Below is the second part of a conversation with George Petroka, Director of BioPharma/EHS Services at IES Engineers, about trends and changes he sees within the industry, specifically related to Risk MAAP assessments.
George Petroka: With so much pharma work going to contract manufacturers, [contract manufacturers] have to demonstrate they’re not getting cross contamination from your product to my product and they have to be able to show that. The Food and Drug Administration (FDA) or European Medicines Agency (EMA) wants to see [proof labs aren’t cross contaminating and causing safety risks for producers and end users] because of the potency or the fact that you’re dealing with certain therapeutic classes such as cytotoxics or if you have two hormones, one is male one is female, you want to keep them from mixing.
For a while there – 10-12 years ago – the industry was saying, “You need to build dedicated facilities [for one-run productions].” Even the regulatory agencies got in on it. That’s really expensive and restrictive. So, the International Society of Pharmaceutical Engineering’s containment committee said to the FDA, “This isn’t science based. We have to be able to show scientifically that you need these proved segregations [of pharmaceutical components].”
So they put together this document, Risk MAAP. It came up with a couple of things, the most important of which was defining standard methodology for cleaning verification because all across pharma, we used different methodologies; we used 1/1000 of the Acceptable Daily Intake (ADI), LOD (Limit of detection), we used 10 parts per million, which was just arbitrary. Or you’d use visual, which meant, if you can see it, you’ve got a lot there.
So that was the first thing, come up with a standard methodology. It’s an ADI, but they called it an ADE – Acceptable Daily Exposure. It’s like setting an OEL. You use a “No observed effect level” then you apply safety factors. The safety factors are different than in an occupational setting because you’re looking a broad population – elderly and children versus worker population – and you’re not usually compromised (?)[4:45] so you’re safety factors are higher and your numbers (Average Daily Exposure (ADE)/ADI) are lower. The ADE is usually micrograms per day.
That pretty much stays with the compound the way an Observed Effect Level does. Except you do base it on the dosage form. An ADE would be different for solid dosage than for parenteral (injectable). With the solid dose you have a built in safety factor of taking something orally versus injecting it directly
Question: So, once you’ve determined your ADI, what then?
George Petroka: So you come up with that number, then you look at the manufacturing process. Am I making a solid dose, am I making a tablet? Then you look at the batch size, number of batches and surfaces you want to clean. You put those numbers into a calculation along with your ADE and you come up with a clean limit. Cleaning limit for something with 10kg would be different from 100g. You have much greater potential for exposure. You then have a good, scientifically based cleaning limit that you then can use to evaluate your potential cross contamination.
Cross contamination comes from airborne – not so much airborne actually, but it’s one method – mechanical, where you get it on surfaces, that’s the one they’re really concerned with; product mix up, again that can be managed through bar coding.
You do all that then do a failure mode and effect analysis to evaluate your risk level by getting a number.
Where Flow Sciences come in, by doing certain levels of containment and establishing certain containment controls, particularly containing at the source, you control and reduce your risk potential for cross contamination. So, you don’t have to build a full facility [for one product run]. It’s better, obviously, like occupational, for cross contamination, it gives you a control at the source, lower cost, less impact.
Jason Frye produced this story with the assistance of Flow Sciences Inc., which produces containment systems for laboratories, pilot plants and manufacturers. These products are designed to protect operators from exposure to hazardous particulates and vapors while performing delicate operations.