sponsoredIntegrated Containment Safety in Tablet Production

Sponsored by

Fette Compacting GmbH

The revised Hazardous Substances Ordinance raises the bar for closed systems in tablet production and promotes system integration. Containment is becoming the new standard for highly active ingredients. How Fette Compacting is dealing with the increasing requirements for active ingredient safety and process control.

The market for highly active pharmaceutical ingredients is growing rapidly. With the triumph of innovative therapies – for example, in oncology and precision medicine – and the continuous development of regulatory guidelines, the demands on containment solutions in tablet production are becoming increasingly complex. The focus is no longer on individual machines but on the interaction of entire plant networks. Their process reliability and efficiency must be guaranteed throughout their entire life cycle.

With the amendment to the Hazardous Substances Ordinance (GefStoffV) in December 2024, German legislation has significantly strengthened the principle of integration. Of particular importance is the adoption of the risk-based approach from the Technical Rules for Hazardous Substances (TRGS). For carcinogenic, mutagenic, and reprotoxic substances (CMR categories Ia and Ib), the use of closed systems is explicitly specified as the preferred protective measure for the first time. This makes containment the new standard and reference for all further measures as a technical solution.

Gallery

A key innovation also concerns the introduction of clear acceptance and tolerance concentrations as exposure limits. If these values are exceeded, technical or organizational corrections must be initiated immediately. The regulation also revises access, training, and reporting requirements: entry to production areas where highly potent substances are processed must be strictly controlled. Training becomes mandatory, and reporting procedures in the event of an incident are clearly defined and linked to threshold values. This means for operators: A coherent, comprehensive containment concept that includes all interfaces, maintenance, and cleaning processes is required as early as the planning stage.

SMEPAC: Focus on Life Cycle and System Integration

The SMEPAC (Standardized Methodology for the Evaluation of Pharmaceutical Ergonomic Particle Emission from Containment Systems) practical guide from the ISPE (International Society for Pharmaceutical Engineering), also updated in 2024, accompanies the regulatory changes and has evolved from the evaluation of individual components to a holistic view of complex production systems. The guide requires that containment performance is not only ensured and validated during operation but also during cleaning, changeovers, and maintenance. The focus is particularly on continuous production lines with multiple containment levels and transfer sections. Test protocols that previously applied to individual machines are now designed for entire plant networks – a decisive change for practitioners and authorities.

Another new feature: the selection and handling of surrogates are regulated practically. Mixtures with excipients are permitted, and statistical methods for evaluation are adapted to real production conditions. Containment measurements should already be carried out during factory acceptance testing. Repetitions after maintenance or modifications are recommended. In this way, performance is documented from the very beginning and remains verifiable throughout the life cycle.

System Integration: Fewer Interfaces, Greater Safety

Practical experience shows that it is not leaks but transfer points between process steps that pose the greatest risk of exposure. Every material transfer and every change between systems carries potential hazards for operators and the environment. Modern plant concepts therefore rely on end-to-end integration: as few technically secure interfaces as possible are crucial.

A clear example of the advantages of modern system integration is continuous direct compression: in this closed system, material feeding, dosing, mixing, tableting, and quality control are combined into a continuous process line. The modular design not only enables a compact plant structure, but also ensures that all process steps are directly integrated into the containment and that validation is carried out as a complete system.

The importance of this approach is also highlighted in the current SMEPAC guideline, which explicitly mentions continuous manufacturing.

Test Laboratories and Exposure Measurements as Success Factors

The importance of practical test environments at containment system manufacturers is growing steadily. To ensure the safe processing of active to highly active substances, extensive tests are carried out even before commissioning at the customer’s site. The current SMEPAC guideline also recommends that the initial verification of containment performance should be carried out during the factory acceptance test (FAT) at the manufacturer’s plant. This early qualification allows potential weak points to be identified and rectified immediately. Standardized methods are used here with both substitute substances and real active ingredients, always with the aim of maximizing reliability and safety in later operation.

The focus is on a comprehensive analysis of the containment performance. Tools such as the Containment Guard enable precise measurements in various practical situations – from routine processes and maintenance work to the simulation of disruptions or power failures. The test protocols developed in accordance with SMEPAC ensure reproducible results, which in turn serve as a solid basis for the approval of the system.

A New Level in Containment Systems

Considering stricter requirements for active ingredient safety and process control, Fette Compacting is increasingly focusing on highly developed, fully integrated containment solutions. Even the basic equipment of modern tablet presses is designed to be dust-tight and operates with negative pressure to prevent active ingredients from being released. Additional protective barriers are available as optional containment packages – for example, glove ports and transfer systems (Rapid Transfer Ports, RTP) ensure safe and contamination-free handling during operation. For the highest safety requirements, high-containment systems with isolators, integrated wash-in-place technology, and air management are used.

A new innovation coming in 2025 is washable air management. This advanced system not only ensures constant negative pressure in the plant, but can now also be cleaned and validated automatically. Flow simulations are used to position the wash nozzles optimally along the air ducts so that all areas are reliably decontaminated. This significantly reduces manual intervention and the associated exposure risk for operators, while at the same time strengthening compliance with regulatory requirements and operational safety.

Conclusion: Understanding Containment Holistically

The amended Hazardous Substances Ordinance and the revised SMEPAC practical guide mark the beginning of a new era in containment: complex, integrated production systems must be viewed holistically, validated, and continuously monitored digitally – throughout their entire life cycle. The close interlinking of process technology, cleaning, data analysis, and system integration forms the basis for sustainable safety and efficiency. Future-proof containment solutions are increasingly being developed in close partnership between plant manufacturers and pharmaceutical companies.

(ID:50614611)