In the highly regulated world of biopharmaceutical and advanced therapy product (ATP) manufacturing, maintaining strict environmental control is not just recommended — it’s required. One of the most critical components of this environment is the classification and maintenance of cleanrooms. Among these, the Grade B cleanroom plays a pivotal role in ensuring contamination-free manufacturing of sterile medicinal products.
This article aims to provide a comprehensive understanding of what environments are, why they matter, and how manufacturers can remain compliant while optimizing operations.
What is a Grade B Cleanroom?
A Grade B cleanroom is a highly controlled environment used in the manufacture of sterile pharmaceutical and biopharmaceutical products. It is typically designated as the background environment for high-risk operations, such as aseptic preparation and filling, which occur in an even cleaner Grade A zone. Grade B cleanrooms must meet strict cleanliness standards for airborne particles and microbial contamination, both at rest and during operation. These cleanrooms are equipped with high-efficiency particulate air (HEPA) filtration, controlled airflow, and rigorous cleaning protocols. Compliance with regulations such as the EU GMP Annex 1 ensures that Grade B cleanrooms support the production of safe, sterile products by minimizing the risk of contamination during critical manufacturing processes.
Air Quality Standards for Grade B Cleanrooms
The Grade B classification requires:
At Rest:
Maximum of 3,520 particles per cubic meter ≥0.5µm
Maximum of 20 particles per cubic meter ≥5.0µm
In Operation:
Maximum of 352,000 particles per cubic meter ≥0.5µm
Maximum of 2,900 particles per cubic meter ≥5.0µm
To achieve this level of cleanliness, cleanrooms are equipped with High Efficiency Particulate Air (HEPA) filters, monitored airflows, and strict protocols for personnel entry and gowning.
Role of Grade B in Sterile Manufacturing
The area is typically the surrounding environment for Grade A zones, which are the most critical parts of a sterile process—such as filling lines, open vials, or clean benches. While zones are under unidirectional airflow and subject to intense scrutiny, Grade B provides the clean, controlled support area that prevents airborne contamination from reaching sensitive processes.
A well-maintained cleanroom reduces microbial and particulate contamination, thus upholding product sterility and patient safety.
Compliance with cGMP Standards
Maintaining a environment is not just about infrastructure.
Environmental Monitoring:
Regular testing for airborne particles and microbiological contaminants.
Personnel Protocols:
Strict gowning procedures with sterile garments.
Training in aseptic techniques and cleanroom behavior.
Cleaning and Disinfection:
Use of validated disinfectants.
Routine cleaning schedules to prevent biofilm formation.
Facility Design:
Smooth, cleanable surfaces.
Proper airflow and pressure differentials to prevent cross-contamination.
Challenges in Maintaining Grade B Conditions
Ensuring consistent Grade B conditions is operationally demanding. Common challenges include:
Personnel Movement: Human activity is the highest source of contamination. Even with gowning, movement can release particles.
Facility Aging: Deterioration of cleanroom surfaces or HVAC systems can result in non-compliance.
Overcoming these challenges requires a combination of automation, robust quality systems, and regular audits.
Grade B in the Context of Advanced Therapies
As cell and gene therapies (CGT) become more prevalent, the need for flexible and compliant spaces is increasing. These therapies often involve living cells and viral vectors that require aseptic handling in controlled environments.
Unlike traditional pharmaceuticals, many CGT products are personalized, produced in small batches, and require faster turnaround times. Grade B cleanrooms, when integrated with modular cleanroom designs and real-time monitoring systems, can support the agility and precision required by CGT manufacturing.
Future Outlook
Technological advancements are now allowing facilities to better monitor and control environments. Innovations like real-time particulate monitoring, cleanroom robots, and AI-driven environmental controls are helping manufacturers uphold stringent standards while increasing efficiency.
The integration of digital validation tools and risk-based environmental monitoring will further enhance how Grade B cleanrooms are maintained and audited.
Final Thought
Maintaining a compliant Grade B cleanroom is foundational to successful sterile and biopharmaceutical manufacturing. From meeting regulatory expectations to protecting patients, this classification is far more than just a clean space — it’s a cornerstone of quality and safety.
At Xellera Therapeutics, our commitment to GMP compliance and advanced therapy production includes designing and maintaining world-class facilities that meet the needs of the most complex biologics and cell-based products. We ensure your therapies are manufactured in an environment built for trust, precision, and innovation.
