USP–NF PF 51(5) Draft: Updates in Microbiology, Distribution, and Dosage Form Guidance

〈1117〉 Microbiological Best Laboratory Practices

Status: Revision

The revision of 〈1117〉 reflects the Microbiology Expert Committee’s intent to modernize best practices for microbiological laboratories. The proposal builds on the official version as of August 1, 2025, and introduces expanded requirements in media preparation, sample handling, equipment control, and data governance.

Key Revisions

• Preparation and Quality Control of Laboratory Media: Greater detail is provided on the use of Purified Water, accurate weighing, and controlled dissolution of media. Emphasis is placed on avoiding overheating, ensuring clean glassware, and validating sterilization cycles.
• Incubation Times: The representation of incubation periods is clarified, distinguishing between hours (for tests shorter than three days) and days (for tests exceeding 72 hours).

• Laboratory Equipment: Requirements are expanded to include qualification, calibration, and preventative maintenance, with specific reference to data integrity for software-controlled instruments.
• Sample Handling: Updated expectations cover aseptic techniques, storage conditions, and full documentation of microbiological samples.
• Risk Assessments and Investigations: Principles for conducting microbiological risk assessments are detailed, providing a structured approach for handling deviations and investigations.
• Method Transfer: The section is rewritten to describe comparative testing and waiver strategies to ensure reliable transfer of microbiological methods.
• Enumerative Microbiology: The former quantitative microbiology section is revised to standardize colony-forming unit (CFU) enumeration practices. New criteria define how colonies should be distinguished, while second-person verification and the application of automated digital technology are introduced.
• Data Integrity: The ALCOA principles (Attributable, Legible, Contemporaneous, Original, Accurate) are explicitly applied to microbiological data, with recognition of the challenges associated with manual methods and the role of validated automated enumeration systems.
• Structural Changes: Standalone sections on technologies, analyst qualification, documentation, and laboratory records have been integrated into relevant parts of the revised chapter for a streamlined format.

SEE ALSO: Data Integrity and Data Governance in GMP

GMP Impact

The proposed revision requires microbiology laboratories to enhance media quality control, equipment governance, and data management practices. Risk-based evaluations will become central to investigations, and firms must be prepared to integrate second-person verification and validated digital tools for enumeration. 

Training, SOPs, and quality agreements with contract labs will need to be reviewed to align with these updated requirements.

〈1079.5〉 Transportation Lane Temperature Mapping and Qualification

Status: New Chapter

The General Chapters—Packaging and Distribution Expert Committee has proposed a new chapter focused on the evaluation and qualification of transportation lanes to ensure temperature control during distribution. 

Unlike storage qualification, transportation presents unique risks due to environmental variability, limited control by shippers, and exposure to multiple stakeholders. This chapter outlines best practices for mapping and qualifying transportation routes to ensure the integrity of drug products.

Key Provisions

• Purpose: Establishes temperature lane mapping as a technique to evaluate whether transportation modes and lanes maintain conditions supported by product stability data.
• Risk Factors: Identifies influences such as transportation mode (air, ground, rail, sea), insulation, airflow, door openings, season, geography, and customs delays as critical to maintaining control.
• Mapping Protocols: Requires a documented protocol covering lane details, monitoring devices, shipment frequency, and training. Worst-case lanes and routes should be selected to represent typical distribution conditions.
• Monitoring Devices: Mandates calibrated temperature monitoring devices (TMDs) and clear data management processes. Placement of devices must ensure representative exposure to environmental conditions.
• Data Evaluation: Out-of-range data must be assessed against USP 〈659〉 and related chapters 〈1079〉, 〈1079.2〉. Deviations trigger mitigation actions such as changes in transport mode, additional packaging controls, or lane rejection.
• Qualification and Requalification: Defines the qualification of lanes based on data and risk assessment, with requalification required following significant changes (e.g., supplier changes, weather conditions, or introduction of new lanes). Continuous verification may be applied through real-time logging.
• Documentation: Requires formal study reports with executive summaries, deviations, data analysis, and approval by quality and operational leadership.

GMP Impact

The introduction of 〈1079.5〉 formalizes lane-level risk management in pharmaceutical distribution. Companies must establish mapping protocols, qualify critical routes, and integrate lane performance into their GDP and change control systems to ensure seamless operations.

This chapter will directly impact logistics providers, distributors, and manufacturers relying on ambient or temperature-controlled transport, requiring stronger oversight and documented evidence of distribution robustness.

〈1113〉 Microbial Characterization, Identification, and Strain Typing

Status: Revision

The Microbiology Expert Committee has proposed a major revision of 〈1113〉, the last official document before 2013. The update reflects advances in microbial identification technologies, modern taxonomy, and the growing importance of reliable strain-level characterization in contamination investigations.

Key Revisions

• Identification Strategies: A new framework outlines minimum recommended identification requirements by sample type (sterile products, nonsterile products, utilities, environments, and drug substances).
• Expanded Methodologies: Incorporates phenotypic, proteomic, and genotypic approaches, with detailed guidance on sample preparation, instrumentation, and limitations. MALDI-TOF MS and whole genome sequencing (WGS) are now recognized as core techniques.
• Method Qualification: “Verification” of microbial ID methods is replaced by “Qualification”, emphasizing accuracy, reproducibility, specificity, and database validation. Parallel testing, stock culture challenges, and reference laboratory comparisons are recommended.
• Taxonomy Updates: Encourages adoption of current microbial nomenclature, with cross-references to legacy names to preserve trending continuity.
• Strain Typing: Expands the role of WGS, multilocus sequence typing (MLST), and core genome MLST (cgMLST) in determining strain-level relatedness, supporting contamination source investigations.
• Glossary Modernization: Adds precise definitions for terms such as phylogenetic species, SNPs, polyphasic taxonomy, and strain typing, aligning with contemporary microbiology standards.

GMP Impact

The revision elevates expectations for microbial identification and trending in GMP settings. Manufacturers must evaluate current laboratory capabilities, validate databases, and prepare to adopt advanced methods (MALDI-TOF MS, sequencing) where appropriate. 

Trending programs will need to incorporate new nomenclature standards, and contamination investigations will increasingly rely on strain-level resolution to support root cause analysis and regulatory defensibility.

〈789〉 Subvisible Particulate Matter in Intraocular Solutions

Status: Revision

This revision clarifies testing requirements following the 2024 update, which had eliminated the mandatory two-stage testing for ophthalmic drug products. Since then, questions from stakeholders prompted USP to confirm that while two-stage testing is no longer required, it remains an acceptable and viable option.

Key Revisions

• Flexibility in Testing: Confirms that manufacturers may select either a one-stage or two-stage approach depending on product characteristics and risk profile.
• Testing Methods: Reinforces that intraocular solutions may be tested by light obscuration (LO) or microscopic particle count, consistent with 〈788〉.
• Particulate Limits: Restates acceptance criteria for particles ≥10 µm, ≥25 µm, and ≥50 µm, aligning intraocular solutions with established parenteral limits.
• Product-Specific Considerations: Acknowledges that certain products, due to viscosity, volume, or formulation, may require the microscopic method or quantitative dilution.

GMP Impact

Manufacturers of ophthalmic solutions gain flexibility in method selection but must maintain scientifically justified testing strategies. Quality units should reassess method suitability protocols, particularly for high-risk intraocular products, and document rationale when adopting or retaining two-stage testing. This ensures both regulatory compliance and patient safety.

SEE ALSO: PDG Publishes Major Revision to General Chapter on Sub-Visible Particulate Contamination

〈1664.5〉 Oral Dosage Forms

Status: New Chapter

This new chapter complements 〈1664〉 by focusing specifically on leachables in oral dosage forms (ODFs). It addresses liquids, semisolids, and solids, considering both manufacturing equipment and packaging systems as potential sources of leachables. 

While oral dosage forms are generally considered low-risk compared to parenterals or inhalation products, the chapter establishes a structured approach to assess packaging and process-related risks.

Key Provisions

• Scope: Covers liquid oral dosage forms (solutions, suspensions, emulsions, syrups), semisolids and pastes, and solid oral dosage forms (tablets, capsules, powders, granules, premixes).
• Packaging Systems: Evaluates bottles, blisters, tubes, pouches, and auxiliary dispensing devices, with attention to barrier properties, materials of construction, and nitrosamine risks (e.g., from nitrocellulose lidding foils).
• Manufacturing Systems: Recognizes that stainless steel equipment poses negligible risk for organic leachables, but polymeric components require assessment. For solids, leachables risks are considered minimal.
• Regulatory Alignment: Reflects FDA guidance on container closure systems and emphasizes that compliance with compendial standards and food-contact regulations (21 CFR Parts 174–186) is often sufficient to demonstrate safety.
• Testing Requirements: Extractables and leachables testing is required only when risk assessments indicate potential concern (e.g., aqueous liquids with cosolvents or surfactants).

GMP Impact

The chapter provides a risk-based framework for leachables in oral formulations, guiding when testing is warranted and when regulatory justification is sufficient. Manufacturers must update packaging assessments, evaluate the risk of nitrosamines in oral dosage packaging, and integrate these considerations into their overall leachables and extractables strategies.

Implementation and Industry Feedback

The USP–NF PF 51(5) draft proposals collectively strengthen standards across microbiology, distribution, particulate control, and packaging. They reflect a clear shift toward risk-based evaluations, integration of modern technologies, and heightened data integrity expectations.

For the industry, the immediate priority is to:

• Review draft chapters and evaluate potential gaps in existing SOPs, risk assessments, and validation programs.
• Submit comments during the public review period to address technical feasibility and align compendial language with current practices.
• Update quality systems in anticipation of adoption, particularly in areas of media quality control, method transfer, transport qualification, and packaging assessments.
• Engage cross-functional teams (QC, QA, supply chain, regulatory) to assess the broader operational impact of these changes.

These proposals underline USP’s direction of aligning compendial standards with regulatory expectations for lifecycle-based control and scientifically justified risk management. Proactive engagement with these drafts will position companies to implement necessary adjustments ahead of final adoption.