Regulatory Focus™ > News Articles > New Biologic Sterility Regulation Issued by FDA

New Biologic Sterility Regulation Issued by FDA

Posted 02 May 2012 | By Alexander Gaffney, RAC 

The US Food and Drug Administration (FDA) is announcing its amendment of existing sterility test requirements for biological products, which it said will provide greater flexibility for manufacturers and encourage the use of cutting-edge technologies to assure the safety of biological products.

In its 2 May Federal Register posting entitled Amendments to Sterility Test Requirements for Biological Products, FDA said its rule is "intended to promote improvement and innovation in the development of sterility test methods by allowing manufacturers the flexibility needed for sterility testing of some novel products that may be introduced to the market, enhancing sterility testing of currently approved products, and encouraging manufacturers to utilize scientific and technological advances in sterility test methods as they become available."

FDA notes that while absolute sterility is unable to be demonstrated without the destruction of an entire lot, manufacturers will have the responsibility to assure their products are free from "viable contaminating microorganisms" to ensure their product's safety.

FDA's updated rule is the first amendment to biologic sterility testing requirements since 1995, when it adopted the US Pharmacopoeia's (USP) procedures for membrane filtration testing.

Because of the length of time between the last guidance and the present rule, FDA acknowledges that "advances in technology in recent years have allowed the development of new sterility test methods that yield accurate and reliable test results in less time and with less operator intervention than the currently prescribed methods."

As a nod to these technological advancements-and likely to avoid the promulgation of regulations that would be almost instantly outdated-FDA's new final rule on sterility requirements eliminated specific requirements for most products, and instead moves towards a system in which manufacturers can adopt product-specific and appropriate testing procedures.

Manufacturers will be required to "establish, implement, and follow written procedures for sterility testing that describe, at a minimum, the test method used, the method of sampling, and the written specifications for acceptance or rejection of each lot," wrote FDA in its Federal Register posting.

The final rule promulgated by FDA also:

  • Eliminates specified sterility test methods, culture media formulae (or formulation), and culture media test requirements.
  • Eliminates specified membrane filtration procedure requirements for certain products.
  • Eliminates specified sterility test requirements for most bulk material.
  • Modifies the repeat sterility test requirements, so that repeat tests will occur only once for each lot.  These repeat tests are limited to situations when the quality control unit conclusively determines, after conducting an investigation upon detection of viable microbial contamination during the initial test of the lot, that the contamination is the result of laboratory error or faulty materials used in conducting the sterility test.
  • Replaces the storage and maintenance requirements for cultures of test organisms used to determine the "growth-promoting qualities" of culture media with: (1) Validation requirements specifying that any sterility test used is able to consistently detect the presence of viable contaminating microorganisms and (2) verification of "growth-promoting properties" or microorganism-detection capabilities of test and test components.
  • Replaces the sample size or amount requirement with a requirement that the sample be appropriate to the material being tested.
  • Replaces the Interpretation of test results section under § 610.12(c) with a requirement that manufacturers establish, implement, and follow written procedures for sterility testing that describe, at a minimum, the test method used, the method of sampling, and the written specifications for acceptance or rejection of each lot.
  • Simplifies and clarifies the Exceptions section under § 610.12(h); and identifies the Director of CDER as one of the two Center directors authorized to grant an exemption under the exception provision at § 610.12(h)(2).  In the proposed rule, the Center for Devices and Radiological Health was erroneously identified in this exception, instead of the Center for Drug Evaluation and Research.
  • Revises the definition of the term "sterility" under § 600.3(q); and eliminates certain exceptions for allergenic products related to sterility testing under § 680.3(c).


Read more:

FDA - Amendments to Sterility Test Requirements for Biological Products

FDA Voice - Enabling Innovation for Biological Product Safety


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