Author: Maria Cristina Balducci

Diatheva operates a state-of-the-art GMP (Good Manufacturing Practice) facility, essential for producing active pharmaceutical ingredients (APIs) and sterile products that meet rigorous pharmaceutical standards. This article examines the facility’s structure, its environmental control systems, and the specific types of controls implemented to ensure the highest levels of quality and safety.

Facility Structure and Environmental Control Systems in Pharmaceutical GMP

Diatheva’s facility is designed with different levels of environmental control to prevent contamination. The areas are classified by the criticality of the processes performed in them.

Class D Environments are the least controlled and are used for initial steps like receiving raw materials and washing equipment.

Class C Environments are used for the more critical process of producing active pharmaceutical ingredients (APIs). These areas have stricter controls to reduce contamination during API synthesis and handling.

The most advanced level of control is the Isolator for Sterile Filling. This technology creates a barrier between the operator and the product to ensure a virtually contamination-free environment for the critical processes of filling and sealing sterile vials.

The facility’s layout also emphasizes the segregation of material and personnel flows, with controlled transfer points between different cleanliness classes to minimize cross-contamination risks. Construction materials for walls, floors, and ceilings are chosen for ease of cleaning, resistance to disinfectants, and lack of particle shedding.

Continuous and Periodic Environmental Monitoring for GMP Compliance

To ensure constant compliance with GMP requirements, Diatheva’s facility incorporates a sophisticated and integrated environmental control system, overseen by a robust HVAC (Heating, Ventilation, and Air Conditioning) system. A computerized monitoring system constantly records critical environmental parameters in all controlled areas, these include: temperature, humidity and differential pressure between different cleanliness classes.

Beyond continuous monitoring, Diatheva implements a rigorous program of periodic environmental controls, which are essential for verifying and validating cleanliness conditions and for early identification of potential issues:

  • Microbiological Controls of Surfaces: regular samples are taken using contact plates from all significant surfaces within controlled areas (floors, walls, equipment, workbenches, operator gloves). This allows for the quantification and identification of microbial load, verifying the effectiveness of sanitization procedures.
  • Microbiological Controls of Air: these are performed using active air sampler (which draw a known volume of air onto culture plates) and/or passive plates (exposed to the air for a defined period). These controls provide an indication of the microbiological quality of the air and the presence of airborne microorganisms.
  • Environmental Particulate Monitoring: these controls quantify the number of particles of specific sizes (e.g., ≥0.5μm and ≥5μm) present in the air. They are conducted using laser particle counter, which are crucial for the classification and maintenance of area cleanliness grades. The frequency of these controls varies based on the cleanliness class of the environment and the criticality of the process.

Ensuring Compliance and Corrective Actions in GMP Manufacturing

All controls, both continuous and periodic, are performed and documented according to strict Standard Operating Procedures (SOPs) and in compliance with current Good Manufacturing Practices (GMP) regulations. The data collected is analyzed, and any deviations or anomalous trends are promptly investigated to implement corrective and preventive actions (CAPAs).

To facilitate this process, specific files have been created for environmental trend analysis. These files are periodically updated with each control check, enabling continuous monitoring of contamination trends over time. The data from these files is then compiled into a comprehensive environmental monitoring summary report. This report not only consolidates the control data but also defines specific alert and action limits. These limits serve as critical thresholds: alert limits are an early warning, indicating a potential drift from normal operating conditions and prompting closer monitoring and action limits signal that an excursion has occurred, requiring an immediate and through investigation to determine the root cause and implement corrective measures.

Diatheva’s GMP facility stands as a testament to how advanced infrastructure design, state-of-the-art environmental control systems, and a meticulous monitoring and control program can ensure the production of the highest quality active pharmaceutical ingredients and sterile products. This unwavering commitment to GMP compliance and the application of best industry practices ensures that every batch produced by Diatheva is safe, effective, and meets international standards, significantly contributing to patient health.

 

Maria Cristina Balducci is Quality Control Analyst at Diatheva. With a degree in Biological Sciences from the University of Urbino and a specialization in Microbiology and Virology from Università Politecnica delle Marche, she has over 20 years of experience in quality control.