Contamination Fears Pose Big Challenges in Aseptic QC

Many of today’s urgently needed medicines cannot withstand irradiation or heat sterilization during processing. Consequently, the pharmaceuticals industry is placing greater emphasis on aseptic manufacturing. Controlling virtually every step from formulation to packaging is essential in order to minimize the risk of microbial contaminants being introduced to patients using injectables, drops, or sprays.

How serious are the risks? In a recent issue of the PDA Letter, David Jaworski of the Parenteral Drug Association (PDA) notes that the U.S. Food and Drug Administration listed 37 microbial contamination recalls in 2022. In addition, Jaworski identifies five subsequent recalls of sterile drug products due to microbial contamination – with three people dying from eye infections caused by contaminated products.

FDA listed 37 microbial contamination recalls in 2022, plus five subsequent recalls of sterile drug products due to microbial contamination.

Errors at any step of aseptic manufacturing have the potential to damage patient health by introducing live pathogens. They can also result in costly production delays and loss of product. That leaves little margin for error if you’re specializing in small-batch vaccines or personalized cell and gene therapies.

Small wonder, then, that Jaworski identifies an effective environmental monitoring (EM) system as “a prerequisite that must be established before aseptic operations can commence.” In facilities where everything from containers to employee garb must pass rigorous standards for sterility, automating the EM function with our Growth Direct^® System helps pharmaceutical manufacturers to pursue product safety with confidence.

Minimizing Human Sources of Contamination and Error

In its 2022 revision of Technical Report No. 13, Fundamentals of an Environmental Monitoring Program, PDA urges consideration of rapid microbiological methods (RMM) and automated monitoring by makers of sterile pharmaceutical products. TR-13 notes that RMM and automation have come a long way since the original report was issued in 1990, becoming “more convenient, performant and accepted, or even recommended, by regulatory bodies.”

A variety of EM uses are identified in Section 5.5 of the report, including:

• Confirmation in real-time (or close to real-time) of microbial control during manufacturing activities such as manual aseptic manipulations, filling, and packaging
• Confirmation of microbial control in manufacturing suites or gowning rooms
• Rapid assessment of controlled areas during facility qualification activities
• Evaluation of contamination remediation efforts, from finding contamination sources to assessing cleaning and disinfection procedures

Reducing traditional environmental monitoring from 15 steps to two via automation, the Growth Direct^® System can detect bacterial contaminants twice as fast as manual processes* while eliminating subjective enumeration, repetitive sample analysis, and error-prone recordkeeping. Equally important, aseptic facilities can minimize human sources of contamination – integrating digital imaging, robotic handling, incubation, and software control within a self-contained test instrument.

Enhanced Mold Detection

While bacterial contaminants are the most common concern in aseptic manufacturing, fungal contaminants also pose very significant threats that range from product spoilage to high mortality rates among immune-compromised patients, not to mention infection outbreaks and product recalls. Typical compendial workflows require a microbiology staff to wait until the end of sample incubation before manually verifying the presence of mold colonies. Even when performed expertly, these labor-intensive processes make it challenging to head off the spread of mold contamination before it compromises a facility.

Now, however, enhanced mold detection capability in the Growth Direct^® System offers an expedited alternative, enabling earlier confirmation of contamination and cleaning efficacy. This can result in a lower cost to return aseptic manufacturing facilities to a decontaminated state, while also reducing the risk of human error.

A Higher Level of Confidence

“With aseptic manufacturing practices, there is also the option to introduce bioburden testing of product throughout the process,” points out Rapid Micro Biosystems director of industry affairs David Jones. “Combining environmental monitoring and bioburden testing can yield earlier notification if there’s an issue with the product, resulting in much more confidence in the production process.”

Because the Growth Direct^® System has bioburden testing capability, many customers use it to realize significant time and cost savings. In one striking example of in-process bioburden reduction, a Top 20 global pharmaceutical company installed a unit for water testing at a site producing therapeutic proteins. During a serious water contamination event, an organism excursion that would traditionally require seven days to identify was instead detected in 24 hours; the entire water system was sanitized immediately and rapidly brought back online, saving up to six manufacturing days and potentially millions of dollars in product that would have otherwise been lost to contamination.

The Growth Direct^® System gives aseptic manufacturing facilities an ideal complement to their existing containment strategies, while automating compendial methods and streamlining data integrity practices for biologics, vaccines, cell and gene therapies, or other parenteral drugs. To learn more, contact Rapid Micro Biosystems today.

*Internal data on file