Pharmaceutical cleanrooms have gone through drastic changes in recent years as mergers, acquisitions, facility closures, drug patent-cliffs, and other industry dynamics have forced manufacturing facilities to continually adapt to remain both competitive and compliant with U.S. Food and Drug Administration (FDA) regulations. The one constant element is the FDA requirement for monitoring non-viable particle counts in cleanrooms to ensure that the manufacturing of injectable drugs is performed in a safe, sterile environment.
As with all regulatory environments, a substantial portion of daily work must be dedicated to managing cleanroom data and completing the paperwork associated with cleanroom particulate contamination control. The manual management of cleanroom particle count data presents challenges, but more efficient approaches can overcome change control barriers.
Figure 1. A typical portable particle counter with on-board thermal printer. (MET ONE 3400 portable particle counter.) All figures: Hach Co.
Pharmaceutical manufacturing environmental monitoring (EM) managers, production managers, QA/QC professionals, and many other team members responsible for ensuring their cleanrooms are particle-free, generally approach particle monitoring with broadly similar methods. Portable air particle counters, typically equipped with stainless steel isokinetic probes, are placed on a cart and wheeled around cleanrooms, sampling the air and measuring particle contamination levels. The task of measuring particles is routine and mundane, with pre-established points of measurement being sampled at regular intervals. Location selection and sampling recipes are dependent upon each cleanroom’s area classification.
Typically, the collection and management of particle counting data at each sampling locale can be summarized by the eight steps detailed in Table 1.
Theses eight steps are repeated for every sampling location in every cleanroom in the facility. For a given particle count sampling location, the operator of the portable particle counter will spend an average of three minutes per location following the eight steps, which does not include time required to perform the sampling at each location. For facilities where multiple injectable drugs are being produced, the daily sampling locations can exceed a thousand points a day and dozens of operators. With a thousand sampling points, a facility staff can spend 50 hours per day—representing 13,000 hours annually—to complete the eight steps at each sampling location.
Roadblocks to change
The primary reason pharmaceutical facilities manually manage cleanroom particle counting data is that change in FDA’s Good Manufacturing Practice (GMP) processes is very difficult. In pharmaceutical GMP environments, risk aversion and strict change control processes are well understood. A change to established procedures may require approval from many stakeholders in quality, metrology, production, and management, or revalidation of the entire process. Some may question the need to change a drug production process that has not had any compliance gaps raised by the FDA.
Figure 2. Portable particle counter with integrated USB drive. (MET ONE 3400 simply paperless particle counter)
The second reason for manual data management is that the particle counters do not meet the application needs in any other way. Most particle counter manufacturers offer a three-tiered product portfolio for sampling and data management:
• A portable air particle counter that offers an on-board thermal printer is the most common method particle counter sampling in the industry today.
• Particle counting software for use with portable air particle counters is installed on a computer or laptop, requiring new standard operating procedures (SOPs) to be created and validation qualification of a new process to manage data in the cleanroom. Most change control processes typically deter this solution.
• Facility monitoring systems (FMS) or online, fixed location remote particle counters require a continuous monitoring software suite generally installed on the network. A continuous monitoring solution with fixed online particle counters is a complex and costly solution, requires substantial change, and does not entirely eliminate the need for portable particle counters in environmental monitoring of other cleanroom areas. As FMS systems are primarily suited for the Aseptic cleanroom filling suite, the only reasonable solution for an environmental monitoring department is a portable air particle counter.
Each option has advantages and disadvantages, but these solutions have been available to pharmaceutical cleanrooms for more than 25 years.
Figure 3. The sampling process using printer paper.
In spite of the cost of 13,000 man-hours per year to manually monitor cleanroom particle counting data, the use of particle counting software has not been widely adopted. When particle counting software is considered for cleanroom use, the software becomes an additional product that injects a new set of risks and imposes substantial change to established, approved, and validated cleanroom management processes. Some change-adverse cleanroom operations choose to follow the eight steps of manual data management rather than incur the risk and change their manufacturing processes. Furthermore, given limited manufacturing capacity, production uptime is critical to profitability for pharmaceutical production; changes can take weeks or months to complete.
A new portable particle counter, the MET ONE 3400 (Hach Co.), features internal software that creates an electronic PDF and a separate Microsoft Excel spreadsheet record written directly to a USB memory stick plugged into the particle counter. The system eliminates the need for printing on thermal paper, attaching to larger A4 paper, and data entry into a spreadsheet.
Particle counter operators can take samples throughout the cleanroom and return to their offices with the data in the secure electronic PDF format desired on a USB memory stick. In most cases, the environmental monitoring manager or quality control department will only require minimal change to SOPs, or the changes will be minimal and easy to accomplish.
Paul Yates has a degree in chemical engineering and an MBA from Iowa State University. He has worked in the process control and life science pharmaceutical manufacturing industries, and has developed multiple particle counting products. Contact: firstname.lastname@example.org
This article appeared in the November/December 2012 issue of Controlled Environments.