Reprinted from PHARMACEUTICAL ENGINEERING®

The Official Magazine of ISPE

July/August 2011, Vol. 31 No. 4 Manufacturing Systems Solution
www.ISPE.org ©Copyright ISPE 2011

This article
presents a Manufacturing Systems Solution –
three phased
approach to More than Manufacturing Execution
implementing a
Manufacturing System (MES)
Systems
Solution
using real life by Gilad Langer
examples to
demonstrate the
benefits.

Learning From the Past but if we reflect on current day manufacturing

About Our Current solutions it looks like we are still struggling with
Manufacturing System’s State

I
some of the same issues and that this vision is
n 1985, the Computer and Automated Sys- still very relevant.
tems Association of the Society of Manufac- The original CIM wheel concept was focused
turing Engineers (CASA/SME) published its on automation and integration inside the en-
vision of enterprise-wide teaming or as it terprise. The concept was revised in 1993 and
was known the “CIM Enterprise Wheel” - Figure took a more holistic approach to include the
1.1 Computer Integrated Manufacturing (CIM) manufacturing organization as a whole. This
presented a vision in which manufacturing newer model (from 1993) puts the customer at
operations are managed and enabled by one the center, which is an idea that is not much
software system with a common information different from modern operational excellence ap-
model at its core.2 The vision was targeted at proaches. For example, Lean Thinking advocates
addressing the problem of managing production focusing on adding value to the customer and the
operations, its materials, resources, and infor- central concept in Process Analytical Technology
mation. A novel idea at the time – so it seemed, (PAT) is achieving process understanding.
Figure 1. SMEs CIM Over the last three decades,
Enterprise Wheel. companies across a variety of
industries have been imple-
menting solutions in an at-
tempt to conform, at least in
part, to the CIM concept. These
“Manufacturing Systems” solu-
tions have provided companies
with some of the benefits that
the CIM concepts suggest, but
many challenges still remain.
The CIM concept is less known
in the pharmaceutical industry;
however, some of its elements
have trickled into more popular
concepts such as ISA-95.3 In both
models, the software system
that provides the fundamental
functionality is a Manufacturing
Execution System (MES).
A Manufacturing System
solution is comprised of all the
manufacturing resources (ap-

July/August 2011 PHARMACEUTICAL ENGINEERING 1

 Manufacturing Systems Solution
plication, equipment, and people) and associated information holistic approach is a central element in understanding the
working together to create a quality product, or Manufactur- objectives of a Manufacturing System and also sometimes
ing System. This Manufacturing System solution concept is referred to as the “Shop Floor Management Problem.”
very similar the “MES Domain” concept presented in the Some definitions of Manufacturing System are focused on
ISPE GAMP® Good Practice Guide: Manufacturing Execution describing a solution or more precisely the functionality and
Systems – A Strategic and Program Management Approach.4 architecture of the solution. For example, the Manufacturing
Ruklic and deSpautz defined it as follows:5 Enterprise Solutions Association (MESA) model6 presents a
number of functional categories from a business perspective,
“The concept of Domain recognizes that inherent func- whereas the ISA-95 model7 provides solution architecture
tionality within applications and systems often span the based on functional decomposition. These models have been
Enterprise-Control system Integration layers.” successfully used in many cases by companies seeking to
explore and standardize their Manufacturing Systems, such
The MES Domain concept seems to be similar to the CIM vision as Pfizer, Merck, Genentech, and Amgen.8 They are most effec-
of the 90s. They all point to a solution composed of different tive when the system’s objective is clear and where a specific
systems driving manufacturing operations that are based on functionality set has been identified. Yet, these models do not
information and have customer value as their goal. It seems adequately address the fundamental challenges of defining
that we are re-inventing the wheel – the CIM wheel. the problem and scoping a solution.
The goal of this article is to review the current state of In an attempt to aid in the definition of the “Shop Floor
MES solutions and the challenges that they present. In ad- Management Problem,” a specific model is present here that
dition, the term “Manufacturing System” is used rather than is referred to as the “Integration of Flows.” This model pro-
Manufacturing Execution System (MES) to differentiate vides a perspective that is targeted at defining and scoping
between MES – a software system that can be purchased, the objectives of the Manufacturing System. The model as-
and Manufacturing System – the solution that is provided sumes that a manufacturing organization can be described
by integrating a variety of shop floor software systems. This as a composition of two information flows and one physical
perspective will bring some clarity to the selection and design flow as depicted by Figure 2.
process of these solutions focused on addressing the challenges
of enabling successful deployments and realizing the true Product Information Flow
value from these solutions. This flow represents the business processes that manage
and generate product information including R&D, product
Understanding the design, process engineering, quality engineering, etc. This
Manufacturing Systems Challenge product information is required by the production processes
Typically, a Manufacturing System solution involves a multi- and may include formulations, recipes, SOPs, BOMs, etc. It
tude of systems each aimed at addressing a specific functional is important that this information is delivered to the shop
need, such as quality, operational efficiency, compliance, batch floor in an effective and timely manner. In addition, these
records, etc. These systems are sometimes referred to by the processes rely on accurate feedback from the shop floor pro-
specific function that they serve or the problem that they are cessing activities.
implemented to solve, e.g., electronic Batch Record (eBR),
Batch Management, Recipe Manager, Barcoding, Deviation Logistical Information Flow
Management, etc. The naming is not important, but it does This flow represents the business processes that manage and
reflect a common reality that systems sometimes have been generate the information, relating to order and material man-
implemented to solve a particular problem or provide a specific
function. For example, using a system that provides an eBR
replacing the paper based batch record is a common and valu-
able solution implemented by many companies. It addresses
the issue relating to compliance and most importantly, enables
release by exception. However, the electronic batch record is
just one piece of a full Manufacturing System solution. This
scenario where systems are used for specific and sometimes
isolated functions is referred to as “Islands of Information”
and interestingly the CIM concept, drafted more than three
decades ago, already recognized this as a shortcoming.
In most cases, companies realize that they have challenges
in managing the wealth of information and operations in their
manufacturing shop floor, as well as specific challenges in
supporting process and operations. Yet, to clearly define the
relevant Manufacturing Systems solution it is important to
have a clear understanding of the problem as a whole. This Figure 2. Manufacturing systems and shop floor management.

2 PHARMACEUTICAL ENGINEERING July/August 2011

 Manufacturing Systems Solution
agement. This includes master scheduling, demand manage- facturing Systems solution.
ment, capacity planning, MRP, etc. The resulting information Experience shows that a relatively common challenge that
includes manufacturing schedules and plans in the form of many life sciences companies face is that they may have a
production, work, and shop orders. Here again, it is important variety of different systems on their manufacturing shop
that the information is delivered to the shop floor in an effec- floor. Many of these systems are “Commercial Off The Shelf”
tive and timely manner. In addition, these processes rely on (COTS) with home grown custom solutions built on top of
accurate feedback from the shop floor processing activities. these or even stand-alone custom solutions. Sometimes a
Manufacturing Execution System (MES) is also implemented,
Material and Resource Flow but commonly to address a specific process or function, such
This flow represents the physical flow of material and resources as Weigh and Dispense (W&D) or to manage the Batch Record
on the manufacturing shop floor. It is the actual manufactur- electronically (eBR).
ing process and includes the equipment, automation systems, When the manufacturing plants for a BioPharmaceutical
and people. The outputs of this flow are the finished products company were analyzed to determine their current state
or batches. using the “Integration of Flows” model, it was clear that
The intersection of the three flows represents an impor- their solution was not ideal. A multitude of enterprise level
tant and complex integration and coordination challenge. It systems and an even more complex landscape of site level
is where information converges with the real-world, where systems existed. In addition, they had identified some major
models, specs, and schedules are put to use. This intersection deficiencies in one of their manufacturing sites. This site was
of the virtual and the real is the puzzle that Manufacturing geographically isolated and with time had a host of different
Systems attempts to solve and can be described as: systems implemented including both custom home-grown
systems and COTS. They identified specific problems around
How to make best use of the information provided by the batch release and tracking and had some fixes in place with
Product and Logistical flow to efficiently and effectively the existing solution landscape.
manage the physical flow of Materials and Resources To illustrate the different solutions in this example, the
(also known as the production process). “Integration of Flows” model was used and the systems
mapped on top of the flows. This provides a perspective to the
Although it may seem as a simplistic definition, it really functionality that each system provide for the Manufacturing
embodies what a Manufacturing System is designed to do. Systems or System Landscape - Figure 3.
It is analogous to the job of a production supervisor or plant Looking at the model in Figure 3, it is apparent that the
manager. Imagine a scenario where a seasoned and effective current state fits the description from CIM about “Islands of
production supervisor or plant manager is running a simple Information.” The systems and solutions that were in place are
operation and think about how increasingly complicated and point solutions each intended to provide specific functionality
hard this task becomes when it is scaled both in volume, com- for a specific need, yet they are all part of the MES Domain.
plexity, and product variance – this is what the Shop Floor The solution for this specific organization was to implement a
Management problem is. COTS MES product that would replace the home grown MES
The “MES Domain” concept as introduced in the ISPE and could effectively interoperate with the other systems to
GAMP® Good Practice Guide4 has some significant similari- provide a complete Manufacturing Systems solution. This
ties to the “Integration of Flows” model. It defines the Manu- solution did not only provide the needed traceability and
facturing System space (MES Domain) as all the systems efficient release by exception, it also provided the capability
that are currently in place, as well as new ones that may be to better manage Work In Process (WIP) materials, informa-
implemented as part of a solution. The guidance describes the tion that could be used for Nonconformance (NC) analysis,
Manufacturing System problem as one of the fundamental and a way to directly implement and measure the impacts
aspects of systems implementation where MES is involved. of Corrective Actions and Preventative Actions (CAPAs). In
These set of systems and the interoperable solution that they addition, the solution provided more accurate and frequent
provide to the overall problem is what the focus should be, not information about the progress of production orders to ERP
a specific system or isolated problem and that is essentially that was invaluable both for financial performance and for
the same as the CIM model’s definition. production planning and scheduling.
In this example, the new Manufacturing Systems solution
Analyzing Current State of a Manufacturing became much clearer after the system was commissioned and
System – An Example in operation. The challenge is to convey this value and benefit
Why do all these different models and their history matter? in the initial assessment phase. Ultimately, the difference
Well, they help gain a perspective about the current state of was in using a modern COTS MES not as another localized
systems in the manufacturing landscape and importantly system, but as the central system with effective interopera-
they exemplify the fact that in most cases, there is no cohesive tion with the other systems. In addition, the MES was made
solution to the “Shop Floor Problem.” The realization that a responsible for all process execution and material tracking,
solution is more than the sum of its parts is important and including data collection of pertinent information to product
is a fundamental element in the design process of a Manu- quality and process compliance.

July/August 2011 PHARMACEUTICAL ENGINEERING 3

 Manufacturing Systems Solution
One of the important lessons learned from this exercise of the system landscape, was instrumental in developing a
was that using this approach that included an initial assess- common understanding of the problem at hand. It was an
ment phase, with an analysis to determine the “As-Is” state invaluable tool that helped everybody in the organization
gain a common understanding and gain alignment with the
objectives of the solution. This is not to say that it was an
easy accomplishment. There were quite a few compromises
that had to be made both with objectives and functionality
that makes the final solution far from ideal and as in many
implementations involving MES, it was “painful” at times. Yet,
it was a big step in the right direction and provided a valu-
able solution with a substantial impact to improving process
efficiency, product quality, and risk of regulatory exposure.
Hopefully this company will use this solution to drive even
more efficiencies and improvements, and in the process let
the solution evolve.

Why Do We Need a
Manufacturing Systems Solution?
To most, the question of why is there a need for a Manufactur-
ing Systems solution is evident. The simple answer is that a
Figure 3. Example of system landscape. Manufacturing System solution provides substantial value
to a manufacturing organization, yet it is seemingly difficult
Abbreviation Description to convey the specifics. In Table B there is an example of the
specific benefits and value that a cohesive Manufacturing
ERP Enterprise Resource SAP with substantial customizations. System solution provides. These are only a subset of the
Planning
benefits and specifically relate to the example described in
BI Business Intelligence Only used for financial data the previous section.
PLM Product Lifecycle Not implemented
Management Selecting an MES Product and Justifying
PDM Product Data Mainly with Documentum but other file the Manufacturing Systems Solution
Management based and paper passed records existed. In the example above, it seems that the benefits are appar-
QMS Quality Management Custom home-grown system that was ent and can be easily quantified. Unfortunately, that is only
Systems used to manage nonconformance recognizable after the fact, in other words, it is not typically
information (NCR) and Corrective
Actions – Preventive Action (CAPA) easy to provide that level of clarity regarding the benefits
information. before the solution is in place. In addition, the quality and
MES Manufacturing Custom home-grown system with very efficiency gains are inherently tied to the process and may be
Execution System limited tracking capabilities and perceived as part of the process improvement and not neces-
implemented on a legacy platform. Batch sarily the Manufacturing Systems solution. It is a “chicken
Records were mostly paper based, no
eBR (electronic Batch Record). and egg” scenario where the process improvement could not
be achieved without a system, yet consequently, the benefits
SCADA/ Supervisory Control Automation systems included a variety
DCS and Data Acquisition/ of disparate mostly SCADA systems. are attributed to process improvements.
Direct Control System It is not surprising that Manufacturing System solutions,
CMMS/ Computer Managed Only calibration management was involving an MES, are typically the last ones to be imple-
EAM Maintenance System/ implemented using legacy system that mented in the Manufacturing Systems landscape. They are
Enterprise Asset was no longer supported and did not notoriously difficult to justify and rationalize based on ROI.
Management manage all of the relevant equipment
calibration. They are inherently tied to the value adding process and it
is hard to attribute benefits to a system by itself. In some
TMS Training Management Training/Certification management was
System implemented in an SAP module, part of cases, it is straightforward to provide quantifiable benefits
ERP. when there is a specific, and typically catastrophic, event that
RMR Raw Material Receiving Raw material receiving was managed by needs to be remedied, such as a recall, 483 (FDA warning
a home-grown system that letter), detrimental quality issues, etc. In most other cases,
communicated with ERP. the Manufacturing System should really be perceived as an
MI Manufacturing Not implemented, basic reporting used enabler and its justification has to be rooted in the process
Intelligence from whatever the standards systems that the solution is intended to support. The MES system
provided. Much of the data and
information visualization was performed needs to be considered as a platform that enables operational
in Microsoft Excel spreadsheets. excellence, i.e., more efficient process, better quality, effective
Table A. System landscape abbreviations and descriptions. material management, traceability, etc. This brings clarity to

4 PHARMACEUTICAL ENGINEERING July/August 2011

 Manufacturing Systems Solution
of this approach are performed to some extent; however, the
Category Value Description
value of executing these three phases correctly and in se-
Release by The ability more effectively “Release by Exception.” quence should not be underestimated. Each successive step
Exception The burden of batch record review is minimized to a
bare minimum. The system configuration and recipes builds on the previous one helping to acquire knowledge, gain
are “qualified.” This means every batch, lot, or order understanding, align the organization, and disseminate the
executed is guaranteed to be performed exactly value of the solution. Experience shows that companies that
as prescribed. If anything is not as prescribed an
exception is logged with relevant e-signatures and have adhered to this simple process have been able to realize
approvals. a complete Manufacturing Systems solution faster and more
Compliance Ensure compliance through elimination of paper, and efficiently, minimizing the “painful” experience that typically
availability of quality records. More effective and error- accompanies these initiatives.
proof data entry reduction in batch record creation Once the three phases in Table C have been completed
and review time, and reduction in incident and rework
handling. successfully, the next steps that may include MES vendor
selection and on to commissioning and go-live become much
Process Effective process execution including order dispatching,
Execution tracking and execution that enables improved Work more streamlined. In most cases, MES products are aligned
In Process (WIP) management of all raw material, with specific industries and hence it is straightforward to
intermediates, and final product. In addition the system make an initial short list. But, this may not always be the best
can provide real time inventory reporting to ERP.
approach and it may be valuable to broaden the search for a
Quality Minimizes risk to product quality, such as risk of losing suitable product. For example, in some scenarios a vendor may
a batch and other scrap of material. Ensure quality by
increased use of in-line QC and more effective SPC.
Visibility into quality sources to localize and disposition
materials in process and post-process.
Data Integrity Seamless integration with automated equipment
and automation system allowing download batch
information, recipes and set-points. Recording of order
and batch information in context and not only in time-
series and capture of data for engineering analysis and
investigation work.
Intelligence/ Provides the data and information fundament
Reporting for Manufacturing Intelligence and Performance
Management.
Employee Increase employee satisfaction and reduce operator
Satisfaction training time by eliminating redundant data entry and
paper handling as well as empowerment through better
visibility to the production operations.
Process Drive operational excellence across the organization by
Standardization effectively propagating operational improvement and Figure 4. The three phases of solution design.
efficiency gains to different sites and processes.
Table B. Specific benefits from a Manufacturing Systems solution. I – System What is the solution for? Gain a clear understanding
Objectives of the specific Manufacturing Systems problem with
the benefits of the solution and also helps in aligning people focus on determining existing system or “As-Is,” and
the future solution’s objectives or “To-Be.” What are
around the solutions and its objectives. the goals of the system? i.e. Release by exception,
Once the solution’s objectives are defined and the system reduce bottlenecks, lowering scrap, improve quality,
landscape is mapped, the next element in the process is the etc. Use objectives to streamline the decision
process, implementation process, and also to align the
requirement analysis and development of a User Requirement organization around a solution.
Specification (URS). In this phase, it is common practice to
II – System Draw up the “MES Domain.” This is a map of
use formal (true and tested) models, such as the MESA model Landscape process and current state of the system solution
or the ISA 95 standard. This is the tedious, but necessary landscape. Use this to get a clear understanding of
part of the preparatory and selection phases for the MES what already exists in the MES Domain including
production systems, business systems, automation
platform. The detail involved in the process is important and systems, and interoperability solutions. It is also
these models provide a beneficial tool; as the saying goes, “the valuable to define a long and short term strategy based
devil is in the details.” However, using these models with no on the goals for the existing system landscape and
future solution.
clear focus is risky since the significance of each requirement
may not be clear and their prioritization is even more difficult. III – Requirement Using accomplished industry best practices and
Analysis standards such as ISA-95 embark on a detailed
The models should assist to ensure that all aspects of the requirements analysis to develop a URS. The URS
required solution have been examined and that the scope of scope and detail should be driven by the solution’s
the solution is valid. objectives and understanding of system landscape.
The URS should also include requirements for
Based on the experiences and finding conveyed so far in interoperability, deployment, compliance, scalability,
this article, a three phased approach to Manufacturing Sys- and upgradability.
tem solution design appears evident. In most cases, elements Table C. Description of the three phased approach for solution design.

July/August 2011 PHARMACEUTICAL ENGINEERING 5

 Manufacturing Systems Solution
be trying to penetrate the pharmaceuticals or biopharmaceu- will serve many other companies that are working to design
ticals industry, which could provide a unique opportunity to and deploy a Manufacturing System solution.
potentially influence the particular vendor or collaborate with
them to obtain a solution that fits well to a specific company References
or process needs. There are many other factors that can and 1. SME Blue Book, Process Reengineering and the New
do play into system selection and “It depends” is always a true Manufacturing Enterprise Wheel, SME, 1994.
statement when talking about fit of a specific MES product 2. Langer, G., Sørensen, C., Schnell, J., Larsen, M. H., Ja-
to the specific environment. A clear understanding of your cobsen, P. and Lenau T., Computer Integrated Production,
particular needs, specifically your “Shop Floor Management DTU Course no. 80206, Pub. no KPD-18-99, Lyngby 1999,
Problem” or “MES Domain” is invaluable. ISBN 87-90855-28-0.
3. ISA Standard, ISA-95 Enterprise Control Systems, ISA,
Conclusion 1998.
The nature of Manufacturing System calls for a solution design 4. ISPE GAMP® Good Practice Guide: Manufacturing Ex-
process that involves not only flexibility and ingenuity, but ecution Systems – A Strategic and Program Management
also a great deal of good engineering. The MES Domain is Approach, International Society for Pharmaceutical En-
inherently complex and this complexity means that providing gineering (ISPE), First Edition, February 2010, www.ispe.
a clear and concise return on investment is challenging, given org.
that MES typically involves a substantial capital investment. 5. deSpautz, J.F., Ruklic, G., “Domain Methodology for Com-
The result of this is that MES implementations are commonly puter System Specification and Verification Applied to
surrounded with uncertainty and implementation experiences Manufacturing Execution Systems (MES),” Pharmaceutical
that typically are described as “painful.” Engineering, May/June 2008, Vol.28, No.3
It is therefore important to consider that a Manufacturing 6. Langer, G. and Alting, L., “An Architecture for Agile Shop
System is not a single system or software from one vendor. Floor Control Systems,” The Journal of Manufacturing
It involves a composition of all the different systems in the Engineering, Vol. 19, No. 3, 2000.
manufacturing environment, interoperating to solve the 7. MESA, The MESA Model, Manufacturing Enterprise
“Shop Floor Problem.” The focus should be on the solution Solutions Association, http://www.mesa.org/en/modelstra-
and not the software system. This may be challenging since tegicinitiatives/MESAModel.asp, 2008.
it involves many different applications and different parts 8. World Batch Forum (WBF), ISA-88 and ISA-95 in the Life
of the organization, each with somewhat differing goals. Science Industries, Chapters 13 - 14, Momentum Press,
Understanding this problem or MES Domain is crucial and Vol. 4, 2011.
the more time that is devoted to describing it the better the
solution gets. About the Author
Therefore, using a regimented approach that focuses on Dr. Gilad Langer has more than 15 years
the three elements of the solution including objective, systems of experience in the manufacturing and
landscape, and requirements in a sequential manner is invalu- quality system domain and spans a variety
able as the initial stage of the solution design. This approach of industries where he has spearheaded
not only provides superior technical perspective, but is also projects involving strategic complex software
invaluable in aligning the organization with the solution. It solutions in both Europe and the Americas.
helps in generating interest in the solution and establishing He has served as trusted advisor and busi-
its importance in the organization. Experience shows that a ness consultant in the areas of technology
key element in a successful Manufacturing Systems solution directions, industry strategy, and manufacturing systems
deployment is that people in the organization believe in the implementations for companies such as GE, Caterpillar, J&J,
solution. Bang and Olufsen, Abbott, Maersk, Roche, Zimmer, Novo
Learning from experience is an important aspect of any Nordisk, BioMarin, and Amgen. He is an accomplished leader
engineering exercise and Manufacturing Systems solution with experience from military, academic, and multiple manu-
design is no different. Considering the history behind these facturing industries. Dr. Langer has a MS in manufacturing,
systems designs over the last three decades from the CIM industrial and software engineering, and a Doctorate from
concept to current day standards, such as ISA-95 and GAMP the Technical University of Denmark, one of the top technical
MES GPG, there should be ample fundament to design such institutes in Europe. His research was focused on advanced
a system. Yet, it seems that it is still a challenge and one that concepts for highly agile manufacturing systems, where he
is becoming more and more important as companies attempt has pioneered agile methods for software development and
to deal with the dynamics of modern manufacturing environ- has been involved in major European research projects. He
ments. The three phased approach described in this article can be contacted by telephone: +1-919-763-1800 or by email:
presents an answer to this challenge, one that has been tested gidl@nnepharmaplan.com.
in industry and has so far shown great success. Hopefully, it NNE Pharmaplan, 150 Executive Park Blvd., Suite 4550,
San Francisco, California 94134, USA.

6 PHARMACEUTICAL ENGINEERING July/August 2011