Serving approximately 3,000 customers across 12 facilities in the United States, Mexio, Asia and Europe, Nelson Labs is a global leader in outsourced microbiological and analytical chemistry testing and advisory services for the medical device and pharmaceutical industries. With an array of over 900 laboratory tests and the expertise of Regulatory Compliance Associates, the company supports its customers from initial product development and sterilization validation, through regulatory approval and ongoing product testing for sterility, safety and quality assurance.

In this conversation, Christine Walton, Senior Scientist, Nelson Labs, dives into the proposed regulatory chapters USP <1119> and <1119.1>, discussing their purpose, scope, limitations, potential impact and more.

Contract Pharma: What are the new proposed regulatory chapters USP <1119> and <1119.1>, and what impact will they have on bioburden testing and biopharmaceutical manufacturing?

Christine Walton: Before we look at the specifics of these new chapters it may be helpful to review the history that led to these chapters’ creation. The new general chapters in USP were proposed by the microbiology expert committee to help clarify a long-held misunderstanding that USP <61> Microbial Enumeration testing is interchangeable with Bioburden testing.

USP <61> defines the methodology for microbial enumeration in nonsterile pharmaceutical products, including critical parameters such as sample sizes, media types, dilution, plating techniques, and suitability testing. These procedures are directly tied to USP <1111>, which establishes acceptance criteria for total aerobic microbial count (TAMC) and total yeast and mold count (TYMC) specific to product types and routes of administration. Together, these chapters provide a structured framework for assessing microbiological quality of finished drug products.

However, confusion arises when manufacturers attempt to extend the use of USP <61> to bioburden testing outside of this intended scope. While bioburden testing has traditionally been applied in the context of medical devices and materials destined for terminal sterilization, it also involves quantifying viable microorganisms which are similar in technique, but distinct in application. This overlap has led some manufacturers to modify USP <61> methods to function as general-purpose bioburden tests, particularly when working with materials that don’t clearly fall under the nonsterile drug product or pre-sterilization medical device categories.

In response to this gap, USP introduced informational chapters <1119> and <1119.1> to support a broader, risk-based approach to bioburden testing and monitoring. USP <1119> focuses on building a bioburden monitoring strategy rooted in process understanding and risk assessment. Although it promotes a tailored, risk-based approach, the chapter includes recommended bioburden limits that are largely based on legacy expectations (such as pre-filtration thresholds) rather than product-specific risk. Notably, the small print in the chapter acknowledges that alternative limits and sample plans may be applied if supported by a scientifically justified rationale.

USP <1119.1> works in parallel with <1119> and provides a general method for aerobic bioburden testing. The chapter outlines a standard membrane filtration procedure and allows for flexibility in areas such as media selection, incubation conditions, and dilution schemes—provided these adjustments are properly validated and scientifically justified. The intent is to support a standardized, but adaptable, enumeration method applicable to materials not covered under USP <61>.

It’s important to recognize that these new chapters do not address the detection of specific or objectionable microorganisms. That remains under the purview of USP <62> and is recommended in USP <1115>. This omission contributes to further confusion. In an effort to add organism specificity, some manufacturers performing bioburden testing turn to <62> methods, which are intended for a different regulatory context. This practice has led to the misconception that bioburden methods and USP microbial enumeration methods are interchangeable or should be used in combination. In reality, each is designed for distinct product types and regulatory expectations and applying both concurrently without clear justification can result in unnecessary complexity and misalignment with compendial intent.

The introduction of USP <1119> and <1119.1> provides useful guidance for implementing bioburden programs for materials that fall outside the current scope of USP <61> and <1111>. However, these chapters are informational and not regulatorily binding. As such, it is essential for manufacturers to develop their programs in collaboration with experienced microbiologists, using a risk-based rationale that reflects the specific materials, manufacturing processes, and product lifecycle. Simply defaulting to the example methods and limits in these new chapters without proper assessment can undermine the flexibility and intent that USP designed into them.

CP: What key differences do you see between the bioburden test method described in the new regulations and current standard methods, and how might these affect test sensitivity or specificity?

Walton: A critical point to recognize is that the newly introduced USP chapters <1119> and <1119.1> are informational only – they are not compendial requirements. Their primary aim is to distinguish bioburden testing from USP <61>, which is frequently misapplied as a general bioburden method, despite being designed specifically for microbial enumeration of nonsterile pharmaceutical products.

One of the most significant differences lies in the intended use and scope of these methods. USP <61>, when used in conjunction with <1111>, provides defined test methods and acceptance criteria for nonsterile pharmaceutical products. Though not a bioburden method, USP <61> is often referenced in that context, leading to confusion. By contrast, ISO 11737-1 is a globally accepted standard specifically designed for bioburden testing of medical devices and sterilization validation. It includes detailed procedures such as product-specific extractions and handling of entire or partial device units. These elements are not addressed in the new <1119> and <1119.1> chapters.

USP <1119> significantly broadens the scope of application. It explicitly states that the chapter is intended for use with nonsterile, sterile, and low-bioburden products, including in-process materials, finished drug products, components, and pharmaceutical waters. USP <1119.1> provides only a generalized aerobic bioburden test method, designed to be broadly applicable across this wide range of materials.

However, this broad applicability introduces challenges. The recommended bioburden limits presented in <1119> appear to be adapted from multiple sources, including pre-filtration limits and water system criteria from USP <1231>. Without clear differentiation between material types or process stages, these limits may lack context and can be misleading if applied without proper justification.

From a methodological standpoint, the general nature of <1119.1> means that it may not be optimized for the specific characteristics of certain sample types, which could affect both sensitivity and specificity. For example, device surfaces, viscous formulations, or products requiring extraction may not be appropriately addressed by a standardized membrane filtration approach without modification.

Given this, manufacturers are strongly advised to rely on the risk-based framework outlined in <1119> when designing bioburden testing programs. This includes establishing appropriate sampling plans, sample sizes, and acceptance criteria based on process understanding, product type, and intended use. Blindly applying the generic test method or limits from <1119> and <1119.1> may result in under or overestimation of bioburden levels, misinterpretation of microbiological risk, or regulatory misalignment.

In summary, the key differences between current standard methods and the new USP chapters lie in their scope, specificity, and regulatory status. The new chapters aim to provide flexibility and broaden applicability, but this comes at the cost of precision. As such, their value lies in providing a framework for risk-based decision-making – not as prescriptive test methods or limit standards.

CP: What steps is Nelson Labs taking to validate and implement the bioburden testing methods outlined in <1119.1> ahead of the standards becoming official?

Walton: Nelson Labs is well-prepared for the implementation of USP <1119> and USP <1119.1>, even ahead of its potential formal adoption. The organisms, media, and methodologies outlined in <1119.1> already fall within our current microbiology capabilities and scope of testing. Our teams have deep experience not only with USP <61> and <62>, but also with a wide range of bioburden methodologies, including custom method development and validation, which will allow our teams to help support consulting or regulatory justifications needed as part of the risk-based system review. We are available to support clients through the method selection and validation process.

While USP <1119.1> offers a general bioburden test method, its broad applicability means that method suitability remains critical. For clients electing to adopt <1119.1> for bioburden testing, a suitability assessment will typically still be required for each specific product or material type. This ensures that the method is appropriate for the sample matrix, microbial recovery expectations, and test objectives – especially given the diverse materials covered under <1119.1>. Nelson Labs is able to help with this assessment and determine the correct approach for your company.

Nelson Labs is also actively evaluating the potential integration of emerging technologies referenced in USP <1119>, such as digital colony counting and automated enumeration systems. These innovations may offer enhanced accuracy, efficiency, and consistency across a range of sample types, and we are assessing their feasibility within the context of our microbiology service offerings.

Ultimately, our goal is to guide clients in selecting and validating the most appropriate microbiological test method, whether that involves adopting <1119.1>, refining an existing approach, or aligning more closely with other standards. We view these new chapters not as prescriptive mandates, but as flexible frameworks that support risk-based, scientifically justified testing strategies tailored to each product and process.

CP: In cases where bioburden levels exceed the recommended limits in <1119>, what investigative and corrective action protocols do you follow, and how do you support clients in root cause analysis?

Walton: When bioburden results exceed the recommended limits outlined in USP <1119>, the first step is to assess whether the limits applied are appropriate for the specific product, process, and material tested. It’s important to remember that both USP <1119> and <1119.1> are informational chapters—not compendial requirements—and the limits provided are intended as guidance. Therefore, any investigation should begin by confirming that the applied limits were established using a sound, risk-based approach tailored to the product’s intended use and manufacturing controls.

Once that has been established, Nelson Labs works collaboratively with clients to conduct a thorough investigation of the out-of-specification (OOS) or atypical result. This process typically includes a review of the test method and suitability, evaluation of recent manufacturing activities, environmental monitoring data, raw material or component changes, and any relevant deviations or process excursions that could contribute to increased microbial load.

Our microbiology, and regulatory compliance teams provide comprehensive support for both the technical and compliance aspects of the investigation. This includes helping to identify the likely source(s) of contamination, assessing the impact on product quality, and recommending corrective and preventive actions (CAPA) as needed.

Where appropriate, we assist clients in refining sampling plans, modifying test methods, or implementing procedural or process controls to better align with their product’s risk profile. Whether the resolution involves test optimization, process remediation, or documentation updates, our goal is to help clients maintain bioburden control, ensure data integrity, and meet applicable quality and regulatory expectations.

CP: How might the new standards in <1119> and <1119.1> impact the turnaround time, cost, or reporting format for your bioburden testing services?

Walton: The impact of USP <1119> and <1119.1> on turnaround time, cost, and reporting format will depend entirely on how a manufacturer chooses to apply the guidance. Since these chapters are informational and not compendial requirements, any changes are discretionary and should be based on product and process specific risk assessments.

If a manufacturer has not yet conducted a risk assessment or needs to revalidate an existing method to align with the general approach outlined in <1119.1>, there may be some initial impact to cost and timeline. For example, changes in sample volume, media selection, or incubation conditions may require additional validation or suitability testing, which could temporarily extend turnaround times and increase upfront testing costs. However, these steps are only necessary if changes to the current method are warranted.

Once a test method is established or confirmed to be appropriate, ongoing turnaround times are expected to remain consistent with standard bioburden testing timelines. The chapters themselves do not mandate extended incubation periods or other procedural elements that would inherently lengthen routine test durations.

In terms of reporting, minor updates may be needed to reflect the use of product-specific bioburden limits or customized sampling plans developed through the risk assessment process. These adjustments are typically made during method implementation and should not impact routine reporting once in place.

Overall, while there may be some initial investment in reviewing methods, updating documentation, or validating changes, the new chapters simply provide an alternative framework and not a requirement to change testing. For many clients, the net effect on testing operations will be minimal once the appropriate method is selected and implemented.

CP: Looking ahead, how do you expect these standards to evolve, and what proactive measures can clients take now to minimize disruptions in their supply chain or regulatory submissions?

Walton: Microbiological standards are expected to continue evolving in response to emerging product types, advanced manufacturing technologies, and new microbial detection methods. The introduction of USP <1119> and <1119.1> reflects this shift toward a more risk-based and process-driven approach to bioburden control.

Although these chapters are informational and not yet enforceable, they offer manufacturers an opportunity to critically evaluate their current bioburden testing strategies. Now is the ideal time for companies to review and update their bioburden programs, starting with robust risk assessments for each product and manufacturing process. This includes ensuring sampling plans, microbial limits, and test methods are scientifically justified and appropriate for the material being tested. If current methods have not been reassessed in light of changes in formulation, equipment, or regulatory expectations, now is the time to do so.

Early engagement with experienced microbiology laboratories or consultants can help streamline this process and reduce the risk of non-compliance or delays during regulatory submissions. Proactively addressing potential gaps now will also help minimize disruption to supply chains if these chapters become more widely adopted or formally recognized.

It’s also important to view <1119> and <1119.1> as tools for improvement rather than prescriptive requirements. For manufacturers who have historically used USP <61> in parallel with bioburden methods, these chapters may not draw a clear line between the two testing strategies. However, they do provide guidance for building a bioburden control program that is grounded in risk assessment and tailored to the specific needs of a product and process.

In summary, manufacturers can take proactive steps now like reviewing test justifications, validating sampling strategies, and aligning with risk-based principles. This will ensure their microbiological control programs remain robust, flexible, and compliant as standards continue to evolve.