The containment industry is evolving – are you? Asks the Dec Group
Realising the desired levels of containment to minimise operator exposure while protecting sterile products is a complex process in which nothing can be left to chance.
Containment
Aseptic high-potency API processing calls for specialised facility design to help pharma improve and maintain the sterility of its drug products.
It is essential to partner with vendors that understand both containment and the requirements for sterile potent-compound handling. Equipment should be purpose built and provide the necessary flexibility to deal with process changes, especially for multipurpose facilities. Many technologies help improve the safety and efficiency of aseptic drug manufacturing. These include mobile cleanrooms and restricted access barriers (RABs), laminar flow cabinets or glove boxes and increasingly isolators – this article presents a recent application in the field of animal health.
The customer faced the challenge of how to charge a reactor with sterile high potent ingredients assuring operator and product protection.
The isolator had to meet the following requirements:
- OEL (Occupational Exposure Limit) of < 1 µg/m3 time weighted average over 8 hrs (TWA)
- Provide a safe barrier between the operator and the active drug substance to ensure both operator and product protection
- Achieving and maintaining an ISO 14644-1 class 5 environment for particles and viable micro organisms
- Plant designed to operate in both positive and negative pressure modes and in sterile and non-sterile conditions
- Multi-product use of OEB 5 category (sterile potent compounds)
- CIP / SIP / temperature mapping
Dec’s process containment experts designed this high level environment isolator as an L-shape twin chamber isolator consisting of a fast gassing airlock and a main charging chamber which are connected via an internal transfer door. The system is designed for the charging of either sterile or high potent compounds supplied in various number of bags of different sizes and weights max 15 bags x 10 kg into a process reactor by means of a powder transfer system (PTS).
For cleanliness the isolator features a through-the-wall design creating a dedicated technical area for maintenance and services at the rear which is accessed separately to the process area. The process operation mode is selectable either in positive or negative pressure via the HMI.
Sterile mode operation - Both chambers are initially loaded with bags of sterile APIs in various weights and sizes through the front visors. Both visors are then closed and the isolator environment started. Before production an automated pressure decay test is performed.
The operator then removes the outer foil bag from which each bag which is disposed via a non-sterile endless liner in the airlock. Each one is hung in a specific validated position using Dec’s automated bag rack system.
Both isolator chambers are biologically decontaminated using Vaporised Hydrogen Peroxide (VHP). This achieves a 6-log reduction using a validated decontamination cycle and an integrated open loop VHP generator.
The bags are then removed from the rack and those from the airlock are transferred into the main charging chamber. The internal transfer door is then interlocked closed.
The weight of each bag of powder is then manually verified on an internal scale prior to manually opening the bag and manually charging the sterile APIs into a pre-sterilised (with clean steam) powder transfer hopper. The APIs are then conveyed into a sterile process reactor using Dec’s patented powder transfer system, which is installed directly on the process reactor in an adjacent vessel room.
Due to the campaign requirements the process is continued by using the airlock as a fast gassing airlock and the internal transfer door between both chambers interlocked until the next VHP cycle has been completed. This enables the charging chamber to remain sterile at all times.
Potent mode operation – The isolator operates in the same principle as the sterile product but the isolator operates in negative pressure. There is no requirement for biological decontamination of the incoming product.
Due to containment in this mode the main charging chamber operates at a lower negative pressure to the airlock and the airlock is operated as a conventional transfer airlock chamber.
The PTS conveys and doses dry and wet powders and granules. To convey powder, the system operates with vacuum and pressure. It is composed of a cylindrical body which is alternately filled by vacuum and discharged by pressure. A flat filter membrane in the upper part prevents fine dust particles from entering the vacuum line. The membrane is cleaned by each discharging cycle by means of sterile compressed air or inert gas.
The system including charging hopper and transfer hose to the process reactor is sterilised in place (SIP) with clean steam with full thermal mapping. Sterility is assured throughout the whole dispensing and charging process.