Changes to Regulatory Policy in Bioburden Testing

Changes to Regulatory Policy in Bioburden Testing

How will the new USP regulations affect bioburden testing?

The United States Pharmacopeia (USP) recently proposed two new regulatory chapters, impacting bioburden testing in both sterile and non-sterile manufacturing settings. These expand on existing regulations such as USP <61> - but how do they differ and what are the implications for manufacturers?

Bioburden testing is a key part of quality control (QC) processes within biopharmaceutical manufacturing. By determining the quantities and types of microorganisms present at different stages of production, pharmaceutical manufacturers can effectively assess the cleanliness and sterility of their products. This meticulous monitoring serves as an early warning system, ensuring compliance with regulatory standards while also safeguarding the integrity of the final product.

For complex biologics manufacturing, bioburden control is especially important in relation to the quality of the finished product and as an indicator of process control. QC analysts extract samples from starting materials and intermediate product at defined stages, allowing for continuous monitoring of microbial levels throughout upstream and downstream processing.

Bioburden assessment provides data on both the expected microbial load of the product and the presence of specific microorganisms, enabling you to make targeted interventions to prevent product spoilage or adverse effects on end-users.

But how and why are bioburden testing policies changing?

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Bioburden testing and regulatory policy

Most biological products can’t tolerate terminal sterilization by heat or irradiation, and so are typically manufactured in aseptic environments. Despite this, many manufacturing steps still take place under non-sterile conditions [1].

Protein purification, conditioning, and formulation often occur in aqueous systems at ambient temperature under neutral pH conditions, making the largescale production of biologics susceptible to microbial contamination. As a result, biologics manufacturing requires comprehensive bioburden monitoring throughout the production lifecycle.

Traditionally, the methodology for releasing non-sterile products and monitoring in-process sterile products has relied on the microbial enumeration test outlined in USP <61>. However, it's important to note that USP <61> was primarily designed for the release of non-sterile finished drug products and associated substances, as specified in USP <1111>.

While previous regulations have suggested the use of USP <61> as a generic test for bioburden testing, there were no specific details or directions on how to achieve this.

The release of USP chapters <1119> and <1119.1> for public comment changes this.

These chapters provide distinct guidelines for the release of non-sterile products and other areas of both sterile and non-sterile manufacturing processes. They give a standardized framework for testing bioburden, designed to help ensure consistency and reliability in pharmaceutical practices.

This regulatory policy development reflects the growing importance of bioburden testing across a broader spectrum of applications and is particularly relevant for the production of biological therapeutic products – such as vaccines, protein therapies, and advanced therapeutic medicinal products (ATMPs).

A rapidly changing regulatory landscape

USP <1119> and <1119.1> now provide comprehensive guidelines for bioburden testing that extend beyond the scope of release testing of non-sterile products. Specifically, USP <1119> outlines requirements for establishing a robust bioburden monitoring program, including guidance for risk-based sampling and testing, as well as recommended acceptance criteria.

USP <1119.1> takes things a step further by providing a framework that’s adaptable to a wide range of samples and testing scenarios. This flexibility is key, as it enables you to tailor your approaches to fit the unique challenges of specific materials and processes.

Crucially, both USP <61> and USP <1119.1> outline specific procedures for sample preparation, growth promotion tests, negative controls, and suitability of colony counting methods to ensure accurate and reliable bioburden testing practices. These regulations specify the types of media, incubation conditions, and the selection of microbial strains for testing.

As such, it’s essential that any bioburden testing method adheres closely to these guidelines to maintain consistency and reliability in microbial enumeration and bioburden assessment.

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Adapting to change

These changes in regulation underscore the evolving landscape of pharmaceutical manufacturing, particularly in regard to the production of complex biologics. It’s crucial that manufacturers can keep pace with changing regulatory policies and efficacy standards.

However, traditional methods for bioburden testing require long testing times, leading to process and inventory bottlenecks. Since breaches in bioburden limits can be extremely costly in terms of time, materials, product, labor, and even human life, the faster you can get results, the more effectively you can mitigate potential risks and reduce the impact of contamination-related losses. As such, many testing labs are now adopting rapid microbiology methods (RMM) to reduce turnaround time, automate workflows, and eliminate the potential for error.

Contact us today to see how the Growth Direct® system can enhance your bioburden testing practices.

Part 2: to learn how automation can streamline workflows and help ensure compliance with the latest USP policy changes.