When it Comes to API Manufacturing, Face Masks and Clean Environments Have Always Been Part of Life

Best Practices for Maintaining Cleanroom Operations

When you’re a Contract Development and Manufacturing Organization (CDMO) working with sensitive materials, you worry about bacteria, virus, fungus and other dangerous organisms every day. If they get into pharma products, they can enter the human body and cause serious harm – especially when you consider the potency of injectable drugs. For this reason, cleanrooms are not only essential, but required if you want to be considered a GMP-compliant organization.

If you want to understand the dangers of less than clean manufacturing operations, consider, the Meningitis outbreak that occurred at the New England Compounding Center. Unclean practices caused 76 deaths and sickened hundreds of people through contaminated steroid injections.

But what exactly is a cleanroom and how are they maintained? The goal of a cleanroom is to remove pollutants, particles, and contaminants from the air, as well as surfaces. A cleanroom is a contained space that is designed to reduce particulate contamination by filtering the air, and maintaining other environmental controls, such as temperature, humidity and pressure.

Cleanroom staff are specifically trained for these environments and they wear protective clothing designed to trap contaminants that are naturally generated by skin and the body.

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 Seqens NA, we operate three validated class 100,000 cleanrooms, which means that if you take a cubic foot of air and put it into a filter you would not find more than 100,000 airborne particles. Typically, however, the level of particles is much lower. 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.

It’s also important to note that a cleanroom is not the same as a sterile environment, which would contain less than 10,000 particles. Sterile environments are not required in API manufacturing, since most organic chemistry is done in solvents, in which viruses and bacteria cannot survive. Aqueous chemistry, however, which is fairly rare, would require a sterile environment, since viruses and bacteria can survive in water

Here at Seqens NA, there are three things that we are diligent about maintaining in order to ensure cleanrooms: control and quality of the air, internal surfaces and equipment. We have strict, validated protocols in place for cleaning GMP suites in between each project; we conduct regular monitoring and testing and we’re recertified annually


From execution of cleaning protocols to interim and annual testing and constant review by our Quality Assurance (QA) team, below are five of the steps we take to ensure we are providing effective cleanroom operations, consistent with ISO EN14644-1 and FDA guidelines:

  1. 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.
  2. Each unit is maintained at a positive pressure in relation to the outside environment to protect the integrity of the atmosphere.
  3. We also follow 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.
  4. Controls such as full-body suits, dust masks and respirators, and hairnets ensure human contact is not a source of biological contamination.
  5. We maintain temperature controls to ensure stable and consistent conditions for materials and equipment. Humidity control prevents corrosion and condensation of internal surfaces and eliminates static electricity.

While we are now living in unprecedented times, when contagions and how they’re delivered are fast becoming  a way of life, for the API manufacturer, the dangers of viruses, bacteria and fungi have always been top of mind. A committed focus to cleanroom operations in the API stage can ensure safe and effective products downstream – there’s simply no cutting corners.

For other articles from Seqens NA, check out Controlling Impurities In Drug Manufacturing, API Quality Risk Management, or How to Select a Drug Substance Contract Manufacturing Organization.