Assurance of Sterility for Sensitive Combination Products and Materials: New Paradigms to Bring Innovative Healthcare Products to Patients

Description

Assurance of Sterility for Sensitive Combination Products and Materials: New Paradigms for the Next Generation of Medical Devices and Pharmaceuticals discusses the medical device industry and existing challenges regarding the exciting new world of sensitive combination products (SCPs) and their terminal sterilization. This book reassesses the current assumptions to assure the patient’s best interests are met in the development of increasingly rigorous sterilization methods used to counteract MRSA and other 'super-bugs'. In addition, the book discusses the special challenges faced with implantable medical devices, sterilization requirements and further methods needed for material selection and the design process. This book is unique in taking a holistic, end-to-end approach to sterilization, with a particular focus on materials selection and product design. Introduces sterilization principles at the material selection and design stagesAddresses the industry need for new sterilization processes for new medical devices and biomaterialsProvides guidance to select the appropriate sterilization technique for newly developed sensitive combination productsExamines forward thinking tactics for matching new developments in material compatibility with possible regulatory and QSR strategies Cover Assurance of Sterility for Sensitive Combination Products and Materials Copyright Contributors Foreword 1 Introduction: Sterilization or aseptic processing of single use combination products Introduction Sterility assurance terminology 2 Sensitive combination products: Devices, pharmaceuticals, and biologics Introduction to combination products Considerations for sterilization of combination products Drug-enhanced devices Drug delivery systems: Traditional and novel Regenerative medical devices with biologics Electronics, bioabsorbables, and other novel materials and the future of combination product development References 3 Terminal sterilization The history of sterilization History of radiation sterilization History of EO sterilization History of dry and moist heat sterilization Sterile validation of current methods Product qualification Equipment qualification Sterilization validation approaches Bioburden-based approach Bioburden and BI-based approach BI approach Validation overview Future approaches to sterilization Conclusion References Further reading 4 Aseptic processing Aseptic processing of sterile combination products Drug product sterility Aseptic processing Aseptic process design Sterility by design Line of sight [9] Defining aseptic process requirements Basis of design User requirement specification (URS) Aseptic practices Interventions and activities in the aseptic processing critical area First air principles Environmental monitoring Personnel monitoring Clean room design Airflow or air profile visualization (smoke) studies Isolators, RABS, BFS, and other advanced aseptic barrier systems Critical utilities Aseptic process qualification and validation Aseptic process simulation design Microbial contamination case study Aseptic process simulation study design When should aseptic process simulations be performed? What process steps should be included in the aseptic process simulation? How many aseptic process simulations should be run for the simulation study? How should the “worst-case” parameters or conditions be included in the study? How long should the aseptic process simulation be? What are the aseptic process simulation acceptance criteria? The future of aseptic processing Conclusion: Quality risk management and risk-based critical thinking References 5 Package/container closures History of sterile packaging Technologies Introduction Packaging functions Differences between requirements of medical device and pharmaceutical packaging Container types/definitions/dosage form Considerations for plastic selection-pharmaceutical and medical device packaging Stability issues related to packaging Challenges for packaging combination products Validation principles Validation and patient safety Package integrity and the limitations of sterility testing Test methods Integrity test methods Integrity testing—Conclusions Microbial barrier test methods Seal strength test methods Validation of test methods Design validation Material qualifications, chemical, and biological compatibility Microbial barrier properties Biological compatibility and toxicological attributes Extractables and leachables Performance qualification Defining the distribution and storage environment Clinical use: Aseptic technique and usability aspects Stability studies Forming, sealing (closure) and assembly process validation Process design Installation, operational, and performance qualifications Process control and monitoring (continuous process verification) Packaging and device families Managing changes and revalidation Examples of validation approaches Power and sample size considerations for medical and pharmaceutical device packaging A conceptual overview of power and sample size A power and sample size example for packaging Power and sample calculations in practice for significance testing An overview of equivalence testing Power and sample size considerations for equivalence testing Sample size for process capability in process validation Concluding remarks for power and sample size New developments References 6 Review of current practice in preventing health care associated infections Introduction Background in HAIs Assessment of risk Identifying HAIs Assessing the burden/impact of HAIs Causes of HAIs Patient-related factors Source of microorganisms Susceptible host Means of transmission Procedural-related characteristics Risks based on the procedure HAI classification Non-device-associated infections Device-associated infections Industrial single-use devices Reusable devices Surgical site infections Preventing HAIs WHO safe surgery saves lives initiative CDC SSI guideline 1999 Behavior Isolation precautions Standard precautions Transmission-based isolation precautions Surgical hand scrub Health-care personnel attire Nonsurgical setting attire Surgical setting attire Procedural interventions Engineering solutions—HCFs Suite/room design Airflow and ventilation Traffic patterns Protection and barriers Facial protection Hoods, caps, and shoe covers Gloves Gowns and drapes Cleaning Cleaning validation Disinfection Sterilization at the HCF Steam under pressure Terminal sterilization Immediate use steam sterilization EO sterilization Hydrogen peroxide Hydrogen peroxide/ozone Peracetic acid Conclusion References 7 Risk to the patient—Quantifying assurance of sterility Risk concepts applied to sterility assurance Statistical concepts applied to sterility assurance Point estimates Confidence interval example Confidence bounds Statistical analysis types Nonparametric analysis Parametric analysis Statistical analysis of risk associated with packaging and sterilization Introduction to scenarios analyzed Point estimates and confidence bounds—Packaging Point estimates and confidence bounds—Aseptic processing Conclusion—Point estimates and confidence bounds—Aseptic processing Point estimates and confidence bounds—Terminal sterilization; bioburden-based approach Section A Section B Conclusion—Point estimates and confidence bounds—Terminal sterilization; bioburden-based approach Point estimates and confidence bounds—Terminal sterilization; overkill method Section A Section B Conclusion—Point estimates and confidence bounds—Terminal sterilization; overkill method Summary of statistical analysis Relative patient risks from various industry sectors compared to real-world infection rates Estimates of infection probabilities Probability of P1 Probability of P2 Probability of P3 Probability of P4 Other factors influencing the assurance of sterility Patient’s immuno-compromised status and ability to treat the infection Bioburden control in the manufacturing environment Sterilization validation methodology Comparison to real-world infection rates Risk acceptability—Bringing it all together, the real risk to the patients Conclusion References 8 Developing new products Background Sterilize at 10 − 6 SAL Aseptic processing Alternative SAL Improving device compatibility Reducing exposure time Reducing bioburden Other SAL options Identifying the risks Identifying the benefits Conclusion References 9 Regulatory pathway for labeling combination products as sterile Labeling products as sterile Communicating with regulatory authorities Seeking FDA feedback Additional points to consider EU submission process Regulatory classification Marketing authorization as a medical product CE-marking for a medical device FDA guidance on labeling devices as sterile Methods of sterilization Content recommendations for 510(k)s Documents pertaining to terminal sterilization and SAL Guidance from the Association for the Advancement of Medical Instrumentation European standards for terminal sterilization New guidance from ISO Documents pertaining to aseptic processing and assurance of sterility ISO 13408 series EN 556-2 Evaluation of medicinal products Summary Further reading 10 Path forward What is next with combination products? Sterility assurance landscape in the 2020s Pan-industry sterility assurance risk framework Sterility assurance risks in health-care facilities Sterility assurance risks related to single-use products What is next for sterility assurance professionals? End-to-end sterility assurance Bringing it all together in a risk management framework What is next for the patient? References Index A B C D E F G H I L M N O P Q R S T U V W X Back Cover