Originally Published PMPN November
2004
Regulatory Focus
FDA Publishes New
Guidance on Aseptic Processing
The document
contains new sections on blow-fill-seal technology.
Ben
Van Houten
Senior Editor
FDA has published a long-awaited aseptic processing guidance that includes
new sections on personnel, isolator technology, blow-fill-seal processes, and
rapid-test methods for identifying microbes. The finished guidance explains
FDA’s current thinking on sterile drugs produced by aseptic processing
in the context of current good manufacturing practice (CGMP) regulations for
drug and biological products.
“Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing—Current
Good Manufacturing Practice,” was originally issued for public comment
in September 2003. Since then, FDA has received more than 60 letters and electronic
submissions in response to the draft. That draft was an update of the original
aseptic processing guidance issued in 1987.
The guidance’s goal, according to FDA, is to provide clear and consistent
communication of regulatory expectations to promote voluntary compliance. The
Office of Compliance in FDA’s Center for Drug Evaluation and Research (CDER)
led the guidance revisions. The finished guidance is officially a joint document
from CDER, the Center for Biologics Evaluation and Research, and the Office
of Regulatory Affairs.
The major issue in the revised guidance is the enhanced requirement for media
fills in process simulation. As a result, the document now puts more emphasis
on worst-case conditions, such as conducting media fills with operators who
are fatigued, rather than at the beginning of a shift. Since science has evolved
since the 1987 guidance, the new version contains the new technology topics.
In the introduction, the guidance states, “Clarifying relevant regulatory
standards for sterile drug products will help reduce the incidence of manufacturing
problems with this class of pharmaceuticals, thus facilitating the ready availability
of these therapeutically significant pharmaceuticals and avoiding drug shortages.”
It also says, “It is critical that containers be filled and sealed in an
extremely high quality environment.”
One of the features of the guidance is a new appendix devoted to blow-fill-seal
(BFS) technology and its critical control points. For example, the guidance
recommends that BFS machinery and its surrounding barriers should be designed
to prevent the potential for extraneous contamination. In addition, a validated
steam-in-place cycle or equivalent process should be used to sterilize the equipment
path through which the product is conveyed.
The guidance also notes that the classified environment surrounding blow-fill-seal
machinery should generally meet Class 100,000 (ISO 8) or better, depending on
the design. HEPA-filtered or sterile air provided by membrane filters should
also be used during the steps when sterile products or materials are exposed.
Air in the critical area should meet Class 100 (ISO 5) microbiological standards
during operations. Finally, a well-designed system should achieve Class 100
(ISO 5) airborne particle levels.
There are new sections on validation and qualification and a section on batch
monitoring and control. “Equipment sterilization, media fills, polymer
extrusion, product-plastic compatibility, forming and sealing integrity, and
unit weight variation are key issues,” according to the guidance.
The guidance also contains a new appendix on processing prior to filling and
sealing operations. This appendix covers aseptic processing from early manufacturing
steps onward. In addition, a new appendix is included that covers containers
and closures. Topics in this chapter include presterilizing glass containers,
subjecting glass containers to dry heat, sterilizing of plastic containers,
cleaning rubber closures, and inspecting container closure systems.
Copyright ©2004
Pharmaceutical & Medical Packaging News
