Industry software Paperless manufacturing in the ... · agement systems (LIMS) and distributed...

siemens.com/pharma

WhitePaper

Edition 2015

Paperless manufacturing in the pharmaceutical industryAn integrated solution for the MES and automation level

Industry software

2

AbstractWith growing cost pressures and new regulations, manufacturers and quality managers in the pharmaceutical industry are always looking for ways to improve their processes and procedures. A new electronic batch record solution enables complete paperless manufacturing within regulated processes and helps achieve operational and manufacturing excellence from the design of the batch record to the release of the batch report, both in manual and in highly automated environments.

The Siemens software solution for electronic batch record management offers native integration between the manufacturing execution system (MES), using SIMATIC IT eBR, and the distributed control system (DCS), using SIMATIC PCS 7 and SIMATIC BATCH. This expedites the design, execution, and review steps of master batch records (MBR) and electronic batch records (eBR). Moreover, this solution provides real flexibility in the MBR design, as the selection of the master recipe name and version makes all master recipe information from SIMATIC BATCH available for use in the MES design tool. Through seamless integration between batch pro-cessing in the DCS and workflow management in the MES, SIMATIC IT eBR can streamline and significantly accelerate the implementation of a solution for paperless manufacturing, reducing typical implementation times from one year to only two months for one recipe.

Paperless manufacturing in the pharmaceutical industryAn integrated solution for the MES and automation level

Andrew Whytock, Jean-Jacques Lieners, Clemens Kersten, Nicolas Tessie et. al., Siemens AG

3

Contents

1. Introduction 4

2. eBR as the core of paperless manufacturing 52.1. Definition 52.2. The regulatory framework 52.3. Benefits of paperless manufacturing 52.4. Paperless manufacturing and automation 62.5. System and solution evaluation 72.6. Implementation strategy 7

3. SIMATIC IT eBR: an integrated solution for paperless manufacturing 93.1. Solution overview 93.2. SIMATIC IT eBR key functionalities 103.3. The MBR template 113.4. Collaboration between SIMATIC IT eBR and the automation layer 123.5. The eBR process 143.6. Functional details 153.7. Implementation options and use cases 16

4. Abbreviations 19

4

1. Introduction

The life science industries are currently facing many chal-lenges, ranging from increased competition and cost pressures to ensuring regulatory compliance and patient safety to reducing time to market.

Product variety and diversity have increased tremendously in recent years with the emergence of new, targeted drugs and novel dosage forms. High-potency active phar-maceutical ingredients (APIs) require smaller batches and increasingly stringent operating procedures to ensure product quality and safety. All this leads to growing requirements for greater production flexibility without impairing compliance with regulations.

The ability to produce better and faster has become crit-ical for the life science industries, and achieving opera-tional excellence is a key strategy for today’s life science manufacturers. One barrier to more efficient manufac-turing in the pharmaceutical industry is the frequent use of paper-based processes. While paper-based batch manu-facturing and reporting is a proven and well-established practice, it impedes improvements, as it is time-con-suming, offers poor visibility, and involves lengthy review cycles. So in recent years, regulatory bodies have encour-aged the pharmaceutical industry to exploit the capabili-ties of modern IT and automation solutions and make the move to paperless manufacturing.

While there is a heightened awareness that introducing paperless manufacturing principles provides substantial benefits, companies have been hesitant to introduce such systems on a large scale. Concerns exist regarding the actual costs, risks, and benefits of paperless manufac-turing, especially in the context of highly automated envi-ronments. Until recently there have been no truly inte-grated solutions for paperless manufacturing that could encompass the manufacturing execution system (MES), production, and automation levels and that could inte-grate both manual and automated processes.

With SIMATIC IT eBR, Siemens now presents a solution that can bridge the gap between ISA-95 and ISA-88 stan-dards for interfacing MES and automation, batch control, and manufacturing IT. The solution helps guide manufac-turing operations, whether manual or automated, via seamless interaction between the MES, automation system, and enterprise resource planning (ERP) system. With SIMATIC IT eBR, companies can more easily introduce paperless manufacturing based on electronic master batch records and become more efficient in their opera-tions without compromising quality and product safety.

5

2. eBR as the core of paperless manufacturing

2.1. DefinitionIn principal, the electronic batch record (eBR) adopts the traditional paper-based manufacturing procedures estab-lished in the pharmaceutical industry. Production pro-cesses are specified in a master batch record (MBR) that serves as a general recipe for how to produce a pharma-ceutical product. The MBR contains the product specifica-tion (what is produced), the work procedures, conditional framework, equipment, and workflow (how to produce), the critical-to-quality parameters (how to verify the process), and the necessary tests for ensuring product quality (how to prove product quality). During manufac-turing, the required data and information are compiled and documented in the matching batch record, which serves as a document of proof both for use in quality management and for presentation to the regulatory bodies.

In paperless manufacturing, all these specifications and information are designed, collated, and maintained using electronic documents (Fig. 2.1). The eBR approach in its

most basic form can be an electronic representation of previously paper-based processes (paper-to-glass). By using the capabilities of state-of-the-art IT systems and by networking the electronic batch information with other production systems, such as laboratory information man-agement systems (LIMS) and distributed control systems (DCS) or building automation systems, eBR can help streamline workflows, eliminate errors and deviations, enable higher production quality (Right First Time), and facilitate batch review and release.

2.2. The regulatory frameworkBy taking a risk-based approach to pharmaceutical manu-facturing, regulatory bodies have encouraged pharmaceu-tical companies to adopt the available technologies to improve production efficiency and performance. Specifically, both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published guidelines that specify how to create and manage quality production records in an electronic system to provide an electronic record that precisely

Is the equipmentprogrammed properly?

Is the process clearlydocumented?

Are corrective actionsdefined?

Is sufficient qualitybuilt into the process

Are people properlytrained?

Is work efficiencyacceptable?Is human error a

possible factor?Are materials handled

properly?

Are raw materialsproperly tested?

Materials Manpower/Operators

Method &Process

OperationalExcellence

Today’s Pharma Manufacturing Reality: Operational excellence is based on 5Ms

Machines &Equipment

Am I using the rightequipment?

Is the equipmentmaintained?

Milieu/Environment

Is the process affectedby environmental

factors?

Are materials tracedaround the plant?

Is the productionenvironmentcontrolled?

* Based on Ishikawa cause/effect diagram, also known as 5Ms

Fig. 2.1: A completed batch record must record all the information relevant to the production of a batch

6

details how a drug has been produced. Following the requirements documented in 21 CFR Part 11, an eBR system for paperless manufacturing must encompass three steps: design, execution, and review. Any eBR solu-tion must include these three steps. To facilitate the review and release process and reduce the workload for the quality assurance teams, reviews should be exception based.

2.3. Benefits of paperless manufacturingPaperless manufacturing offers a number of benefits and improvements when compared to traditional procedures. It helps build error-resistant processes that are more robust and less prone to deviations through a more detailed recording of process data, conditions, and results. Specifically, paperless manufacturing enables

• securing materials and equipment usage and workflow (the right material – the right place – the right time – the right status – the right people),

• preventing the loss of batches and reducing discard (especially losses related to human errors), and

• reducing exceptions and the associated effort to inves-tigate and set corrective action plans, leading to improved cycle times.

As paperless manufacturing provides a single point of storage and access for all batch-related documents, it also simplifies batch record management by

• reducing the effort and time spent on batch record preparation and maintenance as well as batch review and release, and

• reducing delays and the time required to capture infor-mation in the batch record.

Moreover, by providing a simple framework for both manual and automated operations and effective docu-mentation of actions and results, paperless manufac-turing also enforces compliance with standard processes, procedures, and regulations. This helps

• reduce variability in manufacturing operations by enforcing standard workflows (driven through elec-tronic instructions) and

• enforce systematic capture and management of abnormal events.

Paperless manufacturing also improves many aspects of investigation, analysis, and audit and inspection manage-ment, as it

• provides full traceability of actions, materials, equip-ment, and people (including integration with enter-prise resource planning and plant automation);

• increases responsiveness in providing critical informa-tion during audits (with enhanced reporting capabili-ties); and

• provides access to information and data in a form that facilitates analysis and investigation.

Altogether, paperless manufacturing can significantly reduce the time and effort associated with entering data, reduce work-in-progress and documentation complexity, reduce the amount of paperwork to be transferred between teams, help significantly lower the number of defects, and contribute to shorter cycle times.

2.4. Paperless manufacturing and automation

Implementing a solution for paperless manufacturing in an automated environment will pose a specific challenge, as most manufacturing execution systems (MES) for paperless manufacturing have been designed as workflow tools to manage manual production operations (Fig. 2.2). The approach originated in the requirements of secondary processes, where the operations use dedicated equipment and machines for specific processes. The material flow can be represented by a linear transfer of material from one machine or equipment unit to the next, with a very limited number of deviations identified through a manual operation or an external trigger (e. g., a sample being taken for an in-process control, or out-of-spec product being discarded).

These production approaches are quite different from the requirements of the production of active pharmaceutical ingredients (APIs) or for the formulations of drugs. These processes are highly automated, and manual tasks (e. g., taking of samples) are triggered by the batch engine. One recipe features an automated sequence of processes involving different sets of equipment, and each piece of equipment can be assigned a state that indicates its avail-ability to the batch control (e. g., in use, used, clean,


7

sterile). These plants must rely on automated processes, as the sheer number and complexity of operations is beyond manual control. In a given plant, as many as 300 recipes will be executed that involve several thousand process parameters and several hundred production steps.

In the past, implementation strategies for automated plants needed to recreate the batch control in the MES, often resulting in system conflicts and requiring substan-tial amounts of engineering time. Solutions were custom-built and mostly not reusable. One of the key challenges was the identification of the relevant process data and parameters – of all the information recorded during pro-duction in the batch system, only a fraction needs to be acquired for the eBR. Additionally, the eBR system must be designed to make good use of the capabilities and information available in the batch system, for example, from deviations recorded in the automation system during process execution, or from the reports that are archived in the batch historian of the automation system.

An ideal eBR solution for automated plants needs to be capable of incorporating both manual and automated procedures and of collaborating with the automation systems instead of competing with them, resulting in an integrated and aligned solution for both process control and MES.

2.5. System and solution evaluationTo fully benefit from paperless manufacturing, companies need to establish a platform that provides seamless inte-gration between the MES and DCS during process defini-tion (engineering) and manufacturing execution (opera-tion), regardless of whether the operations are manual or automated. The system should provide a framework for matching business processes with manufacturing opera-tions and collate the related data for evaluation as well as for presentation to the regulatory bodies.

When evaluating available systems, it is important to assess the IT and production environment and asses both implementation effort and usability issues to ensure a

MES

Logistic centric

Expected availability: > 99,9%

Typical update time: < 20 sec.

Mainly manual driven tasks

DCS

Process centric

Expected availability: > 99,99 %

Typical update time: < 2 sec.

Mainly automation driven tasks

Workflow engine (MES)

Recipe engine (DCS)

Fig. 2.2: Comparison of workflow-centric and recipe-centric systems


8

smooth, risk-free shift to paperless manufacturing for the design, execution, and review steps (Fig. 2.3).

The solution for designing the electronic master batch record should ideally be as intuitive to use as possible to allow for specification by non-IT staff and to reduce devel-opment effort. It should be possible to transfer data and documents between the MES and production/DCS level without impediments to ensure efficient execution and eliminate risks. It is mandatory that staff be able to use the system to develop standardized libraries of process operations to ensure uniform batch execution and to facilitate modifications without quality risks.

A suitable eBR solution should improve manufacturing control, provide interfaces for seamless data exchange with the DCS, and support efficient and safe batch execu-tion by providing a solid paperless process for capturing production data.

For batch review and release, the system should serve as a single point of review for all batch-related information to allow review by exception.

Additionally, the system should support production opera-tions by providing an easy-to-use, easy-to-understand electronic form that supplies the operators with all rele-vant information and work instructions. The system should provide interfaces to other systems, such as labo-ratory information management, inventory management, and building automation.

And finally, the system should be able to support a step-by-step, product-by-product or site-by-site implementa-tion strategy to help mitigate risk, enable learning, and facilitate system rollout.

2.6. Implementation strategyConsidering the significant market pressures they face, pharmaceutical companies generally understand that it is important to reduce the cost of quality and that paperless manufacturing is an important means to achieve this goal. In greenfield projects, a new plant or facility can be designed from the ground up to include the necessary systems and processes for paperless manufacturing, which of course is more straightforward than making the transition to paperless manufacturing within an existing facility.

Making the shift to paperless manufacturing always involves changing established procedures and requires a change in the mind-set of both employees and manage-ment. It is important to address the concerns and require-ments of all parties involved. In pharmaceutical manufac-turing, these specifically include the production staff, the quality management department, and IT. In order to fully reap the benefits of the new system and to ensure both smooth implementation and full support and compliance, it is important to take a strategic approach to the implementation.

First, the project team needs to create a common under-standing and commitment by defining the business and production objectives the company wants to achieve by going paperless. These objectives must incorporate the specific needs of the quality, production, and IT teams, such as the following:

• How will the new solution improve manufacturing quality, regulatory compliance, and review workflows?


Intuitive Tool – No IT skillrequired

Mas

ter

Bat

ch R

eco

rd

Reduction of developmenteffort and risk between MES and DCS

Ability to develop and reuseof standardized libraries forProcess Operations

Design

Paperless process

Ele

ctro

nic

Bat

ch R

eco

rd

Faster and safer dataacquisition

Secure and control theexchange between DCS and MES

Improved manufacturingcontrol

Execute

Single point of review of allbatch relevant information

Bat

ch R

evie

w &

Ap

pro

val

Review by exception: Fastand safe review alreadythrough the productionprocess

Review

Fig. 2.3: Requirements for a paperless manufacturing solution

9

• How will the new system support production opera-tions and help operators make informed decisions and manage the process correctly?

• How will the new solution interface with existing systems and workflows?

Illustrating how paperless manufacturing can make a con-tribution to improved performance in each of these areas will help create a mind-set that views change as an oppor-tunity, not as a threat. This is the precondition for suc-cessful implementation.

The next step is addressing the critical aspects for imple-menting paperless manufacturing. Most commonly, these are as follows:

• Defining goals and benchmarks – to illustrate the implications and benefits to both the operational and management levels

• Securing management commitment – to provide the necessary resources for the project

• Compiling user and documentation requirements – to assess the current state, to ensure a risk-free transition,

and to exploit added benefits (this might also include a feasibility study)

• Specifying the operational design and system require-ments – to define expectations and requirements, taking into consideration the existing system and developing appropriate migration strategies and system interfaces where needed

• Defining the appropriate technical solution – to define the system configuration and integration requirements

• Developing the implementation approach and project time frame

• Assigning the project team and responsibilities

• Developing suitable key performance indicators to demonstrate the project’s success

As pharmaceutical companies are very diverse in terms of their product portfolios, production processes, and number and function of sites, the sizes and responsibili-ties of the business units involved vary greatly, and there is no one-size-fits-all solution. A careful assessment of all these factors is needed to ensure that the system matches the specific requirements.


10

3.1. Solution overviewThe Siemens solution for electronic batch record (eBR) management offers native integration between the man-ufacturing execution system (MES) and the distributed control system (DCS) layer. This expedites the design, exe-cution, and review steps of eBR and provides real flexi-bility in the master batch record (MBR) design. In the DCS, a robust and powerful batch engine manages complex low-level S88.01 recipes related to automatic control of the process. Fig. 3.1 provides a full overview of the Siemens solution for paperless manufacturing and its integration within the Siemens industry software and automation portfolio for life science.

SIMATIC IT eBR enables all regulated processes to be managed without paper-based procedures or documents. The system offers easy configuration and out-of-the-box functionality and allows users to design any process without specific IT skills.

Fully compliant with US Food and Drug Administration (FDA) and Good Manufacturing Practice (GMP) regula-tions, the system optimizes the batch manufacturing

processes and helps streamline resources, such as user guidance, equipment allocation, and standard operating procedures (SOPs). It also systematically controls the correct execution of all stages, either human operations or operations controlled by the programmable logic con-troller (PLC).

The SIMATIC IT eBR module ensures the reliable acquisi-tion of critical process data. It allows forward and back-ward searches through genealogy and audit trail tools. In this way, it significantly reduces manufacturing, review, and release times and enables faster time to market.

The solution is fully compliant with NE 141:2012, NE 139:2012, and ISA S88/S95 and is based on a proven plat-form that has been successfully applied by many pharma-ceutical manufacturers in projects varying from single sites to global systems.

The solution was designed with specific regard for ease of use and flexibility, and it can be implemented in a staged approach to minimize project risk and ensure excellent return on investment (ROI). Section 3.7 provides some case studies that demonstrate the ROI of SIMATIC IT eBR

3. SIMATIC IT eBR: an integrated solution for paperless manufacturing

SIMATIC ITR&D Suite

SIMATIC ITPreactor

SIMATIC ITIntelligence Suite

LIMS Prod Specs APS/GPMS

SIMATIC IT eBR

Enterprise Integration

Warehouse

Automation – SIMATIC

BATCH DCS HMI PLC

Sensors, Drives, Field Instrumentation, ...

Native DCS integration Control / Command integration

Weigh & Dispense eBR Packaging

LIMS Prod Specs Dashboard Reporting

XHQ

OperationsIntelligence

SIMATIC IT LMS

Down Time Monitor(DTM)

Overall EquipmentEffectiveness (OEE)

Quality-by-Design

SIPAT

Fig. 3.1: Siemens solution and platform overview

11

implementations in various set-ups. SIMATIC IT eBR offers comprehensive out-of-the-box functionality that facili-tates implementation and supports both a top-down implementation from the MES level and a bottom-up approach through the integration with the SIMATIC PCS 7 DCS. The solution is prevalidated and meets all current standards for pharmaceutical manufacturing.

The proven platform and the scalability and modularity of the solution ensure that users benefit from

• better standardization of procedures and processes,

• a low total cost of ownership, and

• higher productivity and quality in their operations.

3.2. SIMATIC IT eBR key functionalitiesSIMATIC IT eBR is a dedicated MES solution for the phar-maceutical industry. Recent enhancements to this product have included a batch integration layer that permits inte-gration with the SIMATIC PCS 7 DCS, ensuring seamless interaction and data exchange between SIMATIC IT eBR and SIMATIC PCS 7 with SIMATIC BATCH. SIMATIC IT eBR enables paperless manufacturing and gathers critical data in an electronic format, offering a comprehensive set of out-of-the-box features.

Key functionalities:

• Vertical integration from the enterprise resource plan-ning (ERP) level to the automation level

• Batch and operations management (including operator guidance and production steps)

• Materials and inventory management (weighing, dis-pensing, mixing) at the container level (with ERP integration)

• Equipment management over the complete lifecycle of the plant

• Sample management (with laboratory information management system [LIMS] integration)

• Deviations/alarms/alerts management

• Batch reporting

• Full batch and materials genealogy

• Batch release by exception

An electronic definition of these production factors, whether manual or automated, is the first and most important step for an eMBR/eBR solution. This is why SIMATIC IT eBR is designed to be “MBR driven”: the eBR is the starting and end point of the paperless manufacturing process, as defined in Fig. 3.2.

The design phaseDuring the design phase, an MBR template is created that contains all the parameters concerning product defini-tion, process definition, quality procedures, and the resources and equipment that will be used during the pro-duction process. To provide a unified solution across the different levels, Siemens uses industry standards to define the roles of different systems and how they can communicate with each other: ISA-95 as the adopted standard for operations and ISA-88 as the standard for batch control systems.

An easy-to-use design tool allows users to design pro-cesses and implement parametric MBR without the need for IT skills. Recipe information is available in the MES design tool. MES workflow steps are integrated by simple selection from the list of released master recipes. Combining reusable process-specific building blocks and


Critical parametersare defined in theeMBR template

Design

Duringproduction,the relevantinformation isrecorded inthe electronicbatch record

Execute

The definedcriticalparametersare reviewedby qualityassurance

Review

Fig. 3.2: The master batch record specifies the information that is gathered during production and presented to quality assurance

12

out-of-the-box functions allows standardization, reduced development effort, reduced risk, and faster release.

The execution phaseDuring production, every operation and resource is con-trolled, tracked, and traced. All the systems coordinate real-time control at every level, synchronizing operations and sharing parameter values. Process rules and sequences are enforced through the workflow engines. The systems manage all operations, such as orders from the ERP system, guided manual operations, quality testing, and tracking and tracing of materials and resources.

Alarms and alerts generated automatically or manually during the process are centralized in SIMATIC IT eBR. All the alarms can be accessed at any time with real-time information. Alerts can be grouped for easier review. This allows the review process to be shortened with reduced risk. Mass data, such as trends, curves, and reports, can be aggregated as part of the eBR. Process tasks from any system are accessible from any HMI or workstation. Batch records can be constituted and visualized in real time.

The review phaseAll relevant information is compiled in the completed batch record and stored centrally in the SIMATIC IT eBR system. The review can be performed following the review-by-exception approach: potential deviations are flagged so that quality assurance need review only these reports, speeding up the review process. SIMATIC IT eBR provides additional investigation tools, such as equipment logbooks, a complete audit trail, and a graphical gene-alogy tool. Other tools allow the reporting, monitoring, and analysis of critical data for the batch and across batches, facilitating process improvements and opera-tional excellence.

3.3. The MBR templateThe basis for an MBR-driven solution is the design of an MBR template that makes sure quality assurance will have all the information needed to assess the quality of the product: What was produced? How was it produced? Were all relevant parameters and actions verified? And is there proof of the correctness of the parameters and procedures?


Automation level

Level 0, 1, 2 Automation

Level 3 MES

Level 4 ERP

Link workflows to batch recipes and the SCADA/HMI systemat a design levelBatch creation in SIMATIC Batch when starting an operation

ERP levelInterfacing helps synchronize critical to quality andproduction parameters and trigger events

MES levelSynchronizing between MES and automation during production

Workflows can be used to track progress

Information on batch execution can be gathered with timestamps and e-signatures made in the batch system

Note: Business, manual, and automated operations are traditionally classified on three basic levels (Level 4 ERP; Level 3 MES; and Level 0, 1, 2 Automation).

Fig. 3.3: Vertical integration of paperless manufacturing

13

Accordingly, the MBR will contain a product definition, including bills of materials and processing parameters; process definitions, including manual and automated process steps, control procedures, and records; quality management information with in-line, at-line, or off-line quality tests and protocols; and resource requirements (people, materials, and equipment).

Accordingly, the MBR template is designed to contain four sections to gather information on the key questions in relation to batch execution:

• Who, what, where: product, person, location, and required equipment information with reference to the master recipe

• How to prepare for production: work instructions on preparation, execution, and logistics

• How to produce: automatic execution of batches and interfaces to the DCS/automation system

• What was the result: finalization of the batch (manual/automatic), including logistics information

Based on this template, the paperless manufacturing process can then be initiated.

3.4. Collaboration between SIMATIC IT eBR and the automation layer

SIMATIC IT eBR is able to connect to other systems via standard OLE for Process Control Data Access (OPC DA) interface or through native integration to exchange data during the execution of the process for networking with third-party automation systems. The definition of the OPC must be established up front between the different systems.

When working with an integrated paperless manufac-turing solution based on Siemens components, SIMATIC IT eBR provides added benefits through an extended frame-work for collaboration and model sharing with the Siemens portfolio for batch automation (SIMATIC PCS 7 with SIMATIC BATCH) . This model sharing greatly simpli-fies and streamlines data acquisition and batch processing (Fig. 3.3). On a technical level, the interfacing of data occurs via an integration layer compliant with ISA-95/88. Data can be shared at design and execution time. Resources (such as material definitions, equipment, product segments) defined in Level 1 and 2 can be accessed directly in the MES level during the definition of the MBR. During the execution, the values of the param-eters defined at all levels are then exchanged seamlessly.

Four steps of collaborationCritical to the collaboration between the automation and MES layers is the sharing of the S88 model and the related information between the workflow and recipe management systems.

The collaboration between automation and the MES follows the rule of sharing capabilities rather than com-peting for control. Each system is equipped with a set of triggers and features that enables it to call on the other and process the information provided.

The model sharing in SIMATIC IT eBR encompasses four steps: creation of the MBR and automatic updating of the eBR, synchronizing workflows, collecting deviations in the DCS, and integrating reports from the information server as annexes in the eBR.

Step 1: Creation of the MBR and automatic updating of the eBRThe first step is the creation of the S88 recipe in the batch engine. This recipe is uploaded into the workflow engine as a batch element, where the parameters relevant to the eBR are selected and linked to the corresponding variables in SIMATIC IT eBR. In the workflow engine, the MBR can be designed consistently with the standard tools. Batches can be created automatically, and the eBR chapters are updated automatically with the corresponding batch events. The recipe can be validated as usual, for example, through a three-batch test, and the uploading and inte-gration of the recipe in the eBR system is then only a matter of a few days.

This integrated process provides substantial benefits in both the engineering and operation phases:

• Fast creation of MBR

• Reduced risk

• Lower costs

Step 2: Synchronizing workflowsDuring the S88 modeling, a number of phase types can trigger MES workflows:

• Phases consuming, producing, or moving identifiable material (having a batch ID and material code): the MES needs to book or unbook materials or update the inventory

• Phases changing quality relevant states (hygienic state): the MES needs to update the equipment state

• Phases requiring manual interventions (e. g., equip-ment set-up or removal; sampling, including results; docking and undocking of a container): the MES needs to launch electronic work instructions (EWI) and/or related tasks

These workflow triggers are integrated into the phase type and are thus not instance-specific. As a result, they are reusable like the phase types and become an inherent part of recipe creation in the batch engine.

The next step is uploading the phase types into the work-flow engine and linking a workflow to an event in the uploaded phase type. Workflows and phase types can be


14

designed with the standard tools without added imple-mentation effort in the MES.

Step 3: Collecting deviations in the DCSIn an automated environment, process deviations are identified in the DCS. Those deviations that can impact product quality need to be included in the eBR. In SIMATIC PCS 7, this is simply performed by providing a filtered list of system messages that is collected by the MES every five minutes.

Step 4: Integrating reports from the information serverAll batch data are recorded as reports on the information server of the DCS. Through a simple trigger event, these reports can be included in the eBR as pdf annexes for the review process.

The result of this integration is considerably reduced effort in implementing paperless manufacturing in an automated environment (Fig. 3.4). Compared to other approaches, which typically require one year to create a paperless manufacturing process for one recipe, this type of collaboration can cut the time to implementation to a few weeks or a few months (depending on the time required for batch validation). The integration of the recipe into the MES itself will require just two or three days.

3.5. The eBR processThe eBR process as proposed by Siemens is a comprehen-sive approach that extends beyond the MES layer and also encompasses interfacing to the ERP and automation layers.

eBR at design timeThe first step is to model and define the MBR. The user can graphically design the high-level process workflow using a library of standard process operations either from the MES or the DCS layer. Then the user binds the relevant parameters of the batch recipe to the MES parameters and identifies the key performance indicators (KPIs) for the MBR. After that, the eMBR can be checked, reviewed and approved, and then exported.

eBR at execution timeAt execution time, the eMBR process compiles all relevant data and information and compiles them into the eBR. This includes procedures for guided paperless manufac-turing, information on resource allocation and verifica-tion, and tracking of all materials (consumption and dec-larations). At this point, the seamless interaction of the MES and automation levels that SIMATIC IT eBR provides enables the execution of manual and automated opera-tions in a batch with automatic parameter synchroniza-tion between MES and DCS, automated download of


Traditional implementationfor paperlessmanufacturing,competingworkflowsapp. 1 year

Implementationof paperlessmanufacturing,collaboratingworkflowsapp. 2 months

Fig. 3.4: Time savings of a collaborative workflow between the manufacturing execution system and automation

15

recipes and parameters into SIMATIC BATCH when the workflow step is activated, and automatic triggering of MES workflows from SIMATIC BATCH recipe steps. Measurements and alerts or alarms from both the MES and the automation level are recorded in real time and can be grouped for easier review. All operations use one common interface, regardless of whether they are per-formed at the MES or automation layer, which facilitates handling by operators. The result of the execution step is an eBR that contains all the information specified in the eMBR and is ready for review.

eBR at review timeFinally, the eBR is reviewed and released based on review by exception, that is, only an eBR that is flagged for devia-tions or errors needs to be reviewed by quality assurance staff. The entire eBR is available in a central location, complete with all reports attached during or after execu-tion (e. g., instrument readings and analysis results), which facilitates the review process. The eBR also provides a time stamp and electronic signature (where required) and specifies the equipment used. All alarms and alerts can be reviewed from a single electronic document and classified and grouped to facilitate the review process. The eBR also aggregates mass data such as trend charts and reports.

3.6. Functional details

eBR DesignThe first step of a typical SIMATIC IT eBR project is to design the MBR, sometimes known as a master recipe (Fig. 3.5). eBR Design is a powerful tool used for designing the electronic Batch Record Master with out of the box features developed for FDA-GMP industries and conforming to the ISA 88 Standard. More than a restric-tive “paper-to-glass” oriented system, eBR Design signifi-cantly reduces loss of time and increases the efficiency and added value of the operations. Version control of the MBR is a standard functionality, which reproduces the paper way of working but prevents the user from using an incorrect or nonvalidated master.

eBR ExecutioneBR Execution ensures the execution of the eBR as a set of process instructions to be followed either by the operators or by the SCADA system in order to guarantee the correct manufacture of a product associated with the work order (Fig. 3.6).

During the manufacturing process, the system

• supports the operator in manufacturing the work orders, through the display of the manufacturing instructions;


Fig. 3.5: Master batch record definition in SIMATIC IT eBR Fig. 3.6: Execution of the electronic batch record with SIMATIC IT eBR

16

• ensures the collection of data and remarks associated with manufacturing;

• controls and executes the various manufacturing tasks;

• manages deviations during manufacturing in real time; and

• automatically generates the batch records.

The eBR Execution system displays and executes the dif-ferent tasks corresponding to the manufacturing process, according to the sequential workflow.

Based on the configuration, operators can visualize their work by task or by work instruction. An option can restrict the display to the tasks of a particular operator in his or her work center. In addition, this graphical tool helps operators easily identify what they need to do.

eBR Execution offers the following functionalities:

• Controls and records production data in real time (it controls each critical process parameter and compares it with the expected value, therefore preventing human error)

• Ensures the enforcement of tasks and events throughout the process

• Allows the user to activate the reprinting of a label issued via the labeling tag at any time during the man-ufacturing process

• Authorizes a correction mode to modify a filled tag with the recording of a trace

• Automatically records deviations for tags for which the data are outside the tolerance

• Allows manual recording of remarks or deviations at any time during the process

eBR RevieweBR Review enables the easy release of the product batch by reviewing the corresponding batch record with a direct focus on deviations that occurred during the process (Fig. 3.7). Any deviations occurring during the manufac-turing process are displayed on the screen in a clear way and in a form that is similar to a report on paper.

The signature path defined for the record review enables the definition of the various stages before the final valida-tion. The signature order should respect the order defined in the approval workflow. The review path assigned to the MBR imposes the number of signatures.

The eBR is updated and filled with batch production infor-mation in a read-only format. Production data such as


Fig. 3.7: Batch review and release with SIMATIC IT eBR

17

deviations, quantity, and events can be manually entered, can come from skid automation, or can be automatically calculated by the MES.

With the eBR Review module, the batch records can be analyzed using exception rules. This means that only potential deviations are flagged, which speeds up the review process because there is no need to review every single manual entry. In addition, the review can take place during production, from a workstation in the quality assurance area, which has the potential to considerably reduce batch release cycle times.

3.7. Implementation options and use cases

Depending on the context, the strategy, the system land-scape, and the processes to cover, there are multiple ways to deploy a fully automated MBR/eBR that satisfies the requirements of both primary and highly automated pro-cesses and secondary processes involving many manual operations. SIMATIC IT eBR has the flexibility to support many different approaches, always offering the benefits of tight integration between the MES and DCS and simpli-fying the overall technical architecture and its configuration.

However, the solution is especially designed to be able to accept a DCS-driven approach. From an existing SIMATIC PCS 7 environment, SIMATIC IT eBR can bring additional MES functionality (such as an interface to the corporate ERP, material tracking and tracing, complex EWI, MBR/eBR reporting capabilities, and so on) in a very integrated and flexible way, with minimal modification to the existing DCS/batch installation.

SIMATIC IT eBR can be deployed in many set-ups and envi-ronments, either as a single-site or a global solution, and via a staged roll-out across facilities, products, or units. While many use cases are conceivable, three very typical use cases can serve to illustrate the requirements and benefits of implementing SIMATIC IT eBR: single-site process standardization through paperless manufacturing, standardizing a process or procedure across several sites, and improving manufacturing excellence in a global pro-duction environment.

Single-site process standardization through paperless manufacturingIn a site-wide implementation, the focus is on standard-izing manufacturing processes across work centers to reduce errors and to improve both productivity and resource utilization. In such a context, SIMATIC IT eBR will promote lean manufacturing by providing full traceability of actions and resources, by reducing human errors and batch reruns, and by accelerating batch release and time

to market. Depending on the scope and type of project, the standardization will result in significant savings and will typically provide an excellent ROI, with costs often recovered in well under a year.

Standardizing a process or procedure across several sitesStandardizing a procedure will contribute to operator effi-ciency and flexibility as well as reducing the cost of quality by eliminating errors and deviations and improving resource efficiency. As a procedure is typically applied at several facilities, standardization at one site should be quickly adoptable by other plants or locations to ensure uniform production performance and quality. SIMATIC IT eBR, with its comprehensive out-of-the-box functionality and modular structure, supports a fast roll-out. At a recent project, a standardized paperless manu-facturing procedure for one process unit was subse-quently rolled out to more than 15 sites.

Improving manufacturing excellence in a global production environmentThe principal objectives of such a large-scale project can be cost reduction, improved quality compliance, enhanced flexibility, or acceleration of batch release pro-cedures – or, very often, all four together. The solution also needs to accommodate many different operational areas, such as material flow and inventory management, weighing, counting and dispensing, directed manufac-turing, daily equipment checks, mixing, printing, filling, sterilizing, eBR, batch testing and reviews, packaging and labeling operations, and data warehousing. The shift to paperless manufacturing in such a context signifies a con-siderable investment, and the solution must be able to be integrated into many different environments. With a modular structure and built-in interfaces, SIMATIC IT eBR can easily accommodate a diverse range of requirements and provide a uniform foundation for full paperless manu-facturing across multiple sites. In a specific project, the benefits of going paperless far exceeded expectations, with cost reductions of more than twice the expected amount and batch planning times reduced from several days to less than an hour, while at the same time pro-viding a Right First Time share of more than 99% of batches produced.


18

4. Abbreviations

API active pharmaceutical ingredient The substance in a pharmaceutical drug or a pesticide that is biologically active

IPC in process control Inspection of process during production to ensure that it delivers on-spec products

eBR electronic batch record An electronic document containing quality-related batch data and information

MBR master batch record Work instructions specifying how a product must be produced

MES manufacturing execution system Computerized systems used in manufacturing to enable real-time control of elements in the production process (e. g., inputs, personnel, machines, and support services)

DCS distributed control system A computerized control system used to automate process plants or industrial processes

FDA Food and Drug Administration A regulatory body in the United States that is responsible for protecting public health by assuring the safety, efficacy, and security of human and veterinary drugs, biological products, medical devices, the nation’s food supply, cosmetics, and products that emit radiation

EMA European Medicines Agency The agency responsible for the scientific evaluation of medicines developed by pharmaceutical companies for use in the European Union

SOP standard operating procedure Detailed, written instructions to achieve uniformity in the performance of a specific function

ERP enterprise resource planning Business management software (usually a suite of integrated applications) that a company can use to collect, store, manage, and interpret data from many business activities

EWI electronic work instructions An electronic document defining the specific tasks and activities associated with a procedure

KPI key performance indicator An indicator for performance measurement used to evaluate the success of a particular activity or process in terms of a specified level or goal

SCADA Supervisory Control and Data Acquisition

A system operating with coded signals over communication channels so as to provide control of remote equipment (typically using one communication channel per remote station)

Further information

Learn more about SIMATIC IT eBRsiemens.com/simatic-it

If you have further inquiries, please send us an e-mail:

[email protected]

The information provided in this brochure contains merely general descriptions or characteristics of performance which in case of actual use do not always apply as described or which may change as a result of further development of the products. An obligation to provide the respective characteristics shall only exist if expressly agreed in the terms of contract.

All product designations may be trademarks or product names of Siemens AG or supplier companies whose use by third parties for their own purposes could violate the rights of the owners.

Subject to change without prior notice 08/15 © Siemens AG 2015

Siemens AG Process Industries and DrivesSiemensallee 84 76181 KARLSRUHE GERMANY

siemens.com/pharma

Industry software Paperless manufacturing in the ... · agement systems (LIMS) and distributed...

Documents

Transcript of Industry software Paperless manufacturing in the ... · agement systems (LIMS) and distributed...