Design a clean room for maximum quality assurance
ORLANDO, FL -- While the cleanroom should prove to be grounds for sterility assurance, this room is the location where FDA sometimes finds discrepancies. Looking past the factors of personnel and cleaning practices, the design concept of a clean room can certainly impact the success of aseptic processing. By acknowledging the importance of the seemingly simplistic concept of design and its role in the overall product quality, steps can be taken to make the most of this aspect for maximum results.
"Clem rooms are to be designed to meet environmental conditions that maintain the product specific qualitative requirements and/or quality attributes: purity, safety and efficacy," said Franco De Vecchi, Vectech Pharmaceutical Consultants International of West Bloomfield, MI.
He told PDA's spring conference here March 11-13 that a facility should be designed to appropriately house equipment and supplies, allow for suitable flow of both material and operators, accept cleaning and disinfecting and include environmental monitoring and control systems.
"In the case of a clean room, we cannot go to a book and say this is the way to design a facility for the pharmaceutical industry," De Vecchi explained. He adds that the processes, equipment and facilities, which may have to consider aspects like financing and location, are constantly changing and even problems differ frequently.
De Vecchi considers an essential component of yielding sterility success to be clean room designers who work to the best of their ability and analyze risks beforehand. Determining what risks lie ahead help show what is needed for decontamination. "The bottom line is we are designing a facility that is designed to prevent microbial contamination."
He said FDA and European Union regulations strongly recommend pharmaceutical clean rooms should be designed and run so as to prevent, control and monitor every single potential cause of contamination and mistakes. While narrow and generalist in terms, guidelines for what the FDA will accept are mentioned in the Aseptic Processing Guideline of 1987. ISPE and PDA also give suggestions in broad-based terms, which designers need to assimilate on a case-by-case basis.
"FDA and in general, GMP regulations, indicate what to do and not how to do it," De Vecchi added. He said the manufacturer holds the key to unlocking the best design scenario after looking at the necessary requirements and expectations. Quality requirements should be satisfied at every stage (User Requirements and Functional Requirements clarify requirements and implementation policies.)
Addressing user and functional requirements, De Vechhi said "quality is communication and documentation is a way to communicate." These documents deal with all the elements involved including research and development, manufacturing and quality assurance, which eventually validate the system.
FDA compliance issues in relation to clean room design come from inspections and comments from the pharmaceutical industry. One current debate is that of clean room classifications. The Europeans classify by use--via ISO--rather than USP parameters, but De Vecchi contends FDA does not favor one system over another. "But if we classify by use it probably will be more practical and then we can attach one of these parameters to the classification."
The issue of air cleanliness and adjacency requirements also is under scrutiny. While FDA in the past classified environments into two groups, critical and controlled, today's FDA is looking at gradual and adjacency criteria as well.
"Primary consideration for clean room design cleanliness definition are typically based on the degree of product exposure; normally sterile products, containers or closures are not exposed other than to a Class 100 area."
Current regulatory issues with classifying transfer and crimping machine areas are also under scrutiny. Usually using a Class 1,000 to 10,000, "Design criteria basis has been: the vial is sealed and protected by the stopper thus requiring limited protection."
The unidirectional airflow from the crimping machine led to its transfer out of the aseptic processing area to limit personnel in critical zones, avoid aluminum cap sterilization and limit aluminum particles located within aseptic core. The somewhat related issue of transferring partially stoppered vials from the filling machine to a freeze dryer deal more with loading/unloading procedures than clean room design.
The issue of the HEPA filter integrity testing frequency is up for debate as well. "Currently, many firms do it [test HEPA filter integrity] every six months and this is perceived to be regulatory expectation."
Since the aerosol test requires touching the filter itself, De Vecchi said testing and fooling around with the filter can actually increase the risk for damage and present needless risks. Rooms that operate well time after time may not gain added value from constant re-testing. He recommends that HEPA filter integrity testing be scheduled according to system performance (viable or non-viable air), air velocity drop or filter pressure, amount of use the facility gets and sufficiency of HVAC system maintenance.