Aseptic/Sterile Processing

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Before formal cleaning validation programs were instituted, visual inspection was the primary means of determining equipment cleanliness. The use of visual inspection is still typically a component of a cleaning validation program and for routine inspections of cleaning effectiveness, but the use of visual inspection as a sole criterion for equipment cleanliness has not been successfully implemented as a valid approach for cleaning validation.

This article summarizes changes to the Akers–Agalloco aseptic processing risk analysis model (first presented in Pharmaceutical Technology's November 2005 issue) as well as some of the underlying thinking behind the revision. The simplified model makes the method easier to use because of its greater flexibility of environmental control practice. It maintains the emphasis on human activity as the primary consideration in risk management for aseptic processing.

Any aseptic processing technology that allows intervention by gowned personnel during operation cannot be considered an advanced technology. Although a standardized definition of restricted access barrier systems has been developed, these systems fall well short of being classfied as advanced technologies.

The author explores the importance of the proposals to revise Annex 1 of the EU GMPs in the context of the desire for science-based, internationally respected GMPs. Commentary also is provided about the relationship between this annex and CEN–ISO cleanroom standards.

Model organisms are useful when validating sterile filtration, but successful retention of the model organism does not always guarantee that effluent is sterile. The authors explore the various factors that influence sterile filtration.

Calculations show the predicted contamination levels in cleanrooms with turbulent mixing air and with vertical unidirectional airflow when people are dressed in modern cleanroom clothing systems. Comparisons are made between operation theatres and cleanrooms.

The industry has acknowledged only recently the significance of the contamination risk posed by humans. The authors assert that this realization, together with technological advances, will lead to the elimination of human intervention and, hence, improved sterility.

There are few, if any, valid reasons not to install an isolator in a new aseptic processing facility.

Performing D-value and population verification is critical in the acceptance criteria for allowing a new lot of biological indicators into a facility before acceptance and use of the lot in validation work or routine monitoring of sterilization cycles.

Cell-culture technology and financial incentives give influenza vaccine makers a much-needed shot in the arm, but many downstream processing issues remain unaddressed.

Adding a cleaning step to the field-testing protocol, and combining it with the data generated to register sanitizing and disinfectant agents under FIFRA and the CEN TC 216 work program, produces a sanitation-and-disinfection validation methodology that is cost-effective, simple, and time-saving.

Analytical tools and methods that require less water and detergent are gaining interest for faster, more efficient cleaning.

The authors encourage the investigation into whether the occurrence of grow-through and the diminution in the size of certain organisms when in contact with given liquids are the same phenomenon manifested under different circumstances.

Because of the growing popularity of single-use materials, the identification, characterization, and qualification of new materials used for disposable processes have become increasingly important for both regulatory and production purposes. This article describes one approach to identifying and validating the materials used in a disposable filling process.

Clean rooms are areas in which it is essential that microorganisms are not allowed to proliferate because they could contaminate pharmaceuticals and directly affect human health.

The authors present a new approach to risk assessment for aseptic processing that emphasizes the contributions of personnel.

The authors focus on the effects of cellulosic materials during the performance qualification validation of a transfer barrier isolator used for the purpose of sterility testing.

Formulation residue, observer viewing distance, light intensity, viewing angle, observer viewing position, and observer-to-observer variability affect the ability to confirm the cleanliness of manufacturing equipment.

Formulation residue, observer viewing distance, light intensity, viewing angle, observer viewing position, and observer-to-observer variability affect the ability to confirm the cleanliness of manufacturing equipment.

This article provides an overview of the important factors associated with air handling systems within pharmaceutical and biopharmaceutical facilities. It provides information on the need for these systems, design considerations and advice on the approach to commissioning and qualification.

Possible cross-contamination issues should be eliminated at the early stage of the project. The project sponsor should ensure that all relevant personnel from the production, quality control, logistics, and maintenance departments, as well as engineering, are involved in the conceptual stages of a design.

New technologies and improvements to existing ones can reduce contamination risk in aseptic processing.

A ready-to-fill closed vial can improve aseptic filling quality and reduce process complexity.

The complete elimination of human-derived contamination is possible only with the elimination of human intervention.

The appropriate barrier system should be selected using a logical, risk-based approach, with awareness of all the possible sources of contamination.

Study results show that the state of a cleanroom clothing system–new or much used–influences the protection efficacy of the system.

The validation of alternative microbiological testing is an opportunity for a manufacturer to decrease the amount of time required for laboratory results.To properly validate these alternatives, a practitioner must first identify what is being studied. The regulatory effect on established product and process specifications and levels must be completely evaluated, as changing the method of analysis may well change the pparent number in the sample.

The sterility testing of samples from an aseptic process may be considered an entirely separate aseptic process that is subject to the same types of adventitious contamination as the aseptic process itself.

An increasing number of new compounds are being introduced into pharmaceutical pilot plants.The knowledge base for these compounds regarding their toxicities,physical handling, and cleaning is limited.The authors examine various approaches for addressing the cleaning validation of new compounds and discuss the role of determining appropriate visible residue limits.