Best Practices in Cleanroom Operations for cGMP Manufacturing


In the event of Active Pharmaceutical Incidents (APIs), special precautions must be taken to prevent contamination of final products. Strong quality assurance and quality control systems ensure raw materials and consumables meet internal and external standards, and this is where cleanrooms come into play

While equipment qualification and preventative maintenance are designed to prevent equipment malfunctions that would jeopardize product safety and quality, and proper cleaning changeover from one process to another prevents cross-contamination between processes, one area that is often overlooked as a potential microbial or particulate contamination source is the packaging and production environment. To control this contamination, especially in final packaging and sensitive processes, cleanroom environments are often used.

The FDA defines a cleanroom as “a room designed, maintained, and controlled to prevent particle and microbiological contamination of drug products. Such a room is assigned and reproducibly meets an appropriate air cleanliness classification.” Cleanrooms for API manufacturing are used for drug products with high sensitivity to airborne particulates and microbes. Cleanroom quality is maintained through room architecture, air filtration, and control of personnel.

Following are key steps PCI Synthesis performs to ensure a cleanroom environment consistent with ISO EN14644-1 and FDA guidelines in our GMP kilo suites:

  • Each GMP suite has its own air make up unit with a capacity of 1000-1600 cubic feet per minute (cfm)[1]. Air entering the makeup units is first filtered through a Weather Guard and wire mesh to keep out insects, birds, and debris.
  • The air finally is filtered into the units using three Micropak HEPA filters with a 99.99% efficiency on 0.3 micron particles.
  • Each unit is maintained at a positive pressure in relation to the outside environment to protect the integrity of the atmosphere. PCI also follows FDA and ICH Q7 guidelines for personnel working inside each unit. Each suite is connected via a hallway which is used as a gowning area. Access to the gowning area is controlled using an electronic keypad, and only personnel trained on internal SOPs regarding GMP manufacturing are permitted in this area.
  • Controls such as full-body suits, dust masks and respirators, and hairnets ensure human contact is not a source of biological contamination.

While some of these processes have been implemented for years at PCI Synthesis, we’re always thinking of ways we can continue to innovate to ensure a safe environment and safe products.  In addition to our GMP labs, PCI Synthesis is moving toward a cleanroom environment in our production area. Our packaging rooms have been renovated into FDA and ICH Q7-compliant cleanrooms. This will ensure all of our final products are packaged in a controlled environment. PCI is also making strides to institute a continuous liner system to keep our products under containment.

Our next post will look at ensuring safe measuring instruments.