In the First part of this article We explore the foundations of the design of facilities under GMP, focusing on flows, contamination control, scalability and documentary support.

In this second installment, we take another step and analyze the advanced aspects of the GMP design, including ergonomics, zoning, critical profits and maintenance, as well as the main strategic challenges and conclusions that mark the future of the pharmaceutical industry.

1. Security and ergonomics

The design of pharmaceutical facilities must not only meet the GMP standards in terms of quality and processes, but also guarantee a safe and efficient environment for staff. Occupational security and ergonomics directly impact productivity, reduction of human errors and the operational sustainability of the plant.

1.1. SAFE PEOPLE AND MATERIAL FLOWS

As we saw in the previous article, they are established Differentiated routes that strictly separate the transit of personnel, raw materials, product in process, finished product and finished product, supported by controlled access by personnel and material locks. These elements, combined with progressive clothing procedures and independent circuit planning for maintenance and production operations, allow preserving the integrity of the GMP environment and facilitating regulatory compliance during inspections.

1.2. Protection against chemical and biological risks

The implementation of Primary and secondary containment systems, such as biological security booths, insulators and barrier technologies, that avoid the exposure of personnel and the dispersion of pollutants in the environment.

These equipment are complemented with dedicated and controlled ventilation systems by differential pressures, which ensure a safe and directed air flow. Likewise, the manipulation of compressed gases, flammable solvents and hazardous waste must be governed by specific protocols Security, validated and documented, which minimize the risks during the operation and protect both people and the product and the environment.

1.3. Critical Services Security

The security in critical services is of the utmost importance, that the operational continuity of the facilities must be guaranteed and avoid interruptions that may compromise the quality of the medications.

To do this, systems are designed with double power double, which guarantees redundancy and minimizes the risk of unplanned stops. They are also incorporated detection and alarm systems capable of identifying gas leaks, variations in differential pressure or incidents in the supply of water and clean steam, facilitating an immediate response.

These elements must be complemented with well -planned and safe emergency accesses, which allow the rapid evacuation of personnel and the immediate intervention of security equipment in case of incidents.

1.4. Operator -centered design

Operator -centered design seeks to optimize the interaction between staff and facilities, reducing the risk of human errors and improving efficiency in operations. To achieve this, control equipment, instruments and systems must be strategically located, minimizing unnecessary displacements and facilitating accessibility to work areas.

In addition, it is basic to ensure that operating heights and control panels are adapted to Ergonomic criteria, avoiding forced postures and fatigue for prolonged shifts. The automation of repetitive or physically demanding tasks also contributes to a safer and more efficient environment, releasing activities that could generate physical wear or distractions that compromise the quality of the process.

1.5. Adequate work environment

The Homogeneous lighting and adapted Each area is fundamental, with higher intensities in visual inspection areas to reduce eye fatigue and facilitate defect detection. Likewise, the precise control of the temperature, the humidity and the Noise level It contributes to the comfort of the staff, which directly affects the reduction of human errors and productivity.

To these elements are added support spaces, such as changing rooms, rest areas and offices near production rooms, which must be designed with functional criteria to favor the operation and well -being of the equipment.

1.6. Training and security culture

It is not enough to have adequate infrastructure and equipment; It is necessary that the staff be duly formed to use them safely and according to the GMP standards. To do this, they must be implemented Continuous training programs that update the personnel in good ergonomics practices, security protocols and specific procedures of the plant.

It is essential to promote a proactive culture, where workers participate in the identification and report of incidents or "near miss", integrating these observations into a Continuous improvement system. This approach not only protects people, but strengthens the reliability of processes and quality of the final product.

1.7. Current trends in safety and ergonomics

• Use of digital twins (digital twins) to simulate flows of people and materials before construction.
• Integration of real -time monitoring systems of environmental and security conditions.
• Application of user -centered design principles (Human-Centered Design) in clean rooms and support areas.

2. Zoning and classification of areas

The correct zoning and classification of areas ensures the Cross contamination prevention, he regulatory compliance and the Product security. GMP demand a design based on the logic of controlled flows of personal, materials, equipment and residuity, where each area must be clearly defined and backed by regulatory and technical criteria.

2.1. Functional separation of areas

The functional separation of areas allows to organize the spaces so that, each stage of the production process is developed in controlled conditions and without interference. To do this, The areas are defined destined to the storage of raw materials, preparation, production, quality control, packaging and storage of finished product, ensuring that each meet the specific cleaning and safety requirements. This segregation is reinforced by the corridor design, LEVELS and access independent, that avoid the intersection of personnel and material flows, thus minimizing the risk of cross contamination and facilitating traceability within the plant.

2.2. Classification of clean areas

The classification of clean areas in pharmaceutical facilities is established in accordance with international standards, such as Annex 1 of the EU GMP and ISO 14644, which define cleaning levels based on the maximum concentration of particles in the air.

These areas are usually organized in Grade A, B, C and D, where degree A corresponds to the most critical environment, such as sterile filling cabins; Grade B works as a support of aseptic operations; and grades C and D are destined for less critical processes, such as initial preparation or manipulation.

The maintenance of these classifications depends on use of HVAC systems With high efficiency filtration, Differential pressure Between areas and a strict environmental control, which ensures that the conditions are stable both in a "rest" and "in operation" state.

23. Personnel and material flows

The design of personnel and material flows is a critical element to preserve the integrity of classified areas and avoid cross contamination. For staff, locks or costumes are used in waterfall, where the clothing is changed progressively according to the degree of cleaning required, while the materials and equipment They are transferred through specific locks that incorporate disinfection and controlled transfer protocols.

The route design must be Unidirectional, which means that tickets and exits are clearly differentiated, minimizing setbacks that may compromise the classification of areas. This approach guarantees that both people and materials follow safe and traceable trajectories, aligned with the regulatory requirements of GMP.

2.4. Environmental control

Environmental control is a pillar in the design of pharmaceutical facilities, since it ensures that the conditions of pressure, temperature, relative humidity and particle load They are maintained within the ranges required by the GMP. To do this, HVAC systems must be designed in a way that guarantee a constant supply of clean and filtered air, accompanied by continuous monitoring that allows to verify its real -time effectiveness.

In the critical areas, as those classified in degrees A and B, this control must be even more rigorous by incorporating permanent surveillance systems that detect deviations immediately. In this way, it is ensured that production operations are developed in a stable, controlled and aligned environment with international regulatory requirements.

2.5. Cross contamination prevention

Cross pollution prevention in the zoning of pharmaceutical facilities requires an approach that combines physical separation, design of validated flows and procedures.

For high -risk products, such as HPAPI or certain biological ones, it is necessary to have segregated production areas or dedicated facilities that eliminate the possibility of transfer unwanted between processes. In cases where total separation is not viable, containment technologies, such as insulators or rabs systems, which create effective barriers between the product and the environment.

This design must be complemented with rigorously validated cleaning and decontamination protocols, so that each area recovers its control conditions after each campaign or product change, ensuring both the quality of the medication and the safety of the personnel.

2.6. Current GMP Zoning Trends

• Use of barrier technologies (rabs, insulators) that reduce dependence on the degree of environmental cleaning and raise process safety.
• Incorporation of digital zoning through digital sensors and twins that allow simulating and verifying air flows and people before construction.
• Flexible design that allows reclassifying areas according to future production needs, without compromising regulatory compliance.

3. Critical Profit Management

The Critical profits They are those auxiliary services that directly impact the quality of the product and, therefore, must be designed, validated and maintained under the same control criteria as the production areas. They include: Purified water (PW), water for injectables (WFI), clean steam (PS), compressed gases, nitrogen, oxygen and HVAC systems for classified areas.

A poor design or inappropriate management of these profits can compromise the Sterility, data integrity, regulatory compliance And, ultimately, the patient safety.

3.1. Design and installation

The design and installation of critical profits in a pharmaceutical plant must guarantee both the quality of the service like the Ease of operation and maintenance. To do this, the pipes and equipment are manufactured in Materials compatible with pharmaceutical use, such as 316L stainless steel or validated polymers, always with sanitary finishes that avoid the accumulation of pollutants.

In addition, the design must contemplate appropriate earrings that ensure a Complete drainage and eliminate the possibility of dead points, where water or steam can stagnate and favor microbial growth.

All this approach must be executed following international reference standards, such as Ispe Baseal Guides of their USP <1231>, that establish good practices in the design of water systems and critical utilities.

3.2. Qualification and validation

This process includes stages of Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (Oq) and Performance Qualification (PQ), which verify from the conformity of the design to the performance of the system in real conditions.

In each of these phases, they must be established Acceptance criteria based on normative and pharmacopoeic parameters, such as the microbiological and physicochemical quality of water, the Gase purity o to Efficiency in the generation and distribution of clean steam.

3.3. Monitoring and control

Capable systems are implemented measure in real time variables such as temperature, pressure, conductivity, total organic carbon (TOC) and particles. These systems are usually integrated into SCADA or BMS Validated Platforms, which allow draw all records in accordance with the principles of data integrity. In addition, the presence of configured alarms To detect deviations, it guarantees an immediate response before the processes are compromised.

3.4. MAINTENANCE AND OPERATION

Water, steam and gas systems require periodic sanitization strategies, which may include the use of steam, ozone or hot water, always validated and documented. He Preventive and predictive maintenance It becomes a key practice to preserve the reliability of the equipment, reduce the risk of unplanned stops and maintain the facilities in validated state.

All this must complement the Specific staff training Responsible for the operation, ensuring that both associated risks and security procedures in the manipulation of critical profits.

3.5. Risk management

Risk management in critical profits is an essential component of design and operation under GMP, since it allows identifying, evaluating and mitigating possible impacts on product quality and patient safety. Applying the principles of the ICH Q9, the risks associated with each system Considering the criticality of processes, technological complexity and the possibility of failures. From this analysis, the critical control points (CCPS) are defined that must be monitored and maintained under strict parameters, thus ensuring that profits are maintained within validated conditions and that any deviation is detected and managed before affecting the final product.

3.6. Trends and current best practices:

• Use of Water systems without storage tank (continuous loop) to reduce microbiological risk.
• WFI decentralized generation through Inverse osmosis membranes + electrodeionization + ultrafiltration, recognized by EMA since 2017.
• Integration of Advanced analytics and predictive maintenance through artificial intelligence to anticipate deviations.
• Standardization of Data Integrity protocols in electronic records of critical profits.

4. Maintenance and accessibility

The design of pharmaceutical facilities must contemplate from the beginning the maintainability of systems and safe accessibility to critical equipment and infrastructure. It is not enough to meet the process requirements in the construction phase: a plant that does not facilitate maintenance is exposed to Unplanned stops, regulatory deviations, high costs and safety risks.

4.1. Accessibility to equipment and services

The incorporation of dedicated technical spaces, such as service corridors or traffic roofs, which facilitate intervention in critical systems without accessing classified areas. These spaces must be designed to Allow component replacement such as pumps, valves, filters or HVAC modules safely and efficiently. Likewise, the modular design of equipment and production lines helps to simplify disassembly, cleaning and reconfiguration tasks, guaranteeing that maintenance is carried out in an agile manner and with minimal impact on operational continuity.

4.2. Separation of technical and process areas

This approach minimizes cross-contamination risks and ensures that maintenance activities do not interfere with production. To achieve this, equipment and service lines are installed in adjacent technical areas or maintenance corridors, facilitating both safe access and component replacement. In this way, you get a more controlled environment, efficient and aligned with regulatory requirements, while reducing operational interruptions.

4.3. Preventive and predictive maintenance

The preservation of the validated state of the facilities and the reduction of risks associated with unexpected failures is the result of preventive and predictive maintenance. For this, the Integration of IoT sensors and supervision systems, such as SCADA or BMS, allows continuous monitoring of critical variables, such as vibrations, pressures, flows or temperature, providing real -time data to anticipate deviations.

These tools, combined with advanced analytical techniques and artificial intelligence, allow to implement predictive maintenance strategies that They identify failure patterns before they materialize, avoiding unplanned stops. In turn, preventive maintenance plans, aligned with the criticality of each team and with the provisions of the Validation Master Plan (VMP), ensure that the equipment is preserved within controlled parameters and that the facilities continue to operate reliably and safely.

4.4. Document management and traceability

Each intervention, whether preventive, corrective or predictive, must be registered in validated electronic systems such as CMMS or EQMS, ensuring compliance with Alcoa+ data integrity principles. These records not only document the tasks performed, but also allow them to link them with the history of each team, facilitating the evaluation of trends and the planning of future interventions.

In addition, the integration of maintenance documentation with the change control system guarantees that Any replacement, adjustment or improvement is found justified, validated and traced within the life cycle of the installation, thus maintaining its validated status and its compliance with international regulatory requirements.

4.5. Safety of maintenance personnel

To protect personnel, the design must consider safe access with ergonomic criteria, adequate work platforms, handrails and anchor points for work at height.

The application of lockout and tagout procedures (LOTO – Lock Out Tag Out) is essential to ensure that the equipment is isolated and without power during interventions, avoiding accidents for unexpected starts. These technical elements must be complemented with continuous training programs in specific risks of GMP areas, such as exposure to biological, chemical, pressure or energy agents, ensuring that personnel always act under standardized protocols and in maximum security conditions.

4.6. Current Maintenance and Accessibility Trends GMP

• Digital twins (Digital Twins) to plan maintenance interventions and evaluate impact without the need to interrupt processes.
• Modular Design of Critical Profits (eg purified water skids or clean steam) to facilitate your replacement or update.
• Remote maintenance and augmented reality (AR/VR) for real -time technical assistance and staff training.
• Focus on Sustainable design, optimizing accessibility to prolong the life of equipment and reduce the consumption of resources.

5. Challenges in the design of GMP facilities

The design of pharmaceutical facilities under GMP standards faces multiple challenges that go beyond the simple construction of a building. Among the main challenges are:

1. Integration of complex flows. Coordinate the safe movement of people, materials, waste and products without compromising segregation or integrity of the product.
2. Contamination control and critical areas. Maintain the classification of clean areas during operation and facilitate the cleaning, disinfection and continuous monitoring, as well as incorporating containment and isolation technologies for high -power or sterile products.
3. Critical utilities management. Ensure the availability, quality and traceability of water, steam, gases and HVAC systems, with the ability to climb or adapt to new needs.
4. Flexibility and scalability. Design facilities that can adapt to changes in production, introduction of new products or new technologies, without compromising regulatory compliance.
5. Maintenance, accessibility and ergonomics. Ensure that critical equipment is accessible to preventive and corrective maintenance without interrupting the operation or putting the quality of the product at risk. Together with the design of a safe and ergonomic environment that minimizes human errors and protects staff.
6. Documentation and regulatory compliance. Coordinate the US, DQ, VMP and all the validation and control documents, ensuring data integrity and preparation against regulatory inspections.
7. Technological integration and digitalization Incorporate automation, remote monitoring systems, advanced analytics and digital tools maintaining compliance with regulatory standards and cybersecurity.
8. Sustainability and efficiency. Reduce energy consumption, optimize resources and plan a sustainable design without compromising quality and safety.

Conclusions

The design of pharmaceutical facilities under GMP is a multidimensional process that combines engineering, quality control, regulatory compliance and operational experience. The main elements identified, Controlled Flows, Contamination Control, Critical Profit Management, Flexibility, Maintenance, Ergonomics and DocumentationThey constitute the basis for guaranteeing safe, efficient and sustainable processes.

In practice, an effective design allows:

• Minimize risks of contamination and human errors.
• Ensure product integrity and compliance with international standards (EMA, FDA, WHO).
• Facilitate the validation and management of the life cycle of the facilities and equipment.
• Adapt to new products, technologies and regulations without significant interruptions.

In short, investment in an integral design translates into Patient security, regulatory compliance and industrial competitiveness.