Biopharma EHS Podcast Episode 28 - PDE reports

BioPharma EH&S Podcast Episode No. 28.

Hello everybody and welcome back to another Episode of the BioPharma EH&S Podcast, my name is Dean Calhoun of Affygility Solutions and this is the podcast dedicated to discussing critical environmental, health and safety issues facing the biopharma industry, helping you take your environmental, health and safety programs to the next level.

Well, it’s Monday, June 14th, 2021 and I’m excited to be back today recording today. We have full show for today and a lot of great things to talk about, so let’s go ahead and get started.

As always I like to mention what are we going to discuss in today’s podcast. In today’s podcast, we’re going to talk about the following topics.

First, I’ll briefly cover what we talked about last time in episode number 27

Then I will cover our main topic for today, which is titled, “Top mistakes and tricks used by cheap providers of PDE reports.”

So, let’s go ahead get started. Last time in Episode 27 we discussed the topic of “coronavirus and precautions that should be taken by business travelers.” That was recorded back on Feb 3rd, 2020. Who would have thought at that time that this would have become such a huge global crisis. We are going to be short on time today, so I would suggest if that topic interest you that you go back to episode and listen to the entire episode.

Alright, so let's now move into our main topic for today, which is titled the “Top mistakes and tricks used by cheap providers of PDE monographs.” The talk is about 15-20 minutes long, so let’s go ahead and get started.

At Affygility Solutions we see dozens, if not hundreds, of PDE reports each year from different providers. Some of the PDE reports are excellent and others have a lot of room for improvement. Often, when reviewing reports from cheap providers, we see many technical errors and tactics to fool you into thinking that you’re getting quality reports. These technical errors and tactics include:

1. Relying too heavily on animal data for the selection of the point of departure (otherwise known as the PoD) and ignoring currently available human clinical data. Well, if you carefully read the EMA guidance document, on page 6 of the document, in section 4.2 it states,

“If the most critical effect identified to determine a health-based exposure limit is based on pharmacological and/or toxicological effects observed in humans rather than animals, the use of the PDE formula may be inappropriate and a substance-specific assessment of the clinical data may be used for this purpose.”

This is important. Often, we see cheap providers get in a rush to find a NOAEL value to use as the point of departure, which, as you may know, is typically from an animal model. Then in the process, cheap providers may ignore the human clinical data which may show adverse effects as the minimum effective dose. This is a mistake. Selection of the appropriate point of departure requires a thorough analysis of all the possible points of departure by an expert toxicologist, then selection of the PoD that results in the most restrictive PDE that is relevant to humans. This takes time.

1. Over aggressive use of F factors and adjustment factors. Often this is due to lack of experience of the toxicologist and that they are not confident in their abilities. It should be mention that if you start seeing a composite F factor mathematical product approaching 10,000 or more; it means you really don’t know much about your molecule or that there is so much missing data that the F-factor method is not appropriate. When you see the happening you should carefully examine how they justified their factors.
2. Performing a limited search strategy or not acquiring important primary sources of information or using old data. Often, a good way to discover to see if the search strategy was too limited is to look at the number and quality of the references. If they only have 4 or 5 molecule-specific references and all of those are from “free sources” they likely didn’t do a good search job other than looking for free data. High quality data sources, such as proprietary scientific databases and journal articles cost money. Cheap providers don’t have that kind of budget, so they ignore it. Also, how current is the data? If data is over 6 years old or more, it’s probably outdated, and more current studies may be available.
3. Ignoring conflicting or missing data. This typically occurs in the evaluation of genotoxicity data; where you’ll have mixed results (some positive and some negative). Did the author of the PDE report do a good job of analyzing this conflicting data or did they ignore it? How did they address missing data such as missing reproductive and developme...