Historically the handling of solids to and from process within API dedicated GMP production areas has only been possible by ‘open transfer’ using drums and manual handling. This is partly due to the difficult flowing cohesive solids used in API production and the possible discharging concerns.
Due to the increasing trend for more and more potent actives, ‘open transfers’ are no longer acceptable for health and safety reasons. Developments initially focused on enclosing the drum tipping operation using isolators or disposable bag within bag concepts, all of which continued to be very manually orientated.
More recent developments include the use of IBCs with ‘direct’ containment connections to and from the process, effectively achieving ‘closed transfers’ with no operator involvement.
Solids handling first – containment second
In achieving closed transfers it is imperative that all solids handling risks are fully understood and designed for. Containment of the closed transfer is not just a matter of selecting a valve, as it is simply not possible to ‘hit’ or ‘rod’ inter-connections or IBCs to overcome blockages. Consistent solids flow must be achieved first.
Any IBC system must be able to ensure flow of ‘wet’ solids from filter press or centrifuge, which may have 30%-40% solvent content, down to free flowing milled solids, when feeding to pack off machines.
It is also necessary to understand issues of pressure / vacuum that may be generated during processing but more importantly on disconnection of the IBC. This includes nitrogen purging of the system prior to solids transfer and a modern purpose-built API facility recognises the importance of material handling and containment.
Modern API facility – solids handling
It must include specific material handling floors above and below process to allow for complete easy batch transfer using gravity, whilst maintaining a close system.
Cleaning-in-place of these closed transfers is also a requirement to minimise operator involvement and to maintain containment.