Putting Together the Pieces

The pharmaceutical industry is a fairly old industry, and as such, the modern manufacturing facility really reflects an evolution—the aggregate of incremental changes. For example, the plant today is far more automated than its antecedents. It can be managed in part through software that didn't even exist when the industry was young.

Illustration by M.McEvoy. Images: James Hardy, AtomicSupersonic, Photodisc (Getty Images)

The software packages that have evolved include manufacturing execution systems (MES) and enterprise resource planning (ERP) systems. MES helps pharmaceutical companies monitor and control the plant floor. ERP systems help manage and monitor business processes.

Integrating these new applications into a cohesive whole can bring a manufacturer great control, speed, and flexibility, but is a difficult project. Information technology (IT) standards, newly emerged tools, and planning, however, can make it easier to link the factory floor to the management suite to achieve great benefits.

What are these systems?

MES. The Instrumentation, Systems, and Automation Society (ISA) defines MES in its ISA-95 standard by providing data structures that represent the information that it manages (e.g., material, equipment, personnel, machine capability, and machine schedule).

The manufacturing benefits of MES are manifold. The system automatically checks whether manufacturing equipment is operating within the correct parameters. It also verifies that components (e.g., containers) are appropriate for a particular production. Thus, it can reduce a site's number of material exceptions. Exceptions can be handled immediately, and deviations can be channeled into a corrective action/preventive action system.

In conjunction with these checks, MES includes a process for electronic signatures and approval for each manufacturing activity. This function provides additional oversight of the production cycle and facilitates regulatory compliance.

Manufacturing-data management also can be enhanced by MES. The system collects production data and creates electronic batch records that are available for analysis after production is complete. Electronic batch records enable review by exception, says Brian Leinbach, MES deployment lead for Wyeth Pharmaceuticals (Madison, NJ). MES's initial equipment and material checks reduce exceptions and, consequently, batch-record review time—often dramatically. Leinbach reports that MES helped one of Wyeth's sites reduce its cycle time from 36 h to 4 h, largely because it streamlined the record-review process.

MES identifies processes that could be modified to improve efficiency, so it helps reduce manufacturing-cycle time. The process optimization that MES enables can yield labor efficiencies, improved compliance, process robustness, and repeatability.

ERP. ERP systems are likewise designed to collect, monitor, and store near-real-time data from various sources within a company and archive them in a single repository. Their goal is to improve business planning by providing easy access to current, detailed information. Most ERP systems store data for various functions (e.g., purchasing and supply-chain management) in a unified database. In other cases, a company will create an interface to allow its ERP system to access data in other systems.

ERP systems can help companies streamline business processes and workflows. The systems also enable various departments in a company to share data easily and help improve project and inventory tracking, demand forecasting, and resource planning.

If an ERP system replaces several smaller systems (e.g., supply-chain management and warehouse management), it reduces a company's software-maintenance requirements. When the ERP system establishes a single database for several departments, it can provide detailed reports easily.

How does integration help?

For an ERP system to provide the greatest advantages, a pharmaceutical manufacturer must integrate it with MES. Integrating the two systems helps companies perform global supply-chain planning by facilitating real-time monitoring of productivity, quality, and throughput. Integration also allows management to see the current location of inventory, work-in-progress, and raw materials.

Another benefit for supply-chain planners is the ability to identify ingredient suppliers and contractors that could take part in a lean manufacturing process, according to Jim Sabogal, vice-president of industry solutions for life sciences at SAP (Newtown Square, PA).

Integration also enables production orders to be sent to the plant floor—or multiple plant floors—quickly. Manufacturing personnel can thus fulfill orders sooner and reduce cycle time.

Tight integration of MES and ERP systems provides accurate inventory counts to the enterprise level and also ensures that a company only picks released material for batch manufacturing. Integration prevents the site from "using batches that could be quarantined," Leinbach says.

If the ERP system is integrated with MES and other systems, with a laboratory information management system (LIMS), for example, it can facilitate batch release, says Rolf Blumenthal, senior director of international consulting at Werum Software and Systems (Lüneburg, Lower Saxony, Germany). For example, the ERP system can collect the MES batch records for approval along with the inspection data from the LIMS system and present them together, thus providing improved visibility of information.

If a company has unconnected information systems, collecting and collating data for document requests during inspections by the US Food and Drug Administration is a considerable effort, according to Herschel Kenney, senior director for IT planning and resource management at Purdue Pharma (Stamford, CT). MES–ERP integration speeds up this process by collecting the data in real time and allowing manufacturers to submit them to inspectors in minutes.

MES–ERP system integration also has advantages for manufacturers even before they face inspections. MES and LIMS reduce the time needed for compliance activities. Because they automatically check equipment, materials, and production data, these systems, when properly integrated, make results available to the ERP system, which allows management to respond to exceptions or failures quickly. SAP's ERP system includes tools that ensure audit trails and electronic signatures, says Mandar Paralkar, one of the company's solution managers for life sciences. These functions help reduce the occurrence and effect of products manufactured outside specifications and enable the company to maintain regulatory compliance more easily.

How do you do it?

The right information infrastructure, tools, and applications are prerequisites for integrating MES and ERP systems.

Standards. Because manufacturing plants are not all built the same way, pharmaceutical companies need standard processes and definitions to choose the kind of information to communicate between the MES and the ERP system. ERP-system vendors point out that the ISA-95 and Manufacturing Enterprise Solutions Association (MESA) International standards provide a strong foundation for integrating enterprise and production systems (see Figure 1). For example, Sabogal says SAP uses ISA-95 and MESA to identify the key business processes, interfaces, and integration points essential for this integration. And SAP's software presents process orders to the production level in the ISA-95 standard.

Figure 1: The manufacturing levels described in the Instrumentation, Systems, and Automation Society ISA-95 standard., Illustration by M.McEvoy. Images: James Hardy, AtomicSupersonic, Photodisc (Getty Images)

Blumenthal says that Werum based its recently developed "PAS ECMI" software package on the ISA-95 standard. The product is designed to directly integrate SAP's ERP system with Werum's MES for certain defined business processes in the weighing and dispensing area.

It's also important to standardize MES and ERP systems within an organization. "If you have one or a limited number of SAP instances, and they're all the same, then integrating MES and SAP can be simplified and the risk reduced" because only two applications (i.e., one MES and one ERP) are being integrated, says Richard Lemire, head of global production IT at Novartis (Basel).

Shared languages. Companies can simplify integration further by choosing a single format in which standardized MES and ERP systems communicate data within a messaging layer. A precedent has already been established, according to Kenney. "Right now it looks like XML is going to be the leading language for integrating packages," he says.

XML provides a format to exchange information about items such as orders, materials, and the status of an operation. SAP software supports XML for "the customers who are ready to use cutting-edge technology," adds Paralkar.

Novartis's harmonized MES and ERP systems use adapters that convert messages into XML so they can be exchanged, Lemire explains. He says that this solution is easy and takes only hours to execute. Similarly, Wyeth uses IBM's "MQSeries Integrator" application as an interface between its MES and ERP systems. The integrator converts XML messages into readable formats so they can be exchanged between the ERP system and MES.

In addition to XML, which defines the general structure of data to be exchanged, manufacturers need a specific way to define data content. SAP developed the intermediate document (IDoc) structure to enable data interchange and distribution through electronic messages.

Many companies now use Business to Manufacturing Markup Language (B2MML), which consists of XML schemas that implement the data models in the ISA-95 standard, to exchange data between their production and enterprise levels. When Genentech (San Francisco, CA) began integrating its MES and ERP systems, "SAP was publishing messages in the IDoc structure, and we had to convert them into the B2MML format" to communicate with the MES, says Govi Sridharan, senior automation engineer at Genentech. The conversion required Genentech to build custom integration. The widespread adoption of B2MML led SAP to provide B2MML content packages.

Messaging layer. Establishing uniformity within the messaging layer also helps integrate a single ERP system with various MES systems. Genentech bought manufacturing facilities that used different MES systems from the one used at the company's other production plants. "We actually used the messaging layer for standardization," Sridharan says. The company gave the new plants the necessary touch points to publish data in a standardized XML format and introduced them to its common messaging layer. The strategy allowed Genentech to successfully integrate its ERP system with three different MES systems.

Middleware. Middleware can enable production-level applications to view enterprise-level information. For example, business application programming interfaces (BAPIs) facilitate external access (e.g., by an MES) to business data in SAP's ERP system. BAPIs also enable data exchange between MES and ERP systems, says Paralkar.

Workflows. Pharmaceutical manufacturers also should create clear workflows to assign responsibility for each part of the production process to their MES and ERP systems. Blumenthal says that when a company's business processes are well-known, tight integration is easy and systems can be deployed without customization. If a company does not use best-practice business processes, the software vendor must take time to understand these processes to adjust standard data migration exchange for each of them.

Procedures such as documenting, measuring, and mitigating risk are performed in more than one IT system, notes Ruediger Dorn, managing director of the pharmaceutical industry at Microsoft (Redmond, WA). Microsoft's "Sharepoint"-based solutions can establish an infrastructure that provides uniform workflows to MES and ERP systems. This arrangement facilitates a continuous trail of control and allows companies to document a process, identify the employees who modified it, and prove the results. This information must ultimately be accessible to the ERP system, he explains.

Integration and intelligence platform. SAP's "Manufacturing Integration and Intelligence" (MII) platform is a solution that allows users to bridge the gap between SAP's ERP system and plant-floor systems such as MES and LIMS. Andy Dé, SAP's senior director of solutions marketing in life sciences, says MII includes prebuilt adapters for the most common MES, LIMS, and quality systems. Once MII has been implemented, it extracts real-time data from the user's plant-floor and ERP systems and presents them within role-based dashboards. MII delivers analytics, reports, and alerts to improve decision-making and monitor performance. Firms such as Merck, Wyeth, Roche, and Novartis are using MII to integrate their MES and ERP systems.

EAI tools. Enterprise application integration (EAI) tools, particularly those that offer application-interface level EAI, use the process and data interfaces that the source and destination systems expose to extract and translate information between two or more systems. Commercial offerings include IBM's "WebSphere," Microsoft's "BizTalk Server," TIBCO's application, and Oracle's "BPEL Process Manager," says Alison Smith, research director at AMR Research (Boston).

These EAI tools are much more sophisticated than MII, Smith says, because they're not specifically geared to SAP. Instead, they are designed for highly heterogeneous environments. The manufacturing industry is just starting to adopt these technologies, especially companies with an IT infrastructure complex enough to warrant a bus architecture that allows systems to exchange message-based information.

EAI tools require a level of IT expertise and architecture awareness that typically isn't found in operations environments, says Smith. MII is not a plug-and-play solution, either, because users must have HTML programming skills to realize all of the tool's benefits. "None of these tools is easy to use," Smith says. "Any way you cut it, you don't get to do these integrations in a purely point-and-click way."

Werum's library approach. Blumenthal describes a way that Werum is working to facilitate MES–ERP system integration. MES and ERP systems are controlled by recipes, and integration entails synchronizing the systems' recipes on certain touch points. A master batch record (MBR) is an MES recipe that describes how to manufacture a given product. Werum's customers have asked it to provide "typical" MBRs to reduce their workload and help them adhere to best practices.

Responding to demand, Werum is collaborating with its users to develop best-practice business-process descriptions. These descriptions are being transformed into reusable MBR parts and made available in libraries as typicals. The typicals will become part of Werum's MES and facilitate synchronization with SAP recipes, and thus integration with SAP's ERP system.

What's the answer?

Choosing the system of record. Various strategies and tools enable pharmaceutical companies to integrate their MES and ERP systems, although no current solution is ideal. Sabogal points out that a company must decide which of its IT systems is the system of record for regulatory purposes. Firms would be inclined to choose the system that could provide the relevant data the fastest during an inspection.

Yet the required data might not be stored in one place. The MES contains batch records, detailed workflows, recipes, and other manufacturing-process information. An inspector would need this data, but would also need information about ingredients and quality-control inspections from the LIMS and supply-chain data from the ERP system.

The ERP system should probably be the system of record because data about all of these elements ultimately flow to the enterprise level, advises Kenney. Though ERP systems do receive these data, such systems have traditionally focused on outcomes, planning, and timeliness of delivery. A thorough integration of the ERP system with MES and LIMS might be necessary for quality and compliance data to be available at the enterprise level.

Storing work-in-progress data. The question of where work-in-progress (WIP) data should be maintained is also important for regulatory compliance. When MES and ERP systems are fully integrated, the enterprise view retrieves WIP data no matter where it is located and no matter how many places store it. Viewing WIP data at the enterprise level not only facilitates compliance, but also assists a company in its inventory and financial planning.

But according to the MESA model, tracking and managing inventory, including WIP data, is MES's responsibility. WIP data need material-identification numbers for the ERP system to track them. Because MES identifies WIP data with its own rules, separate identification numbers in the ERP system could create confusion.

On the other hand, maintaining WIP data at the production level is complicated if the manufacturing process takes place at several plants—particularly if the plants use different MES. This situation would require MES to be standardized.

If a company's MES and ERP systems were integrated, then "all of the systems would be looking at the same inventory without having to worry about ownership," as Kenney points out. "The question of which package owns the inventory indicates that the integration is not where it could be."

Wyeth used a collaborative strategy to avoid the problem of managing various manufacturing plants with different products and processes. Leinbach explains that, before adopting MES, representatives from the company's various sites met with an MES vendor and a corporate project team to develop a standard set of user requirements to be deployed across Wyeth's entire supply chain. Although each site has different products and processes, each plant could incorporate the common user requirement specification (URS) according to its specific purposes. Thus, in addition to the common URS, each of Wyeth's facilities had a site-specific URS that described its local functionality. With this strategy, the company achieved a standard MES model that it adopted rapidly at many of its sites.

Variable recipes. Integrating MES and ERP systems can bring flexibility to production processes. Rather than establishing complete master recipes that include all the specifications for each product, a company could create recipes that contained variables. If the ERP system contains a master list of variables and their acceptable value ranges, the enterprise level could send an order to MES that defines the variables, thus selecting the product to be manufactured. This arrangement would eliminate the need to create a new recipe in MES for each new product.

If a company wants centralized maintenance of its master data or if its products are familiar and established, this would be a good solution. Likewise, if equipment operation remained consistent, this strategy could also facilitate personalized medicine and order-based manufacturing.

But keeping a master list of variables and alternate values on the enterprise level would make data management more complex. Managing such a repository would require knowledge of all recipes, and changing one parameter might affect many recipes. This arrangement could make for a complex validation process.

Conclusion

Integrating an MES and an ERP system is no simple task. It requires pharmaceutical companies to know their facilities and equipment, understand various software applications, and have the skill to create custom interfaces to facilitate integration.

Yet software vendors and users all acknowledge that integration has gotten easier through time. Manufacturing technology has improved, vendors' solutions have evolved, and pharmaceutical professionals have become more software-savvy. The industry has benefited from this progress, and drugmakers are optimistic that MES–ERP system integration will become even simpler, and provide even greater benefits, in the near future.

For more on this topic, see Integration the Easy Way