Cleanroom Qualification: Ensuring Compliance & Quality

What Makes a Cleanroom Compliant?

Cleanrooms must control airflow, workflow, and staff flow to minimize contamination and cross-contamination. Compliance extends beyond ambient conditions—such as temperature, humidity, and air quality—to include equipment and process qualification. Companies investing in cleanrooms must allocate resources for these critical steps to avoid costly retrofits later. Particle concentration levels, classification standards under ISO-14644-1, and microbiological control are crucial factors in designing a compliant cleanroom.

GAMP®5: A Framework for Computer System Validation

GAMP®5 (Good Automated Manufacturing Practice) is a guidance document that provides a framework for risk-based computer system validation. Under the GAMP® model, a computer system is evaluated and classified depending on its intended use and complexity. The latest GAMP® approach uses a V-model diagram to illustrate the consecutive steps in system validation and contains the specifications established for a particular computer system and tests that constitute the verification process.

Key Elements of GAMP®5

Design Qualification (DQ) – Checks that cleanroom design, systems and equipment align with regulatory requirements. It's important to consider space capacity, layout efficiency, contamination prevention measures and the placement of HEPA filters to control airborne particulates.

Installation Qualification (IQ) – Verifies that installation adheres to design specifications. Comparing installation records with standard procedures ensures readiness for operational testing. Equipment like particle counters and photometers can validate proper installation.

Operational Qualification (OQ) – Evaluates system performance under worst-case scenarios. Tests may include recovery tests to measure how quickly the cleanroom returns to compliant particle concentration levels after simulated contamination, as well as airflow pattern testing to ensure consistent clean air delivery.

Performance Qualification (PQ) – Assesses system performance under normal operating conditions. Simulations test load capacities, contamination control and workflow efficiency. Microbial and particulate monitoring is essential to maintain compliance.

Centralized Monitoring System Validation

Contamination in any cleanroom can introduce discrepancies in product quality, eventually affecting process outcomes. Through environmental monitoring, you can sample process areas to confirm they are operating within the defined parameters.

Autonomous monitoring systems are replacing low-cost manual sensors. With a centralized system, you can integrate all your sensors into one central dashboard, thereby bringing all your data under one roof. This centralization helps eliminate the manual tasks of sensor activation, resetting, and data collection. Additionally, you will enjoy the benefits of automated and seamless data acquisition, distribution, and analysis.

What is Included in a monitoring system?

A monitoring system is a crucial tool in cleanroom requirements and maintaining compliance within a sterile facility. It provides a way to log prevailing ambient conditions that prove compliance to regulatory standards. Additionally, the monitoring system can log deviations from the expected conditions and generate alarms to trigger remedial procedures. Through environmental monitoring, you can avoid product loss and improve process efficiency and product quality.

The system hardware is any programmable device applicable in a quality-related process. A computerized system validation must also include software validation, which provides documented evidence that the software performs according to the design and user requirements. Identifying and eliminating software bugs is part of software validation under the 21 CFR Part 11. The GAMP® requires that every monitoring system maintains information confidentiality, integrity, and availability.

What are the requirements?

Documentation is an essential GMP requirement for any validation process. Without accurate and authentic documentation, it is impossible to prove compliance. The documentation includes user requirement specifications that show the system's intended use. However, system requirements vary depending on the use and complexity, the more complex systems requirements, the more stringent measures are needed. The design qualification process considers the user requirement specifications and establishes whether the system can function efficiently before installing and commissioning.

When designing a new cleanroom, you can incorporate a built-in building automation system. Usually these systems are controlling and steering systems that are connected with the climate control and air quality systems. Nevertheless, depending on the requirements of your cleanroom, you may need to install an additional independent environmental monitoring system to comply with the regulations. Regarding security requirements, it is important to follow the 21 CFR Part 11 guidelines on electronic signatures. With these guidelines on electronic signatures in place, you not only assure but can also prove that your documentation has not been tampered in any way.

These signatures prove that the documentation is authentic and unaltered. Additionally, through passwords and system access restrictions, you can establish information confidentiality and security. Real-time monitoring will provide audit trail capabilities, showing any deviations in ambient conditions and whether they affected process and product quality. Even without predicate rule requirements to document, audit trails and other physical or logical procedural security measures must be in place to prove the reliability of records from the monitoring system.

GxP Temperature and Humidity Mapping

Pharmaceutical products are sensitive to changes in ambient conditions, making GxP-compliant temperature and humidity mapping essential. It provides a means to ensure the environment within the cleanroom remains at the required temperature and humidity. Mapping also contributes immensely to establishing a robust and effective environmental monitoring solution.

What is GxP?

GxP is an abbreviation for good practice, and the “x” refers to various fields which includes the pharmaceutical industry. GxP is a collection of guidelines that ensure pharmaceutical products are safe when they reach the consumer and offers a mechanism to prove their quality. These guidelines also help companies comply with production and distribution procedures. In the pharmaceutical industry, GxP includes good manufacturing practice, good distribution practice, good laboratory practice, good automated manufacturing practice, and good documentation practice.

Why Map?

Environmental control aims to have uniform ambient conditions in the entire cleanroom. However, it is difficult to achieve a uniform distribution of temperature or humidity. Based on the floor plan, data loggers are strategically placed to monitor the temperature and humidity throughout the room. The data collected in the exercise is processed through a system which produces a GxP compliant mapping report. Mapping helps to determine the best sensor placement positions where humidity and temperature excursions are most likely to occur.

How to Map

The first step is installing temperature and humidity data loggers in uniform distances across the entire facility. These loggers should collect data for up to 14 days, after which you can download the data for analysis. The mapping report will show cold spots and hot spots in the facility. These areas form the perfect sensor placement positions where it is possible to detect the slightest excursion.