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For many years, the pharmaceutical industry has been waiting for the new
FDA "Guideline On Sterile Drug Products Produced By Aseptic
Processing." In the meantime, a non-authorised version has been
circulating through the pharmaceutical industry since 1998.
At the end of September 2002, FDA finally published an official
Preliminary Concept Paper with the title "Sterile Drug Products Produced By Aseptic
Processing" as Draft for commenting by the industry.
The document is subdivided into 12 chapters:
- Introduction
- Background
- Scope
- Buildings and Facilities
- Personnel Training, Qualification, & Monitoring
- Components and Containers/Closures
- Endotoxin Control
- Time Limitations
- Process Validation and Equipment Qualification
- Laboratory Controls
- Sterility Testing
- Batch Record Review: Process Control Documentation
In addition, at the end of the document you will find the 3 appendices:
- Aseptic Processing Isolators
- Blow-Fill-Seal Technology
- Processing Prior To Filling/Sealing Operations
as well as the points References, Relevant Guidance Documents and Draft
Glossary.
On the whole, one can say that - in comparison with the current
Guideline - FDA has included topical subjects as well as much-discussed
topics of aseptic production. The main chapters of the Guideline are "Process Validation"
and "Laboratory Controls" with the subchapter "Environmental Monitoring."
Besides, the isolator and blow-fill-seal technologies have found their way
into the Guideline.
As an example, here some notes on "Environmental Monitoring."
On the whole, the environmental monitoring programme is assigned a central
role. Monitoring data are meant to serve both as quality information on
the batch and as trend data for the production environment.
The chapter is subdivided into the 4 subchapters:
- General Written Programme
- Establishing Limits and a Trending Programme
- Sanitisation Efficacy
- Monitoring Methods
The "General Written Program" regulates the points: sampling
location,
frequency of sampling,
when the samples are taken,
duration
of sampling,
sample size, specific
sampling equipment and techniques,
alert and
action limits, appropriate
response to deviations from alert or action limits.
As to the limits and trending programme, importance is given to
the individual results. The calculation of mean values is considered as
critical. Trending is to be divided into near-term and long-term trends.
Whenever a result is at the alert or action limit, measures have to be
taken. In case atypical microorganisms (which ones?) are detected, further
investigations have to be conducted. The responsible managers have to be
informed regularly about trends and investigations.
As regards sanitisation efficacy, the document requires that the
sporicidal efficacy of disinfectants is proved and that these agents are
applied regularly. Another requirement is that sanitisation efficacy is
proved regularly within the framework of the monitoring programme.
Under "Monitoring Methods" you can find surface monitoring as
well as active and passive air monitoring. The efficacy of passive
monitoring by means of petri dishes has to be proved (effect of the
desiccation of the plates on the recovery rate of microorganisms).
Surely, some of the requirements, especially in the chapter
"Environmental Monitoring", may (by far) overshoot the mark and
give rise to uncertainty. This is one of the reasons why the
pharmaceutical industry should take this Draft seriously and seize the
opportunity to make contributions to the incipient discussion.
CONCEPT HEIDELBERG and well-known European speakers present the Draft Guideline "Sterile Drug Products Produced by
Aseptic Processing" to the participants of the European
Aseptic Conference 2002, taking place in Barcelona, Spain, on
26-27 November, and offer a forum for discussing the presented
requirements to interested persons from pharmaceutical industry and
supplier firms at the event.
Author:
Dr Andreas Mangel
CONCEPT HEIDELBERG
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