Neal Wesley is Technical Director at SCM Pharma.

Neal Wesley

Many pharma companies cite personnel training as the main challenge in maintaining cleanroom conditions. Do you agree with this point? 

It is universally accepted that the principle source of cleanroom contamination is personnel. Primary consideration should be focused on reducing personnel interactions as far as possible from any process—and many novel technologies have helped to achieve this. If the use of such technology is not possible, however, the main challenge in maintaining satisfactory cleanroom conditions lies with the training and a culture of correct cleanroom behaviour of personnel.

A primary change area within the facility ensures that outside garments are removed and cleanroom undergarments are used prior to entry to a separate cleanroom gowning change area. At our company, access to both these areas is restricted by means of biometric control, which provides added protection against unauthorised entry. Contamination risks are mitigated through a number of different training programmes, a proven changing regime, restricted access and a deep-seated culture of the importance of contamination control and the potential consequences of control deficiency. 

What training programmes do you have in place for new cleanroom personnel? 

All personnel who require access to cleanrooms to perform their job undergo both an induction and cGMP training upon recruitment. All cleanroom operators also undergo specific training that focuses on cleanroom behaviour, as well as training sessions within the microbiology laboratory. This provides theoretical and practical exposure to microbiology and enables first-hand experience of the sources and types of potential microbiological contamination. In addition, operators involved in aseptic processing undergo specific training relevant to each process and the equipment used. 

How do you ensure that standards and best practices continue to be met by personnel after training is completed? 

Upon completion of the initial training, we issue a cleanroom operator entry license, which is renewed on an annual basis following a reassessment to ensure satisfactory standards are achieved in cleanroom entry and gowning. Cleanroom behaviour is continually monitored by production supervision and periodically through quality audit. Process Simulation Trials (PST) are conducted on a regular basis and a comprehensive system for aseptic operator licensing is employed where licenses are only issued following an assessment of an individual’s performance during a PST. 

Over the years, are there any common, personnel-related issues or mistakes that you’ve seen time and again? 

A simple and logical facility layout and changing regime provides for consistent maintenance of satisfactory cleanroom conditions. In our company, there is a strong culture of peer monitoring and awareness so fortunately we haven’t observed any common personnel-related issues. However, we do have a comprehensive environmental monitoring system that has enabled the development of a wild-type database, providing valuable information regarding microbiological population trends within the facility. The results and any adverse trends can be used to target specific areas for attention either with respect to cleaning or process modifications or improvements.

Some experts claim that activities conducted prior to entering the workplace can affect contamination levels within a sterile environment. How can risks like this be controlled? 

There is an ongoing debate about this issue and, arguably, there is a risk that activities outside the workplace have the potential to influence cleanroom conditions. Specific risks can be controlled through the use of specific criteria for cleanroom entry. Where there is a risk of adventitious viral or prion contamination to a downstream process that has undergone viral clearance or filtration, then strict entry requirements, changing regime and movement through the facility can successfully be employed. Where there is a risk of bacterial contamination to an aseptic process, isolator technology is the most effective way of mitigating this risk. 

Neal Wesley is technical director at SCM Pharma. 

Articles

Training cleanroom operators can be one of the most challenging aspects to maintaining cleanroom conditions. PTE speaks to Neal Wesley, technical director at SCM Pharma, to find out the best practices for training and ensuring continued compliance.

Mitigating Personnel Risks

 Neal Wesley. Technical Director at SCM Pharma.Contract Manufacturing Organisations offering manufacturing capabilities to suit specific industry sectors, niche segments or perhaps simply to meet the demands of individual clients’ processes face a greater challenge when designing their facilities and cleanrooms when compared with an originator company or a single-product manufacturing facility.

The numerous clients’ varied drug substances and drug products, their constituent raw materials and APIs create a potential risk of cross-contamination, which demands that due attention and consideration is afforded to implementing satisfactory cleanroom designs, systems and procedures to address the main challenges of attaining and maintaining cleanroom conditions.

The most difficult challenges are often centred around building as much flexibility as possible into any facility and equipment investment. 

Factors which are not necessarily unique to CMOs but still of concern are often with regard to equipment. A successful CMO needs to be flexible and reactive to customer project requirements, which often utilise differing equipment and manufacturing environments. You can rapidly become overwhelmed with equipment and available space to store it following its use on a specific project. Many clients’ processes will require that the CMO addresses the possible issues surrounding potential hazards and risks associated from introducing their products into the facility.

Addressing clients’ product contamination profiles will create certain restrictions on the design and operation of the facility and its cleanrooms. This will necessitate all process flows for staff, incoming raw material, intermediates, components, process equipment and process waste streams be assessed in relation to the potential risk for cross contamination.

Manufacturing containment strategies should be developed with consideration given to certain aspects of design, such as cost 

 multiple batch production, closed versus open processing systems, and multi-use versus dedicated or disposable equipment while maintaining the drive to implement and maintain flexible and/or adaptive cleanroom and air handling designs and process flows.

Having a dedicated team to fully evaluate the risk involved with contamination and cross-contamination is paramount. In some instances, total dedication of facility, equipment and personnel is required. The CMO must have an effective internal procedure to assess and manage perceived or potential risks from client processes and starting materials at the initial stage of all proposals for new process introductions. 

There is an inherent risk of cross-contamination from the use of non-dedicated cleanrooms and equipment, such as dispensaries, wash areas, corridors, autoclaves, ovens and washing machines. This may require an extended scope for cleaning validation requirements and total segregation of project specific API, intermediate bulk and finished products.

The CMO will need to implement demanding procedures and systems to manage onerous cleaning validation challenges and strict management for suppliers of starting materials and APIs.

The management of perceived risk will include risk assessment tools such as FMEA or HACOP to initially identify then look to eliminate, reduce, manage, control, monitor and review the potential risk.

The CMO quality system should have robust procedures in place to manage the introduction of new and novel raw materials into the facility.

 Identifying critical process flows will assist in the development of materials handling philosophies, segregation strategies and entry and exit transfers of equipment, materials and operators. The CMO should also evaluate and control process waste streams and define upset conditions within areas of the facility such as cleanrooms.

The formulation characteristics of client products may be hazardous to such a degree that certain restrictions are placed on the production operator team.

Cleanroom operators are generally viewed as being responsible for introducing over 80% of the particulate contamination recorded by cleanroom monitoring systems.

Mitigating the risk of potential contamination to manufacturing processes can be limited through the use of isolator barrier technology and employing mechanisation or automation to reduce human aseptic interventions in critical processing areas.

Thought should be given to preventing contamination reaching cleanrooms by the use of appropriate sized rooms with defined maximum occupancy and limitations for staff changing in and changing out to mitigate the amount of contamination. The pre-assembly and sterilisation of components may also be employed to reduce the amount of manual aseptic manipulations and connections in the critical zone.

On-the-job training and annual training programmes for aseptic operators should cover topics such as aseptic manipulations, basic microbiology training, human sources of cleanroom contamination and concepts of HEPA filter air systems and laminar and turbulence airflows. Effective aseptic operator gowning validations should also be in place. However, just as important is a strong GMP company culture with regular reinforcement. 

Contract Manufacturing Organisations offering manufacturing capabilities to suit specific industry sectors, niche segments or perhaps simply to meet the demands of individual clients? processes face a greater challenge when designing their facilities and cleanrooms when compared with an originator company or a single-product manufacturing facility.