Liveyon Pure Cast – Stem Cell Manufacturing Lab Compliance. (E20)

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Episode 20 – Liveyon Pure Cast – Stem Cell Manufacturing Lab Compliance

Dr. Gaveck: Welcome back to the Liveyon Pure Cast podcast. I’m Dr. Gaveck, director of medical education for Liveyon, and we have back with us today Erin Sairafe, chief of compliance. Welcome back.

Erin Sairafe: Thanks, Alan.

Dr. Gaveck: Last time you were here, we had a discussion about what you have to do on the end, forget the umbilical cord, all the regulatory … Those three steps you have to take. Getting the cord to the lab, doing all the processing, all of the testing, and all that sort of thing. It seems like a natural progression now that we should go what does it really take to make a lab? We talked about it a little bit at that time, but I think it’s important to know for people out there that it’s not a small task. I mean, we see labs popping up all over the place, right?

Erin Sairafe: Yeah.

Dr. Gaveck: Yet you know specifically what it takes to make a lab. So give us an idea. What is day one when you met with John and said, and the CEO, John Kosolcharoen, said, “Hey, Erin. You’ve got a lot of experience in this field. Let’s make a lab.” Where’s your start?

Erin Sairafe: Well, first, all these little labs that pop up here and there, it takes years to get a good lab up and going. It’s not just buy a building, stick some lab equipment in there, and then start making a product. It is find the right building that has what you need, first of all, electricity-wise, space-wise. You have to buy all the equipment from a vendor that’s qualified, calibrate all the equipment, construct a clean room, which Liveyon Labs has two ISO 7 clean rooms, an ISO 8 gowning room. That is a huge step in constructing a lab. It takes a long time.

Erin Sairafe: It takes, I would say, at least a year, and that’s including you have to write all kinds of protocols and validation protocols for every single progress that goes on in the lab.

Dr. Gaveck: That’s really where you start out, isn’t it?

Erin Sairafe: Yeah, and I say lab, it’s not just the lab. Every single component of a laboratory business … I mean, you have to have protocols for every department, for QA, for lab, for customer service, for shipping. The list goes on and on. It’s not just a few protocols for laboratory employees.

Dr. Gaveck: So give us an idea. When you start out, you’re going, “Okay, we’re going to put a lab together,” but even before you get a building, before you find a lab, before it meets all those qualifications, before you get on to that sort of thing, you have a ton of standard operating procedures that have to be written, because otherwise you can’t move into that building, you can’t do anything unless everybody has a specific set of paperwork that says, “You’re this,” “You do this,” and “This is how it must be done,” in order to fall under certain guidelines.

Erin Sairafe: It’s part of establishing a quality system. Any kind of business like this needs a quality system. If you don’t have one, then everything else is pointless.

Dr. Gaveck: I think that’s a great point. How do you know if a lab has a quality system in place?

Erin Sairafe: I would suggest going to take a tour, asking to speak to their chief compliance officer or any senior member of the quality assurance team or compliance department. Do a supplier audit. Go down there and ask to see their records, or ask to see their validations. Where do they keep their lot release records? Take a quick little look around. I think it’s pretty easy to see when a lab isn’t doing things correctly when you actually go there and start asking questions. A lot of places can show whatever they want on a website, or tell you they have something, but going there to see it and asking these kind of questions are what counts.

Dr. Gaveck: I think that makes a great point, because our reps in the field, many doctors in the field, know of Erin Sairafe, who’s the chief of compliance, but compliance is not just made up of you.

Erin Sairafe: No, it’s not. I have a great team. We have several PhD’s. We have quality assurance members, regulatory affairs members, that do all kinds of different functions. There’s everything from checking in supplies. When supplies arrive they have to be checked in against what we call material specifications, so you make sure that everything has a … If it’s supposed to be sterile, it comes in sterile with a certificate of sterility, or certificate of conformance. That all gets filled out and put in its proper areas. All of that’s done by a big team of people. There’s no way that I can do everything by myself.

Dr. Gaveck: I’m assuming if somebody says, “Hey, I’m going to come into the lab. I want to take a look at your lab,” and you have all of this documentation for all of this product that’s come in, we’re not even talking about the cord,

Erin Sairafe: No. Just from …

Dr. Gaveck: We’re talking about materials.

Erin Sairafe: Just materials. Materials alone, that’s a huge portion of a quality system. From materials to actually releasing those materials, to the laboratory, to where the lab personnel keeps those, to in-process testing of those materials, so sending out to a sterility lab to test what are those components that we’re using to make the end product, testing the end product. All of that along the way through from A to Z, there’s records involved with all of that so we can prove that we’re doing these things.

Erin Sairafe: A lot of these other labs out there, you ask to see records of such a thing, they don’t know what you’re talking about, first of all, and, of course, don’t have records to show they’re doing any of it.

Dr. Gaveck: Coming from a clinical background, I was pretty amazed in the beginning when you got in equipment, or even pipettes that they use in the lab. Yet you have to send them out and have verified what the manufacturer has already verified, because you have to have verification of a verified product.

Erin Sairafe: Yeah. We need calibration records for every equipment that’s used in manufacturing our product. So from the smallest pipette to the largest centrifuge, or hood, everything needs to be calibrated. That’s not a one-and-done thing. It’s done every six months or annually. We have different time points for different equipment. Every equipment gets logged and maintained. We have records of it all that anybody can come ask to see, and we can show it very easily.

Dr. Gaveck: Heaven forbid, a manufacturer stops manufacturing it or they run out of materials and you have to change to another manufacturer of the same type of product, then you have to go through that same process?

Erin Sairafe: Yeah. So part of validation is with the types of supplies that you’re going to use on a consistent basis. That’s the supply that you have to use during each manufacturing. Every lot that you manufacture uses the same supplies that are from the same vendor. So if there’s a problem with a vendor … That’s why we like to have secondary sources just in case there’s an issue with a vendor, and that secondary source has also been qualified, their product has been validated so that way we don’t have any hiccups along the way.

Dr. Gaveck: So for all the multiple cords that are processed every day, all of that stuff has to be set up and consistently done.

Erin Sairafe: Yeah, and that’s part of the validation. We’ve validated the entire manufacturing process for each concentration; each product that’s made has it’s own validation. If you differ from that, then it’s a deviation, and it gets written up, and then QA gets involved to decide what’s going to happen with that product. It’s not released for the general public if it’s a deviation involving a critical issue.

Dr. Gaveck: So all of you work together, but in reality, you’re all watchdog for everybody, because if something goes wrong or it’s not up to one department’s qualifications of where it has to be, they shut it all down. It’s not like, “No, no, no, let’s work together in order to have a quality system.” Everybody has to carry their own load.

Erin Sairafe: Yeah, and everybody follows their set of protocols that we’ve written for that particular process. Lab has protocols, QA has protocols, shipping has protocols. So if anything along the way differs, a deviation is written up, or a nonconformance, then QA keeps track of those monitors we trend, is it the same person that’s making a mistake? Or is it a certain supply that we’ve having an issue with? All of that gets trended and then, if necessary, we do a CAPA, which is a corrective action, preventative action. Then those, too, get trended and traced, and we follow up to make sure that whatever issue was coming up, that that gets corrected and solves the problem.

Dr. Gaveck: So we went from months up to a year of creating your protocols and your standard operating procedures and finding a building and fitting it out and getting your lab equipment, having everything validated and tested and on and on and on and on and on, and finally you’re ready, and you’re ready to go. Are there not multiple processes that every single day … It’s not like, “Okay. We’re done. Here we go.”

Erin Sairafe: Oh, no. No.

Dr. Gaveck: Now we can produce stuff. We don’t have to do it anymore.

Erin Sairafe: No, it is ongoing. There’s always something to do. There’s always something to check, continuous monitoring. Environmental monitoring, for instance, that is done on a continuous basis. It’s not a one-time thing where you certify a clean room and then you’re done. No. You can get a clean room certified, but then you have to maintain that clean room. You have to do constant dynamic and static monitoring that includes viable and nonviable air particle counting that we use machines that actually suck up the air in the room onto plates that tell us whether there’s growth, whether there’s viable air particles.

Erin Sairafe: We do swabbing. So every single hood that’s used gets swabbed to see if there’s anything growing in there. Every personnel that’s involved with manufacturing also gets swabbed. Then all of those plates and swabs and all of our testing gets sent out to a third party laboratory so that there’s no bias, there’s no subjectivity. We can’t say, “Oh, there was no growth.” No. We get a report back from a third party that tells us what our counts were, and if it’s passing, if it’s an alert level, if it’s an action level, if it’s passing, so that way we are constantly making sure that that clean room is within the ISO 7 specs.

Dr. Gaveck: Just for the viewers, some of them may know that there’s an ISO 8, there’s an ISO 7, there’s an ISO 5. The lower the number, the less particulate count you can have in the room, right?

Erin Sairafe: Correct. The lower the number, the more stringent the requirement is.

Dr. Gaveck: More stringent it is.

Erin Sairafe: Our hoods are ISO 5. That is where the blood is being processed inside of the hood, or bio safety [crosstalk 00:11:41].

Dr. Gaveck: An ISO 8 clean room going into an ISO 7, pretty super clean room, going into an ISO 5, wow. Super clean, where all the processing is done.

Erin Sairafe: Right. So the ISO 8 is just the gowning room. It’s the anteroom where we gown up. Then it goes into the ISO 7, and then in an ISO 5 hood.

Dr. Gaveck: Even in that, you still have regular cleaning that has to be done by an outside professional cleaning company, right?

Erin Sairafe: Absolutely.

Dr. Gaveck: And it has to follow a certain schedule, and they have to change the chemicals so that you never get resistance and blah, blah, blah, and yada, yada, yada. Does it ever stop?

Erin Sairafe: No.

Dr. Gaveck: I think the funniest thing that I read one time was, most people think that CGMP stands for certified good manufacturing practice lab, and the quote was, “It’s only current because the regulations are moving so rapidly, the only thing you could hope to be would be current for that day.” I think it makes sense in everything you say.

Erin Sairafe: That’s funny.

Dr. Gaveck: The same thing is, you can have that clean room put in today, and everything is certified in that clean room. If you’re not following a massive set of protocols, by tomorrow you’re no longer certified clean room.

Erin Sairafe: Yeah, you have to follow those protocols. For the FDA regulations of part 1271, which we do follow like the Bible, it says to follow GTP standards, which is good tissue practice standards. We’re following them, plus CGMP standards, which is more stringent. It’s more for a pharmaceutical. If you’re manufacturing anything aseptically, or what we call the aseptic processing standards, you follow the CGMP standards. That’s what we’re doing. I forgot what I was going to say.

Dr. Gaveck: No, that’s amazing. It’s amazing, and I know everybody at the company and all the reps and all the doctors out there are very appreciative of you. If you have time, if you could come back later, even tonight, we would love to be able to talk about the next step. We talk about procuring it, we talk about what it takes to make a lab. What’s the next [inaudible] step that we can walk through, which would be obviously getting a biologics license and possibly be involved in investigation of new drug study, and IND study. Would you have time to possibly come back later?

Erin Sairafe: Sure.

Dr. Gaveck: That would be awesome. Again, thank you so much.

Erin Sairafe: Thanks, Alan.

Dr. Gaveck: Thank you so much. That is another Liveyon Pure Cast. This is Erin Sairafe. I’m Dr. Gaveck. See you next time.

Erin Sairafe: Thank you.


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This site was intended for education purposes only and strictly for use by medical professionals. The FDA recently re-confirmed, there is only one registered stem cell product, and while there is enormous promise in stem cell therapies, and thousands of ongoing experimental applications trying to establish efficacy, these are not at the point where they would meet the scientific standard.
The FDA has stated:
Stem cells, like other medical products that are intended to treat, cure or prevent disease, generally require FDA approval before they can be marketed. FDA has not approved any stem cell-based products for use, other than cord blood-derived hematopoietic progenitor cells (blood forming stem cells) for certain indications.
http://www.fda.gov/AboutFDA/Transparency/Basics/ucm194655.htm
This site is not intended for consumers.
If you are considering stem cell treatment in the U.S., ask your physician if the necessary FDA approval has been obtained or if you will be part of an FDA-regulated clinical study. This also applies if the stem cells are your own. Even if the cells are yours, there are safety risks, including risks introduced when the cells are manipulated after removal.
“There is a potential safety risk when you put cells in an area where they are not performing the same biological function as they were when in their original location in the body.” Cells in a different environment may multiply, form tumors, or may leave the site you put them in and migrate somewhere else.
If you are considering having stem cell treatment in another country, learn all you can about regulations covering the products in that country. Exercise caution before undergoing treatment with a stem cell-based product in a country that—unlike the U.S.—may not require clinical studies designed to demonstrate that the product is safe and effective. FDA does not regulate stem cell treatments used solely in countries other than the United States and typically has little information about foreign establishments or their stem cell products.
http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm286155.htm
Stem cell therapies have enormous promise, but the science in each use is still in the developmental stage. Professional judgment and expertise is needed in using stem cells for any therapeutic use, and we urge anyone embarking on the use of stem cell therapies to consult the national health data bases to evaluate current information from clinical trials and the FDA websites on human tissue should also be consulted to get its current evaluation of any therapy.