September 2007

Bridging batch gap in pharma

By Ronald E. Menéndez 

Recent years have witnessed the emergence and success of manufacturing execution systems (MES) in the biotech and pharmaceutical industries. Process manufacturing and automaton literature has seen plenty of success stories about improved operations and Levels 3 to 4 integrations that leverage the ANSI/ISA95 standard to provide interoperability between MES and enterprise resource planning (ERP) systems. However, there is little discussion regarding connectivity of Level 3 systems, such as MES, to Levels 2, 1, and 0 process control systems, particularly in the area of batch manufacturing.

We can attribute the lack of discussion on this topic to the dominance of batch control systems integrated with DCS or SCADA/PLC platforms used in bulk bio/pharmaceutical manufacturing. We can also credit the widespread proliferation of these systems to the introduction of the ANSI/ISA88 models and terminology for batch control, first discussed nearly two decades ago. Whereas batch control systems dominate bio/pharmaceutical manufacturing, MES technology has only begun to see use in these highly automated batch control architectures between the plant floor and the business layer.

The increasing popularity of MES in bio/pharmaceutical manufacturing gives rise to an interoperable MES and batch control system, which promise to return significant benefits in overall manufacturing operations management and plant-floor control. However, the overhead required to design, operate, and maintain two execution engines involved in such architectures is formidable and requires expertise in both MES and batch control. As a result, the industry urgently needs standard terminology and models for data exchange between IT specialists and automation experts for manufacturing control systems to continue to evolve.

ISA95 defines data exchange

Within the ISA95 standard, the control hierarchy model defines functions for Levels 1 through 4. The industry usually views MES as the application servicing Level 3 functions just below Level 4 business systems, but above Level 2 and Level 1 process control systems. 

Moreover, ISA95 defines the typical data exchange from Level 3 systems, such as MES, to Level 4 business planning and logistics applications commonly supported by ERP systems. Adopting these data exchange models has made it possible to develop standard protocols between MES and ERP systems using XML and service oriented architecture principles.

Today, MES deployment in batch manufacturing industries has streamlined process operations by applying production management functions, such as production execution, material tracking, resource management, and electronic work instructions. These applications have enabled facilities to transition from paper-based systems to paperless operations, improving efficiency and reducing inaccuracies in manufacturing.

As MES sees use in more highly automated batch-control architectures, MES and batch-control systems often operate as separate systems that coordinate their different activities in parallel. Using the two as distinct systems, users focus on MES's paper-on-glass technology as a point of synchronization to and from the batch-control system. IT specialists who typically handle MES and engineers who classically deliver process control systems approach design and project executions using varying methods and techniques. This makes it challenging for the two groups to communicate and deliver MES and control systems to the end users (manufacturing operations) that are complimentary and work well together.

Integrated MES, batch control  To meet challenges and deliver integrated solutions, users can employ the concept of interoperability from the MES to the batch control system. Such interoperability can potentially provide access to MES functionality, which is useful in streamlining manufacturing operations. Take a look at some examples:

• Electronic work instructions
One of the most touted of MES functionalities in automated manufacturing circles is paper-on-glass. This functionality provides the user with a single interface point to manual work instructions and SOPs. What makes this functionality useful is the MES's ability to collect electronic signatures when presenting work instructions in accordance with the FDA's 21 CFR Part 11 Electronic Records and Electronic Signatures. A further enhanced feature of typical MES is the ability to provide a complex set of manual work instructions with decision points and looping structures to create manual workflows with the same electronic signature features.

• Material management
This includes bar-code scanning functionality for real-time verification of material use, expiration, item number, and lot ID at the point-of-use as defined by the bills of material (BOM). This enables lot tracking/trace features in the MES, otherwise referred to as a genealogy.

• Equipment resource management
Resource arbitration often extends beyond typical available or in-use algorithms. Multiple status types are available in the MES to coordinate between operational values, such as clean, sanitized, in-process, and dirty. Often the operational status has time limits and may expire, and the MES automatically transitions an operational status from clean to clean-expired or from sterile to sterile-expired. Also, this functionality extends itself to the interconnecting network of piping, common in large bio/pharmaceutical facilities. Connections from one unit class to another include multiple segments of piping, some of which may be exclusive use resources. The same equipment status functionality applies with rule-based operational status and their expirations.

The goal of interoperability between the MES and batch control systems is to leverage the functionality sited above at the control layer. In practice, this is done through a data exchange protocol to access functionality in real time at the point in the recipe execution that the data or functionality is required. Previous initiatives have successfully tackled this task by integrating MES at the Level 2 layer or vice versa. However, the premise here is it is more desirable to leverage configurable-off-the-shelf functionality provided by both mainstream MES and batch-control systems rather than investing in customized solutions. Such an approach should reduce project and maintenance cost, and minimize supportability issues.

Interoperability, data exchange

We can accomplish the goal of interoperability between the MES and batch control system through connectivity from service-oriented protocol between the MES and equipment phase resident in the process connected device, that is, an MES-to-control domain (MES2CD) data exchange protocol. This will allow the user at the control layer to interface with material and equipment management and electronic work-instructions.

The core of connectivity occurs through data exchange with bills of reference that reside in the MES product definition. One common example is the BOM, while others may include bill of production (BOP) to report production of products, bill of test (BOT) to support test sample information and sample results, and bill of instruction (BOI) to support manual instructions and e-signature configuration.

There are four types of MES functions from which the equipment phase can request data exchange. First is material management with the ability to request consumption of material or report production of material. This transaction executes by referencing individual items on the BOM or BOP. We maintain all pertinent material definition data regarding the material in question in respective line items on the bills in the MES. In turn, the MES uses this data to direct the user in manual activities associated with material consumptions or productions, such as bar-code scanning, manual delivery, and the like. Sample management works in a similar method by referencing specific items in the BOT for the user to process floor samples or retrieve sample data results.

Equipment management works by supporting three different requests common in bio/pharmaceutical manufacturing. First is to show the status of an equipment resource and use the current status to make decisions about the proper equipment to use. Second is to confirm required equipment is at a necessary status prior to its use. Third is the ability to change equipment status after an equipment resource has been used. Last, the electronic work instructions support individual work instructions and manual workflows. You can access work instructions through a BOI, similar to other bills, while accessing the manual workflows directly by name. 

While the ISA95 standard opened the communications lanes for MES across the enterprise and ISA88 provided the foundation for batch-control architectures on the plant-floor, the full potential of manufacturing operations and control has yet to be realized. Users can greatly enhance functionality and efficiencies residing in both domains through a new standard that defines a common MES2CD protocol. Undoubtedly, industry organizations such as those sponsored by ISA will emerge to bring system vendors and end users together in this effort. The work-product should be one that enables exploitation of one system over the other. One possible outcome of this direction may be the expansion of MES into Level 2 systems, eroding the preeminence of batch control systems. As such, a new standard may have a wider impact than simply a data exchange protocol but may help to usher along the next generation of manufacturing control solutions.


Ronald E. Menéndez is a senior automation engineer at Genentech in South San Francisco, Calif. ( program.