Abstract In this penultimate section the development of the ‘sterilisation’ of isolators used for sterility testing and aseptic processing will be reviewed. This will include the chemical agents used, the equipment to deliver and remove that agent (in a gaseous form), as well as agents used for manual wet processes and also fogging techniques with associated […]
Abstract The discussion in this part of the history of isolator and containment technology reviews the development and use of various devices that permit the aseptic transfer of components such as sterile vials, syringes, bottles and other types of container as well as the actual product itself into and out of the aseptic filling area […]
Abstract This third paper on the history of isolators describes the development and use of non-flexible film isolators including restricted access barrier systems (RABS). By non-flexible is meant that type of unit that has a metal or a rigid plastic structure. These are referred to as conventional isolators. Many of these models have been designed […]
Abstract This is the second of five papers that will describe the history and development of isolator and containment technology in the fields of research, medicine and pharmaceutical applications. The paper commences with the development of flexible film isolators based on designs similar to Trexler’s later models and the expansion of the use of such […]
Abstract Aseptic transfer is a critical contamination control issue, carried out over a series of stages. If any stage is performed in an uncontrolled manner then microbial contamination of a product can occur. Contamination risks can arise from a number of sources, including incoming materials, air and personnel. To address these risks appropriate controls include […]
Abstract This final section is devoted to the development of various validation methods conforming to GMP when applied to isolators and also a review of the methods in relation to validating the processes used in preparing for aseptic processing and sterility testing. There are brief comments on what the regulators expect.
Abstract The rate of deposition of airborne particles determines the risk of product contamination and demonstrates the operational quality of a cleanroom. The particle deposition rate at a particular location and time depends on the deposition velocity and the concentration of articles. The concentration of particles larger than 10 μm cannot be measured easily; therefore […]
This article traces the history of hydrogen peroxide vapour as used for sanitising pharmaceutical isolators and similar volumes. From an early puzzle as to how the vapour could be so effective in deactivating resistant test organisms, the author moves forward through his own career to develop a clearer comprehension of the hydrogen peroxide vapour process. […]
Jim Agalloco, Russ Madsen and Jim Akers developed a comprehensive set of comments to the draft revision of Annex 1. The authors believe it is essential that the EMA receive comments that outline the difficulties that the draft presents. Their more than 170 comments cover the entire document and detail its many shortcomings. Feel free […]
This article considers some of the risk considerations that need to be accounted for when replacing a steam sterilization autoclave within a pharmaceutical processing facility. In outlining the key risk considerations, the article adopts a risk assessment approach – Failure Modes and Effects Analysis (FMEA).
The nutritional quality of the products as well as microbiological and sensory quality are essential factors in the food industry. The thermal processing of canned food is the most important step in the canning procedure. Currently, a large quantity of canned goods is rejected during production and has to be destroyed or reprocessed due to […]
The transient overheat in empty autoclave chambers is a phenomenon that frequently occurs during validation studies. This article by Italian sterilization practitioner Vittorio Mascherpa investigates the main causes of it and suggests some methods to prevent it or to cope with it. The article also includes a useful table of superheating effects due to adiabatic […]
This paper summarizes the concept of F0 and its related parameters (D, z). Essential notions on sterilization kinetics are explained. The idea of physical and biological “equivalent time” is presented and its application in moist-heat sterilization processes is discussed.
Presentation Importance of Sterilization Processes Current Best Practices Sterilization processes and approaches that everyone, including regulators can agree on. Expected Future Developments Current processes with a modest twist. These may create some angst. Thinking outside the current box that might be a part of our future.
Sterilization is a critical process in the pharmaceutical industry for the control of microbial populations. While most prevalent in the manufacture of sterile products it can be used in a variety of settings where microbes have potential impact on patients or products. Sterilization really isn’t that difficult, but inattention to science through excess criteria and […]
Book chapter – Steam Sterilization: A Practitioner’s Guide (Ch.23) Chapter summary BACKGROUND STABILITY TESTING REQUIREMENTS – Maximum Fo – Methods to Reduce Thermal Degradation of Product – Change in Sterilization Process – Presterilization of Some Components or Difficult-to-Sterilize Areas of the Product – Changes in the Sterilization Model Utilized – Aseptically Filling the Product […]
Book chapter – Steam Sterilization: A Practitioner’s Guide (Ch.11) Summary – How Does One Determine Whether the Product Withstands a Thermal Process That Is Encountered in Moist Heat Sterilization? – Expectations of Regulatory Agencies Concerning Sterilization of the Solution and Cycle Selection on the Basis of Solution Selection—Development Studies That Need to Be Conducted – […]
This short article is an introduction to the basic selection of sterilization autoclaves. It defines this type of equipment, summarizes the varieties available and discuss the preliminary problems to cope with in specification and design of sterilization autoclaves.
Several reports on degradation of Hyaluronic Acid (HA) involving microwaves, UV or γ-rays have been published. Rheological studies also show that Hyaluronic Acid (HA) solutions degrade at high temperature: viscosity of the solutions decreases in time as a function of temperature. Therefore, the thermal sterilization treatment of Hyaluronic Acid (HA) solutions represents a great challenge. […]
Prefilled syringes offer several advantages over traditional packaging in vials. For example, microbial contamination is minimized due to less manipulation.This presentation discusses a method for sterilizing PFSs through a moist heat process, the most common and approved method used by pharmaceutical facilities for this type of products. The main issues to consider while sterilizing PFSs […]
This article is a technical support to the practice of autoclaving aqueous solutions in sealed containers. Two “classical” scientific contributions on the matter are due to Beck and to M. A. Joyce & J. W. Lorenz which are referred in the article. In this article, metric units (abs bar or abs mbar) are used for […]
This article provides basic information on the sterilization of blood bags systems by moist-heat. Problems of pressure compensation and steam penetration into the system parts without water inside, and the process choice between single and double autoclaving are discussed.
This article is intended as a basic introduction on feasibility and risks of autoclaving aqueous solutions in sealed containers. Another article, Aqueous solutions in sealed containers: internal pressure under autoclaving, provides a technical approach to the matter. The feasibility and the level of risk of autoclaving sealed containers of liquid solutions under pure saturated steam […]
The purpose of this Fedegari Technical Note, firstly distributed in 1988 and perseveringly revised, is to clarify the nature of F0 and its related parameters (D, z, PNSU/SAL), and to explain their use and limits for the setting, adjustment, control and validation of moist-heat sterilization processes. The F0 algorithm was first introduced in 1968 in […]
Presentation overview – A balance must be achieved between the need to maintain a safe, stable and efficacious product while providing sufficient lethality to attain a minimum level of sterility assurance •No sterilization method should be considered exempt •Sterilizing processes should be a compromise between the degradation effect on the materials and destruction of microorganisms […]
Book chapter – Steam Sterilization: A Practitioner’s Guide (Ch.01) Chapter summary WHAT DO WE MEAN BY MOIST HEAT STERILIZATION? COMPARISON OF MICROBIAL SENSITIVITY MECHANISMS OF INACTIVATION – Vegetative Cells – Bacterial Spores -Bacterial Spores Defined -Spore Characteristics – Spore Formation – Mineralization – The Transition from Spore to Vegetative Cell – Thermal Injury to Spores […]
Presentation Overview – Terminal Sterilization Fundamentals ■ Steam ■ Radiation ■ Current Best Practices ■ TS processes and approaches that everyone, including regulators can agree on ■ Current processes with a modest twist. Those may that create will likely create some angst ■ Expected Future Developments ■ Thinking outside the current box that might be […]
Steam sterilization kinetics is the base for a correct understanding of industrial practice of moist heat sterilization, but is a too often neglected topic. This article by the well known Italian sterilization practitioner Dario Pistolesi and his former assistant Vittorio Mascherpa provides a simple but rigorous introduction to it.
Many aspects need to be considered in setting up a cleaning procedure. This is certainly a mul-tidisciplinary issue that involves various company areas: from “Regulations” to Engineering, from Quality Control lab to Production department. Contributions of all these areas together can lead to a robust and re-producible cleaning process.
An increasing interest in continued process verification has brought to the spread of on-line assay methods in cleaning processes . This paper deals with two different on-line applications: conductivity sampling and the Total Organic Carbon analysis for washing machines.
A case study of hydrogen peroxide penetration through the load packaging: a customer required support for «A Package Integrity Verification» which involved all the samples and consumables inside the Sterility Test Isolator.
This article compares the concepts of sterilization, disinfection and decontamination with reference to the different scopes thereof. Decontamination by hydrogen peroxide vapor and its use for conditioning the Sterility Test Isolators are discussed. A technologically new method for the vaporization of the hydrogen peroxide and its dosage control is presented.
This article discusses the challenge of the unexpected growth of a positive biological indicator in a chemical decontamination cycle. Specific features to be considered regarding biological indicators used for the validation of decontamination cycles are presented. Some practical solutions are suggested to avoid the risks related to false positives.
Material transfer to sterile suite issue and available technologies; Surface bio-decontamination drivers; QbD and risk assessment and mitigation overview; Surface chemical bio-decontamination cycle; Cycle validation approach;
PART 1 This is the first of five papers that will describe the history and development of containment technology in the field of research, medicine and pharmaceutical applications. The paper commences with the development of containment for various purposes but essentially for experiments to determine if the raising of germ free animals was possible and […]
One of the most problematic issues of aseptic manufacturing is the involvement of personnel. Human presence generates millions of particles every minute. Some of these particles are biologically active and can generate product contamination. Now, technology can create a revolution by removing human intervention from the aseptic manufacturing process to reduce its impact on product […]
This article discusses trends for the pharmaceutical manufacturing industry in the following years. A robotic solution for the next generation of drugs is introduced and its main advantages are presented. The concepts integrated into this innovative solution are explained and technical details are provided.
The use of robotics and automation in the industry is not new. For several decades now, many assembly lines have utilized production robots in different functions to increase productivity. Although human operators result in a potentially risky activity in sterile areas, pharma manufacturing remains heavily human. This article discusses how to apply current isolation technologies […]
This method is an effort to assess risk in aseptic processing. We believe because we have broadened the perspective of risk relative to aseptic processing that if nothing else we have increased awareness that risk can vary substantially in what are perceived by many to be equivalent (and thus equally acceptable) practices and technologies.
Informal risk mitigation brought about the technology advances seen in aseptic processing. Confidence in aseptic processing is not derived from monitoring or testing; it is the result of attention to detail in aseptic processing design. With newer technologies the emphasis must shift even farther from monitoring & testing.
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 […]