The production of beta-lactam antibiotics places high demands on the layout of a pharmaceutical facility. Especially when several antibiotic groups are produced within the same organisation, preventing cross-contamination is a core part of process safety.
A frequently asked question: can meropenem be produced in an existing facility originally set up for cephalosporins?
Both product groups belong to the wider beta-lactam family. That does not mean they can simply be processed in the same production environment. The biggest challenge is demonstrably preventing cross-contamination, with particular attention to highly sensitising substances.
Why beta-lactams require special attention
Beta-lactam antibiotics can cause severe allergic reactions in sensitive individuals. Strict requirements therefore apply to the separation of production processes for these product groups.
In its guidance on non-penicillin beta-lactams, including cephalosporins, penems and monobactams, the US FDA pays specific attention to separate production facilities. The European GMP framework also places strong emphasis on adequate technical and organisational segregation for highly sensitising substances.
The exact requirements must be assessed per product group, process and applicable regulation. The principle: where dedicated or separate facilities are required, cross-contamination cannot be controlled by cleaning between batches alone.
What does physical segregation mean in practice?
Physical segregation is more than a wall between two production rooms. A demonstrably segregated production concept can consist of:
- Separate production areas.
- Dedicated air handling units (AHU).
- Separate exhaust and ventilation systems.
- Suitable pressure differentials and pressure cascades.
- Separate material and personnel flows.
- Separate gowning and access zones.
- Suitable waste routes.
- Dedicated or demonstrably separated process equipment.
A separate facility does not have to be an entirely different building. The segregation must, however, be technically and organisationally demonstrable, and the layout must meet the applicable GMP and legal requirements.
The biggest challenge: shared powder processing equipment
When assessing an existing facility, attention often goes first to rooms and air handling. The greatest contamination risks, however, are often in the equipment that actually processes the powders, such as:
- Raw material dispensing stations.
- Bag dump stations.
- Sieving installations.
- Powder blenders.
- IBC systems.
- Pneumatic conveying systems.
- Filling and packaging installations.
During open operations, such as emptying bags or manually transferring powder, fine particles are released into the environment. They spread via equipment, clothing, airflows and contact surfaces. Assess not only the room, therefore, but the entire material route.
Closed powder transfer limits contamination risks
An important technical measure is limiting open powder operations. In traditional bag dumping, a package is opened by hand and emptied over a hopper, releasing dust. A closed transfer system considerably reduces this risk.
- Split butterfly valves: enable a controlled connection between two process components without a fully open connection to the environment.
- Closed drum and big bag discharge: with suitable docking and containment technology, powder can be transferred from a drum or big bag to the next process step.
- Closed sampling: operators are not unnecessarily exposed and the spread of product residues is limited.
- Containment during filling: closed liner systems and suitable docking solutions limit exposure when filling drums, bags or other packaging.
Closed handling does not replace segregation
Closed powder transfer is an additional control measure. It does not replace the physical segregation required by law or GMP. Its purpose is to limit dust emission at the source. This reduces the load on the environment and the air handling, and makes the effectiveness of the measures easier to demonstrate. Air and surface monitoring also become more manageable, provided suitable validated analytical methods are available.
How do you assess an existing production facility?
In a feasibility study, analyse the entire process chain, from receipt of raw materials to the end product. Assess the following:
- Where are raw materials opened and dosed?
- Which equipment comes into contact with the product?
- Which conveying connections are shared?
- How are material flows and waste separated?
- Which air handling systems are present?
- Which containment measures are available?
- How are cleaning, monitoring and maintenance validated?
Involve the quality department and the relevant regulator in the proposed segregation concept at an early stage.
The role of Hecht Technology
Hecht Technology supports the pharmaceutical industry with powder handling and containment. For high-risk processes we look not only at the required OEB classification, but also at the practical execution of raw material handling, dosing, conveying and filling. Closed transfer systems, containment stations and controlled powder transfer make an important contribution to limiting dust emissions.
Conclusion
Producing meropenem in an existing cephalosporin facility requires a thorough assessment of the applicable segregation requirements. A separate production environment, separate air handling and control of material flows are essential. Closed powder handling reduces exposure and the spread of product residues, but never replaces the required physical segregation.
TL;DR: In the production of beta-lactam antibiotics, demonstrable segregation is essential. Assess not only rooms and air handling, but also all equipment and material flows. Closed powder transfer helps limit contamination risks at the source.