Many a drug facility—Genzyme Allston last summer, to name one—has fallen afoul of FDA regulators over cleanroom contamination. A cottage industry of consultants and solutions providers thrives on helping manufacturers avoid such a fate.
Often the problem is one of negligence. In a Warning Letter sent to one manufacturer a few years ago, FDA stated: “The absence of sterility failures and adverse reporting trends do not indicate to us that sterility assurance has been attained. Sterility assurance is achieved by showing the controls and procedures implemented to prevent microbial contamination.” In other words, contamination control should be a proactive exercise. The Agency continued, “We recommend that you continually evaluate your facility on an overall basis to determine cGMP compliance.”
There are basic tools that manufacturers can use to establish better contamination control—among them, contamination mapping of a facility or its sterile areas, says Philip J. Austin, PhD, director of research of Acorn Industries, Inc. (Livonia, Mich.), a consulting, training, and engineering firm specializing in contamination control. (The firm was founded by Austin’s father, Philip R. “Doc” Austin, S.E., who has consulted and lectured on contamination issues for some 40 years.)
Contamination mapping is a bit of a misnomer, the younger Austin says. Maps aren’t always used, and there are no clearly defined practices.
Some manufacturers actually do use facility maps, upon which they plot contaminant readings and establish “hot zones” in cleanrooms and other locations. And some might go so far as to draw computer-generated maps with color gradients illustrating levels of particulates in various locations. More often, however, says Austin, the “maps” are spreadsheets or tables presenting contamination data from specified locations, which are then referenced against a layout of the facility.
One of the reasons there’s not more consistency in how mapping is done is that most manufacturers would rather not talk about it, Austin says. (Recently, two facilities turned down our requests to be interviewed about their mapping activities.) “Most of the time we’re called in a crisis,” Austin says. “There’s been a problem at the facility, the FDA has asked for CAPA, given the manufacturer a year to do it, and 11 months have already gone by.”
Done right, mapping can be a useful diagnostic tool, Austin says, something that goes beyond mere compliance. Many manufacturers map certain particles (eg, bacteria) out of protocol, Austin says, but “they’re not really mapping.” Rather, they’re doing the minimum to ensure compliance for whatever cleanroom standard they must meet.
He offers up some advice for those who would map:
Set your objectives. Clearly define your reason for mapping and what you hope to get out of it. Some considerations:
- Compliance and/or control? Are you mapping because you have to, want to, or both?
- Aerosol and/or surface particles? Mapping usually concerns airborne particles, but there are reasons to examine both, Austin says.
- Viable and/or non-viable particles? “Each company must decide what it is they’re worried about,” he says.
- “At rest” and/or “operational”? Baseline data and mapping is usually done at rest, Austin says, since operators are not present and readings will be consistent (and the manufacturer is more likely to obtain favorable results). “Operational” data can vary dramatically depending on level of workers’ activity.
Have a plan. Once you’ve defined what particles you’re looking for, what work areas you want to monitor, and what activities pose the most risk, and so on, establish clear monitoring procedures accordingly, Austin says.
Make mapping systematic and proactive. “Smart companies are doing it as part of a routine,” Austin says. They say, “This is something we need to do to control our processes and troubleshoot potential problems.”
Make use of new testing and monitoring technologies available. Anything that cuts down on the two weeks or so it takes to receive bacterial results, for example, is helpful. “While waiting for a test result, you may have been running for 14 days with a contamination issue,” Austin says. “If the tests show a problem, then what are you going to do?” It goes without saying that more timely data will make maps more current and relevant.
Make sure data is meaningful. “Some manufacturers do continuous monitoring and mapping, but they usually stick [the test plate or sensor] in the corner of the room . . . it makes you feel good, but the data’s not that important.” One good practice, he says, is to monitor near critical work areas, particularly where product is exposed. This will provide the most meaningful contamination data.
Resolve issues immediately. “If you find a problem, you have to deal with it.” Smart manufacturers know that any contamination issue ignored will come back to haunt them.
Go with the pros. Contamination is a complex issue which is not well understood by those most often assigned the task of contamination control, Austin says. “There is no formal college training for the discipline. There are a variety of issues to consider, and every facility and manufacturing process is different. . . . .For mapping and contamination control in general, it makes sense to defer to those who do it for a living.”