USP Draft Chapters on Contamination Control Strategies (CCS): What You Need to Know

Contamination control is the cornerstone of sterile drug product manufacturing. As therapies become more complex and patient safety expectations rise, regulators and standards-setting bodies are sharpening their focus on holistic contamination control strategies. When the European Union, World Health Organization (WHO) and the Pharmaceutical Inspection Co-operation Scheme (PIC/S) revised the GMP Annex 1 guidelines for sterile medicinal products, it raised the bar on expectations of manufacturers and their sterile product suppliers, by extension. Since the publication date, several other global jurisdictions have adopted these guidelines into their national law or developed complementary requirements.

Notably, the regulatory framework in the United States, although aligned with the same goals as the EU and WHO, provides less prescriptive methodology to allow manufacturers flexibility. The guidance Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice has not been revised since 2004 and relies heavily on the requirements in the 21 Code of Federal Regulations (CFR) Parts 210 and 211. This includes overarching requirements such as the following from 21 CFR 211 and the related guidance Considerations for complying with 21 CFR 211.110, January 2025: “The flow of components, drug product containers, closures, labeling, in-process materials, and drug products through the building or buildings shall be designed to prevent contamination”. More recent guidance such as Risk Management Plans to Mitigate the Potential for Drug Shortages, May 2022 and Inspection of Injectable Products for Visible Particulates, December 2021, along with the adoption of International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q9, May 2023 stress the importance of a risk-based approach to reduce the likelihood of contamination across the entire supply chain but stops short of requiring a contamination control strategy.

Understanding the potential gap, the United States Pharmacopeia (USP) released two chapters for public comment in 2025, with the intent to guide manufacturers in developing robust Contamination Control Strategies:

1. Draft USP Chapter <1110> Microbial Contamination Control Strategy Considerations

   This chapter emphasizes a risk-based approach to contamination control, integrating facility design, personnel practices, cleaning, training, and monitoring into a unified strategy. It also stresses that any container closure system intended for packaging sterile product should be robustly studied as recommended in USP <1207> to ensure sterility is maintained throughout the product lifecycle. If any parts of the processes are outsourced to a supplier, the expectation of contamination control is governed in accordance with a quality agreement between all parties. Lastly, the chapter encourages manufacturers to document how each process element (end to end) contributes to contamination prevention and to maintain that document as a living strategy that evolves with process changes.



2. Draft USP Chapter <1114> Microbial Contamination Control Strategies for Cell Therapy Products

   This chapter builds on the foundational elements present in <1110> with specific considerations for cell therapy products. Because cell therapies are living organisms, they cannot be terminally sterilized. Therefore, contamination control can be more complex with these highly sensitive advanced therapies. The chapter includes guidelines for aseptic processing, raw material qualification, and rapid microbial detection methods.

Both chapters reinforce the principle that contamination control is not a single procedure—it’s a comprehensive, interconnected system with a foundation in risk understanding. This approach echo themes found in the 2022 EU GMP Annex 1 revision. Key parallels include:

• Holistic approach: Both Annex 1 and USP drafts advocate for integrating facility, equipment, personnel, and monitoring into one strategy.
• Risk-based thinking: Manufacturers must justify decisions scientifically, with a focus on patient safety and product quality, rather than relying on prescriptive rules.
• Continuous verification: Ongoing assessment and adaptation of contamination controls are essential to maintain compliance.

Why This Matters

Although chapters above 1000 in the USP are considered guidelines, the US Food and Drug Administration (FDA) and the USP work together on compendial chapters to ensure alignment with the guidelines ultimately becoming regulatory expectations. In addition, for manufacturers of sterile drug or cell therapy products that are intended for global markets, the closer the regulatory expectations can mirror one another, the easier it is for manufacturers to develop one strategy to meet global requirements.

Next Steps

All Pharmacopeial Forum (PF) comments have now been received on the USP drafts and are under review. However, the timeline for subsequent revisions and/or final publication remains undefined. The extent of changes based on stakeholder feedback will determine when these chapters become official. For now, manufacturers should view these drafts as a preview of the future—and an opportunity to align internal practices with emerging global expectations.

Key takeaway

Contamination control is evolving from a checklist to a comprehensive, risk-based strategy. By acting now, manufacturers can stay ahead of regulatory expectations and reinforce their commitment to patient safety.

Interested in learning more? Visit our Container Closure Integrity page.