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Introduction: Sterilization or aseptic processing of single use combination products
CHAPTER 1
Introduction: Sterilization or aseptic processing of single use combination products Joyce M. Hansena, Trabue D. Bryansb a
J&J Sterility Assurance, Johnson & Johnson, Raritan, NJ, United States BryKor, LLC, Marietta, GA, United States
b
Contents 1.1 Introduction 1.2 Sterility assurance terminology
1 2
1.1 Introduction New patient treatment options continue to drive the need for the development of combination products. Sterility assurance innovation is critical to bring these combination products to market. This innovation requires sterility assurance professionals to collaborate across the broad spectrum of the demands of the healthcare industry. Not only does a successful sterility assurance professional need to be an expert in their field, but also they need to be aware of the broad challenges and opportunities associated with bringing a combination product to the market. This book provides an overview as well as introduces exciting new opportunities in each industry sector. The sectors addressed include combination products and their design, terminal sterilization, aseptic processing, packaging, healthcare practices as well as the worldwide regulatory environment. The topics associated with each sector are introduced with the perspective of facilitating the development of innovative new combination products. Combination products emerged in the 1990s to reduce the potential for infection and the time healthcare providers needed to treat patients. Original combination products typically consisted of a means of connecting multiple products to reduce the manipulations required. Over the last few decades, combination products have evolved to consist of a combination of medical devices, biologics, pharmaceuticals, and electronics to support the next level of patient care. Assurance of Sterility for Sensitive Combination Products and Materials https://doi.org/10.1016/B978-0-12-805082-8.00001-3
© 2020 Elsevier Inc. All rights reserved.
1
2
Assurance of sterility for sensitive combination products and materials
The regulatory evolution of combination products has provided manufacturers with an opportunity to envision a new subset of products that utilize various combinations of medical devices, biologics, pharmaceuticals, active electronics, and/or bioresorbables in unique manners. Therefore, the regulatory climate for combination products necessitated the use of a blend of requirements that would be specific for the appropriate combination of medical device, biologics, and/or pharmaceutical products. Until recently, healthcare products were typically classified as medical devices, biologics, or pharmaceuticals. The different classifications of products were traditionally regulated through different parts of regulatory agencies, which have for years operated independently. The requirements for different categories of products did not typically involve coordination across agencies.The development of combination products has required that manufacturers as well as regulators learn to navigate the diverse requirements across the different agencies. A successful sterility assurance professional—with the convergences of this changing regulatory landscape—requires the ability to connect the dots across the different sectors of the industry that have traditionally, all too often, been in silos. Combination products may need terminal sterilization and/or aseptic processing; and sterilization professionals need to understand both. The majority of healthcare risks to patients include those associated with healthcare facilities themselves; hence, sterilization professionals need to understand how the product is used in the healthcare facilities and the magnitude of hospital-acquired infections (HAI). One of the unique value streams of this book is its perspective integrating discussion of sterility assurance topics across industry sectors. This presents a terminology challenge since different sectors use different but related terminology. This is addressed as follows.
1.2 Sterility assurance terminology The term ‘sterile’ is generally defined as an absolute state, for example, the absence of viable microorganisms. Different terms are used in different sterility assurance sectors as follows: Sterility assurance level (SAL) is specific to terminal sterilization, defined as the “probability of a single viable microorganism occurring on an item after sterilization.” Probability of a non-sterile unit (PNSU) is sometimes used for terminally sterilized components feeding into an aseptic process.
Introduction: Sterilization or aseptic processing of single use
3
Contamination rate is used to describe the results of process simulations in aseptic processing validations. The definition of SAL is the probability of survival of a single microorganism. Microbiological reduction associated with terminal sterilization processes is expressed by an exponential function. The values of SAL and PNSU are a negative power to the base 10. All of the terminal sterilization methods explicitly use the term SAL and this mathematical construct in the validation scheme. This construct differs from the term PNSU, which is based on a product being non-sterile, whether due to a single microorganism or multiple microorganisms. Typically, the first step in the development of a new product is understanding patient needs. Based on this information, an initial product design is developed, and integral to the product design is the determination of whether the product can withstand a terminal sterilization process. This is particularly challenging for combination products because of the need to use different materials that might not be suitable for traditional overkill sterilization processes. Materials such as active electronics, bioresorbable materials, and biologics are particularly challenging. The option of aseptic processing can be considered after demonstrating that the product cannot be terminally sterilized. The regulatory agencies and industries are adapted to accommodate sterilization challenges of combination products that cannot be terminally sterilized by developing aseptic processing standards for solid combination products (e.g., ISO 13408-7). Chapters in this book explore the options for both terminal sterilization and aseptic processing, as well as the selection of an alternate SAL for those products that cannot be terminally sterilized to an SAL of 10−6. The underpinning behind the development of sterilization modalities, aseptic processing, packaging, and healthcare acquired infection is the concept of infection risk to the patient. The independent evolution of the sectors resulted in different methods and vocabulary to quantify the risk. A fundamental statistical approach is presented to attempt to bridge these assessments. The goal of the Risk to Patient chapter is to open the dialog between groups so that informed scientific-based decisions can be made. Regardless of the method of providing a sterile product—terminal sterilization or aseptic processing—the primary packaging is required to maintain the integrity of the sterile claim. Primary packaging is intended to provide the sterile barrier throughout the product shelf life, including handling and distribution activities. Packaging for a combination product
4
Assurance of sterility for sensitive combination products and materials
might include both traditional trays and pouches for medical devices, as well as traditional containers/closures used for biologics or pharmaceuticals. One of the major challenges for combination products is how to achieve the sterile label claim. This challenge dictates the choice of the process used to assure sterility, and the level of manufacturing controls needed for production. This challenge also has resulted in the opportunity to not only reevaluate the traditional SAL but also consider the applicability and risk of alternate SALs. Navigating this challenge has required that manufacturers as well as regulators collaborate on how to achieve the sterile label claim. Combination products and the associated regulatory aspects are dynamic topics that continue to evolve driven by the new types of products that will be needed for the future. This book will help equip sterility assurance professionals to address new opportunities in order to ensure that patients receive the optimal products with optimal risk-based sterilization solutions.
Introduction: Sterilization or aseptic processing of single use combination products Joyce M. Hansena, Trabue D. Bryansb a
J&J Sterility Assurance, Johnson & Johnson, Raritan, NJ, United States BryKor, LLC, Marietta, GA, United States
b
Contents 1.1 Introduction 1.2 Sterility assurance terminology
1 2
1.1 Introduction New patient treatment options continue to drive the need for the development of combination products. Sterility assurance innovation is critical to bring these combination products to market. This innovation requires sterility assurance professionals to collaborate across the broad spectrum of the demands of the healthcare industry. Not only does a successful sterility assurance professional need to be an expert in their field, but also they need to be aware of the broad challenges and opportunities associated with bringing a combination product to the market. This book provides an overview as well as introduces exciting new opportunities in each industry sector. The sectors addressed include combination products and their design, terminal sterilization, aseptic processing, packaging, healthcare practices as well as the worldwide regulatory environment. The topics associated with each sector are introduced with the perspective of facilitating the development of innovative new combination products. Combination products emerged in the 1990s to reduce the potential for infection and the time healthcare providers needed to treat patients. Original combination products typically consisted of a means of connecting multiple products to reduce the manipulations required. Over the last few decades, combination products have evolved to consist of a combination of medical devices, biologics, pharmaceuticals, and electronics to support the next level of patient care. Assurance of Sterility for Sensitive Combination Products and Materials https://doi.org/10.1016/B978-0-12-805082-8.00001-3
© 2020 Elsevier Inc. All rights reserved.
1
2
Assurance of sterility for sensitive combination products and materials
The regulatory evolution of combination products has provided manufacturers with an opportunity to envision a new subset of products that utilize various combinations of medical devices, biologics, pharmaceuticals, active electronics, and/or bioresorbables in unique manners. Therefore, the regulatory climate for combination products necessitated the use of a blend of requirements that would be specific for the appropriate combination of medical device, biologics, and/or pharmaceutical products. Until recently, healthcare products were typically classified as medical devices, biologics, or pharmaceuticals. The different classifications of products were traditionally regulated through different parts of regulatory agencies, which have for years operated independently. The requirements for different categories of products did not typically involve coordination across agencies.The development of combination products has required that manufacturers as well as regulators learn to navigate the diverse requirements across the different agencies. A successful sterility assurance professional—with the convergences of this changing regulatory landscape—requires the ability to connect the dots across the different sectors of the industry that have traditionally, all too often, been in silos. Combination products may need terminal sterilization and/or aseptic processing; and sterilization professionals need to understand both. The majority of healthcare risks to patients include those associated with healthcare facilities themselves; hence, sterilization professionals need to understand how the product is used in the healthcare facilities and the magnitude of hospital-acquired infections (HAI). One of the unique value streams of this book is its perspective integrating discussion of sterility assurance topics across industry sectors. This presents a terminology challenge since different sectors use different but related terminology. This is addressed as follows.
1.2 Sterility assurance terminology The term ‘sterile’ is generally defined as an absolute state, for example, the absence of viable microorganisms. Different terms are used in different sterility assurance sectors as follows: Sterility assurance level (SAL) is specific to terminal sterilization, defined as the “probability of a single viable microorganism occurring on an item after sterilization.” Probability of a non-sterile unit (PNSU) is sometimes used for terminally sterilized components feeding into an aseptic process.
Introduction: Sterilization or aseptic processing of single use
3
Contamination rate is used to describe the results of process simulations in aseptic processing validations. The definition of SAL is the probability of survival of a single microorganism. Microbiological reduction associated with terminal sterilization processes is expressed by an exponential function. The values of SAL and PNSU are a negative power to the base 10. All of the terminal sterilization methods explicitly use the term SAL and this mathematical construct in the validation scheme. This construct differs from the term PNSU, which is based on a product being non-sterile, whether due to a single microorganism or multiple microorganisms. Typically, the first step in the development of a new product is understanding patient needs. Based on this information, an initial product design is developed, and integral to the product design is the determination of whether the product can withstand a terminal sterilization process. This is particularly challenging for combination products because of the need to use different materials that might not be suitable for traditional overkill sterilization processes. Materials such as active electronics, bioresorbable materials, and biologics are particularly challenging. The option of aseptic processing can be considered after demonstrating that the product cannot be terminally sterilized. The regulatory agencies and industries are adapted to accommodate sterilization challenges of combination products that cannot be terminally sterilized by developing aseptic processing standards for solid combination products (e.g., ISO 13408-7). Chapters in this book explore the options for both terminal sterilization and aseptic processing, as well as the selection of an alternate SAL for those products that cannot be terminally sterilized to an SAL of 10−6. The underpinning behind the development of sterilization modalities, aseptic processing, packaging, and healthcare acquired infection is the concept of infection risk to the patient. The independent evolution of the sectors resulted in different methods and vocabulary to quantify the risk. A fundamental statistical approach is presented to attempt to bridge these assessments. The goal of the Risk to Patient chapter is to open the dialog between groups so that informed scientific-based decisions can be made. Regardless of the method of providing a sterile product—terminal sterilization or aseptic processing—the primary packaging is required to maintain the integrity of the sterile claim. Primary packaging is intended to provide the sterile barrier throughout the product shelf life, including handling and distribution activities. Packaging for a combination product
4
Assurance of sterility for sensitive combination products and materials
might include both traditional trays and pouches for medical devices, as well as traditional containers/closures used for biologics or pharmaceuticals. One of the major challenges for combination products is how to achieve the sterile label claim. This challenge dictates the choice of the process used to assure sterility, and the level of manufacturing controls needed for production. This challenge also has resulted in the opportunity to not only reevaluate the traditional SAL but also consider the applicability and risk of alternate SALs. Navigating this challenge has required that manufacturers as well as regulators collaborate on how to achieve the sterile label claim. Combination products and the associated regulatory aspects are dynamic topics that continue to evolve driven by the new types of products that will be needed for the future. This book will help equip sterility assurance professionals to address new opportunities in order to ensure that patients receive the optimal products with optimal risk-based sterilization solutions.