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Quality by design and single-use air sampling

Quality by Design (QbD) is a method approach to developing a quality control system using predetermined objectives. It uses the foundations of risk management and science to ensure a repeatable process to manufacture high-quality products. In 2002, the FDA launched QbD as part of its innovation initiative. This paper outlines resources for increasing productivity, decreasing cost and implementing a quantifiable, conclusive and cost-effective monitoring strategy.

In the 21st century, it is no longer possible to release products or monitor processes (especially aseptically-filled sterile products) using microbiological methodologies and techniques developed in the 20th century. The use of outdated microbiological analytical methods allows the detection of a third of the microorganisms present in the product/process. Therefore, it is not possible to completely identify areas of contamination in the production process.

Strategies and implementation of more sensitive and/or more reliable microbiological analytical methodologies that allow the identification of potential production process problems and their resolution should be a priority.

Microbiological monitoring

Critical pharmaceutical processes, both non-sterile (aerosol) and sterile (injectables), must be monitored in order to ensure quality of the final product. Environmental monitoring systems are an important part of aseptic processing, and an essential component of controlling the presence, distribution, and survival of microorganisms. Examples of critical non-sterile products include aerosol, nasal spray and powder inhalers.

Improved detection results in the improvement of microbiological quality. However, this increase in microbiological quality and sensitivity must coincide proportionately with production costs. To ensure reasonable cost, realistic goals must be set.

Monitoring cannot identify and quantify all microbial contaminants. Microbiological monitoring of a cleanroom is technically a semi-quantitative exercise, given the limitations in sampling equipment. Lack of precise counting methods and limited sampling volumes mean that environmental monitoring is incapable of providing quantitative information regarding sterility assurance.

Decreasing production costs

It is possible for production costs to decrease with an increase in microbiological quality. For example, in production, when two batches are rejected or multiple OOS are found, the investigations can total $15,000-$50,000 each. Areas of poor quality must first be identified and their cost calculated. If possible, operators should be removed from the aseptic process due to the strong impact humans have on microbiological contamination. Inspectors are indicating that the common CAPA towards non-conclusive results – “operator error means operator training/re-training” – is no longer acceptable more than once a year. Poor microbiological techniques and methods contribute to difficulty in quantifying this impact. Critical areas for monitoring include process waters (deionised, RO and WFI), air and compressed gases, and surfaces including personnel, gloves and equipment.

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