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Article Title:
==============

Options for Container and Closure Systems Sterility Testing

Article Description:
====================

While sterility testing can be cumbersome and time consuming,
there are FDA-approved options regarding container and closure
system integrity testing. In fact, the Food and Drug
Administration (FDA) recently released a guidance document on
container and closure system integrity testing in lieu of
sterility testing as a component of the Stability Protocol for
Sterile Products. The document offers an alternative approach, if
the approach satisfies the requirements of the applicable
statutes and regulations.


Additional Article Information:
===============================

656 Words; formatted to 65 Characters per Line
Distribution Date and Time: 2008-04-01 11:48:00

Written By:     Norm Howe
Copyright:      2008
Contact Email:  mailto:[EMAIL PROTECTED]



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Options for Container and Closure Systems Sterility Testing
Copyright (c) 2008 Norm Howe
Validation and Compliance Institute
http://www.vcillc.com



While sterility testing can be cumbersome and time consuming,
there are FDA-approved options regarding container and closure
system integrity testing. In fact, the Food and Drug
Administration (FDA) recently released a guidance document on
container and closure system integrity testing in lieu of
sterility testing as a component of the Stability Protocol for
Sterile Products. The document offers an alternative approach, if
the approach satisfies the requirements of the applicable
statutes and regulations.

Aimed at manufacturers, the guidance offers alternative testing
methods other than sterility testing to confirm container and
closure system integrity as a part of the stability protocol for
sterile biological products, human and animal drugs, and medical
devices.

The purpose of stability testing is to provide evidence on how
the quality of a substance or product varies with time under the
influence of a variety of environmental factors such as
temperature, humidity and light. Products labeled as sterile are
expected to be free from viable microbial contamination
throughout the product's entire shelf life or dating period.
This enables manufacturers to establish or modify recommended
storage conditions, retest periods and shelf life or dating
period, as the case may be.

Currently, manufacturers of drugs and biologics purporting to be
sterile are required to test each batch or lot, to ensure that
the product in question conforms to sterility requirements. They
must also maintain a written testing program designed to assess
stability characteristics and meet stability testing
requirements.

Manufacturers of medical devices are required to validate
processes, including sterilization, for a device purporting to be
sterile, although stability testing should be part of the design
validation of such devices. Also, in vitro diagnostic products
for human use are required to be labeled with stability
information.

The minimum sterility testing generally performed as a component
of the stability protocol for sterile products is at the initial
time point (release) and final testing interval (i.e.,
expiration). Additional testing is often performed at appropriate
intervals within this time period (e.g., annually).

Alternatives to sterility testing as part of the stability
protocol, such as replacing the sterility test with container and
closure system integrity testing, might include any properly
validated physical or chemical container and closure system
integrity test (e.g., bubble tests, pressure/vacuum decay, trace
gas permeation/leak tests, dye penetration tests, seal force or
electrical conductivity and capacitance tests, etc.), or
microbiological container and closure system integrity tests
(e.g., microbial challenge or immersion tests).

Such tests may be more useful than sterility testing in
demonstrating the potential for product contamination over the
product's shelf life or dating period. The advantages of using
such container and closure system integrity tests in lieu of
sterility tests in the stability protocol for sterile products
include: detecting a breach of the container and/or closure
system prior to product contamination; conserving samples that
may be used for other stability tests; requiring less time than
sterility test methods which require at least seven days
incubation; and reducing false positive results with some
alternative test methods when compared to sterility tests.

To implement container and closure system integrity testing as an
alternative to sterility testing, the FDA recommends
manufacturers consider the following: a container and closure
system integrity test may replace sterility testing in a
stability program at time points other than the product sterility
test prior to release; container and closure system integrity
tests do not replace sterility testing methods for product
sterility testing prior to release; any validated container and
closure system integrity test method should be acceptable
provided the method uses analytical detection techniques
appropriate to the method and is compatible with the specific
product being tested.

The guidance document, as well as alternative testing options,
can be difficult to understand. For more about the content of the
guidance, contact CBER's Office of Compliance and Biologics
Quality at 301-827-3031; CDER's Office of Pharmaceutical Science
at 301-796-1228; CDRH's Office of Device Evaluation at
240-276-3747; or CVM's Office of New Animal Drug Evaluation at
301-827-6963. 




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Norm Howe, Senior Partner at Validation and Compliance Institute, 
consultants for the pharmaceutical and medical device industries.
He got his BS at UC, Berkeley, and a Ph.D. in chemistry at UCLA. 
He has held many management positions in FDA regulated industries, 
most at BASF. http://www.vcillc.com


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