What are the key elements to be considered in order to meet the quality system requirements detailed in ICHQ10 for a Contamination Control Program (CCP)? What points need to be considered to support the implementation of such a program within any manufacturing facility?
What makes it robust? Should it be multifaceted to ensure its effectiveness?
These are all valid questions and key to ensuring your CCP is robust is assembling a multidisciplinary team to identify and evaluate the microbiological, particulate, chemical and cross-product contamination risks to your product, thus allowing identification of the key areas requiring focus in the CCP.
Development of a robust plan is critical in all manufacturing facilities – aseptic, terminal sterilisation and non-sterile. Clear regulatory guidance is available on the need for control of contamination at all stages during aseptic processing and manufacture of sterile products, however, the requirements for how to address contamination control in a non-sterile manufacturing environment are less obvious.
A Contamination Control Strategy (CCS) should be developed to provide a summary of the contamination control plan including the methods employed for ensuring contamination controls are effective i.e. commissioning, qualification and validation. The CCS should also detail how contamination levels are monitored i.e. environmental monitoring programme, in addition to other monitoring methods such as environmental management systems, automated alarms and Quality Control testing.
An Environmental Monitoring (EM) programme needs to be risk based and designed to effectively determine the types and level of microbial and non-viable particulate contamination present in the cleanroom. With an effective EM programme in place, analysis of the data collected can quickly support the efficacy of the cleaning and disinfection processes in place or, on the contrary, allow adverse trends be quickly identified. EM is an important tool for determining the state of control of the facility and therefore, is an important part of the monitoring programme for all types of manufacturers.
As the number one source of contamination in controlled areas is personnel, training is key! The CCP must address personnel barriers to contamination whether the manufacturing process is designed for aseptic or non-sterile manufacturing facilities. The CCP should describe the rationale for the level of gowning chosen, the frequency of gown cleaning, behaviour of personnel in the classified areas and the acceptability of the gown materials for the type of manufacturing process. Personnel working in the area must rigidly adhere to the gowning procedures in place. Training should involve a practical element; it should be continuous and ongoing monitoring is an essential part of an effective CCP.
After personnel, the second highest risk of contamination derives from materials and equipment brought into the controlled environment from the outside. For material handling airlocks, it is essential that decontamination practices are in use prior to entry into the controlled environment. A risk-based approach should be adopted depending on the nature of your manufacturing process. Items to be considered include the use of interlocking airlocks between entry points for classified areas of different grades, restricted and controlled access to aseptic areas by use of card readers etc., disinfection of pass-through materials including the use of a sporicidal disinfectant. All such procedures should be sufficiently detailed in an SOP and assessment of pass-through techniques be performed by an SME to validate compliance with your SOPs.
The frequency of your cleaning and disinfection programmes should be risk-based and similar to the training programme, should be regularly reviewed. Two disinfectants should be used in rotation, one a broad-spectrum disinfectant rotated with periodic use of a sporicidal disinfectant. Have you validated your disinfectant prior to use? This is also key to an effective CCP and should include surface challenge testing to calculate the log reduction of indicator microorganisms in the presence of the disinfectant on a surface coupon representative of surfaces in the cleanroom. Other items to be considered under the cleaning and disinfection programme include the frequency and method for residue removal, performance of studies to demonstrate the ability to recover from loss of aseptic control and disinfectant efficacy studies to include contact times and expiry dating.
Finally, ensure your product contact surfaces are cleaned and/or sterilised appropriately and consider how these critical surfaces are protected before, during and after processing. All wrapping materials in use must be of the appropriate quality to ensure a microbial barrier and low particle generation. The considerations in a non-sterile facility are similar as there needs to be evidence that the sanitisation program used is effective and the regular use of sporicidal agents are appropriate.
All of the elements of facility design, process design, automation, quality management, qualification/validation and monitoring must be combined and structured into an overall coherent contamination control plan, that is founded on the identification and assessment of the existing and potential risks, and used to drive continuous improvement in the process and manufacturing facility.
Do you need help in assessing your CCP or in development of a CCP?