SterileAF Podcast Seth DePasquale, R.Ph., BCSCP

Thanks for tuning in to the Pharmacy Inspection Podcast! Today we have Pharmacist Greg Stanley on the show and we're going to be talking about implementation of an IV workflow system!
Greg Stanley received his Bachelor of Science in Pharmacy degree in 1998, having also completed undergraduate research fellowships in Biological/Environmental Sciences and Polymer Sciences.  He has over twenty-five years of experience with compounded sterile products; both in hospital and home infusion settings.  Greg has extensive experience with policy development, staff training, pharmacy management and regulatory compliance. 
Currently, Greg is an Associate Director at SUNY Upstate Medical University.  He is involved with several projects related to USP and USP .  His oversight includes sterile compounding, hazardous compounding, and robotic/automated technologies. 

In this weeks episode we welcome Bryan Prince back to the show to talk about cleanrooms. We discuss common issues that we see with cleanrooms, talk about particle counts and certification reports as well as some cool technology being used to simulate a cleanroom before it's even built (computational fluid dynamics - CFD).

Today on the podcast we welcome Lilit Smith. Lilit is a board certified sterile compounding pharmacist and is currently the Manager of Compounding and Compliance at Baptist Health South Florida. In her role she supports across the pharmacy enterprise with cleanroom design and construction, regulatory compliance and process and policy standardization. We're going to be talking about her experience with building a compliance team to oversee compounding operations at a large health system.

In this episode of the pharmacy inspection podcast I go over some of the changes to USP in the latest revision to the chapter.

In this episode we go over some of the major changes in the revision to USP Chapter and what you need to potentially know if it becomes finalized.

Learning Objectives

Discuss the importance of particulate in relation to microorganisms Explain why 0.5 micron and larger sized particles are of great importance Discuss 3 ways that we can minimize the number of particles in our cleanroom

In todays 483 we're going to be looking at non-viable particle counts otherwise and more accurately known as total particle counts and why they're so important. So let's take a look at the 483 observation first then we'll dive into it a little deeper.








In this 483 it's noted that there was an out of specification result for environmental monitoring samples. I've talked in a previous podcast and posts about viable particles, but this week let's focus on non-viables.


In observation 2 under section "d" it talks about not further investigating sterility failures for two particular compounds.


The investigation documentation did not include and evaluation of production batch record reviews, EM for hoods and rooms (non-viable or viable particulates, personnel monitoring, press plates), cleaning logs for the room, qualification of the hoods, retain samples or previous OOS.
FDA 483 Observation 2


So why does it mention specifically looking at non-viable samples, aside from all of the others? Let's take a quick look at a table that's from USP , which is actually from an international document, ISO 14644.





I'm sure you've seen this before but if you haven't here it is. But what exactly do all of these numbers mean and why are they so important? In the left column you have ISO classes which are the classes of different areas of the clean room. Your primary engineering controls or your hoods are typically ISO class 5 and your secondary engineering controls or your room are typically ISO class 7 or you may have an anteroom that's ISO class 8.


In the right hand column you have the limits of the particle counts per cubic meter, meaning if you have particle counts higher than the numbers in this column corresponding to the particular ISO class that area fails and cannot be classified as such.


One thing to note here, at the bottom of the table in small writing it specifically mentions the numbers pertain to particles of a particular size 0.5 micron or larger. Why are 0.5 micron sized particles of importance? Well, there's one thing you should know about microorganisms. Rarely are microorganisms free floating by themselves. They actually travel on particles, and if you haven't already guessed they're usually attached to particles that are 0.5 micron or larger.


One other interesting point worth mentioning and this may seem like common sense but the larger the particle, the more dense it is and the heavier it is. These larger sized particles are the ones that tend to settle on surfaces. Smaller, lighter particles can stay free floating in the air but it's the job of our engineering controls to push them away from our critical areas and hopefully push them down toward the ground where they're not a threat to our preparations.


Now, if you have high particle counts in your cleanroom or primary engineering control does that mean that every one of those particles has a microorganism attached to it? No, not necessarily. However, taking particle counts is a great, general way of looking at the state of cleanliness of your cleanroom.


Another question is, do we know the percentage of particles that have microorganisms attached to them? To be completely honest, I'm not sure if there's been a study done to make that correlation but one thing that's for certain is that the higher the particle counts in your classified areas, the higher the chance for contamination.


One point I really want to drive home is that when we get our cleanroom certified and we're looking at the numbers of particle counts, you can glean a lot of information from that report. If you have high particle counts in a particular area, you can look inside you