How do you create GMP facilities?

Everything stems from a predefined design. This encompasses the tasks to be done, the timeline for completion, and the personnel required to achieve the objectives. Proper planning integrates all this information. Ideally, such planning should already account for potential project delays, be they in construction, equipment delivery, or installation issues. While we cannot predict every turn of events, we must be prepared to adapt when unforeseen challenges arise. One significant pitfall is the temptation to delay activities, particularly early in the project. While no approach is flawless, it’s vital to establish clear agreements from the outset about how to handle such shifts. Postponing can risk overshooting budget and missing deadlines.

When designing GMP facilities, several key factors must be considered to ensure compliance and to minimize risks related to contamination, cross-contamination, and errors. Logical flow of materials and personnel must be ensured to minimize the risk of contamination. Facilities must have separate areas for different activities. High-risk products should be handled in dedicated facilities. Cleanroom classification should be based on the type of product. Cleanliness criteria must meet air quality standards defined by the ISO 14644 and GMP guidelines. HVAC systems should maintain appropriate temperature, humidity, and air filtration to minimize contamination. Air pressure differentials should be managed to prevent cross-contamination.

GMP guidelines are stricter than ISO 14644 for particle monitoring and sampling. That’s why a monitoring system is mandatory for sterile drug manufacturing under GMP guidelines with different sampling frequencies for each grade. The approximate cost for a 21CFR monitoring system (including pressure/temperature/humidity) can range from $50,000 to $1 million for a GMP facility depending on the number of rooms, your specific requirements, and the number of probes you want/need. You will need to consider this system in your GMP facility’s budget. In a GMP cleanroom facility, First, there is environmental monitoring, but there is microbiological monitoring as well. Environmental monitoring examines air pressure, humidity, and airborne particles.

The layout of the facility must minimize contamination risks by ensuring controlled flows for personnel, materials & products. GMP facilities often have clear demarcations for “clean” and “dirty” areas to prevent cross-contamination. Separate zones for raw materials, processing, packaging, and finished goods storage. Restricted access to critical areas based on personnel qualifications. Incorporate flexibility to accommodate future expansion, changes in production capacity, or new technologies while maintaining compliance. Use materials for walls, floors, ceilings, and surfaces that are easy to clean & resistant to chemicals to avoid contamination. All equipment should be designed for easy cleaning, maintenance, and sterilization.

These qualification steps (IQ/OQ/PQ) are the first part of validation. However, the steps alone aren’t the only part of validation. There’s a little more to it. GMP requires process validation, cleaning and sanitation validation, computer system validation, and analytical method validation. GMP qualification and validation can get confusing, especially if you’re new to the processes. If you’re looking for some help, reach out to a qualified vendor, Angstrom Technology. They will be your guide to designing and installing a cleanroom that’s safe, efficient, and compliant with industry standards.

Installation qualification (IQ): A set of documents for the necessary activities to ensure that the system/device arrives as designed, specified, and is installed appropriately within the work environment, and that this environment is suitable for its operation and functioning as required. Instrument Delivery: Ensure that equipment arrive as planned by the user without any damage. Description: identify equipment, and its components (model , software version , serial number of its component parts, preliminary specifications). Assembly & Installation: Ensure that the assembly and installation are done correctly. Installation Verification: Ensure that the installation will achieve the required functions.

Surprise internal audits help discover where GMP compliance is truly taking place—and where it is not. Thus, it is important to routinely conduct surprise audits of GMP compliance to spot and correct any variance that is unexpected. The results of these internal audits should be shared with employees within all departments related to the facility. In addition to internal audits, monitor instruments, equipment, processes, and staff skills at regular and specific intervals for the assurance of ongoing GMP compliance. Frequently employees in production departments ignore a problem just because it is common. Ongoing monitoring will spot these issues.

Mi consejo es primero de todo leerse la normativa a aplicar y, seguidamente, realizar un análisis de riesgos para ver qué mantenimiento será preventivo, correctivo y predictivo. Lógicamente el realizar auditorías internas, junto con una revisión continua de las desviaciones que ocurren es importante para ir modificando este análisis de riesgos e ir enfocando este mantenimiento a un estado lo más personalizado posible a la planta farmacéutica. Es por ello que este análisis de riesgos es un documento "vivo".

Training is critical in the creation and maintenance of GMP facilities. However, it’s usually underestimated and poorly planned. Training requires an assessment of needed skills and knowledge, and an assessment of personnel. Once needs are known, and personnel knowledge and skills are evaluated, a personalized training plan can be developed. The training plan should include who is performing the training, frequency and times of training activities, documentation and evaluation of training outcomes.

Develop comprehensive training programs to ensure that all employees, including cleaners, technicians, and operators, understand and comply with GMP requirements. Initial and ongoing GMP training is crucial. Specialized training for those in charge of quality control, validation, and regulatory compliance.

Because GMP requirements touch on many areas of a manufacturer, bring awareness of GMP standards across the company and train employees on GMP needs such as record-keeping, sanitation, equipment handling, labeling, constant vigilance, Standard Operating Procedures, ways to minimize errors, etc. Ensure that guidelines and manuals are in place to assist with this process. The foundation for GMP compliance at a manufacturing facility is resource planning software that oversees and standardizes operations across a manufacturer’s operations. This ensures standardized, reproducible operations and procedures necessary for GMP compliance.

●GMP facility design; must be perfect to succeed. Designing GMP facilities necessitates a deep understanding of the regulatory landscape. The proper design, layout, function and control of such facilities is essential. ●GMP facilities demand rigorous control over environmental conditions, particularly in cleanrooms. The design of cleanrooms becomes a critical component for the facility. ●Ensuring that equipment and facilities consistently meet predefined standards is critical for GMP compliance. Validation processes begin with the selection of equipment that meets GMP standards. ●The human element is a critical factor in maintaining GMP standards. Personnel training starts with comprehensive education on GMP regulations.

Uno de los documentos que más me gustan es el "Informe de revisión por dirección" que se realiza anualmente, ya que , en algunos de sus apartados, se puede observar el número de desviaciones, reclamaciones, KPIs, CAPA, resultados de auditorías, etc... y, al ver dichos resultados en un entorno más extenso (1 a?o) se puede realizar un estudio sobre cuáles son los resultados que más se han obtenidos y evaluar si son importantes o no y cuáles se pueden modificar. Con ello se podría modificar el análisis de riesgos de cual he hablado anteriormente (punto 4).

Equipment is also a crucial part of the facility. Equipment must be designed for easy cleaning to reduce contamination risks. The materials used should resist corrosion and degradation. For some products (e.g., biologics or highly potent substances), dedicated equipment or very stringent cleaning processes are necessary to avoid cross-contamination. Equipment should be properly labeled to indicate its status (clean, in use, out of service) and ensure it is used for the correct purpose. All equipment must be regularly calibrated and validated to ensure it performs according to specifications.

Designing spaces that meet regulatory standards for cleanliness, safety, and efficiency. Start by ensuring appropriate layout to minimize contamination risk, with clear separation of critical areas like production, packaging, and storage. Use suitable construction materials that are easy to clean and maintain. Equip the facility with validated HVAC systems, water purification, and waste management systems. Implement robust monitoring controls for environmental parameters like temperature, humidity, and cleanliness. Compliance with GMP guidelines should be integrated into facility design, ensuring smooth workflows and regulatory adherence.