The Long Arm of S88

Batch automation standards are having an impact far from the control room, changing approaches to plant design, specification, and validation

By Nick Basta, Contributing Editor

Economic pressures and regulatory uncertainties are forcing many drug manufacturers today to operate in “hurry up and wait” mode. “Capital expenditures have to be made as late as possible in the drug-manufacturing process, yet companies must be ready to implement them once drugs meet regulatory approval,” says Lou Pillai, IT team leader at Pfizer, Inc. (New York, N.Y.).

“Process design and specification used to be a somewhat unstructured process; now there’s a language and a methodology that allows everyone involved in design and process control to communicate with each other.”

Modular construction (see Pharmaceutical Manufacturing, September 2004, p. 36) is helping drug makers manage these pressures in new plant construction. But for plant design, specification and validation, standards developed in the process control field are having a far-reaching impact on drug manufacturing. S88 (see sidebar, below), which originated as a way to write control logic for batch processes, has become a preferred route for designing and specifying all the production equipment in a pharmaceutical plant.

The standard, first established in the 1990s by the World Batch Forum under the imprimatur of ISA International (Raleigh, N.C.), began as an approach to process control for batch manufacturing. It has also influenced a broader, parallel program, S95, “Enterprise Control System Integration,” designed to rationalize how information leaves the plant floor and is transferred to enterprise IT systems.

Simple structure, significant benefits

S88 is grounded on three principles:

  • Batch functions should be modular sequences of such actions as filling, heating or drying;
  • The “recipe,” or procedural steps, should be written independently of the equipment in which the actions are performed;
  • The “logic,” or capabilities, of the equipment should be captured in a data file.
As the requirements of a recipe are matched up with the equipment logic, an overall production process can be specified, and from this, the actual control logic can be coded. Multipurpose plants, with an array of recipes, can be run on differing sets of equipment, and the overall automation system can keep track of it all.

S88’s success in codifying how processes are analyzed has made a big difference in process design and construction. The standard is providing some companies with a foundation for Six Sigma programs, connecting manufacturing execution systems (MES) to ERP and other platforms, and linking batch control with other efforts such as packaging automation. It also promises to help manufacturers deal more effectively with FDA’s electronic recordkeeping requirements under 21 CFR Part 11, and in handling data from process analytical technologies (PAT) programs.

“S88 is playing a key role in how the pharmaceutical industry specifies, designs and builds its facilities,” says Pfizer’s Pillai, head of the education committee of World Batch Forum. “It helps us speed up the process of validating systems; it is key to designing multipurpose plants; it provides ways to approach re-validating or re-purposing process lines.”

“A lot of smart, far-sighted people got this effort going years ago, and we’re enjoying the benefits of it now,” says Dennis Brandl, president of BR&L Consulting (Cary, N.C.), and editor of the S95 standard committee. “Process design and specification used to be a somewhat unstructured process; now there’s a language and a methodology that allows everyone involved in design and process control to communicate with each other.”

Older facilities still tradition-bound

Most current or new capital projects and control system installations use S88 methodology, according to Brandl, and other industry sources agree. However, the industry is tradition-bound when it comes to industrial automation; currently, only 30% of existing pharmaceutical facilities use S88, Brandl notes.

As time goes on, Brandl feels, the standard’s impact will only broaden. S95 is expected to have a similar impact; at this fall’s annual ISA meeting (Houston, Oct. 5-7), Part 3 of the standard was ratified and will now go out to ISA membership for approval.

Because S88 does not specify control methods or communication protocols, the standard was easy for automation vendors to embrace, and several of them have actively participated in its development. And the same principles of modeling processes and procedures of S88 have been carried into S95. Today, most of the leading automation vendors serving the pharmaceutical industry have control-design software or related IT tools to help clients specify and code their control systems by S88/S95 standards:

  • Rockwell Software (Milwaukee, Wis.) employs S88 methods in RSBatch, for developing control programs, and RSView, its human-machine interface (HMI) software for displaying production activities. Without S88, the company says, writing batch code for its programmable-logic controllers can consume 50-60% of an automation project’s time; S88-based software allows this time to be cut to 15%.
  • Honeywell (Phoenix, Ariz.) offers its POMS manufacturing execution software with S95 compliant features.
  • Invensys’ (London) Wonderware subsidiary features InBatch software for manufacturing execution.
  • ABB’s (Zurich) Industrial IT division offers Produce IT, claiming as much as a 50% reduction in implementation costs through S88 methods.
  • Siemens Energy and Automation (Alpharetta, Ga.) deploys both its APACS+ batch control software and SIMATIC IT manufacturing execution technology with S88/95. The company claims that the largest “paperless” biotech plant in the world, Genentech’s Vacaville, Calif., facility, saved nearly $5 million in implementation costs by going this route.
  • Emerson Process Management (Austin, Tex.) incorporates S88 standards into its DeltaV automation software; in addition, its project services organization has a “Project Builder Library” of predefined models that are used to define control system structures and components according to S88 definitions.
Due to the heavy validation procedures prior to commercial production, and the batch-record responsibilities during production, pharma plant operators are finding that they can speed up the validation process, and head off recordkeeping burdens, by adopting S88 methods early in the process. S88 is general enough, its advocates say, that it can be used to design and organize even manual batch operations.

“Instead of building one vessel 15 times, why not build a class of vessel—or a class of software—once and validate that,” says Phillip Maderia, associate director of automation engineering at Genzyme Corp. (Cambridge, Mass.). Genzyme and Emerson Process Management worked together recently on a program to reconfigure all process and equipment descriptions in this modular, class-based approach. Maderia says the company is seeing benefits in slicing six to 12 months out of commissioning and validation schedules for new facilities and cutting documentation costs by nearly half.

At least one software vendor, SpecSoft PFS (Tel Aviv, Israel) has jumped on this idea as a way to produce design and control-system requirements documents that are easily validated. The company offers a suite of products, including PFS Definition, that follow S88 methods closely. Users can pull relevant data from piping and instrumentation diagrams (P&IDs) automatically to build the control system and control logic. The company counts several pharmaceutical and chemical companies among its clients, and has received backing from ABB Ventures.

In synch with modular construction

There are significant advantages to designing pharmaceutical facilities with modular units that more or less follow S88’s “process cell” definition, according to Lars Peterson, manager of automation at Novo Nordisk (Bagsvaerd, Denmark), who discussed the possibilities at last year’s WBF meeting in a paper provocatively titled, “Is it possible to build a pharmaceutical plant in 18 (or even 12) months with S88?”

Using this approach, multiple equipment vendors or engineering and construction firms could build modules in parallel, with everything coming together (including the control scheme) as the modules are assembled at the plant site. “Automation is time consuming,” Peterson said, “especially when qualifying [the equipment] and documenting the test.” S88 can be implemented without modularization at all levels, but the real savings occur when this is done, he said.

Pfizer’s Pillai sees significant benefits to the pharmaceutical industry if this modularization trend grows, both for speeding up the construction and validation process, and for making multipurpose plants easier to design and operate. “The idea is that plant design proceeds as a pharmaceutical product is going through clinical trials,” he says. “If the plant is designed the right way, its capabilities will be able to handle revised or modified recipes without revalidating.” The separation between the recipe model and the equipment model is key to accomplishing this.

Faster design-build cycles are only one of the benefits cited by proponents of the new standards. Eli Lilly (Indianapolis) used the standard to revamp the control system of a 10-year-old fluid bed dryer and granulator, which had been used for production and process development. While the scale of the system — some 250 control points — was not massive, the number of different control modules (control routines for specific recipes) was greater than 70, in 11 different classes, resulting in thousands of configuration values for the control system.

“Requirements for the regulated industries are much more stringent now compared to what they were 10 years ago,” says Brian DeHaan, a senior process automation engineer at Lilly, who presented results at this year’s World Batch Forum meeting in Chicago. "Legacy documentation has either been non-existent, or too general to be useful."

Lilly’s project was not easy. Overall, more time was spent on gathering necessary information from equipment vendors, plant operators and planners than actually re-engineering the control system, DeHaan said. Nevertheless, the company is now benefiting from new capabilities in running the process smoothly in transition from one state to another, from fewer aborted batches and nuisance alarms, and from better recordkeeping.

Genentech is preparing to manufacture multiple products in an S88-documented monoclonal antibody plant at its Vacaville, Calif., location. The approach reflects the fact that the cell culturing part of the facility changes little from one production campaign to another; most of the changes occur in downstream recovery, where different filtration, chromatographic or other processes might be used to recover the antibodies, according to automation supervisors Mahasti Kheradmand and John O’Connell.

Both note that such a project poses great challenges. For example, when a particular process change is considered for a new product, the master recipes of many of the other products must also be changed. However, they note, having the plant automation systems organized around S88 standards can speed up the changeover from one type of production to another.

Future steps

Work on S88 is nearing completion; efforts now focus on communication protocols, and with building out additional library models. Meanwhile, S88’s success in batch manufacturing has made it a model for S95. Parts 1 and 2 of that standard have been approved; Part 3 could meet ISA membership approval in the next year.

Part 3 defines a preferred method of data exchange, known by the acronym B2MML (business to manufacturing markup language; access attached PDF on this by clicking the "Download Now" button at the end of this article). The goal is to provide a way to allow different systems (an MES, or an enterprise information system, for example) to communicate via a common structure. If it is broadly adopted by IT vendors and pharma company clients, it will provide a way for these systems to communicate without the need for custom-written interfaces.

Meanwhile, the S88 model is also setting the pattern for another control-and-communication effort, PackML, for vendors and users of packaging machinery. Even though packaging involves discrete rather than batch controls, developers of automation systems for packaging have found significant value in the S88 model.

PackML is a subteam of the OMAC Packaging Working Group, which in turn is part of a broad standardization effort, Open Modular Architecture Controls (www.omac.org). If the S88 model can be mapped to OMAC’s PackML State Model, this batch software could be extended into packaging, says committee chair Fred Markham. Since so much of pharmaceutical production winds up going through some type of packaging machine, this could be a very convenient extension of S88 in pharmaceutical production.

At last spring's World Batch Forum meeting, representatives of WBF and OMAC decided to create a joint working group, "Process2Packing," and to aim for developing a draft standard combining their interests by 2006. The draft will then be submitted for ANSI/ISA approval, and IEC approval by 2008. The joint group will hold monthly teleconferences, and schedule periodic meetings toward this goal; industry participation is invited.

The 411 on S88

Historically, batch processing has suffered from a wide divergence in how control engineers dealt with their tasks. “Designing” a control system for a batch process could range from scribbling instructions on a sheet of paper to let an operator know which status lights to watch, to implementing elaborate control processes often run by programmable logic controllers. Batch automation systems from control vendors can tie these disparate elements together, but the reality has always been that other, separate process units had to be tied to the batch system in some fashion.

The batch automation “movement,” if that term can be used, aimed to set some standards. It kicked off with the formation of the World Batch Forum (www.wbf.org; Phoenix, Ariz.) in the early 1990s. The forum brought together control engineers in batch-intensive industries, equipment vendors, and software developers who were exploiting the new capabilities of PC-based control. Members began a multi-year effort to establish a new standard, now known as ANSI/ISA S88 (and IEC 61512-1 in the international arena). Much of Forum’s work was to define a common language—concepts that meant the same thing from project to project, or control system to control system.

S88 requires the use of object-oriented programming to conceptualize batch control, and specifies that the recipe be separated from the process unit or control system where that recipe would be executed. It then shows how to do this in such a way that the same recipe could be run on different process units, as long as those process units had comparable processing capabilities. The reusability also means that once a “library” of process and recipe models was defined, writing the actual control code could proceed rapidly from those generic models.

Although there are numerous subclassifications, the basic elements of S88 are as follows:

  • a physical model of a manufacturing process, which is a description of what the process does, and what its capabilities are.
  • a recipe, which describes the formula (the physical ingredients of a batch) and what actions are to be taken in what order. The recipe is written as a procedural model, which can be subdivided into unit procedures, the unit procedures into operations, and the operations into phases.
  • the equipment logic, which is the description of how the procedure is implemented.
By proceeding in a step-by-step manner, so that each step is defined before the next one begins, the control engineer then has a relatively easier task of writing the control code that matches the equipment logic with the desired phases of the procedure.

When done right, these steps allow the same procedural model to be applied to different equipment (i.e., the same end product being manufactured at two dissimilar sites), and the same equipment logic to be used for other units, saving design and specification time. Other definitions, such as process cell or process model, describe the finished combination of procedure and equipment; in some cases, these can be reused or duplicated as well.

The simplicity and efficiency of S88 models was an influence on the development of S95, “Enterprise Control System Integration.” This standard is a strong influence on how manufacturing execution systems (MESs) are designed and operated, since the MES is the gateway through which information about product demand, or ingredient inventories, filters through to the production floor.

MES and enterprise information systems deal with an even more diverse and heterogeneous environment than the production floor. The models of manufacturing processes, and the distinctions between what business goals are to be accomplished, and how they will be accomplished, are correspondingly more valuable.

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