What is USP <71> Sterility and when should you use it?

Introduction

Sterility testing is critical in the pharmaceutical and medical device industries because it ensures that products intended for patient use are free from viable microorganisms. To perform sterility testing, two commonly referenced standards are available: USP <71> Sterility Tests and ISO 11737‑2: Sterilization of Health Care Products – Microbiological Methods, Part 2: Test of Sterility performed in the definition, validation, and maintenance of a sterilization process, often referred to as ISO 11737‑2 Sterility.

Many users are unsure which method is appropriate for their product. This article explains the differences between these standards and guides you in selecting the most suitable method.

USP <71> Sterility Tests focus on verifying that products are free from viable microorganisms. The standard provides guidance on two methods: the membrane filtration method and the direct inoculation method. Unlike ISO 11737‑2, USP <71> requires two incubation conditions using two different media.

Comparison Between ISO 11737‑2 and USP <71>

Parameter	ISO 11737‑2	USP <71>
Media	Soybean Casein Digest Medium (SCDM)	Fluid Thioglycollate Medium (FTM) and Soybean Casein Digest Medium (SCDM)
Incubation Temp.	30 ± 2 °C	32.5 ± 2.5 °C for FTM and 22.5 ± 2.5 °C for SCDM
Incubation Days	14 days	14 days

When Should You Use USP <71>?

Before answering that question, it is important to understand the distinction between Test of Sterility and Test for Sterility:

• Test of Sterility is used for development, validation, or requalification of a sterilization process and is based on ISO 11737‑2. It is not applicable for routine release testing. Instead, it is typically performed to assess the effectiveness of a sterilization validation process.

• Test for Sterility, also known as Release Testing, is based on USP <71>. It is used for routine batch release, especially for products that are manufactured aseptically and do not undergo terminal sterilization.

  
  

In summary:

• If you need to validate your sterilization process, ISO 11737‑2 should be used.

• If you need to perform sterility testing for product release, and especially if your product is aseptically manufactured without terminal sterilization, USP <71> is recommended.

  
  

However, these are general guidelines. You must also consider other relevant sterilization standards and the regulatory requirements of the specific country in which you intend to market the product. Some regulatory bodies mandate ISO 11737‑2 only, some require USP <71> only, and others require both.

Limitations of USP <71>

Although USP <71> is a widely recognized standard, it has several limitations:

• It does not guarantee sterility because it is a probabilistic test rather than absolute proof.

• Risk of false positives or false negatives, such as contamination during testing or undetected slow‑growing microorganisms.

• Not suitable for rapid decision-making, as the test requires a full 14 days to obtain results

Conclusion

Choosing between USP <71> Sterility Tests and ISO 11737‑2 Sterility ultimately depends on the purpose of the testing and the nature of the product. USP <71> provides guidance for routine sterility release testing, particularly for aseptically manufactured products that do not undergo terminal sterilization, making it the preferred option when verifying that a product is free from viable microorganisms before release. 

In contrast, ISO 11737‑2 is intended for the development, validation, and requalification of sterilization processes, and therefore is not suitable for routine batch release. Understanding this distinction is crucial for ensuring regulatory compliance and selecting the method that aligns with the product's manufacturing process and the requirements of specific medical device or pharmaceutical regulations. Some jurisdictions may require one method, the other, or both, so it is important to review applicable regional standards.

While USP <71> remains a widely recognized standard, it is not without limitations, most notably, its probabilistic nature, the potential for false positives or negatives, and the lengthy 14‑day incubation period, which can delay product release and complicate time‑sensitive decision‑making.

Overall, selecting the correct sterility testing standard ensures product safety, regulatory alignment, and efficient workflow. By understanding the differences between these two major standards, manufacturers can make informed decisions that best support both compliance and patient safety.

Reference

United States Pharmacopeial Convention. (2024). <71> Sterility tests. In United States Pharmacopeia. https://www.usp.org/harmonization-standards/pdg/general-methods/sterility-test International Organization for Standardization. (2019). ISO 11737-2:2019 Sterilization of health care products — Microbiological methods — Part 2: Tests of sterility performed in the definition, validation and maintenance of a sterilization process (3rd ed.). ISO.