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 developmental studies?
4. Creating a different monograph for each salt form of the molecule; thus, requiring you to buy separate monographs. A large majority of all drug molecules used in medicinal therapy are administered as salts. Often, a drug substance has certain suboptimal properties that can be overcome by pairing a basic or acidic drug molecule with a counterion to create a salt version of the drug. Creating a salt version of the drug can improve solubility, stability, taste, manufacturability, and other key properties. In all but a few rare cases, the toxicology of the basic or acidic drug and the salt form are the same. Here at Affygility Solutions, when we are reviewing the scientific literature for a drug compound, the expert toxicologists are mindful of any differences.
5. Making statements that are not scientifically supported. Every source of scientific data must be cited. And you should be able to trace it down. It doesn't have to be word-for-word, as long as the meaning is the same.
6. Relying on data from safety data sheets (SDS) of questionable credibility. The information on safety data sheets may be mentioned in a PDE report, but it should never be used as the primary source of data. This is because the backup studies are generally not available. I should mentioned that the credibility of the content of safety data sheets varies widely, from those that are outright false to those that are quite good.
7. Attempting to disguise a PDE report as a comprehensive document by non-value filler materials. Filler material can includes a report cover, a lengthy, but unnecessary table of contents, a glossary, lengthy tables of irrelevant data, and CVs in every PDE report. In addition, some providers use large header and footer margins with industry association, corporate logos and addresses on every page to make a longer document. These items provide zero value and are there to just give the false impression that it's a lengthy and comprehensive report. I should mention that about a month ago I was speaking at a virtual conference and one of the other presenters indicated that a PDE monograph really only needs to be 15 or 16 pages long, as long as the data is well summarized.
8. Not openly disclosing that their reports expire in 3-5 years; thus, requiring that you purchase a new report upon expiration. Typically, this is buried somewhere in the document or in the terms and conditions. So, it may be a cheap initial cost, but you're going to have to continue to buy replacement reports for many years to come. Not a good tactic.
9. Not using qualified or certified toxicologists to prepare and review the reports. This is a big one. Qualified toxicologists don't work for low wages. And if a person is certified, either a DABT or ERT-registered toxicologist the salary is up there. Cheap providers can't support those kind of salaries.

O.k. That does it for this week's show. You can also stalk us on twitter at twitter.com/Affygility, on Facebook by searching for Affygility Solutions and giving us a "Like", and finally on LinkedIn by searching for Affygility Solutions.

That does it for this week's show. We look forward to having you listen in next time.

Have a great rest of the day.