Aseptic Processing involves risk assessment on an on-going basis
because of the inherent risks due to consequences of management and
process failure and challenges within the detection, isolation, control,
and management of product contamination. Within aseptic processing,
the severity of the consequences of a failure can be severe to the end
user while detection through sterility testing remains rather limited
because of the small number of final products tested.
The FDA and EMA require that any product that may be terminally
sterilized be managed in that fashion. However, almost all large
molecules and some small molecules can only be sterilized by aseptic
processes, i.e., membrane filtration.
With membrane filtration, it is essential to establish acceptable
levels of microbiological contamination to ensure both product safety
and compliance. Meeting sterility claims for Phase 1, 2, 3 and
commercial products in a timely and effective manner is important in
avoiding costly delays. In addition, since aseptic processes are
associated with endotoxin control, it too, must be managed to acceptable
levels.
A variety of variables can impact sterility assurance and the
accompanying endotoxin level. These include the personnel, process,
equipment, components, sterilization, depyrogenation as well as
facilitates and utilities that impact the management and processing of
the ultimate products. Issues that need to be considered include the
monitoring of environmental areas and personnel, water sources, media,
and media fills, gowning and sanitization.
Products that have historically been aseptically filled have relied
upon the use of USP <71> Sterility Tests to demonstrate sterility.
However, since no more than 20 containers are tested per media (TSB
and FTM) regardless of the production lot size, the use of sterility
tests does not provide a high degree of sterility assurance (SAL). Thus,
media fills are now utilized to simulate the actual fills and to
demonstrate at least a 10-3 sterility assurance level of no
contamination. If the facility uses RABS or isolators to meet their
filling requirements, a SAL of 10-5 to 10-6 is possible since the
interactions with personnel and the environment decrease markedly.
Media fills are required during the commissioning of an aseptic
operation within a new facility, when a new container configuration
(volume or neck size) or other unique activities associated with aseptic
filling occur. Following the on-going performance of a new aseptic
filling line, a requalification is required at six-month intervals.
The objective of this live, interactive training seminar is to
explore the role of aseptic filling to assure that manufactured product
will retain the sterility assurance level prescribed by GMPs. It will
review the issues regarding preparing media and setting up the
“filtration train”, environmental monitoring, interruptions that may
occur during the operation of the Clean Room (planned and unplanned) and
the cleaning of the room and its equipment. Equipment used to monitor
the equipment and personnel will also be reviewed along with gowning
issues that periodically arise. The seminar will also discuss media
failures and how to “work through” them. Because of the sensitivity and
importance of media fills, this live, interactive training seminar is a
MUST for anyone in your organization that is involved in aseptic
filling in general and media fills in particular. Please plan to attend
this as part of an interactive group project.
Learning Objectives:
Seminar participants will learn the following:
- Gain an understanding of the fundamental principles and skills
necessary to conduct Aseptic Processing of Sterile Drug Products with
minimum risk
- Analyze issues impacting Aseptic Processing to include the environment, personnel, gowning and sanitization
- Acquire the skills necessary to control the process environment
- Minimize media fill failures to permit production throughput
- Determine how to develop media fill simulations to include the "worst case" scenarios
- Learn best practice techniques for determining media fill sizes
- Understand the "critical factors" required to maintain compliance
- Decrease inspectional observations
- Avoid Warning Letters and Consent Decrees
Who will Benefit:
- Aseptic Processing
- Manufacturing
- Quality Control
- Quality Assurance
- Regulatory Compliance
- Microbiology
- Validation
- Project Management