Coming Clean on Cleanroom Operations in GMP Manufacturing


The Meningitis outbreak that occurred at the New England Compounding Center, sickened hundreds of individuals and resulted in 76 deaths as a result of contaminated steroid injections, providing a hard lesson about the importance of cleanroom operations.

While most Contract Manufacturing Organizations (CMOs) are not necessarily compounding final drug products, ensuring cleanrooms in the development of New Chemical Entities (NCEs), Active Pharmaceutical Ingredients (APIs) and medical devices is perhaps the most basic, yet important requirement of a cGMP-class CMO.

Some basic rules

A typical cleanroom is designed to keep the outside environment from getting in, since two things that cause contamination in it are the people and the process. Ultimately, there are three things that keep a cleanroom clean:

  1. Control and quality of the air.
  2. Internal surfaces and equipment.
  3. Standard operating procedures for workers.

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.

Technically, a cleanroom has a controlled level of contamination that is determined by the number of particles per cubic meter at a specified particle size. The primary authority for cleanroom classifications is the International Standards Organizations (ISO), which ranks classifications from ISO 1-10 based on the number of particles within a specified area. At PCI Synthesis, we operate three class hundred thousand cleanrooms, which means that if you take a cubic foot of air and put it into a filter you would not find more than hundred thousand airborne particles. Our high level of cleanroom standards enables us to meet the needs of different clients and projects – from small-scale to large-scale manufacturing and packaging.

PCI synthesis commitment

Below are steps PCI Synthesis takes to ensure we are providing effective cleanroom operations, consistent with ISO EN14644-1 and FDA guidelines:

  • Each GMP suite has its own air make up unit with a capacity of 1000-1600 cubic feet per minute (cfm). Air entering the makeup units is first filtered through a Weather Guard and wire mesh to keep out insects, birds, and debris.
  • The air 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.

As evidenced by the tragic history behind the New England Compounding Center, air contaminants can put the safety of drugs, medical devices and injectable medicines in severe jeopardy. Putting effective cleanroom operations into place that exceed quality guidelines should be of foremost importance to CMOs and chemical manufacturers everywhere.

For other articles on CMO best practices, check out Controlling Impurities In Drug Manufacturing, API Quality Risk Management, or Top Early Stage Method Validation Mistakes and How to Avoid Them.