483 #1 – Aseptic Technique 101

Learning Objectives:

1. Discuss proper ways to compound inside the primary engineering control and potential risks of having exposed skin while compounding
2. Explain what must be done to materials prior to placing them into lower ISO class areas (i.e. bringing items into the cleanroom then into the PEC)
3. Discuss what must be done to gloves routinely while compounding and prior to re-entry into the primary engineering control
4. Define the term “First Air” and explain its importance while compounding

This particular 483, which of course will be de-identified, will highlight some of the faults that people can have when performing inside the cleanroom; specifically their aseptic technique. One thing I should mention is that all of these observations are taken from the same 483 and they all just happen to do with aseptic technique. A little background on 483 observations and the FDAs inspection process; they tend to focus on particular systems (quality, production, facilities and equipment, laboratory controls, materials, and packaging and labeling) within an operation when they’re inspecting. It seems that in this inspection they paid particular attention to the production system, that is their batch processing. 

So here’s observation 1:

Exposed skin while inside the primary engineering control is a big no-no in the eyes of the FDA. This is not overtly mentioned within the pages of the USP Standard <797>; however they mention you should wear a face mask and various other garbing requirements. In the FDA’s eyes, which there’s certainly merit to this, if there’s skin inside the primary engineering control, there’s a chance for contamination. Generally just a good idea to keep all uncovered parts of your body outside of the primary engineering control to reduce the possibility for any kind of microorganism getting near the final preparation.

Observation 2

This is mentioned in <797> (I’m referring to the 2019 revision because as far as this goes, it’s the better way of operating). <797> says

Before any item is introduced into the clean side of ante-room(s), placed into pass-through(s), or brought inside the perimeter SCA and when packaging integrity will not be compromised, it must be wiped with a sporicidal agent, EPA-registered disinfectant, or sterile 70% IPA using low-lint wipers by personnel wearing gloves. (I bolded)

USP <797> 2019 Revision

It also goes on to say about placing items in the PEC…

Just before any item is introduced into the PEC, it must be wiped with sterile 70% IPA using low-lint wipers and allowed to dry before use. 

USP <797> 2019 Revision

The point here is that before you go into a new level of cleanliness (between or to a lower ISO class i.e. from 7 to 7 or 7 to 5), wipe items off with sterile IPA. When you bring them into the prep area, putting them into the pass-through and then finally your PEC they need to be wiped off prior to entry into each of these aforementioned places.

Observation 3

This too can be found in USP <797>. Gloves must be disinfected frequently, especially when an operator has touched them to non-sterile surfaces or whenever they have left the PEC. 

Application of sterile 70% IPA to gloves must occur regularly throughout thecompounding process and whenever nonsterile surfaces (e.g., vials, counter tops, chairs, or carts) are touched.

USP Chapter <797> 2019 revision Section 3.3 Garbing requirements, Gloves

Observation 4

This observation mentions the term “First Air,” and if you’re unaware of what first air is, it’s the first air that comes directly out of the HEPA filter. This should be the cleanest air and should be allowed to wash over anything that’s inside the primary engineering control without being blocked by other objects or the operator. Depending on what PEC you’re working in, a laminar airflow workstation or a biological safety cabinet, the first air may be coming from different directions. In a laminar airflow workstation (LAFW) the air comes from the BACK of the PEC and is being blown directly at the operator as they compound. Therefore, you shouldn’t block any air coming at you and all items should be lined up in next to each other without anything in front of them. 

In a biological safety cabinet (BSC), the air comes from above and therefore you shouldn’t block anything with your hands or other objects from reaching items inside the PEC from overhead. The air in the BSC exits through front and rear exhaust grills and these should also not be blocked by the operators arms or hands at any time so the air flow is continuously washing over the items and exiting properly. 

This is defined in USP <797>:

First air: The air exiting the HEPA filter in a unidirectional air stream.

USP Chapter <797> 2019 Revision

It’s also mentioned in the engineering controls section, saying that operators should have an understanding of what first air is:

compounders understand how to utilize the unidirectional airflow to maintain first air in the work zone. 

USP Chapter <797> 2019 Revision