Aseptic processing is considered by many in this industry to be among the more difficult activities to execute properly. The number of variables that affect the safety of sterile products manufactured aseptically is substantial. In the design and operation of an aseptic production facility, it is essential that risk to the patient be minimized. This article presents a new approach to risk assessment for aseptic processing that emphasizes the contributions of personnel.
Keywords: aseptic processing, risk analysis methods, sterile manufacturing, validation, aseptic filling,
lyophilizatio, decontamination, isolation, microbial contamination.
In September of 2004, FDA issued a number of guidance documents and regulatory initiatives. Among the guidance documents made available was the long awaited guidance on Sterile Drug Products Produced by Aseptic Processing At essentially the same time, FDA also published “Pharmaceutical CGMPS for the 21st Century – A Risk-Based Approach”. Each of these documents makes reference to the other, but there is no substantive information offered in either to assist the practitioner in establishing a true risk-based approach for the design, and control of contemporary aseptic processing operations.
Numerous, pre-existing risk analysis methods have been adapted for use in the pharmaceutical industry including:
- Fault Tree Analysis – FTA
- Failure Mode and Effect Analysis – FMEA
- Hazard Analysis and Critical Control Point – HACCP
- Hazard and Operational Studies – HAZOP
- Failure Mode, Effect and Criticality Analysis – FMECA – adds “criticality” to FMEA
These methods have proven to be successful in a variety of applications; however, none was ever specifically intended for application with aseptic processing, which relies of a large number of variables and has the least tolerance for failure of any process in the entire industry. Simply put, failure in aseptic processing is unacceptable and a suitable risk analysis method must incorporate all of the myriad factors impacting product sterility, and thus patient safety. The risk analysis approach utilized must be compatible with the recognition that there is no
acceptable level of risk associated with sterile products, regardless of the method of manufacturing. The goal is, and must always be, perfection in all elements of sterile product manufacture, even where they are made using an aseptic process.iii With this in mind we embarked on an evaluation of prior risk evaluation methods models applied to aseptic processing.