“The complete package” is a phrase used to describe something with the ability to perform in such a manner that every element of expectation is satisfied.
In many cases, the application of cleanroom technology to provide particle control during aseptic manipulation falls significantly short of the complete package necessary to protect the product. The elements that must be present for product protection include the proper facility, personnel, and training.
Facilities establish the boundaries, surfaces, pressure differentials, and air filtration systems. Each of these elements is necessary to create and maintain the environment required for aseptic manipulation. Defined boundaries translate into surfaces that make up the cleanroom's walls, floor, and ceiling. These surfaces are essential to maintain, clean, and sanitize the environment. Defining an area as an “open cleanroom” violates the basic fundamental of good practice because of the inability to separate and control the environment.
Guidance from both industry experts and regulatory agencies, such as the FDA, cite the need for a pressure differential between the cleanroom and surrounding environments. The pressure differential ensures that air movement is always out of the cleanroom and minimizes the impact of outside forces. A couple of examples of an activity that changes airflow patterns are the movement of people and opening and closing of the doors located in areas adjacent to the open cleanroom. Simple changes in seemingly unrelated activities, such as how materials are stored in surrounding areas, can create a pathway for the migration of nonfiltered particles into what is thought to be a clean area.
Regulatory agencies use the air-quality classifications, as defined in Federal Standard 209, to describe their requirements for the environments in which parenteral products are manufactured and prepared for administration to patients. Controlling the environment to meet these requirements is a function of exchanging the air within the clean area through a high-integrity HEPA or ULPA filter. The number of air changes is dependent on the size of the area and the quantity of particles being generated within the environment. Defining the source and location of the particle generation is critical to good design because control of particle migration is the result of the placement of both inlet and return air sources. In addition, proper placement of the inlet and outlet air sources is necessary to ensure uniform air quality throughout the environment, without creating dead spots in the airflow that would result in high particle counts. To ensure that the environment is functioning at the proper classification, map and test it in a dynamic state.
The location and size of entrances and the frequency of movement of materials and people will impact the air-flow and quality within the environment. To understand the impact of these activities, testing by taking particle counts as they are conducted.
People are the single greatest source of contamination within a cleanroom. The two methods of controlling contamination from this source are the use of gowning and training in proper techniques. Simply because the physical facility is capable of achieving a given level of control in a static state is no assurance that this level of particle control is maintained during operation.
For operations requiring Class 10,000 and below, gowning becomes a major factor for successful contamination control. One of the best resources for understanding proper gowning and personal hygiene practices, both of which are necessary for successful contamination control, is the CleanRooms supplement published in December 1998 entitled “Cleanroom Basics.” Documented training of both gowning and aseptic techniques is a must for successful contamination control within the cleanroom environment. Make sure to put formal programs into place to reinforce good practice.
Hank Rahe is director of technology at Contain-Tech in Indianapolis. He has over 30 years' experience in the healthcare industry. He is the past chairman of the board of the International Society of Pharmaceutical Engineers, and is a member of the CleanRooms Editorial Advisory Board.