES/LIMS solution provides a more • Limits manufacturing staff from having to access
streamlined overall process and delivers benefits that multiple systems for performing steps that
reduce manual efforts while improving data quality. require analytical results from downstream
Data quality benefits: • Limits effort to record and retrieve data that can
be stored easily for future processing
• Eliminates multiple manual transcriptions in
both MES and LIMS • Eliminates secondary reviews of data transcribed
to both LIMS and MES
• Increases accurate chain of custody
as times and operator actions are • Eliminates generation and reconciliation of
automatically recorded in MES labels by laboratory
• Reduces handoffs between manufacturing • Reduces handoffs between manufacturing

and laboratory. and laboratory.
“The seamless synchronization of LIMS and MES data is useful for

companies looking to harmonize performance and quality, as sample
data triggers batch release decisions. It bridges the gap between
quality control laboratories and manufacturing line—from one
to many—structuring innovation and agility to facilitate the
adaptation to product and process variability.”
Clément Glace, Life Sciences and Healthcare Solution Consultant
Dassault Systèmes

Data exchange
The following data exchanges are required to create a fully integrated MES/LIMS system.
Batch plan sample request TO LIMS Sample plan requests including: Start of batch or stage*
• Product code
• Batch number
• Batch stage*.
Sample plan information FROM LIMS Sample plan by batch stage including: Response to request
• Sample counts
• Sample sizes
• Sample containers
• Batch stages
• Storage conditions
• Sample IDs.
Sampling confirmation TO LIMS Sample confirmation that a sample has been Upon sample creation/storage
pulled and ready for testing:
• Sample IDs
• When pulled (date/time)
• Who pulled (manufacturing operator)
• Storage location.
Sampling result request TO LIMS Result request including: Before needed in

• Sample ID downstream operation
• Assay result.
Sample result FROM LIMS Assay results including: Upon result request
• Sample ID
• Assay result
• Approval status.
* Depends on how to stage sample plan. Can be either for the entire batch or at different stages in the process.
Challenges and limitations Another challenge identified relates to the exchange of

data between MES and LIMS. MES is a critical system
While the benefit of interfacing MES with LIMS can
for production operations, so requires high availability
easily be achieved for operations that have medium to
to maintain ongoing operations. As such, they tend
high sample volumes, it is understood that the strategy
to integrate with other systems leveraging some sort
for this integration is primarily limited to process
of data storage buffer that allows them to continue
samples that are routinely pulled as part of the batch
processing if the interfaces are not available. This can
manufacturing process. It presents further challenges
be achieved by having temporary storage buffers like
for being able to execute for non-routine samples
staging tables that maintain data requested to minimize
like those used to support environmental monitoring
the real-time requests for data. Data staging may
or validation studies. Additional investigation would
require the addition of a middleware solution to create
be needed to further assess options for tying these
storage buffers for on demand data.
samples to production batches.

13.0
Data Historian
Use-case
A key interface for consideration when expanding the integration of MES is the Data Historian (DH). The role
of the Data Historian in information management architecture is to provide raw or calculated, aggregated data
from the processes. A continuous stream of production data is sent to the DH including, recorded events and
alarms collected from the process, and data required for the batch documentation in calculated, accumulated
form (e.g. min, max, average, other types depending on modality). Additionally, GMP-relevant critical alarms and
events need to be transferred for further evaluation as MES exceptions. Outliers, logs and statistical evaluation
can be shown within the DH but are not relevant for the MES.
Without integration between the MES and the DH, operators must manually find and transcribe process data related
to the batch or a specific time frame and perform related calculations individually.
A typical scenario where a manufacturing operator is required to do this may look like this:
Query the
Upload the
DK for the
data manually Document
associated
Look up the to the MES and review
Access the DH production
batch ID* and generate the result
results,
exceptions as in MES
including
appropriate
alarms
*It should be noted that not all DH have a mechanism to correlate Batch IDs to relevant historian datasets.

An interface between a DH and a MES should include Benefits
the following:
An integrated MES/DH solution provides a more
• Data acquisition: The interface should be able to streamlined overall process and delivers benefits that
acquire data from the Data Historian, which stores reduce manual efforts while improving data quality.
historical data collected from various sources. This
data may include process data, production data, and
quality data such as alarms, time series and event data • Eliminates the manual transfer of GMP data
from the Data Historian to the MES
• Data transformation: The interface should transform
the acquired data into a format that can be consumed • Increases the accuracy of the chain of custody
by the MES. This may include converting data to of production data and alarms, as times and
different units of measurement, aggregating data, data fields are automatically transferred to MES
and cleaning data • Reduction in data transcription errors as the
• Data integration: The interface should integrate the data is now automatically transferred using
transformed data into the MES, which is responsible validated systems, increasing the control and
for managing and controlling the manufacturing accuracy of the data
process. The integrated data can then be used to • Increased speed for review of alarms as they are
reduce the need for manual data entries, additional now automatically transferred to MES and can
verification signatures, optimize production, improve be further evaluated as exceptions in a single
quality, and reduce waste location by supervising and quality staff.
• Data access on demand: The interface should Productivity benefits:
provide data to the MES on demand. This enables
• Increased productivity as the integration
the system users or the system itself to make
removes the requirement for manufacturing staff
manual or automated decisions based on current
having to access multiple systems to perform
production data such as monitoring process
steps that require entering production results
variables (e. g. peak max chromatography, tank
from downstream equipment
levels, calculating protein loads), tracking product
quality, and managing equipment performance • Reduction in the effort to record and retrieve
raw or cumulated data that can be easily stored
• Alarm management: The interface should include
for future processing
alarm management capabilities, allowing the MES to
receive alerts when certain production thresholds • Second checks of data ingested into the DH
are exceeded or when equipment fails. This can help from the equipment after transfer to the MES
prevent downtime, reduce scrap rates and allow for are no longer required, increasing the speed
the correct documentation of excursions from the towards batch release
controlled process and defined control strategies. • Central evaluation can be completed for all
• Reporting: The interface should enable the MES to exceptions to allow ‘Review by exception’ for
generate reports based on the historical data stored key stakeholders. Note that the operator still
in the Data Historian. This can include production needs to resolve and acknowledge the problem
reports (as part of the batch record report), quality on the equipment itself.
reports, and equipment utilization reports
• Security: The interface should be secure and ensure
that only authorized users can access the data
stored in the Data Historian. This can include user
authentication and authorization, data encryption, and
network security. As this interface is built with a read
only mechanism, there is no ability to alter existing
datasets within the DH and therefore no potential to
breach data integrity regulations.

Data exchange
The following data exchanges are required to create a fully integrated MES/DH interface.
Request for production TO DH Query including Can be any time but mostly
and alarm data • Batch header data ‘End of batch’
• Time frame to be requested
• Type of data request
Production data FROM DH Production results: Response upon request

• Batch header data
• Raw or calculated data
Alarm and event data FROM DH Alarms and event messages: Response upon request
• Prefiltered by alarm level
• Alarm identification
• Alarm pre-categorization
Challenges and limitations The interface to a DH is limited to uploading raw or

aggregated production data and alarms from the DH to
From the continuously produced data stream within
the MES. Any transfer of order header data (batch number,
the DH, only summarized information during a specific
order number, recipes to be used etc.) to the equipment
batch or certain time frame needs to be transferred
will be covered by level 2 systems, refer to Figure 1.
to MES (e.g. at the beginning and end of an operation
as well specific time points during it). If the DH is not For real-time evaluation of production data as part of
capable of providing that event frame, an interface adaptive production (e.g. in the context of PAT), the MES
can be very challenging. will be interfacing to a control system. This is also valid
for downloading order/batch header data, including the
applicable recipe for the production equipment.

14.0
Autonomous mobile
robots and guided vehicles
(AMR, AGV)
Use-case
As biopharmaceutical manufacturing companies seek to automate repetitive manual operations, use of robotics
elements will increase in manufacturing supply chain processes. Material movement, loading material, unloading
material and palletizing operations are some of the most common automated activities with the use of robotics
elements such as Automatic Guided Vehicles (AGVs), Autonomous Mobile Robots (AMRs), Material Inventory
and Retrieval Systems (MIRS), Automatic Storage and Retrieval Systems (ASRS), palletizers and robotics arms.
Integration between MES and these robotics elements is critical to ensure the correct control and management of
materials (raw, components, semi-finish and finish) and to create the concept of continuous manufacturing in which
the machines continue to work without manual interventions to load components and/or load raw materials.
MES will drive the materials needed for the bill of Benefits
materials (BOM) for each of the batches. This will require
Use of this integration minimizes manual activities,
an integration with the ASRS to ensure a pallet(s) is/are
increasing control and reducing variability in the process.
created with the material dispensed for the batch. The
MES will send the information to the AGV system to Data quality benefits:
move the material to a staging area in which it will interact • Reduces manual activities, improving data integrity
with the MIRS to move it close to the manufacturing
• Ensures the product moves across all the process
areas. At that moment the MES will be required to
without human interaction, minimizing variability.
integrate with the robotics arms to ensure the product is
loaded to the manufacturing machines or so that material Productivity benefits:
bins are delivered and placed on the proper overhead line • Reduces safety risks across the entire process
that is connected to the correct recieving tank, and to
• Minimizes micro-stoppages, increasing line capacity
send the recipe to the machine to start the process (see
Section 14). From there, the MES will control the loading/ • Allows agile manufacturing for rapid introduction
unloading processes and the movement of the material of new products
until it returns at the end of the process to the ASRS to be • Increases inventory management efficiencies.
stored, bin cleaned or otherwise distributed.

Data exchange
The following data exchanges are required to create a fully integrated MES/Autonomous Robot system:
Material movement TO AUTONOMOUS ROBOTS • From location A to location B Any time
Material preparation TO AUTONOMOUS ROBOTS • BOM item needs to supply item information Any time
• Number of pallets and locations
Load/unload TO AUTONOMOUS ROBOTS • Material ID Any time

• Machine ID
• Quantity
• Location
Material movement FROM AGVs AND MIRS • Delivery status Any time
• Pallet ID.
Material preparation FROM ASRS • Material ID delivered Any time

• Pallet IDs
Subteam 2
• Location
• Type of material
Load/unload FROM ROBOTIC ARMS or • Movement status Any time

AGV delivery point systems for • Material ID
materials delivered in a bin
• Duration
“The seamless synchronization of LIMS and MES data is
useful for companies looking to harmonize performance and
quality, as sample data triggers batch release decisions. It
bridges the gap between
Challenges and limitations Quality Control laboratories &
• Material and pallet dimensions are
critical for automation
manufacturing lines •-from
• Some processes are not designed to have automated
loading and unloading processes
one to many- structuring innovation
Automated robots and AGVs that facilitate the
• Common protocols areand agility to facilitate the adaptation to the

product and process
movement of bins can increase complexity of a
required to support
recipe’s development
variability”
autonomous robots which interface with MES. This
Clément Glace
is required for an event-driven, exception-based • A further level of support is required when using
Life Sciences & Healthcare
ecosystem that Solution
maintains high availability andConsultant,
can automated robots
Dassault and AGVs, as engineering, IT and
Systèmes
handle asynchronous data transmission automation are now even more critical to the process
• Usually, a BOM does not consider movement of • Some of the material loading processes such as
components, meaning a secondary solution is movement orders can be handled by ERP. Therefore, the
required to track this movement company should decide where these are to be handled.
“As we continue with our journey of use different methods to

“As we continue with our journey of use different methods to
minimize execution variability on our manufacturing process,
minimize
robotics execution
and automated variability
processes on our
integrations manufacturing
with the MES of the process,
robotics
future and automated
will become processes
critical. The ideas integrations
and knowledge sharing thatwith the MES of the
were fostered by this white paper have helped me to develop a
future will become critical. The ideas and knowledge sharing that
deeper understanding about where the industry is going and how
was
to enablefostered byofthis
the future whiteprocesses.”
automated paper has help me to develop a deeper
understanding
Francisco Gonzalez, ITabout where the industry
Senior Director—Parenteral is going and how to enable
Operations,
Eli Lilly
the future of automated processes.”
Francisco Gonzalez Unlocking efficiency: a deep dive into MES integration
36
IT Senior Director - Parenteral Operations, Eli Lilly
©BioPhorum Operations Group Ltd | March 2024
15.0
Batch execution (BE) application
Use-case
Process manufacturers often use BE applications to control and orchestrate the execution of automated
equipment used in the production of a batch. BE applications are architected based on the ANSI/ISA88: Batch
Control standard2 that breaks production into physical and procedural models that define the equipment
and steps required to produce the batch. While the concept of batch control is primarily targeted at process
manufacturing, the use-cases presented here may still hold true for discrete manufacturers as well and can
be applied in the same context. The same can be said for supervisory control and data acquisition (SCADA)/
distributed control systems (DCS) systems implemented without a BE layer.
Like MES, BE applications have defined recipes that are A typical production execution scenario may look
used to acquire the equipment needed to execute an something like this:
operation along with steps and operating parameters
1. Manual activities like equipment set-up, material
for running the automated equipment needed to
staging and preparation would be executed per
produce an output or batch.
procedures as directed and recorded by the MES.
When BE applications are leveraged to control
2. Once complete and the automated manufacturing
automated production, they typically need information
is ready to begin, an operator would be required
on the batch to execute and record data about the
to select the batch recipe to be run on BE
production. BE applications can also provide feedback
applications and enter information about the
to the MES on status of execution to enable further
batch to be produced (e.g. batch ID, production
downstream processes to execute.
output quantity) and start the batch.
BE applications can capture critical data during
3. The operator may need to perform certain
execution but they lack the ability to apply limits to
manual actions like pulling in process samples
and approve exceptions to be resolved during batch
or manually adding material as directed by
record review processes once production is complete.
the MES but supported by BE applications
Data recorded in BE applications are often needed
executing automated operations.
to perform calculations that enable execution of
operations in further downstream processes. 4. When the process gets to critical points where data
is needed for downstream MES processing, the
Without integration, manual data entry is required on
operator would generate BE application reports or
both BE applications and MES to execute and record
execute queries to pull that information.
critical process information.
5. The operator would acknowledge when the BE
application recipe is complete and then go on to the
next process as directed by the MES and the whole
processing may begin again.

An integrated MES/BE applications solution provides a • Eliminates redundant data entry in the MES
more streamlined overall process and delivers benefits for information already tracked in the BE
that reduce manual efforts while improving data quality. application and vice versa
Data quality benefits: • Eliminates time lags where interaction is

required between BE applications and MES
• Ensures accurate batch information is used
in BE applications • Eliminates time spent querying and/or
generating reports for data.
• Ensures appropriate status of equipment is set
correctly when starting/ending activities
Data exchange
• Sharing operational statuses reduces the
The following data exchanges are required to create a
potential that activities progress on one system
fully integrated MES/BE system:
when not ready for the other
• Improves data integrity by eliminating transcriptions.
Batch information TO BE APPLICATION • Batch ID Prior to start of BE

• Batch size application recipe execution
• BE application recipe ID.
Operation start TO BE APPLICATION Flag to indicate that manual activities are Start of BE application recipe
complete and that the BE application can execution
begin execution
Operation FROM BE APPLICATION Flag indicating that the BE application has End of BE application recipe
complete completed all automated operations and that execution
the batch is ready to proceed in MES
Operation status Either TO or FROM BE Indicates when critical processes are During operation execution
updates (optional) APPLICATION completed in either the MES or BE application
to tell the other system to take further action
Critical process FROM BE APPLICATION Process information that is identified as CPP is As recorded by the BE
parameters (CPPs) required for downstream processing application or at the end
of operation

Challenges and limitations on premises to ensure they can reliably manage the
controllers that exist on the shop floor. While MES
Both BE applications and MES can play similar roles in
have come a long way in their ability to deliver high
process manufacturing, so it is important to understand
availability using redundant databases and application
the domain of each of these key systems to avoid
servers, they are not designed to provide real-time
overlap and define system boundaries clearly. For
control and are unreliable when required to provide
instance, both systems can acquire and manage status
continuous connection to shop floor controllers.
of equipment. It is important to understand which
system is responsible for equipment at the different To this end, particularly when MES are hosted off
levels of the physical model. MES typically operates premises, extra caution should be taken when deciding
at the unit/unit procedure level and above, while how tightly to couple MES and BE applications. BE
BE applications manage levels from the unit/unit applications must be able to continue to control the
procedure and below. process in the event of any disconnect. So, in these
situations, it is best to employ strategies that allow
In setting system boundaries, it is important to
the BE application to override inputs with manual
understand the relative robustness of the two
intervention and allow the MES to catch up from data
solutions. BE applications were born out of the process
in the BE application or Data Historian. Tightly coupling
control industry. Typically, they have more features
BE applications and MES with status checks across
built in to ensure that they not only achieve high
the system boundaries, without providing override
levels of availability but are also able to gracefully
capabilities, will likely lead to production downtime or
handle failure recovery, which is key to controlling
batch abortion when the systems become disconnected
systems running in the plant. They are always hosted
for extended periods of time.
“For companies is
“Integration that leverage
key batch execution
to creating systems, a
a connected
‘connected plant’ cannot be achieved without integrating that
enterprise and raising our digital maturity;
system to MES. This is key to driving right first time thinking
increasing
and minimizingproductivity and improving data
operator interactions.”
integrity”
Robert Gamber, Business Systems Principal Analyst
Vertex Pharmaceuticals Incorporated
Robert Gamber
Business Systems Principal Analyst, Vertex Pharmaceuticals Incorporated

16.0
Computerized maintenance
management system (CMMS)
Use-case
One of the key functions of an MES is to manage the use of production equipment. As such, it is critical that the
MES has up-to-date information on the operational readiness of all equipment. Typically, the MES is responsible
for initiating and tracking routine operational statuses such as clean/steam in place, in use, clearance or
standardization. However, there are some statuses that are driven by activities outside of the MES and these are
typically tracked as part of a CMMS.
A CMMS is responsible for the overall equipment 4. Once the maintenance activity is complete, the
lifecycle and as such it tracks activities like preventative maintenance technician must return the equipment
maintenance (PM), corrective maintenance (CM) to service in both the CMMS and the MES
and calibrations. While tracking these activities, the
5. Maintenance technician must set cleanliness
CMMS has the most up-to-date information on certain
status in the MES, as appropriate, based on the
operational statuses of equipment like ‘calibrated’ or ‘in/
type of maintenance performed and update the
out of service’ (which may be inclusive of calibration
MES operational status (calibration status or
status). Interfacing this information between CMMS and
date), if applicable.
MES allows for a more robust and streamlined process
within MES as well as CMMS. Other optional interfaces between CMMS and MES
would include the following:
Without integration, the MES is required to put in
additional workflows to track maintenance activities • Ability to send cleaning and/or operation status
which also requires maintenance technicians back to MES to enforce the likes of activities
to operate in two systems when executing such as cleaning or standardization after a
maintenance-related activities. maintenance activity is complete. This would
alleviate the need for maintenance technicians
A typical maintenance scenario may look to go into the MES to update these statuses
something like this:
• Having the capability to automatically create
1. Maintenance activity (either PM, CM or equipment in the MES when it is added to the
calibration) is either initiated by an operator or CMMS. The CMMS is the master of equipment-
the CMMS according to a time-based schedule related information and is typically the first place
or operating conditions that new equipment is defined. An interface
2. Maintenance technician receives a work order from with the capability to create/update equipment
the CMMS system which logs that the equipment is in MES when entries are made or altered would
being taken out of service for maintenance prevent the need to manually communicate
when assets need to be created or updated. It is
3. Maintenance technician logs in the MES that the
recognized that the CMMS would not have all
equipment is now out of service and cannot be
the specialized operational information like clean
used for production
expiry durations, equipment class designation,
etc. so these would only create a base object
that would need further definition in the MES.

An integrated MES/CMMS solution provides a more • Eliminates need for maintenance technicians to
streamlined overall process and delivers benefits that operate in two systems when executing an activity
reduce manual efforts while improving data quality. • liminates redundant data entry in MES for
E
Data quality benefits: information already tracked in CMMS
• Sharing operational statuses from CMMS reduces • Reduces training load on maintenance
the potential that operators execute production technicians to maintain access to two systems.
on equipment that is not ready for use
• Ensures appropriate status of equipment is set
Data exchange
coming out of maintenance activities. The following data exchanges are required to integrate
MES/CMMS systems. They are listed in descending
order of importance.
In/out of service FROM Flag per equipment unit to take the Start/end of maintenance activities
status CMMS equipment out of service for any maintenance that require the equipment to be out
activity as required. of service
Note: when taking a room out of service, all
equipment within the room would also be set to
out of service.
Calibration status FROM Either a flag to indicate if an equipment unit has As calibrations are executed or expired
or date CMMS instruments that have exceeded their individual
calibration due dates, or the earliest date of any
instruments requiring calibration.
Update clean/ FROM Used to flag required cleaning or standardization At completion of maintenance activity
operational status CMMS after a maintenance activity is complete.
Create/edit FROM Base information for the following: Upon equipment creation or update
equipment CMMS • Equipment ID
definitions
• Description
• Location
• Asset class.
Challenges and limitations The ISA S88 Hierarchy Model (Figure 3) defines
equipment from the process cell all the way down to
While the benefits of interfacing MES with CMMS
individual instruments. The MES typically only acts and
can be achieved, it is highly dependent on the CMMS
tracks information at unit level as recipes/MBRs within
being able to roll up and share data at unit level. Most
the MES are typically defined at the unit procedure
CMMS systems can model equipment in a hierarchical
level. It is not feasible or beneficial for the MES to track
structure, but they are often challenged to roll up
information at lower levels.
operational status information within those models.

Figure 3: ISA S88 Hierarchy Model
Process cell Cell culture
Unit Bioreactor
Equipment module Vessel Input line
Control module
Temperature DO pH Pump
(instruments)
For example, in this model if any of the instruments at control module level (temperature, disolved oxygen (DO), pH, pump)
had an expired calibration this would need to roll up to bioreactor at the unit level indicating that it is out of calibration.
“The integration between CMMS and MES can be a crucial integration

within the client’s digital journey, ensuring the ability to streamline
the manufacturing process by guaranteeing the equipment
lifecycle is reflected appropriately within the MES. Working with
BioPhorum and collaborating across a wide range of vendors and
biopharmaceutical manufacturers enabled us to identify the
critical data transfers required to support this integration.”
Bernard Corcoran, Senior Informatics Pre-Sales Engineer
Lonza

17.0
Quality management
systems (QMS)
Use-case
In biopharmaceutical manufacturing, the integration of QMS and MES is crucial to ensuring the quality and safety
of the final drug product. The focus of this integration should be on managing quality exceptions, investigations,
deviations, out of specifications or change controls that can occur during or outside the manufacturing process.
This integration will allow manufacturers to automate the quality control process and capture critical data in
near real time. If a quality exception is detected in manufacturing, it can be flagged immediately and routed
to the appropriate quality personnel for review and resolution. In contrast, if a deviation is found outside the
manufacturing process but related to the batch, it can also be captured to ensure holistic batch review. Once
the investigation and deviation are flagged, the appropriate corrective and preventative action (CAPA) can be
completed within the QMS itself.
Examples of integration: Productivity benefits:
• QMS to MES—contamination of environmental • Eliminates duplicate data entry between
system, power outage QMS and MES
• MES to QMS—exceptions upon investigation, • Provides near real-time notifications of
when they are a deviation. manufacturing issues
• Speeds up and facilitates resolution of
Benefits manufacturing issues and lowers cycle time.
An interface between MES and QMS would provide
near real-time data capture alongside improved
operational efficiency.
• Provides accurate data about exceptions and
deviation recording between systems
• Provides analytics of data to identify
trends for future preventative measure
and process improvements.

Data exchange
The following data exchanges are required to create a fully integrated MES/QMS system:
Non-conformance/deviation FROM Non-conformance/deviation from QMS includes: During manufacturing run

QMS • Non-conformance/deviation number
• Non-conformance/deviation type
• Non-conformance/deviation priority/severity
• Non-conformance/deviation description
• Non-conformance/deviation status
• Manufacturing order number(s) (optional)
• Date of occurrence
• Raised by.
Non-conformance/deviation TO QMS Non-conformance/deviation to QMS includes: During manufacturing run

• Exception from MES number, to then align with
non-conformance/deviation number
• Non-conformance/deviation type
• Non-conformance/deviation priority/severity
• Non-conformance/deviation description
• Non-conformance/deviation status
• Manufacturing order number(s) (optional)
• Unit operation (optional)
• Related manufacturing step and context (optional)
• Date of occurrence
• Raised by.
Challenges and limitations deviation is owned by QMS and has comments in

QMS. Not all manufacturing incidents will become
One of the challenges in investigating deviations
non-conformances and deviations, so the process to
across two systems is a lack of standard processes for
filter out incidents and deviations is needed prior to
documentation. To overcome this limitation, a standard
integration from MES to QMS. The integration will align
process needs to be established to facilitate the
status and critical fields between the two, whereas the
investigation during identification of the deviation and
process helps identify ownership of data. The unique
issue across two systems. The process should outline
non-conformance/deviation number needs to be
the key steps required to identify and communicate
aligned across the systems to ensure traceability.
the deviation, alongside which system is responsible
for the documentation at what stage of the deviation. Deviations can be created against closed orders
For example, a manufacturing investigation is owned if manufacturing has finished but the deviation
by MES, and has comments in MES. A confirmed was found later.

18.0
Learning management
systems (LMS)
Use-case
Proper training of manufacturing operators is of utmost importance in the biopharmaceutical manufacturing
industry. A LMS is commonly used as an essential tool that can assist in training manufacturing operations.
Prior to manufacturing, a check is required to ensure that employees are fully trained and compliant with
processes. An integration between LMS and MES in biopharmaceutical manufacturing is an enhancement for
manufacturers who want to ensure compliance with manufacturing and quality requirements. The integration
enables near real-time flow of data and information between the two systems, allowing for system
verification of operator training prior to performing manufacturing tasks.
Typically in LMS, trainings are handled as a set of courses Benefits
or a curriculum. Completion of the training would ensure
An interface between MES and LMS would provide
that the individual is certified to execute any task to
verification of training alongside operational efficiency.
be performed by them in the MES. The courses and
curriculum would have a focus on the product/material/ Quality benefits:
process/equipment and user training to ensure that the • Ensures the operator has the appropriate
individual is fully trained for the task to be performed training prior to manufacturing execution
in the MES. Key to the LMS/MES integration would
• Reduces deviations by having operators perform
be where the user’s training is cross-checked against
actions that they are not currently trained for.
the product/material of the batch, equipment used
and general system training to ensure that the user can Productivity benefits:
execute against the manufacturing record in the MES, or • Reduces burden on supervisor for compliance
against the roles that they are assigned in the MES. checks, allowing operations to focus on their
manufacturing tasks.
While there are benefits for the MES/LMS interface,
LMS is not typically a mission-critical system.

Data exchange
The following data exchanges are required to create a fully integrated MES/LMS:
Product curriculum training FROM LMS Products/materials/processes certifications from LMS include: Any time
• Username/ID
• Certified/uncertified for executing product/material/process.
Equipment curriculum training FROM LMS Equipment certifications from LMS includes: Any time
• Username/ID
• Certified/uncertified for executing equipment.
User system curriculum training FROM LMS User system certifications from LMS includes: Any time
• Username/ID
• User group/ID
• Certified/uncertified for using MES.
Challenges and limitations The equipment or process user may not necessarily
be the executor and other operators may help with
Within biopharmaceutical manufacturing, materials,
execution steps versus the documentation of this process
equipment and batch record workflow execution have a
in the MES. In this case, the interface should not be used
direct impact on product quality. However, curricula and
without appropriate guidance surrounding this process.
training do not, but it is still a compliance and regulatory
expectation. So, while the LMS and MES interface can It can be costly to maintain the mapping between
provide a lot of value to ensure compliance, there may training and MES recipe activities due to its complexity
be limitations with MES software capability to review and frequency with which it has to be carried out. The
curriculums and trainings required, as this is typically not use-case focuses on the curriculum trainings which
standard MES functionality. are considered for the integration. The execution
of the training, such as on-the-job training, is out of
Assuming that the interface and functionality is available,
scope. It should be noted that there should be a grace
then the naming conventions to map product/material/
period added to the LMS, in the same way a paper-
process/equipment and users or user groups between
based system would have, for updating the status of
LMS and MES is a challenge. Each training has a lot of
certification of training if the SOP is updated or if the
complexity regarding whether the user is trained or not
training has expired. While the LMS is offline, in order
and cross-checking the trainings is complex. Ensuring
to prevent blocking MES, it is important to consider
operators are following procedures is a separate aspect
the timing of the integration type; real time versus
and the spectrum of possibilities of integration needs
near real time (one day).
to be discussed further, as this would be a deviation
closer to MES/QMS integration. As a starting point
for implementation, checking user training can be
implemented initially.

19.0
Product lifecycle
management (PLM)
Use-case
The integration of PLM and MES has become essential as companies are looking for centralized ways to manage
information and create a closed loop that streamlines the flow of data from drug research and development to the
execution of manufacturing processes.
PLM can support multiple users in this process, from For example, by integrating scheduling between PLM
R&D, tech-transfer and even regulatory-related and advanced planning and scheduling systems (APS),
departments. Overall, it supports modeling, managing manufacturers can ensure that the production schedule is
as configuration, optimizing and validating recipe aligned with the product and process design. Scheduling
master data, related to operational processes and integration allows automatic update of the production
analytical methods, easing the application of the schedule, taking into account variants or changes made
S88 standard. Bill of process, bill of material, bill of in the manufacturing process. Moreover, PLM can share
equipment and related routings can therefore benefit the appropriate instructions with operators and machines
from the capabilities a PLM can offer versioning, involved in the manufacturing process. This ensures
change management, branching, maturity assessment, that both humans and machines have access to the right
knowledge management, approval management, information needed to perform tasks correctly.
search capabilities, collecting data and reporting, use
Closing the loop, the MES can capture data during
of libraries and multiple collaboration capabilities. In
operations, such as the status of each batch being
addition, PLM encompasses the product and process
produced, the process effectiveness and any quality
definition, the definition of the specification, and will
measure or issue, providing feedback on the drug
serve as a single source of truth during execution,
and manufacturing process design. These data can
especially for quality control and batch release.
be reported, analyzed, as ‘real-world evidence’,
Therefore, data are structured and traceable, and used as new boundary conditions for further
which gives the capability to simulate various investigations and simulations in the PLM, enabling
scenarios in a virtual manufacturing context and continuous improvement.
share an optimized process seamlessly with the
MES without any manual export/import.

Research and
Preclinical development Clinical trials Submission Commercialization Discontinuation
discovery
PLM
mBOM and BOA

ERP
Master recipe*
LIMS (for quality control)
Master recipe* and change to maintenance processes

MES
Quality,
production and
maintenance
data
Master recipe*
APS
Master recipe*: mBOM, BOA, BOP and routings
Benefits
An integrated PLM/MES solution provides a more streamlined process and delivers benefits to multiple departments
that reduces manual efforts while improving data quality.
From manufacturing engineers to shop floor operators:
PLM | Manufacturing PLM | Manufacturing Production PLM | Manufacturing

engineer engineer operator | MES engineer
Author master recipe Review the master Access the Access and analyze
(mBOM, BOP, BOE recipe with the work instruction production outputs
and routings) right stakeholders Simulate and
Define data to be Execute the process optimize the process
collected on the Release the and collect the data for continuous
shop floor master recipe improvement
Author work Re-work the recipe
instructions

From manufacturing engineers to production planners:
Manufacturing engineer | PLM Manufacturing engineer | PLM Production planner | APS
Author master recipe Review the master recipe Access the master recipe
(mBOM, BOP, BOE with the right stakeholders
and routings) Access the work orders
Release the
Define equipment master recipe Plan under constraints
attributes
Data quality benefits: Productivity benefits:

• Ensures that all manufacturing data is up to • Ensures structured data visibility for the right person
date through a single source of truth, helping to make informed decisions and ensure quality
eliminate multiple manual transcription errors by design, starting from product development
and reduce data updating time considering execution data or to ensure overall
• Structures the data in a consistent way using alignment and enhancing continuous improvement
PLM capabilities such as versioning, change • Speeds up the drug product and process
management, branching, maturity assessment, development workflow with accurate and traced data
knowledge management, approval management, which can be aggregated in reports and speeds up
search capabilities, use of libraries and multiple regulatory dossier submission
collaboration capabilities
• Provides detailed and standardized manufacturing
• Settles routings to understand the product and instructions to manufacture medicines to the
processes through traceability and genealogy. highest quality standard
• Integrates data on inventory, materials and
equipment to have better control over supply chains.
“We see more and more pharmaceutical organizations

investigating PLM solutions and how they can integrate with MES.
This is a great way for organizations to improve data integrity and
overall manufacturing agility to meet evolving demand needs.”
Clément Glace, Life Sciences & Healthcare Solution Consultant
Dassault Systèmes

Data exchange
The following data exchanges are required to create a fully integrated MES/PLM system:
Manufacturing bill FROM PLM mBOM including: When the mBOM maturity
of materials (mBOM) • Name of raw materials, intermediate products and reaches a release state
(must have) finished products
• Quality specifications (product quality attributes
(QA)/critical QA)
• Acceptable range based on jurisdiction
• Header frame (batch numbers)
• Consumables such as single-use bags.
Bill of equipment FROM PLM BOE including: When the BOE maturity
(BOE) (must have) • Primary and secondary resources reaches a release state
• Capable resources
• Resources parameters
• Equipment calibration instructions
• Shift patterns and calendars.
Bill of process (BOP) FROM PLM BOP including: When the BOP maturity
(must have) • Type of operations reaches a release state
• Sequence of process
• Process parameters (PPs/key PPs/critical PPs)
• Normal operating range (NOR) and proven
acceptable range (PAR) based on jurisdiction
• Routings
• Data to be collected during process
• Work instructions.
Quality control or in- TO PLM Quality control or in-process control results including: Start of quality process
process control results • Type of method
(must have)
• Batch number
• Control specifications
• Assay results
• Status
• When executed
• Who.
Manufacturing TO PLM Operators’ manufacturing reviews: When review is created

reviews (nice to have) • Review ID
• Review description
• Actions.

One of the biggest challenges in integrating PLM and MES is ensuring that data are well synchronized. Changes made in
the PLM must be available in the MES soon after the maturity state is changed. It is also challenging because there can
be different MES across a site.
PLM and MES are often built on different technologies with different data models, which require working with software
vendors or system integrators to adapt the solution to meet specific needs. Integrating PLM and MES requires the
transfer of intellectual property (IP) or GxP data, which increases cybersecurity requirements. Biopharmaceutical
companies should implement robust data security measures, such as encryption, access controls and data monitoring,
to ensure data are protected.
The PLM concept is not fully understood and therefore not well utilized, it is often used siloed by plants or production
lines where the true benefit is having a referential of recipes at the business unit or corporate level.

20.0
Conclusion
This white paper discusses the importance of integrating MES with
other biopharmaceutical manufacturing software solutions, such as
ERP, QMS and LIMS. The current process is not standardized in the
industry, is complex and is not user-friendly, which leads to difficulties
in implementation, set-up, and configuration. These complexities
discourage biomanufacturers from integrating their systems, limiting
manufacturing scalability and digital maturity, which in turn stalls the
benefits of a digital ecosystem. Without proper integrations, manual
data entry leads to increased deviations, longer release times and
higher costs in biopharmaceutical manufacturing operations.
While biopharmaceutical system integration is a vast and complex

ecosystem, addressing these challenges by focusing on function and
business use-case and processes will specify the intended use and
improve overall operations and speed of implementation. Each of the
specific integrations mentioned in this white paper can streamline
operations, improve efficiency and reduce costs, and provide additional
benefits of real-time visibility into manufacturing operations and a
holistic view of the entire manufacturing process, across different
departments and business units.
These guidelines and recommendations for integrating MES benefit

both biopharmaceutical manufacturers and MES vendors so that there
is an aligned understanding of the value proposition alongside business
and functional guidance on ‘why’ and ‘what’ to integrate MES to.
This guidance details industry recommendations and provides an
end vision of what a holistic MES of the future solution would be.

“Integration to and from MES is key to ensuring flawless and
“Integration to and from MES is key to ensuring flawless
paperless production processes. The technical possibilities are
and paperless
endless, production
and establishing processes.
a set of preferred The
interface technical
methods and
possibilities
defined are endless,
responsibilities has been anand establishing
important frameworka for
setus.”
of
Rebecca Julie Nørgaard, System Architect
preferred
Novo Nordisk interface methods and defined responsibilities
has been an important framework for us”.”

System Architect, Novo Nordisk
By understanding the relationship between MES and other
biopharmaceutical manufacturing systems, companies can plan
appropriately to deploy, and ultimately optimize their production
processes, and evolve
“Wheninto youaintegrate
higher level of systems
your digital plant
withmaturity, at
MES, it suddenly
their own pace.requires
During the implementation,
data it is important
correctness, robustness andto consider
harmonized
several key factors andItassess
usage. can takethe away
impact of these
some when but
flexibility, deploying
the benefit of
interfacing systems, such as quality, automated interfaces,
connecting your MES system with eg. ERP is that it business
continuity, security and and
ensures data requires
governance.
highWhile
quality allof
ofdata
the details of
and reduces
these impacts were
manualnot errors.”
addressed in the paper, consideration during
deployment is critical for a successful delivery.
In conclusion,
System integrating
Architect, Novo Nordisk MES with other biopharmaceutical
manufacturing systems is essential for improving operations
and achieving digital maturity. Following the guidelines and
recommendations provided, this paper will help companies and
vendors align and realize the benefits of a comprehensive and
efficient manufacturing ecosystem.

Glossary
Term Definition Term Definition
AGV Automatic guided vehicles LIMS Laboratory information management

system
APS Advanced planning scheduling
LMS Learning management system
ASRS Automatic storage and retrieval system
MBR Master batch record, in general in
BE Batch execution application
electronic form unless stated otherwise
BOE Bill of equipment MES Manufacturing execution system
BOM Bill of materials MIRS Material inventory and retrieval systems
BOP Bill of parameters NOR Normal operating range
CM Corrective maintenance PAR Proven acceptable range
CMMS Computerized maintenance
PDF Portable document format, standard and
management system
archivable document format
DCS Distributed control system
PLC Programmable logic controller
DH Data Historian
PLM Product lifecycle management
DO Disolved oxygen
PM Preventative maintenance
EBR Electronic batch record
PP Process parameters (critical = CPP)
EDMS Electronic document management
QA Quality attributes (critical = CQA)
system
ERP Enterprise resource planning QMS Quality management system
GxP Good practice SCADA Supervisory control and data acquisition
ISA 95 Framework for classifying system by SOP Standard operating procedure

hierarchical level

References
1 Digital Plant Maturity Model 3.0 - Digital Plant Maturity Model 3.0 - BioPhorum
2 ANSI/ISA88: Batch Control standard
3 ANSI/ISA95, Enterprise-Control system integration

Permission to use
The contents of this report may be used unaltered as

long as the copyright is acknowledged appropriately
with correct source citation, as follows ‘Entity,
Author(s), Editor, Title, Location: Year’
https://doi.org/10.46220/2023IT009
Disclaimer
This document represents a consensus view, and as

such it does not represent fully the internal policies
of the contributing companies.
Neither BioPhorum nor any of the contributing

companies accept any liability to any person arising
from their use of this document.
The views and opinions contained herein are that of

the individual authors and should not be attributed
to the authors’ employers.
CONNECT COLLABORATE ACCELERATE

is a trademark of BioPhorum Operations Group.


A Deep Dive Into MES Integration For Enhanced Biopharmaceutical Manufacturing

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MES OF THE FUTURE

2.0 Problem statement ........................................................................................................................................................................... 7

3.0 Benefit statements . .......................................................................................................................................................................... 8

4.0 General points to consider for interfaces ................................................................................................................................. 10

5.0 Scope ................................................................................................................................................................................................ 12

6.0 Interface considerations and guidance . .................................................................................................................................... 13

7.0 ERP (material management) ......................................................................................................................................................... 15

8.0 ERP (batch management) . ............................................................................................................................................................ 18

9.0 ERP (order management) .............................................................................................................................................................. 21

10.0 ERP (inventory management) ...................................................................................................................................................... 24

11.0 Electronic document management system (EDMS) ................................................................................................................ 26

12.0 Laboratory information management system (LIMS) ............................................................................................................. 28

13.0 Data Historian . ............................................................................................................................................................................... 32

15.0 Batch execution (BE) application ................................................................................................................................................ 37

16.0 Computerized maintenance management system (CMMS) .................................................................................................. 40

17.0 Quality management systems (QMS) . ....................................................................................................................................... 43

18.0 Learning management systems (LMS) ....................................................................................................................................... 45

19.0 Product lifecycle management (PLM) ........................................................................................................................................ 47

20.0 Conclusion ....................................................................................................................................................................................... 52

Unlocking efficiency: a deep dive into MES integration

Growing from an end-user group in 2008, BioPhorum’s membership now

In each of these Phorums, BioPhorum facilitators bring leaders together to create

BioPhorum IT: MES of the Future

Unlocking efficiency: a deep dive into MES integration

Unlocking efficiency: a deep dive into MES integration

In the current biopharmaceutical manufacturing landscape, efficient

Unlocking efficiency: a deep dive into MES integration

“Unlocking the full potential of manufacturing operations is akin to

Unlocking efficiency: a deep dive into MES integration

Unlocking efficiency: a deep dive into MES integration

“For us, deciding on the priority for implementation of interfaces is

Benefits to biomanufacturers Benefits to MES supply partners

Unlocking efficiency: a deep dive into MES integration

Unlocking efficiency: a deep dive into MES integration

Unlocking efficiency: a deep dive into MES integration

Unlocking efficiency: a deep dive into MES integration

Table 1: In-scope interfaces

Enterprise Resource Planning (ERP) (material management)

Enterprise Resource Planning (ERP) (batch management)

Enterprise Resource Planning (ERP) (order management)

Enterprise Resource Planning (ERP) (inventory management)

Electronic Document Management System (EDMS)

Laboratory Information Management System (LIMS)

Data Historian (DH)

Autonomous Mobile Robots and Guided Vehicles (AMR, AGV)

Batch Execution application (BE)

Computerized Maintenance Management System (CMMS)

Quality Management Systems (QMS)

Learning Management Systems (LMS)

Product Lifecycle Management (PLM)

These topics are in scope for each of the Out of scope

Unlocking efficiency: a deep dive into MES integration

Table 2: In-scope interfaces and proposed order of priority

Enterprise Resource Planning (ERP) (material management) 1

Enterprise Resource Planning (ERP) (batch management) 1

Enterprise Resource Planning (ERP) (order management) 1

Enterprise Resource Planning (ERP) (inventory management) 1

Electronic Document Management System (EDMS) 2

Laboratory Information Management System (LIMS) 3

Data Historian (DH) 4

Autonomous Mobile Robots and Guided Vehicles (AMR, AGV) 4

Batch Execution application (BE) 4

Computerized Maintenance Management System (CMMS) 5