Bes develops side-flow booth solution for biopharma production facility
Early cancer diagnosis, research and treatment have advanced exponentially in recent years, improving patient outcomes. As our understanding of cancer develops and treatments become increasingly sophisticated, there is a need to custom-prepare medication to meet the specific needs of the patient and their condition. This, in turn, demands increasingly sophisticated production facilities, both in the pharmaceutical manufacturing sector and in hospital environments, where biopharma best practice can provide key learnings for safe, effective and energy-efficient drug preparation suites within the healthcare campus.
One of the UK’s leading biopharmaceutical companies has invested in ensuring it keeps pace with cancer treatment innovation and provides the highest standards of facilities in order to maintain quality standards, attract talent and embed staff wellbeing in the work environment. One of the company’s most recent asset development projects has involved the upgrade of an existing production plant to a clean room and the addition of extra production capacity with the fit out of an adjacent redundant building. This project, designed and delivered by BES, has increased specialist processing capability in the manufacture of tailored cancer drugs.
Defining the Scope
BES is a specialist in clean room and aseptic environments, providing an inter-disciplinary approach to integrating architectural and building services design to ensure a fully-compliant facility that supports both health and safety and operational efficiency. As an open book alliance partner for the biopharmaceutical specialist, our remit included interrogating the brief to ascertain where innovative ideas could add value to core concepts and deliver an upgrade to the existing facility based on a philosophy of continuous improvement.
As starting point for design of the upgraded production environment, the BES team carried out a survey of the existing facility, which revealed that fume cupboards were used at several points in the production process. The existing facility featured two purpose-designed down-flow booths for a purification process that is business-critical to the quality of the finished preparations. Each down-flow both contained purification flasks and a low-temperature oven to slow bake the preparation to bespoke requirements. In each booth, conditioned air was fed in at the top of the booth and flowed down to low level extract points at the back of the booth, above the bench area for the flasks.
The BES team noted that operator breathing zones were located close to fume generation points within these down-flow booths in the legacy facility. Down-flow booths are classed as partial enclosures and generally recognised as a reasonably effective means of fume control, with HSE guidance referring to them as a ‘compromise between containment and accessibility’. However, the ACGIH Industrial Ventilation Manual recommends that air should be ‘designed to deliver airflow uniformly through the ceiling face and remove it uniformly from the floor’ in down flow booths and the survey of existing arrangements revealed that the down-flow booths did not meet current design guidelines. The position of the extract points on the rear wall of the booth meant that uniform laminar airflow could not be achieved and the BES team saw an opportunity to reduce production hazards associated with filling the flasks with methanol, fitting stirrers and venting tubes to the flask, and loading the oven by re-engineering the fume management system as side-flow booths.
The survey also provided an opportunity to examine how workflows could be improved in the architectural design of the refurbishment. The previous layout involved filling flasks with methanol on the front edge of the booth, where a controlled air flow could not be maintained, and fitting and removing stirrers took place above the flat surface supporting the flasks, creating the potential for the vertical down flow of fresh air to bounce up off the flat surfaces and create an area of turbulent air. The horizontal surface where the preparation was placed ready for loading into the oven was another potential area of turbulent air in the operator breathing zone.
An Iterative Process
Working closely with the client, including operatives using the booths and fume cupboards, we considered the challenges of improving fume control and reducing manual handling of the methanol required in the production process.
Improvements to the flask filling requirements were addressed by an external methanol storage and piped distribution system, which allows operatives in the refurbished facility to fill a flask by simply opening and closing a spring-loaded valve. This not only avoids the need for methanol to be brought into the building in drums but also means that the operator can work in a position where fumes are not in close proximity to his/her breathing zone because he/she no longer needs to lean over the flask.
Design of the booth was more of an iterative process, with several designs considered in order to achieve the initial design intention of separating the operator from the process as much as possible. A restricted access barrier (RAB) combined with automated flask filling and emptying would have achieved this but this option was rejected due to the workflow implications of a restricted access arrangement. Incorporating the whole of the purification process into a partial enclosure, such as a fume cupboard, was also considered and rejected, as this would involve both restricted access implications and potential exposure to fumes when the fume cupboard was opened for access. After a thorough examination of several options, it was clear that adopting a side-flow booth strategy would answer both the operational and safety elements of the brief.
Side-Flow Booth Solution
The side-flow booth acts like a walk-in wind tunnel, promoting horizontal laminar air flow by inducing air from the face of the booth to the rear. Each of the three booths was designed as a corridor, with the purification equipment on one side and the oven and preparation table on the other. These process areas on opposing sides of the booth form the fume control zones with an operator breathing zone in the centre, providing space for operator movement and unrestricted access to equipment without risk of exposure to fumes.
Consideration of the interface between the operator and the process was vital to ensure unforeseen fume exposure did not take place. ‘Body wake’ was an important factor in this regard as turbulence from the operator’s movement could affect the laminar air flow of the fume control zones in the process areas. Consequently, it was important for the BES team to fully understand the process and model operator movements in the booth to ensure the breathing zone consistently provides uncontaminated air. Every design detail was considered to minimise disturbance of the laminar air flow with expertly engineered design detail. To minimise the extracted flow rate, the air is directed to where it is required and every element of the layout has been designed to accommodate this airflow management strategy. For example, a half-height door has been fitted to each booth entrance and a corner cut off has been used to remove unused cross-sectional area, optimising the air flow.
The arrangement and orientation of flasks, oven and corridor have all been designed to ensure that the operator stands side or shoulder to the airstream, reducing the wake effect of the body by orienting the narrowest point of the operator’s form towards the airflow. Any wake effect that is produced takes place downstream, in the central part of the booth, away from the operator, ensuring it does not affect the fume control zone airstreams on either side.
Energy efficiency has also been considered as an integral part of the design process. The three side-flow booths have been connected to a single variable volume extract system and presence detectors have been fitted to reduce the extract flow rate of each booth when it is unoccupied, reducing energy consumption while ensuring that the production environment remains compliant with its cleanroom classification at all times.
Heating and cooling recovery has also been built into the extract system to pre-warm or pre-cool the incoming air and the air discharge to atmosphere has been designed with a variable area twin discharge stack, maintaining discharge velocity while maximising the fan energy that can be recovered even when the extract flow rate is reduced for low occupancy.
Co-ordination of architectural and building services design expertise was vital in achieving the delicate balance of the facility, ensuring a solution that met both air flow and process efficiency requirements. A full scale mock-up of a side-flow booth was constructed to enable testing and end-user consultation as an integral element of the design process prior to fit out of the facility, ensuring the new facility would address all client requirements. A validation engineer was also consulted at design stage to ensure that commissioning and validation of the facility was straightforward enabling it to become operational as quickly as possible