Chapter 08: The History of ‘Good Laboratory Practice’ at the Keeling Center
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Description
In the beginning of this Chapter, Dr. Satterfield notes that in his role as Attending Veterinarian for the Keeling Center he works for the good of human health and also for the highest standard of care for the animals he oversees. He underscores that research animals are “unsung heroes” in the long process of conducting research and taking drugs to the market; in his view, the FDA has a difficult job in regulating this process, and it has done a good job.
Dr. Satterfield next goes into detail about the FDA’s Good Laboratory Practice [GLP] program and how the Keeling Center work to meets its criteria for quality insurance, training, documentation, and data storage –all to insure a secure and unbroken chain of experimental evidence so that other researchers can have confidence in reported methods and results and replicate experiments. As a contained unit within MD Anderson, Keeling is uniquely positioned to guarantee secure storage of data, for example, and also security of practices by providing in-house pathology services. Dr. Satterfield also explains describes the economic context in which The Keeling Center adopted the GLP standards: the GLP program enabled MD Anderson to retain control over the discoveries (intellectual property) of its researchers, derive royalties from them, and use those funds to fuel the “engine of development.” The Keeling Center, he explains, provides a piece of that development by providing animal models of use to MD Anderson researchers, as in the case of his collaboration with researchers in Plastic Surgery to engineer bone tissue. He then describes how working on projects with very high-quality research practices led him (in partnership with DR SASTRY) to propose that The Keeling Center make the investment to adopt the full GLP program.
Identifier
SatterfieldWC_02_20120725_C08
Publication Date
7-25-2012
City
Houston, Texas
Interview Session
William C. Satterfield, DVM, Oral History Interview, July 25, 2012
Topics Covered
The University of Texas MD Anderson Cancer Center - An Institutional Unit Overview Professional Values, Ethics, Purpose Institutional Processes MD Anderson Culture Collaborations Business of Research The Business of MD Anderson
Transcript
Tacey Ann Rosolowski, PhD:
Today is July 25. The time is about 8:35, and I'm here in Bastrop at the Michale Keeling Center for my second interview session with Dr. Satterfield. Yesterday we ended up—we had a little bit of a conversation about the clinical care of animals. I wanted today to go on and talk—kind of go through in a more organized way the multiple areas in which you have done research. But first I wanted to make sure that you said everything you wanted to at this point about your role as attending veterinarian. We talked about how that was an FDA-designated title [corrected: title established by Animal Welfare Act], but I just wanted to make sure that you had covered everything you wanted to about that role.
Tacey Ann Rosolowski, PhD:
But first I wanted to make sure that you said everything you wanted to at this point about your role as attending veterinarian. We talked about how that was an FDA-designated title [corrected: title established by Animal Welfare Act], but I just wanted to make sure that you had covered everything you wanted to about that role.
William C. Satterfield, DVM:
Sure. Just in general, my work at the center, including this role as attending veterinarian, is really to do whatever I can do to advance human health in the discovery of new treatments based on basic science that we're able to accomplish through working with animal models. And my role is really to make sure that the care of these animals is at the highest standard. The animals are here for us, and so we basically are here for them as well. That carries through to all of the animal care staff. That's an oversight role of the attending veterinarian, but there is a philosophy and a, I guess, well-expressed intent for anyone who has concerns about the way the care of the animals or any individual animal's situation that they can talk about that, either confidentially—so they're concerned about the way research is being conducted—they can speak to me or someone else in a supervisory capacity, and we'll take that seriously and do due diligence on investigating it. It's another means of—another layer of protecting animal welfare.
Tacey Ann Rosolowski, PhD:
You really see this as an analogy to the protection of human patients who are involved in research studies and see the animals as, really, equivalent in importance.
William C. Satterfield, DVM:
Yeah. We have a— There's a poster out here in the hallway that is a picture of a young girl in a hospital bed, and a picture included in that same picture are some little white rats or white mice, and it talks about the unsung heroes that provided the care or the medicines that are making her survive—capable of her survival. There are a lot of behind-the-scenes things that happen before we are able to go to the pharmacy and get products that we have confidence in that will be able to help us. It's a very complicated and long, drawn-out procedure. You know, they talk about how long it takes for drugs to come to the—get to the pharmacy after they're discovered, and out of every 100 to 200 products that have some potential, maybe one will reach the marketplace. It takes an inordinately long period of time, and you'd think that maybe some of these things ought to get there faster. In some countries they do put a lot—let things go through a lot easier, and then they find out the hard way when they get to humans that there are side effects that weren't disclosed or discovered until they were actually put into use. I think the FDA—the Federal Drug Administration—has done a really good job. It's a difficult job. We work within this program called the Good Laboratory Practice program. They call it GLP for short, but it's a regulated program under FDA. FDA has a kind of an auditing arm. It's separate from some of their other things, and they come in periodically, and they will audit us in excruciating detail. It's analogous to a very thorough IRS investigation that a lot of people would be familiar with. But they are here for a week or more until they're satisfied that the studies have been done, can be reproducible, and have been done according to all of their regulations, which are extremely detailed.
Tacey Ann Rosolowski, PhD:
Now I'm noticing that the— I'm a bit confused about the dates because I think 1978 was when the USDA established the Good Laboratory Practice. Is that—? Is that the guideline here?
William C. Satterfield, DVM:
No. That's the Animal Welfare Act.
Tacey Ann Rosolowski, PhD:
Oh, okay.
William C. Satterfield, DVM:
That's the Animal Welfare Act. The FDA's been around for quite a while. I can't give you a date for when Congress established the Food and Drug Administration, but it's been around for a long time. The work that we do with animals is actually one of the early stages before it goes into clinical trials. It has to go through some toxicity testing. They need to determine the stability of the drugs, what effects it has on other organs, what kind of toxic—and there are toxicity studies that are conducted. I guess you could take the example of some kind of common product like Tylenol. You know, Tylenol is a good pain reliever, but taken in excess it can become toxic. So the product that you buy in the pharmacy or in the grocery store is a certain size, and the label recommendations say you can take so much, but if you take more than this, then it can cause problems. All that has to be determined, usually, before it goes into humans.
Tacey Ann Rosolowski, PhD:
Now, with the Good Laboratory Practice program, is that—? I guess what I'm trying to get straight in my mind is how the Good Laboratory Practice program is related to the types of testing that you just described, and I think—
William C. Satterfield, DVM:
Okay. Here's the deal on that. MD Anderson is—in some sense, it's always been a leader in the area of research as well as clinical medicine for humans, cancer therapy. And one of the reasons people come to MD Anderson is that they have a strong research arm. I don't know the exact number, but there are 600 to 700 basic scientists at MD Anderson and another thousand or so clinicians that are also—a number of those are PhD/MD clinicians that do some basic science work at labs and so forth. There are a number of discoveries that were—or, we call them—the legal department calls it "intellectual property"—that was being discovered by the physician scientists and the basic scientists. And sometime late '80s or early '90s, MD Anderson realized they weren't capitalizing all of the intellectual property that was coming out of this laboratory work and basic science work that was being done at the hospital, and they were having to outsource this. So the bottom line for the institution is that, if we can do the development of these products in house, retain the intellectual property and the royalties within the institution, then that can fuel that engine of development to assist patients. And this is, in fact, what's happened. What we have done here at this facility with GLP is that we are capable of providing a critical piece of that development through the use of our specialized animal models to satisfy the government to allow these products to go to new investigational drug status and then to clinical trials. So I started working with a group of investigators—I guess you'd call them orthopedic people—looking at artificial bone substitutes in sheep in the early '90s from the med school in Houston. And then we started looking at what we could do to develop GLP products, and we realized that we were in a unique situation here—that we could develop a GLP program because we were self-contained out here. We can meet the government standards for electronic data. It's called Part 11. Without getting into a lot of regulatory stuff, Part 11 just says that everything that you put into any kind of electronic data is secure, it hasn't been altered, there is no way to delete data or to put in data that isn't somehow tied to whoever put it in, and it can be retrieved at a later time. There is some assurance that we can reconstruct the study, in a manner.
Tacey Ann Rosolowski, PhD:
What are some other elements of that? I hadn't even thought of that. What are some other things that made Keeling unique because it's contained in that way?
William C. Satterfield, DVM:
Well, all of our—we have our own pathology. We have our own pathology—anatomical pathology section. We have our own laboratory data section. All of that stuff that's here is run by folks who are highly qualified and meet the standards for the Federal Drug Administration.
Tacey Ann Rosolowski, PhD:
Now, did you set out to intentionally do that?
William C. Satterfield, DVM:
No, we did not set out to intentionally do that. We just started doing studies for other folks, and they said, "Well, we'd like to have this done in a compliant”—the word 'compliant'—“manner.” We know that you don't have a GLP program here, but can you do it GLP-like?" So we started doing GLP-like, but you can't meet all the federal standards doing GLP-like. You have to do— You either do it, or you don't, or it's not that way.
Tacey Ann Rosolowski, PhD:
Right.
William C. Satterfield, DVM:
But there are certain circumstances that the government will take data that is being developed or studies that are being developed for patients that can be used in applications where there is no other alternative. They're terminal patients, and this is something that is allowed in certain circumstances. So we were able to do that.
Tacey Ann Rosolowski, PhD:
Now, I have the date of 1999 here. Was that when you shifted from being GLP-like to actually being GLP, or—?
William C. Satterfield, DVM:
That's roughly correct. Yeah. We set out on a real determined program with these SOP, Standard Operating Practice—which the FDA wants you to have all this stuff written out, reviewed annually. Everybody has to be trained on it. There's a lot of infrastructure in this. It's an expensive program. People say, "Gee, you know, why are we paying so much? You know—you could do all this stuff without charging us." But we have a quality assurance department. We have a compliance section. Training takes a lot of time. Documentation of every little thing takes forever, and there is a chain of custody on test articles that come in. Temperatures have to be recorded. We have environmental quality monitoring on all of our animal areas. All that has to go into a database that can be recovered later if the FDA wants to look at it. And sometimes the sponsors want to come in—or if a product, for example, is sold. I mean, it gets into the commercialization. We do a study and then for one company and then another company buys that product, then that second company that has brought the product, they want all that data because they want to see if it's—they want to review it to make sure it's something that they want to invest in. So Anderson has developed a whole section to support this—a compliance section. It's got to be a big legal issue that we have to make sure that we cross our "T's" and dot our "I's" and everything. There are two types of work. You have discovery work, which doesn't have all of that—when they do pilot studies to prove the principles just to see if things are going to be worth pursuing—and then you get into the GLP arena, and then you do an actual study to demonstrate the efficacy or the toxicity or the safety of a product. Those are done so that they're statistically valid, all of the data has been documented and recorded, and there is a final report that's given to the PI or the sponsor that they can submit to FDA so they can go to the next step, which is getting an investigational new drug application. Then they can apply for clinical trials, and there are 600 clinical trials going on at MD Anderson at any one time, and they have over a thousand that are out there that maybe they're doing or they're going to.
Tacey Ann Rosolowski, PhD:
Yeah. I read in some of the literature I reviewed for this interview that you thought that the Good Laboratory Practice program was really connected to translational research. I guess now you're kind of connecting the dots on that, so—
William C. Satterfield, DVM:
Oh, yes, absolutely. It is translational. You know, at one point early in my career we could do a study here, and if it looked really promising, they could—we'd call it "bench-to-bedside." But in between the bench and the bedside is the FDA, so it's a lot more complicated.
Tacey Ann Rosolowski, PhD:
Now, what was your role with the Good Laboratory Practice program? Did you have—were you involved in creating that, or—?
William C. Satterfield, DVM:
Yeah. My role in this actually had to do with doing some of these early studies, which were basically good, scientific type of practices. We did everything scientifically. We may not have done all of the documentation that FDA would have desired to have done, but we tried to do it in a manner that could be re-created. We had a quality assurance—someone monitoring that. We started with that and then Dr. Sastry and I proposed the program to Dr. Keeling, who was the chair here at one time, to develop this as a full-blown program. Dr. Keeling took that idea and ran with it. He took that to the administration at MD Anderson. They developed a business plan for it, and Dr. Mendelsohn endorsed it, and then we started putting some serious institutional money towards it.
Tacey Ann Rosolowski, PhD:
Yeah. I was going to ask who was involved, because Dr. Mendelsohn [Oral History Interview] was so interested in growing the in-house resources.
William C. Satterfield, DVM:
He was, and this— Dr. Keeling felt like this was a way that this department could be a vital role—play a vital role—to support research and development at the main campus.
Tacey Ann Rosolowski, PhD:
At this, can you give me some—an idea of some numbers in terms of Good Laboratory Practice program here? How has it changed the revenue-generating capacity of this—of Vet Med?
William C. Satterfield, DVM:
That's—the study—
Tacey Ann Rosolowski, PhD:
Maybe that's not quite the right way to ask the question.
William C. Satterfield, DVM:
Yeah, because it—we had the resource here, and in early 2000, I think we probably did six to eight of these studies, and they would run anywhere from— They would produce anywhere from several hundred thousand to over a half million dollars per study. That is the cost. But that was the total cost. Whatever revenue we were able to generate went back into our programs. And we had to be competitive with outside organizations called CROs, Commercial Research Organizations. We had to do cost accounting with that to see if we were competitive, because if a sponsor wants to do a study and they can have it done at a CRO and it costs less than what we can do it for, then why would they come here? But what we wanted to cater to was investigators at Anderson so we could work with them and be able to customize the studies with them—something that a CRO would not be as capable of doing.
Tacey Ann Rosolowski, PhD:
So that's where the collaborative piece comes back in again, where, I guess, you're trying to partner this department with MD Anderson to craft—
William C. Satterfield, DVM:
Yeah. That's a great way of putting it. Yeah. We definitely wanted to partner with the investigators at Anderson, because that way, whatever resources they have to put into the study, it stays in Anderson, and we're able to work with them because—many times—well, it's still on many cases—physicians and investigators at Anderson do not appreciate the complexities of doing a GLP study, so we have to really work with them to understand and explain why we have to do things in a certain way.
Recommended Citation
Satterfield, William C. DVM and Rosolowski, Tacey A. PhD, "Chapter 08: The History of ‘Good Laboratory Practice’ at the Keeling Center" (2012). Interview Chapters. 1510.
https://openworks.mdanderson.org/mchv_interviewchapters/1510
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