Aseptic/Sterile Processing

A discussion of the validation and operation of two commercially available vapor-phase hydrogen peroxide decontamination systems is presented, based on a hands-on examination of both systems.

Evaluations have shown, in most cases, visual observations are sensitive enough to verify equipment cleanliness. An experiment was conducted to explore the possibility of using a visible-residue limit as an acceptable cleaning limit in a pharmaceutical research facility, including an evaluation of the limits and subjectivity of ?visually clean? equipment.

This article discusses the basics of sterile filter qualification and validation, with emphasis on bacterial challenge protocol development and testing. Reference is made to Technical Report no. 26 of the Parenteral Drug Association.

Single-use products enhance sterile filtration by making it easier to maintain sterility and reduce cross-contamination risks.

The authors suggest a design strategy for an aseptic process simulation that focuses on the basic repeating unit of the process, establishing alert and action criteria for the unit itself, and using worst-case simulations to establish routine operational parameters for the manufacturing process.

The authors examine the VHP resistance of microbial isolates recovered from controlled environments and compared them with commercially available biological indicators under various test conditions.

The limitation-of-risks (LR) method can be used as an engineering tool in risk assessment work for the identification, minimization, and evaluation of potential airborne risks, and for the identification of adequate monitoring points.

The role of microbial testing to ensure the sterility of aseptically filled sterile products is explained, from the product development phase to in-process monitoring to finished product testing.

The article describes the basic principles of blow-fill-seal (BFS) technology together with the advantages it offers. Although BFS technology is an ideal process for aseptic filling of liquid pharmaceutical products there is still a risk of contaminating the product inside the filling area. This, together with regulatory requirements for the microbiological control of critical areas in pharmaceutical production, makes microbiological monitoring a necessity.

Total organic carbon (TOC) analysis is a fast and effective analytical technique for cleaning validation. Understanding the various types of TOC technologies is essential for choosing the best solution.

FDA's draft guidance on aseptic processing contains some inherent difficulties, including unrealistic expectations of sterility and microbial quantification, an absence of harmonization with international rules, and failure to support new technologies or a risk-based approach. The authors propose a science-based alternative.

In spite of regulatory uncertainties, the industry continues to develop improved aseptic processing technologies.

Current microbiological methods cannot measure microbial contamination at the levels that engineers and regulators seek to establish for aseptic processing cleanrooms. New approaches for assessing data and establishing alert and action levels are advocated, and an example of one analytical tool is considered.

Hydrogen peroxide has become the compound of choice for gaseous biodecontamination in the pharmaceutical industry. As some processes operate at vapour concentrations below the dew point, to avoid condensation, and others actually form dew, it is important to understand the relationship between the vapours and to have a method of establishing the dew point.

FDA's aseptic processing draft guidance and the industry's state-of-the-art isolator technologies prepare manufacturers for the next generation of contamination control solutions.

Organic solvents are frequently used in the manufacture of active pharmaceutical ingredients. They have, therefore, normally also been used for process cleaning. However, a number of factors have encouraged the industry to change from solvent-based to aqueous cleaning. This article considers current cleaning practices, related issues and the author's experience of switching from one cleaning method to another.

Isolator technology can be used in clinical product formulation and filling facilities to ensure environmental control and reduce contamination risk in aseptic processing.

When planning the installation of a new stainless steel process pipeline, it is important to understand the significance of using the best possible materials and techniques to ensure it is clean when installed. This article examines the factors that must be considered when planning and constructing a new process line.

The influence of containment classification in facility design cannot be underestimated. It can, for example, determine the extent of the design process and the level of equipment needed to safeguard human life and the surrounding environment. This article discusses factors that should be considered when planning such a containment facility, including material flow, process equipment and regulatory guidelines.

Testing sterilizing grade filters using integrity testers has become a standard method in biopharmaceutical production and quality assurance. In accordance with international regulations and recommendations, these filters should be tested before and after filtration. For these applications, a variety of automatic integrity testers is available. Currently, there are two groups of devices that are used to conduct validated testing procedures, such as the bubble point test, the diffusion test, and the water intrusion test (WIT) and water flow test (WFT). Whereas one group of devices relies on the principle of flow measurement, the other group is based on pressure drop measurements. The following report compares the accuracy of the two test methods, using the WFT as a reference.

In the pharmaceutical and biotechnology sectors, the clean room business is flourishing. Accounting for approximately 25% of the world's clean room expenditure, Europe's drug manufacturing industry is using these facilities to produce an increasing amount of biologics and biopharmaceuticals, and meet the strict legislative requirements for aseptic processing. This article reviews the current and future state of the market for clean rooms in Europe and comments on their applications.

Closed and disposable sterility testing devices reduce the risk of false positive results during sterility testing. To further prevent such results, some pharmaceutical manufacturers use the device inside a sterility testing isolator, which is decontaminated using sterilant gases or vapours. In this study, closed, disposable sterility test devices were exposed to two 90 minute vaporous phase hydrogen peroxide (VPHP) decontamination cycles within a sterility testing isolator and tested for device integrity, bacteriostasis/fungistasis and non-volatile residue content. The results showed that the VPHP used to decontaminate the isolator before sterility testing did not affect the device.

A limit test using ion mobility spectrometry (IMS) has the potential to dramatically reduce the time required for cleaning verification and cleaning method development. The traditional approach to cleaning verification, often using HPLC, is relatively resource intensive and can lead to significant delays in reporting results. The main advantage of IMS is that results are seen virtually instantaneously, so any necessary re-measurement can be done very quickly. If the results demonstrate cleanliness, production can resume in a matter of hours not days.

When FDA reviewed PDA's Technical Report No. 34 about isolator systems, significant differences of opinion between the organizations came to light.