August 24, 2022 PAO-08-022-CL-08
To help ensure patient safety, all drug products must meet strict regulatory requirements for purity and sterility, not only with respect to unwanted byproducts generated during the manufacturing process but also unwanted contaminants from the environment, such as dust, dirt, and adventitious microbial agents. Sources of these contaminants can include the materials and equipment used in biopharmaceutical production processes, as well as the operators themselves.
Comprehensive contamination control strategies leverage enclosed production systems where possible, engineering controls, appropriate material and people flows, careful process design, environmental monitoring programs, and regular disinfection. In cleanrooms, routine cleaning is typically performed using manual approaches, while automated decontamination with a biocidal chemical is increasingly used for extensive disinfection required before the start of a production campaign. Due to regulatory expectations, such as FDA Guidance for Industry, isolators and other enclosed systems generally utilize automated rather than manual decontamination.
Ecolab offers a comprehensive solution for cleaning and disinfection designed specifically for the pharmaceutical industry. In addition to a line of manual cleaning products manufactured to GMP quality and fully validated batch traceability, the Bioquell portfolio of automated decontamination systems includes solutions for decontaminating cleanrooms, isolators, biosafety cabinets (BSCs), and pass-throughs, as well as services such as emergency response contracts, scheduled services, and more.
With access to such a wide range of decontamination solutions, Ecolab experts are able to develop site-specific programs that maximize process efficiency and help manage contamination risk in all types of pharmaceutical manufacturing environments. These programs focus on helping pharmaceutical industry clients maximize product quality while driving safety, regulatory compliance, and operational efficiency.
Ecolab’s team of International Register of Credited Auditors (IRCA)-certified consultants can assess the compliance and effectiveness of existing cleaning and disinfection programs through the performance of on-site surveys and make recommendations for process improvement, cost savings, risk reduction, and complexity reduction. Their expert team has knowledge of the regulations and regulatory environment to ensure compliance with cGMP, assure product safety and quality, and help implement cleaning validation that meets regulatory expectations.
Support for cleaning and disinfection validation includes everything from laboratory testing to assistance with efficacy validation project management, which can accelerate the validation process. On-site training by Ecolab technical experts is also available to ensure that best practices are understood and correctly implemented.
Development of customized solutions that meet specific needs is achieved by working closely with customers at both the local plant and corporate levels to design and provide consistent approaches that optimize use of Ecolab’s resources and expertise.
For manual cleaning and disinfection, Ecolab offers a range of disinfectants, including sporicides and biocides, which are designed for rotational use to effectively control microbial contamination, including bacterial spores, in critical aseptic core cleanroom manufacturing and other areas within pharmaceutical facilities. Ecolab’s Klercide™ range of disinfectants is formulated specifically for the pharmaceutical industry and manufactured in a pharmaceutical GMP production facility with fully validated batch traceability. The Klercide range of sterile products is produced aseptically in cleanrooms using sterility assurance best practices and packaged using Ecolab’s patented SteriShield Delivery System (SDS) on the trigger spray bottles, which works as a closed system designed to prevent contamination from the environment entering the bottle, in order to preserve the sterility of the contents throughout use.
When it comes to automated decontamination in the pharmaceutical industry, hydrogen peroxide (H2O2) vapor is the leading technology. It is known to kill a wide variety of microorganisms, including bacteria, viruses, fungi, yeast, and bacterial spores, while generating only water and oxygen as by-products. As such, it is considered a residue-free technology. In addition, H2O2 vapor is compatible with most materials found in cleanrooms and isolators and is compatible with sensitive electronic devices. Furthermore, decontamination can be performed at relatively low temperatures and achieved with comparatively short cycle times.
Ecolab’s Bioquell automated decontamination systems generate H2O2 vapor by passing Bioquell Hydrogen Peroxide Sterilant (EPA registration number 72372-1-86703), a 35% aqueous H2O2 solution, through a heated vaporizer, which is flash vaporized and introduced to the enclosed area to be decontaminated by a high-velocity stream of air. Once a sufficient amount of H2O2 vapor has been introduced into the enclosure to reach the saturation point, micro-condensation rapidly results in an even exposure of H2O2 forming on all exposed surfaces, leading to a consistent level of microbial reduction in the entire space and delivering a 6-log bioburden reduction on every surface. The process is scalable, repeatable, adherent to strict regulatory standards, and GMP compliant.
During the process, the automated decontamination system measures the H2O2 concentration, temperature, and relative humidity within the area. Once the 6-log bioburden reduction has been achieved, an aeration unit catalyzes the breakdown of H2O2 into oxygen and water vapor. The system is remotely controlled from outside the decontamination areas to ensure operator safety. Furthermore, biological indicators are employed to validate decontamination cycles, and chemical indicators are used to monitor performance during routine operation. The technology is also supported by proven validation procedures performed by trained Bioquell engineers, which is documented to support cGMP compliance.
The Bioquell technology provides additional levels of traceability. RFID tags are included on each bottle of registered H2O2 solution, and every Bioquell system is able to generate audit trails to support compliance with 21 CFR Part 11 requirements.
Bioquell systems cover a range of capabilities, including mobile room decontamination systems for GMP production and lab spaces, integrated and wall-mounted offerings, and units that can connect directly to equipment to decontaminate the internal surfaces only, such as lyophilizers, biosafety cabinets, isolators, cage and rack washers, material airlocks, and more.
The Bioquell ProteQ is a mobile system designed to decontaminate multiple rooms within a facility. The Bioquell SeQure is a wall-mounted system, which inherently eliminates setup time and is designed for customers who require a higher frequency of decontamination for one particular room or pass-through. The Bioquell L-4 and IG-2 systems are designed for use within smaller enclosures in which an H2O2 vapor generator cannot fit. The H2O2 vapor is introduced through a closed loop, with supply and return hoses connected to the enclosure, typically with a nozzle to aid distribution within the enclosure.
After an assessment of a pharmaceutical process, Ecolab experts will recommend the appropriate automated H2O2 vapor decontamination solution to meet the specific requirements of that specific operation.
An additional member of the Bioquell product range is the Bioquell Qube, a configurable and modular isolator integrated with Bioquell’s H2O2 vapor technology. Bioquell Qube isolators eliminate the need for a separate decontamination system and enable decontamination cycles as short as 30 minutes. In addition, the operating pressure in Bioquell Qube isolators can be easily switched from positive to negative to meet the needs of the work being done. The Bioquell Qube provides an ISO 5/Grade A environment, so it is suitable for all types of aseptic bioprocessing, and its compact design also makes it attractive for sterility testing.
The Bioquell Qube is made from polypropylene and comprises standard modules and features that can be combined in a modular fashion to create customized and tailored solutions. Because it consists of standard, off-the-shelf modules, the time from order placement to being live in a production setting can be as little as 8–10 weeks — much less than the months it typically takes for stainless-steel or flexible isolators to be manufactured.
Depending on the intended use (such as fill/finish or sterility testing), different features can be incorporated into the Bioquell Qube isolator and multiple modules can be connected together to provide more space. For sterility testing in particular, switching to the Bioquell Qube can allow significantly greater numbers of sterility tests to be performed per day and can take place outside of the cleanroom, significantly reducing operational costs. Due to its modular nature, the Bioquell Qube isolator can also be readily expanded to meet growing process needs as customer projects advance through their development cycle.
Modules include the QHPV module with an integrated H2O2 vapor generator, which is common to every Bioquell Qube, material transfer devices (MTDs), and QEXT extension chambers, which provide more space within the system. Ecolab experts work closely with each customer to ensure that the chosen set of modules and overall system design provide optimum performance for the specific processes performed in the Bioquell Qube.
Customization of Bioquell solutions is handled by Ecolab’s global technical consultant group. Team members work directly with customers to understand their specific needs. Our highly qualified technical group of engineers then manages the installation and validation of the equipment. If the installation involves the interfacing of Bioquell solutions with other equipment, then Ecolab works closely with those equipment manufacturers (OEMs) to adapt to their equipment (i.e., installation of distribution nozzles and pressure connectors) to ensure effective decontamination.
For equipment installed in a GMP environment, validation of decontamination cycles is essential to comply with regulatory requirements. Ecolab’s global team of dedicated validation experts spends time at the customer site — typically one week — to establish the optimal cycle parameters that will ensure a robust and consistent process that provides the necessary 6-log kill in the shortest cycle time and with minimum H2O2 consumption. The validation process is documented to meet GMP standards.
For pharmaceutical manufacturers that are not in a position to invest in permanent, on-site decontamination equipment or who do not require decontamination at a frequency to warrant the investment but want to reap the benefits of automated decontamination, Ecolab’s Bioquell Rapid Bio-decontamination Service (RBDS) is an ideal solution.
This service entails on-demand or scheduled decontamination of areas ranging from a single room to an entire production facility or factory. The RBDS equipment is dedicated and specifically designed for use in such a service application, as it is more robust and built to withstand transportation and handling. In addition, the equipment is designed so that multiple generators can be connected together to decontaminate large facilities.
One newer aspect of the Bioquell RBDS offering is a business continuity package, which was added in response to the pharmaceutical industry’s heightened focus on business continuity after experiencing the challenges posed by the COVID-19 pandemic. With this package, equipment can be stored at the client’s facility, and Ecolab is essentially then on call and guarantees a response time within 24 to 48 hours. This is extremely beneficial if an unexpected contamination or excursion event occurs, as it allows pharmaceutical manufacturers to get back into production much quicker than they otherwise would have. Upon arrival, the preplanned decontamination process is immediately executed by Ecolab’s expert team of RBDS engineers. As a result, customers have assurance that if a contamination event occurs, they can get it addressed and be back up and running in a short amount of time.
Ecolab was founded in the United States in 1923 and currently has operations in over 170 countries. Since 1923, we have established the company as a trusted partner in leading global pharmaceutical and biopharmaceutical manufacturers and contract service providers. Ecolab is committed to providing exceptional service, total plant solutions, and unsurpassed industry expertise to help customers to reduce bioburden within their critical manufacturing facilities and achieve their business goals.
Ecolab’s manual and automated cleaning and disinfection solutions meet the latest regulatory standards, and all products are manufactured in fully auditable and traceable production facilities. The dedicated Life Sciences team delivers proven cleaning and disinfection solutions that customers rely on to produce effective and compliant products, improve operational efficiency, and achieve sustainability goals, including reducing water and energy consumption. With years of industry experience, the Validation and Technical Support teams assist customers in developing and implementing the best programs for their facilities. The site-specific cleaning and disinfection solutions provided by Ecolab help customers manage risk and improve process efficiency for the decontamination of external surfaces of manufacturing equipment and cleanrooms, in addition to direct product contact surfaces.
With the technology available today and the products that Ecolab has to offer, customers can implement a solution that is fit-for-purpose and able to evolve as their needs change. Any customer at any given point in time can adopt a fully automated decontamination system or start with a hybrid solution using both manual cleaning products and automated technologies. Because Ecolab offers a wide range of solutions from manual cleaning products to state-of-the-art isolators, customers have choices in how they manage their contamination control strategy. They can select from many different options, and Ecolab experts will work closely with them to help improve their workflows and increase productivity by making cleaning and decontamination a simple and easy operation.
Dr. Rolf Hansen is a sales and marketing expert with international exposure in cell and gene therapy. He obtained his Ph.D. in molecular biology and worked on the market leaders in cell therapy and molecular biology applications.