Extending the Validated Workplace

Not so long ago, the utilities and environmental controls of a pharmaceutical manufacturing facility were a given--you needed to have a way to turn the lights on and off, or to adjust the temperature, but beyond that, you'd "set it and forget it." True, specialized areas such as cleanrooms needed extra attention, but the main focus was always on the process control systems to run actual production lines.

Nowadays, building automation systems (BAS) can be nearly as complex as the process control system--a network of controllers, data centers, sensors and video cameras. The reason: 21 CFR Part 11, the electronic-recordkeeping requirements that FDA has imposed on the pharmaceutical industry. On the surface, Part 11 rules simply require that pharmaceutical manufacturers ensure that their electronic production records are stored securely and signed off appropriately.

However, the need to ensure compliance has generated a near-revolution in BAS technology. BASs now feature comprehensive data centers, networking tools, levels of security and redundancy, along with a long list of specification requirements "The pharmaceutical industry, along with semiconductor manufacturing, is leading the way in [adopting] integrated systems," says David Clayton, an analyst with ARC Advisory Group, a Dedham, Mass.-based market-research company.

"We prefer to work with both pharmaceutical clients and BAS vendors at an early stage," says Nejat Babur, mechanical department manager at the engineering-construction company Lockwood-Greene, Somerset, N.J., and now part of CH2M Hill. "We like to have a specific location guide in order to implement the design, and to produce airflow designs that can be as complex as the piping & instrumentation designs used for production systems."

Validation can be inordinately time-consuming. "Speed to market has emerged as the key issue in how BASs are specified and installed," says Simon James, buildings sector manager at Honeywell Building Solutions, Minneapolis. "We have to bring solutions to the market that do not slow down the validation process." While customers remain concerned with traditional performance parameters of BASs, such as energy management and productivity enhancement, getting through the validation tangle is paramount, James adds.

Devices and Interfaces

Most of the leading BAS vendors serve the full range of commercial and industrial clients. The pharmaceutical industry is one of many specialized markets, which, ARC estimates, add up to around $12 billion globally each year. However, those vendors competing in the fast-growing pharmaceutical field offer increasingly comprehensive and tailored systems.

In determining which hardware and software actually goes into pharmaceutical plants, the first decisions are made based on what parts of the BAS can directly affect production (and therefore need full-blown validation) and which parts do not. A dependable starting point for this analysis is the "Baseline Guide on Commissioning," a document produced by ISPE, with advisement from FDA. This Guide (there are several others that have been published or are in the works for other aspects of pharmaceutical manufacturing) defines "direct impact," "indirect impact" and "non-impact" systems with regard to building environmental controls.

If a plant's environmental control system fails and product is adulterated, that is a direct impact. If the system is simply connected to a direct-impact system--say, a chiller that provides cooling to an air-handling unit, with the air-handling unit determined to be a direct-impact system, is an indirect-impact system. And if it doesn't affect product quality at all--for example, the heating and cooling to cafeterias or offices at a facility, it is a non-impact system.

Determining whether a system is direct, indirect or non-impact is "the million-dollar question" for facility designers, says Agostino Renna, director of the life sciences group at Johnson Controls, Inc., Milwaukee, Wis. "An FDA inspector will come into your plant and ask to see how your direct-impact systems are documented. Then that inspector might ask to look at the documentation of your non-impact systems, and ask you to justify that assessment."

However the impacts have been defined, at some point, a validated component will interface with a non-validated part. Here, there is considerable debate about how to handle such interfaces, on both the hardware and software requirements, ranging from using the same networking and supervisory software to installing two completely separate BASs for each "side" of the facility. "When designing a unified BAS, you have to be careful that the unregulated part doesn't affect the regulated part," says Renna. "Otherwise, it's like the sweater with one loose thread--once you start pulling on that thread, the whole sweater could come apart."

Johnson Controls recommends that either "logical" (software) or "physical" (hardware) separation be made between the two components, Renna says. Logical separation is created by employing strict access-control to BAS setpoints and operating parameters, and by ensuring that a change in, say, the lobby airflow will not affect airflow in a temperature-controlled warehouse. Physical separation, while more expensive in terms of installed hardware, might be justified to ensure complete independence of the regulated space.

The distinction between regulated and nonregulated components can also carry over into the BAS's hardware, notes Lockwood Greene's Babur. Typically, the BAS encompasses sensors for temperature, relative humidity and other environmental factors, controllers or other field devices for executing instructions, and centralized data centers or control rooms for supervising overall operations.

"Commercial-grade devices usually don't have the same accuracy or performance as industrial-grade devices," Babur explains. "Industrial sensors might have a +/-0.5-1.0% accuracy, while commercial units might be 5%." In these cases, Lockwood Greene might produce a design that blends the two types of devices, with the industrial-grade units going into the regulated, direct-impact areas.