Mack Powers (00:07):
All right, Wendy. It’s great to be back with you today and chatting with you about a great topic, which is how to interact with health authorities. A topic that everybody in a regulated industry really thinks about a lot. And there’s a lot to know about it. You’re certainly well qualified to tell us how that should look and some of the nuances of that. So it’s good to have you here today and looking forward to our discussion.
Wendy Haines (00:31):
Thank you. And I guess to start off with the best thing to say is that health authority inspectors are not any different from the rest of us. They all went to the same universities, they have similar certifications, continuing education. So I think we need to make sure we think about them as fellow people and humans, and try to not be so anxious or have fear or anxiety because our overall goal, both sides, whether you’re an inspector or whether you’re a company trying to get drug to market, is you’re trying to get safe products to the people who need to take them.
Wendy Haines (01:04):
And we’re not us versus them, we’re working in partnership, we’re working in teams. The FDA, for example, and other health authorities, encourage companies to contact them, have impromptu meetings along the way, not just your scheduled meetings that you need to have to get a drug to market. It really needs to be thought of the process as a partnership where we’re trying to get those life saving medicines to the people who need them and not, “Oh, I’m scared because an agency’s coming.” It’s like I said, it’s really a team effort.
Mack Powers (01:38):
Yeah. And that’s part of what you guys do at PharmEng, which is work with companies to help them prepare so that when the unplanned or the planned visit happens, that no one is scrambling, everybody’s ready, they’ve got everything prepared for the audit and they can leave and have great fruitful discussions with the auditors and the health authorities. What are some of the ways you engage clients to help them so that they’re best prepared to work with health authorities worldwide?
Wendy Haines (02:05):
Right. So one of the certifications that I have is from the American Society of Quality, and I am a certified quality auditor. I’ve held that certification since 2012, and it requires every three years you recertify and to do that, you have to take continuing education, be abreast of current trends, changes in regulations, et cetera, what’s going on. Most, I would say most companies or all drug companies try to be inspection ready mode. So you never know when a health authority might visit you if you’re an owner company, or if you’re a contract manufacturer, you could have either health authorities or owner companies come and visit you.
Wendy Haines (02:42):
For example, Pfizer is very much in the news because of having the first approved COVID vaccine, COVID-19 vaccine. If you’re a contract manufacturer manufacturing a Pfizer product, Pfizer is definitely going to come and audit you to make sure you’re following all their guidelines and procedures and you have the proper documentations in place. And that when you are looking at the laws that are out there, the CFRs that you have references and justification of why you interpreted the law the way you did.
Wendy Haines (03:10):
And that’s what the health authorities are looking for, they don’t tell you how to implement the laws that are out there. They just want to see, what is your interpretation? Are you sticking to your procedures? Are you documenting properly? When there is a deviation, something comes up that is not normal, this happens, we are humans, we we also see things that will happen with the manufacturing process. How do you deal with those deviations? How do you document? How do you put those teams together? And when I’ve come in in an emergency situation, it’s the agency inspectors are there and they have questions and they want to understand what is going on.
Wendy Haines (03:50):
And in one case, for example, there was questions of whether the product was adulterated, if there were extractables and leachables that were in the final product that got to market. And through investigations on my part, a memo, putting references, giving background, steps forward, what to do farther, as far as testing to prove that the product was not adulterated, I was able to do that within hours and send to the head of quality for this company.
Wendy Haines (04:20):
And real time, FDA inspectors were able to look at the memo I drafted, what were the steps forward, what were they going to do to have additional proof that the product was not adulterated. The agency agreed. We did the additional testing and presented to the agency. So again, it’s just acting under pressure, but it’s not really pressure because we’re trying to get the drug to market the safest way possible with no contaminations, with no recall, so that people have the same safe batch lot to lot product every day if they take their A1C product for their type 2 diabetes, it should be the same each time.
Mack Powers (04:58):
So that’s what you guys do primarily then, PharmEng, you and your team. You’re working with clients week in, week out, helping them look for ways that there might be some weaknesses or areas that they might need to shore up in their quality system or their manufacturing process. And you’re helping them look at this might be where you spend your time to make sure those levels of quality there. Not only that, but the documentation is there to support all those efforts. So is that why you were able to pull something together fairly quickly in a one hour timeframe in this case?
Wendy Haines (05:26):
It wasn’t necessarily one hour. Is it within a couple hours that I did it. It’s understanding the process. As a toxicologist, my job as a board certified toxicologist, I do risk assessment. And because I have almost 25 years of risk assessment, even when I’ve given a curve ball and it’s an emergency and it’s maybe not even a product, in this case it was not even a product I’d ever evaluated, but the agency had a question. So because I have done what I have done for more than 20 years, I can quickly do a literature search on almost anything and come up with solutions and path forward. So it’s that experience and it’s always having my quality hat on. It’s always thinking patient first. I don’t want to do harm. I want that product to be safe, efficacious, right first time when somebody takes it.
Wendy Haines (06:20):
So that’s why I was able to function and other people as well, you can function under these type of crazy, if you want to call it, timelines and deadlines, because that’s what we need to do when inspectors come, or when whomever might come to inspect and have questions, you literally have to provide that information as soon as possible. And there’s some times that you have to say, “You know what? We’re going to have to do a little bit more digging, and we’ll give you an answer,” and you have a timeline that’s agreed on by you and the health authority.
Mack Powers (06:50):
That makes sense. So, if you were to go into a young company, we talked about the Pfizers and some of the more established pharmaceutical companies, let’s says it’s a new cell and gene therapy company or something, that’s a phase three or just been approved. What are some of the things that are kind of the typical big boulders that you would recommend that that companies would do first?
Wendy Haines (07:11):
Well, you have to follow good laboratory practices and good manufacturing practice or GxP. So you have to do that. If you are late stage or commercial production, it must meet those type of requirements. For me, as a toxicologist, what I would be looking at is more dealing with their product and the two different patient populations. Meaning, if there’s enough information and data, I can calculate a permissible daily exposure, which they feed into cleaning validation. So that goes into not having cross-contamination, ensuring that your product is the same strength and purity each and every time lot to lot, batch to batch.
Wendy Haines (07:54):
So most companies, if you’re small, you do not employ a toxicologist and I have been a consultant for these companies and I’ve actually created their permissible daily exposure. That value is reported to the FDA. That’s part of the package because it feeds into cleaning and it’s a evaluation of risk and toxicological risk, health based exposure limits, HBL that the agency will look at.
Wendy Haines (08:24):
And I’ve actually been involved in an inspection where they have questioned and wanted more information about a permissible daily exposure of a product, of an API, of an active pharmaceutical ingredient. So anything is fair game. So there’s nothing that’s off the table as far as what an inspector can look at. You never know what their background is, what they could ask. There are certain standard things. You asked me that question. So they are going to look at your documentation. They’re going to look at training records because they want to make sure people are trained on your procedures. They want to make sure you’re following your procedures because that’s a big no-no if you have documentation for laboratory testing or how you manufacture, and you’re not following those, because that impacts the quality of the product. So they usually hit documentation, data integrity, cleaning validation.
Wendy Haines (09:15):
Here recently there’s been some interesting inspections where a facility has been shut down because there was cross product contamination or ingredients were mixed, not segregated properly, for example. So yes, the agency or either owner companies, if you’re at a contract manufacturer can ask and look for anything. So proper documentation is required, proper training is required. And putting on back my quality hat, which I usually never take off, training is key and it’s not just, I’m going to read a standard operating procedure and take a test.
Wendy Haines (09:52):
A lot of the things need to be the tiered level where you read, you take a test, then you demonstrate that skill in front of a trainer and show, “You know what? I really know how to do testing, which then I’m going to take to the quality assurance, quality control lab, do final product testing to confirm this product is what it’s supposed to be.” So that’s not just, I’m checking a box, it’s you have to demonstrate mastery and that you’re going to do it right every time.
Mack Powers (10:21):
Wendy, that’s great information. And especially from PhD toxicologist perspective. Thanks for helping us to get a big picture view today of how should we be thinking about health authorities in terms of our partnership with them and what are some of the things that companies can do, whether they’re startup companies or mature companies, how can they be best prepared. These are all great insights. And we thank you for your time today.
Wendy Haines (10:44):