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Barrier Technology in Pharmaceutical Processing
A major source of pollution in aseptic manufacturing is personal handling. Therefore, the reduction of human interventions in the critical zone leads to higher purity in the products. For aseptic manufacturing in pharmaceutical processing, Restricted Access Barrier Systems (RABS technology) as well as isolators offer improved sterility assurance for the product and an efficient protection of the staff against risks caused by hazardous substances. These aseptic barrier systems fulfill many applications in pharmaceutical production lines, such as finish manufacturing and packaging.
Isolators include an automated bio-decontamination system and are suitable for long-lasting campaigns. A RABS, on the other hand, is an appealing solution for cleanrooms and guaranties the quality needs for applications which require more flexibility. If necessary, a RABS can be opened to allow for process intervention, while the Isolators must be kept closed during the entire operation.
A major advantage of isolator technology over conventional cleanroom technology in aseptic environments is the high security level of protection of the product which is still not achievable with other methods working with aseptic products.
A RABS provides separation by the barrier on the basis of a closed system for processing, which reduces the risk of contamination of the product because of reduced contact surfaces in comparison with handling in a normal cleanroom. In other words: It contains a barrier system with HEPA-filtered air flow, which allows a faster start and handling of processes compared with isolators and more flexible changes. Also, remodelling and renovations are cheaper.
RABS air handling units operate similar to laminar flow fume hoods in a way that they get clean air from fan units through HEPA filters and the air vents from the unit into the RABS (overpressure airflow). Air exits through openings into the environment at a low level on the equipment. During operation, there should be no reason to open the RABS doors. If there is a severe cause to open the doors, the laminar air flow system and other elements must be able to prevent a collapse of the ISO 5 conditions. Each opening of the doors will be considered as a serious intervention and must be documented.
An open RABS enables measurements and monitoring. RABS can – similar to an isolator – be driven as doors close system, with a very low risk of contamination. But a RABS contains not only a clean air maintenance system, it also includes an air lock zone, a well-designed equipment, laminar air flow, ISO 5 conditions in the critical zone, a quality system in place, SIP (sterilization in place), standard opterating procedures for interventions, disinfection plans and a documentation of all processes.
An isolator is a closed system which has to perform two functions. It is a key control measure in preventing staff-exposure to cytotoxic substances, some of which may be carcinogens. It also has to protect the product from microbiological contamination during drug fabrication.
Overpressured or underpressured isolators are enclosed units which rely on a steady flow of filtered air during use supplying ISO 5 conditions. Air entering and leaving the isolator will do so through HEPA filters. Access to an isolator is performed through glove ports and sterile transfer systems. Isolators can work in an ISO 5 to ISO 8 environment.
Cleaning can be done manually or automated. Bio-decontamination of the isolator occurs through an automated cycle with H2O2 decontamination. Should there be a leak of the isolator, the system is not airtight. For an overpressure system, the leak will allow air, which might be contaminated with cytotoxic substances, to enter the workplace. For a negative pressure system, air that may contain bacteria could enter the isolator and contaminate the preparation.
A good leak detection system should therefore be in place in order to ensure that the leak is identified by once. It is included in an environmental monitoring system with built-in sampling ports.
Understanding Closed-System Transfer Devices: Why They Are Important and How to Select an Appropriate System
CLOSED-SYSTEM TRANSFER DEVICES, OR CSTDS, are defined by the National Institute for Occupational Safety and Health (NIOSH) as, “A drug transfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapor concentrations outside the system.”
These systems are important in protecting health care professionals from exposure to potentially cytotoxic and teratogenic medications both during product preparation and administration.1
The Importance of CSTDs in Protecting Health Care Professionals
CSTDs help protect health care professionals from hazardous drugs, including pharmacists preparing medications and nurses administering medication. It has been estimated that 8 million health care professionals are exposed to hazardous drugs each year, increasing the risk of chromosomal abnormalities, teratogenicity, and cancer. More than 100 studies substantiate the increased risk, and more than 50 studies have documented harm to health care workers as a result of exposure.2-4
In a 1999 study published in the Journal of Occupational and Environmental Medicine, Valanis and colleagues analyzed pregnancy outcomes in nearly 3000 nurses, pharmacists, and pharmacy technicians and compared those outcomes with those in more than 4000 women who were not health care workers. In health care workers, spontaneous abortion or stillbirth was 40% more likely (OR 1.4; 95% CI, 1.2-1.7) to occur in individuals who reported handling hazardous drugs.5
In 2010, McDiarmid and colleagues published a study in the Journal of Occupational and Environmental Medicine identifying a higher rate of chromosome 5 and 7 abnormalities among health care workers frequently handling antineoplastic medications than in health care workers who handled such medications less frequently.
Researchers collected blood samples from more than 100 health care workers and analyzed the likelihood of chromosomal abnormalities related to the frequency of hazardous drug handling in each individual. Findings indicated significantly higher rates of structural chromosomal abnormalities in a high-exposure subset of health care workers than in a low-exposure group (0.18/person vs 0.02/person, respectively; P = .04).
Significant outcomes included a 24% greater risk of chromosome 5 abnormalities (P = .01) and a 20% greater risk of chromosome 5 or 7 abnormalities (P = .01) in high-exposure individuals.6 These studies are not merely an academic exercise. Exposure to hazardous drugs has real-world consequences.
Before she died of pancreatic cancer, pharmacist and hazardous drug compounding advocate Sue Crump reported, “One of my friends after another was coming down with either some very rare, exotic, bizarre disease; brain tumors; sarcoidosis; arrhythmias; or cancer.”
When Sue developed pancreatic cancer at the age of 55 after a 23-year career in oncology pharmacy practice, she turned to the media and drew attention to the issue of inadequate protective controls in hazardous drug compounding.7
Sue’s case did not occur in isolation. Pharmacist Bruce Harrison, veterinarian Brett Cordes, and nurse Sally Giles all eventually developed cancer or precancerous conditions in their fourth or fifth decade of life after being exposed to the occupational risk of hazardous drug handling.
Sadly, Bruce Harrison, who had a key role in developing hazardous drug handling guidelines, died at the age of 59. Sally Giles died of bile duct cancer in 1992. Brett Cordes has since recovered from cancer, but has left private practice to advocate for improved compounding safety standards.7
Use of CSTDs can help protect health care workers from exposure to hazardous medications. However, when considering a CSTD, it is important to understand that this set of products have very different design characteristics and, with regard to protective efficacy, some products have been studied extensively with high-quality trials—and others have not.
A major source of pollution in aseptic manufacturing is personal handling. Therefore, the reduction of human interventions in the critical zone leads to higher purity in the products. For aseptic manufacturing in pharmaceutical processing, Restricted Access Barrier Systems (RABS technology) as well as isolators offer improved sterility assurance for the product and an efficient protection of the staff against risks caused by hazardous substances. These aseptic barrier systems fulfill many applications in pharmaceutical production lines, such as finish manufacturing and packaging.
Isolators include an automated bio-decontamination system and are suitable for long-lasting campaigns. A RABS, on the other hand, is an appealing solution for cleanrooms and guaranties the quality needs for applications which require more flexibility. If necessary, a RABS can be opened to allow for process intervention, while the Isolators must be kept closed during the entire operation.
A major advantage of isolator technology over conventional cleanroom technology in aseptic environments is the high security level of protection of the product which is still not achievable with other methods working with aseptic products.
A RABS provides separation by the barrier on the basis of a closed system for processing, which reduces the risk of contamination of the product because of reduced contact surfaces in comparison with handling in a normal cleanroom. In other words: It contains a barrier system with HEPA-filtered air flow, which allows a faster start and handling of processes compared with isolators and more flexible changes. Also, remodelling and renovations are cheaper.
RABS air handling units operate similar to laminar flow fume hoods in a way that they get clean air from fan units through HEPA filters and the air vents from the unit into the RABS (overpressure airflow). Air exits through openings into the environment at a low level on the equipment. During operation, there should be no reason to open the RABS doors. If there is a severe cause to open the doors, the laminar air flow system and other elements must be able to prevent a collapse of the ISO 5 conditions. Each opening of the doors will be considered as a serious intervention and must be documented.
An open RABS enables measurements and monitoring. RABS can – similar to an isolator – be driven as doors close system, with a very low risk of contamination. But a RABS contains not only a clean air maintenance system, it also includes an air lock zone, a well-designed equipment, laminar air flow, ISO 5 conditions in the critical zone, a quality system in place, SIP (sterilization in place), standard opterating procedures for interventions, disinfection plans and a documentation of all processes.
An isolator is a closed system which has to perform two functions. It is a key control measure in preventing staff-exposure to cytotoxic substances, some of which may be carcinogens. It also has to protect the product from microbiological contamination during drug fabrication.
Overpressured or underpressured isolators are enclosed units which rely on a steady flow of filtered air during use supplying ISO 5 conditions. Air entering and leaving the isolator will do so through HEPA filters. Access to an isolator is performed through glove ports and sterile transfer systems. Isolators can work in an ISO 5 to ISO 8 environment.
Cleaning can be done manually or automated. Bio-decontamination of the isolator occurs through an automated cycle with H2O2 decontamination. Should there be a leak of the isolator, the system is not airtight. For an overpressure system, the leak will allow air, which might be contaminated with cytotoxic substances, to enter the workplace. For a negative pressure system, air that may contain bacteria could enter the isolator and contaminate the preparation.
A good leak detection system should therefore be in place in order to ensure that the leak is identified by once. It is included in an environmental monitoring system with built-in sampling ports.
Understanding Closed-System Transfer Devices: Why They Are Important and How to Select an Appropriate System
CLOSED-SYSTEM TRANSFER DEVICES, OR CSTDS, are defined by the National Institute for Occupational Safety and Health (NIOSH) as, “A drug transfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapor concentrations outside the system.”
These systems are important in protecting health care professionals from exposure to potentially cytotoxic and teratogenic medications both during product preparation and administration.1
The Importance of CSTDs in Protecting Health Care Professionals
CSTDs help protect health care professionals from hazardous drugs, including pharmacists preparing medications and nurses administering medication. It has been estimated that 8 million health care professionals are exposed to hazardous drugs each year, increasing the risk of chromosomal abnormalities, teratogenicity, and cancer. More than 100 studies substantiate the increased risk, and more than 50 studies have documented harm to health care workers as a result of exposure.2-4
In a 1999 study published in the Journal of Occupational and Environmental Medicine, Valanis and colleagues analyzed pregnancy outcomes in nearly 3000 nurses, pharmacists, and pharmacy technicians and compared those outcomes with those in more than 4000 women who were not health care workers. In health care workers, spontaneous abortion or stillbirth was 40% more likely (OR 1.4; 95% CI, 1.2-1.7) to occur in individuals who reported handling hazardous drugs.5
In 2010, McDiarmid and colleagues published a study in the Journal of Occupational and Environmental Medicine identifying a higher rate of chromosome 5 and 7 abnormalities among health care workers frequently handling antineoplastic medications than in health care workers who handled such medications less frequently.
Researchers collected blood samples from more than 100 health care workers and analyzed the likelihood of chromosomal abnormalities related to the frequency of hazardous drug handling in each individual. Findings indicated significantly higher rates of structural chromosomal abnormalities in a high-exposure subset of health care workers than in a low-exposure group (0.18/person vs 0.02/person, respectively; P = .04).
Significant outcomes included a 24% greater risk of chromosome 5 abnormalities (P = .01) and a 20% greater risk of chromosome 5 or 7 abnormalities (P = .01) in high-exposure individuals.6 These studies are not merely an academic exercise. Exposure to hazardous drugs has real-world consequences.
Before she died of pancreatic cancer, pharmacist and hazardous drug compounding advocate Sue Crump reported, “One of my friends after another was coming down with either some very rare, exotic, bizarre disease; brain tumors; sarcoidosis; arrhythmias; or cancer.”
When Sue developed pancreatic cancer at the age of 55 after a 23-year career in oncology pharmacy practice, she turned to the media and drew attention to the issue of inadequate protective controls in hazardous drug compounding.7
Sue’s case did not occur in isolation. Pharmacist Bruce Harrison, veterinarian Brett Cordes, and nurse Sally Giles all eventually developed cancer or precancerous conditions in their fourth or fifth decade of life after being exposed to the occupational risk of hazardous drug handling.
Sadly, Bruce Harrison, who had a key role in developing hazardous drug handling guidelines, died at the age of 59. Sally Giles died of bile duct cancer in 1992. Brett Cordes has since recovered from cancer, but has left private practice to advocate for improved compounding safety standards.7
Use of CSTDs can help protect health care workers from exposure to hazardous medications. However, when considering a CSTD, it is important to understand that this set of products have very different design characteristics and, with regard to protective efficacy, some products have been studied extensively with high-quality trials—and others have not.