As a result, Occupational Exposure Limits (Occupational Exposure Level – OEL) are getting ever stricter. Isolators offer very high operator protection, because they represent a physical barrier between the operator and the process. Another advantage of isolators is undeniably the automated cleaning procedure allowing fast product changes and preventing cross-contamination.
Isolators are certainly the right choice for mastering high containment challenges, provided that system providers have the necessary expertise by taking into account all requirements and end-users are given the necessary training to ensure proper system use. Are these requirements not fulfilled, once more, risks cannot be controlled.
In the synthesis of highly potent active pharmaceutical ingredients (HPAPIs) filtration and drying of the moist products is an important process step where isolators can be recommended for optimal workplace safety and full recovery of the expensive materials.
Case Study: Filter Dryer Discharge Isolator
For the market launch of a highly potent solid product a globally active company based in Switzerland was searching for a suitable solution for the discharge from a filter dryer with integrated grinding and packaging features.
Dec implemented a process-integrated filter dryer discharging solution including grinding and filling into bags. This new multi-purpose production is based on three 1000-liter reactors and a filter dryer. In order to ensure very high containment (OEB 6) without the need to wear personal protective equipment, all process steps must be carried out in a closed and highly controlled environment.
Dec’s solution is based on a two-chamber isolator to provide a high containment environment during the automated discharge (via agitator), manual heel removal, milling and weighing product from a filter dryer. Both the upper and lower chamber will be connected directly to each other providing a direct discharge from the upper chamber through the cone mill and into a pack off head in the lower chamber.
The system manages the following requirements:
- Provide a safe barrier between the operator and the drug substance to ensure full protection
- Allow the processing of highly effective category OEB 6 (Occupational Exposure Band) products – Multi product use
- To be designed for operation in a classified ATEX area
- Both chambers being accessible at the same time to enable accurate product weighing
- Nitrogen-enriched atmosphere during production and cleaning
- Continuous liner system for the packing and transfers out of the isolator
- Maximum product recovery through manual heel removal from the filter dryer
- To achieve a weighing precision of +/- 5 g
This purpose designed isolator is designed to achieve very high containment levels (OEL < 50 ng/m3 for operations less than 2 hours TWA and < 25 ng/m3 for more than two hours of activity). To have simultaneous access both to the upper and lower chamber during the product discharge process, they were oppositely arranged providing access to the top chamber from the front via operator access platform and to the lower chamber from the rear side. The weighing indicator is in the upper chamber so that the weight of the liner on the weighing plate in the lower chamber is clearly visible to the operator in charge of the upper chamber.
This chamber is fitted with a gloveport guard system, which is interlocked with the filter dryer to ensure that access via the gloveports can only be achieved when the dryer pressure and agitator controls are in a safe condition.
Sampling, grinding and packing process
The back plate of the upper chamber connects the outlet of the filter dryer with the isolator and allows free product flow by means of a PLC-controlled agitator and specially designed outlet funnel. To help with manual heel recovery from the dryer discharge port, Dec has included a rake tool, which the operator can access by using the gloves.
Product and material transfers into and out of both chambers is achieved by using Rapid Transfer Ports (RTP) allowing both the safe and contained transfer and removal of items to and from the isolator such as product samples, the safe removal of the grinding media or introducing powder for regrinding if necessary.
The lower chamber is connected to the upper chamber via the product discharge chute through which the dried material is transferred to the grinding process in the lower chamber and then through the sieve to be packed into continuous liners.
As with the upper chamber, operator access is provided through gloveports. The built-in weighing plate provides an even bottom surface facilitating the handling of the bags. Absolute security is given as well when introducing new liners, tools and clamps via RTP. Due to the high containment requirements, the product leaves the lower chamber packed in additional liners through an additional continuous liner port.
The system is provided with a nitrogen purge system with oxygen concentration monitoring, differential pressure control and HEPA filtration systems filtering the air before it reaches the ambient atmosphere.
Flexibility and multipurpose
The isolator provides flexibility needed for process changes. Insofar, the scope of delivery included a mill replacement body that can be used if the product for the filter dryer does not need grinding, i.e. the upper chamber can be used for dispensing only. Material can be introduced through the RTP, distributed in smaller quantities and re-packed again.
Easy cleaning, training and validation
Both chambers are equipped with wash-in-place (WIP) systems, consisting of hand-operated pistols and spray hoses. With rounded corners and smooth inner surfaces cleaning is made easier.
It is crucial to verify that the complete process design is working properly and to ensure that operators are familiar with the process before the product is actually manufactured. The same applies to properly validated cleaning methods to make sure there is no cross-contamination when using the same system with other compounds.
Isolators provide highest operator protection when handling highly potent active ingredients, in addition, these systems maintain product integrity and sterility in aseptic manufacturing.Click here for more information on Dec Group