The handling of highly active ingredients during filling and packaging processes poses particular demands on the protection of people and the environment. At the same time, it must be guaranteed that no impurities enter into the final product and that all production processes proceed smoothly and efficiently from setting up to cleaning. A holistic approach, considering all process steps and interfaces, the “Hazard Evaluation”, makes Harro Höfliger a specialist in the field of containment and aseptic systems for reliable operator and/or product protection.
Depending on the application and OEL (Occupational Exposure Limit) requirements, GMP-compliant containment concepts, from simple, controlled local exhaust ventilation up to isolators are used. Harro Höfliger implements systems including APE (Advanced Protection Enclosure), high-containment concepts such as ABS (Advanced Barrier System) in isolator version and RABS (Restricted Access Barrier System) for aseptic product protection.
- Comprehensive approach with individual risk assessment
- Experience in the field of OEL limits below 0.05 µg/m³
- Using mock-up studies, machine ergonomics and processes are optimized and the positions for the transfer systems and glove ports defined.
- Customized and standardized, modular concepts
- Good cleanability of barrier systems
- Intelligent systems for transfer of material into and out of the barrier system
- Numerous implemented machines for processes under an inert gas atmosphere
All containment concepts are designed with an optimum of practical relevance enabling ideal handling and maximum mobility for operator tasks. In addition to mechanical barriers, the personal, product and environmental protection is achieved by maintaining a controlled under- or overpressure, controlled airflow and highly effective seals. The isolator design with integrated glove ports offers additional protection.
In the aseptic processing of sterile products, the first priority is to keep germs, impurities and contamination of all kinds out of the product. This is achieved by means of isolators as well as open and closed RABS (Restricted Access Barrier Systems) with integrated overpressure or laminar flow systems. Rapid transfer ports and active or passive mouse holes ensure the required aseptic conditions at the interfaces.
Harro Höfliger develops and builds barrier systems for complex processes with the highest demands on temperature, humidity or dryness of the air, as well as a particularly clean environment. Even flexible solutions for processes under inert gas conditions such as, for example, under nitrogen or argon atmosphere, can be implemented.
You founded the Barrier Technology Department in 2008. What challenges are you faced with at present?
When manufacturing new drugs, highly active substances (HPAPI) and thus operator protection by means of containment systems play an increasingly important role. At the same time, complex active ingredients are used which cannot be terminally sterilized and thus have to be processed under sterile conditions. Both have an impact on the respective production processes and barrier systems, and strict rules and regulations have to be adhered to.
Which rules and regulations are there in aseptics?
Among others, the FDA Guidance “Sterile Drug Products Produced by Aseptic Processing” and EU-GMP guidelines. When protecting the product – for example from germs, spores or human particles – aseptic processing in RABS and isolators is now state of the art instead of classical cleanroom technology. Basically, our task is to create and maintain a sterile environment, to control it, and to make sure that material can be transferred in and out.
How do you approach the containment subject?
In order to find the optimum containment solution, my team and I always consider the entire process and analyze the production-relevant factors. This includes the permissible occupational exposure limit (OEL) for the operator, toxicological values, dust potential and batch size, as well as material flow and building structures. The peripheral conditions such as dust extractors, exhaust air systems and especially the interfaces are also immensely important in the risk assessment. All components of a machine must be perfectly matched to one another to ensure the complete system meets the containment requirements.
What is possible with containments and what is necessary?
Uncritical sub-processes can be placed outside. This facilitates handling and cleaning. Critical processes must always take place in the containment with the lowest possible development and distribution of airborne particles. In the case of the containment concept for the capsule filling machines of the Modu-C series, for example, we achieve a validated safety level down to an OEL-value of <0,1 µm/m³ with these measures.