The Increased Demand for Immune Globulin Products and Its Effects on Patient Access

In this first episode, we will be talking about the increased demand for immune globulin (IG) products and its effect on patient access. This is our first podcast episode of IG Living Advocate and a transition from our Readers Teleconferences. With this podcast, we have an opportunity for our readers to hear from healthcare experts on topics important to them. 

In this first episode, we will be talking about the increased demand for immune globulin (IG) products and its effect on patient access. Today, we have with us guest expert Patrick M. Schmidt, chief executive officer of FFF Enterprises, also known as triple F, and Nufactor, a Specialty Infusion Company. Patrick has been with FFF since its inception in 1988. In 1995, FFF launched Nufactor to address the high costs and access issues related to IG therapy. Patrick is recognized as a leader in the healthcare community, having introduced several industry firsts that have paved the way to create solutions to challenges faced by both healthcare providers and their patients.

Transcript

IG Living Advocate

Episode 1 - The Increased Demand for Immunoglobulin Products and Its Effect on Patient Access (September 2019) 

Abbie: Hello, and thank you for joining us. My name is Abbie Cornett, and I am the patient advocate for IG Living magazine. This is our first podcast episode of IG Living Advocate and a transition from our Readers Teleconferences. With this podcast, we have an opportunity for our readers to hear from healthcare experts on topics important to them. 

In this first episode, we will be talking about the increased demand for immune globulin (IG) products and its effect on patient access. Today, we have with us guest expert Patrick M. Schmidt, chief executive officer of FFF Enterprises, also known as triple F, and Nufactor, a Specialty Infusion Company. Patrick has been with FFF since its inception in 1988. In 1995, FFF launched Nufactor to address the high costs and access issues related to IG therapy. Patrick is recognized as a leader in the healthcare community, having introduced several industry firsts that have paved the way to create solutions to challenges faced by both healthcare providers and their patients.

Abbie: Good morning, Patrick, and thank you for joining us. In recent weeks, patients across the United States have been notified that their scheduled infusions are either being delayed or cancelled due to a shortage of IG products. Understandably, this has caused concern for patients who depend on these lifesaving treatments for their acute or chronic conditions. Patrick, could you please give us some history and background on IG products and, most importantly, the recent shortages of IG products?

Patrick: Yes, Abbie, thank you very much. I’d be happy to, and it’s an honor to join you here with IG Living magazine and the readers who are listening to the podcast today on a very very important subject. I’m happy to go into a little bit of the background on the IG marketplace and IG products, which you know, from my perspective, is one of the most fascinating products on the planet. 

If we look at the history, intravenous IG (IVIG) was the first IG product introduced in 1981, and I believe it was a product called Gamimune by then a company called Cutter Biologics, which became Cutter and then Miles and then Bayer, and then Talecris, which is also known now as Grifols. Gamimune was the predecessor to one of the very popular products in the marketplace right now, Gamunex-C, which is as I mentioned manufactured by Grifols, a Spanish company. But, the interesting part about the whole plasma-derived product market, which IG is a very important component of, is the first plasma-derived product was used 39 years earlier right after Dec. 7, 1942, which most people remember the day in infamy around Pearl Harbor. And, the first plasma product that was introduced in the United States for healthcare purposes was a product called human serum albumin. And human serum albumin is credited with saving the lives of thousands of our servicemen after World War II. So the whole process to produce plasma-derived products that are derived from plasma was a World War II innovation. And, the manufacturing process that was used then is still used today as a process to produce albumin, and it was later refined and some additional processes were added to produce IG and abstract the antibodies that are in short supply today.

So, from my perspective, there’s nothing on the planet like IG. It’s used to treat more disease states, if you will, from the primary immune deficiencies to the secondary immune deficiencies (the latter of which are one of the recent factors causing some of the shortages we’re experiencing right now the United States) and to a whole host of a growing list of autoimmune disorders. And, I’m sure we have many of our constituents who are very familiar with many of these autoimmune disorders. The only other product in the United States or in the world I’m aware of that treats so many different diseases is a pharmaceutical product called prednisone, and a lot of people are very familiar with that particular product. But IG by itself is unique, and it’s in the 37th year of its lifecycle, or in the 30th-plus year of its lifecycle, and it continues to grow year after year. I was speaking to a senior executive at Grifols recently, and he was reminiscing about when Talecris, the predecessor of Grifols (Talecris was acquired by Grifols), and at that time, the marketplace for IVIG was about 45 million grams, and today, we’re approaching 100 million grams, which shows you the kind of growth areas that IG is used for, and is what’s contributing to many of the shortages today.

Abbie: Thank you, Patrick, for that overview. As you know, prior to this podcast, we had readers submit questions concerning the recent shortages. I was hoping you’d be able to answer a few of those for us today. The first question I’d like to address is: Many of our patients have asked why it takes so long to produce an IG product. Can you please explain the process of producing an IG product for us?

Patrick: Sure, and I touched a little bit on it in the prior question. I also think I compared IVIG and subcutaneous (IG) (SCIG) products to a pharmaceutical product called prednisone. As you know, prednisone is a tablet, and it’s produced from an active pharmaceutical ingredient. And, basically, pharmaceutical manufacturers can crank out thousands and thousands and millions and millions of these pills on demand, unlike plasma-derived products or biologics. 

It starts with plasma collection and the plasma collection industry. And, there’s a whole cottage industry of organizations that collect plasma intended for further manufacturing by the handful of manufacturers in the world right now that make IG products. Just to give an example, in the plasma collection industry in 2007, there were 349 plasma collection centers in the United States that collected 15 million liters of source plasma. In 2018, a little more than 10 years later, that number has almost doubled to 737 collection centers to meet the demand, collecting 49 million liters of plasma. To continue to meet the burgeoning demand for IG worldwide, we need to collect more plasma in the United States. 

So, once collected, plasma goes to manufacturing facilities that, as I said, are still using a technique that was designed originally to produce albumin. And from albumin come a couple of the different plasma fractions, and IG is one of those. The three largest manufacturers of plasma-derived and IG products worldwide are Takeda, Grifols and CSL. And then, there are also Octapharma, BPL and Kedrion. So, from the time the plasma is collected until it goes to manufacturing and for manufacturing after quality control and FDA approval and testing, it goes to large distributors like FFF Enterprises. And, there are three other large distributors that are publicly traded companies: AmerisourceBergen, Cardinal Health and McKesson. And from there, if it doesn’t go directly from a distributor, it goes to a healthcare provider that many of our constituents listening to this podcast are probably getting their infusions from. 

So, from the time of plasma collection through the lengthy manufacturing process and through the distribution channels, until the time it becomes bedside or chairside ready for infusion, it takes between seven and 12 months. So, it’s unlike pharmaceutical manufacturing, and I use prednisone as the example. The collection, the quarantine, the long manufacturing cycles, the testing and FDA approval and the absolute emphasis on product safety and availability, it makes biological manufacturing a lengthy process. So, I’ll stop there for a second to see if we can elaborate anymore if you like.

Abbie: No, Patrick, thank you very much. That really addressed some of the concerns of patients. The next question is: Do the shortages involve only certain brands of IVIG, or do they involve both IVIG and SCIG?

Patrick: Great question! I think somebody wants to know: Why is my brand short, and are other brands short, too? I think we’re going to talk here a little bit about some solutions and how to address a particular brand shortage. But, I think it’s important to recognize there are three basic product categories. There’s IVIG, SCIG and then there are a handful of products that can be administered intravenously and subcutaneously. And, I think at any given time, the entire marketplace is very tight. And back to the manufacturing question, I would just like to tell everybody, because there are a lot of rumors going around, that it’s my solid belief that all the manufacturers are doing everything they possibly can to collect as much plasma to produce as much IG as possible to meet the growing demand. And they’re spending a lot of time and a lot of money and a lot of research trying to improve yield to take a single liter of plasma and to extract as much IG as possible.

To talk a little bit more about which brands are in short supply, I would just look at the entire marketplace industry data. From March 2018 through April 2019, 91.2 million grams were distributed in the United States. That sounds like a tremendous amount of product, and it is. It’s a very valuable resource for everybody who needs IG, but one of the things that’s important to note based on manufacturing, the average is about 7.6 million grams per month if you break it down by 12 months. But, because of the nature of manufacturing, IG is not produced in one-twelfth increments. So, the supply into the distribution channel and to the infusion provider channel is not consistent, and those inconsistencies may make one product seem to be in short supply and unavailable for a period of time, while another one may be available. And to give you the clearest example of the 12 months I am talking about from May 2018 through April 2019, the highest distribution of IG in the marketplace was over nine million grams, and the lowest was slightly over six million grams. That’s about a three million gram difference or half a month’s difference. And in June 2019, of the three major brands manufactured, including Privigen by CSL, Gammagard Liquid by Takeda and Gamunex-C by Grifols, there was one, and I won't mention the name, that didn’t ship any product in the U.S. marketplace that we’re aware of. For the patients who were prescribed that particular product, it created a ton of access issues. So, there’s some timing related to being able to answer that question, and there’s no really easy answer. But it is a very very tight market. Access is a concern, and there’s a growing amount of discussion, including our podcast here today about some of the contributing factors to IG access.

Abbie: Thank you, Patrick, that definitely gives us a better idea of why there are current shortages. Several patients have shared their concerns about their product not being available, which you touched upon. What advice or suggestions do you have for them when they have lost access to their medication or to their brand? 

Patrick: I think there are some real tangible steps, and I think the very first steps are education and understanding. I think those are fundamental steps that we should be grateful to IG Living for hosting this podcast and providing this information. But I think we should look at what we talked about concerning distribution and plasma collection. And I think we need to focus a little bit on the sites of care. Where do readers get access to IG? Is it in a home infusion setting? Is it a hospital, either inpatient or outpatient setting? Is it their physician office, or is it an ambulatory infusion center? All sites of care are not created equal and do not, unfortunately, have equal access through no fault of their own. And I would just amplify that point by saying there are a couple of products in the marketplace that are produced by medium to smaller manufacturers that are not available in all sites of care. Privigen, Gammagard Liquid and Gamunex-C are available in every one of the sites of care — the home, the hospital, the doctor’s office and ambulatory infusion centers. Some of the smaller manufacturers’ products that produce less IG than the major manufacturers are only available in certain sites of care, maybe through a specialty pharmacy or a specialty home infusion company. So, site of care may have something to do with where patients get their IG product. 

So a very simple strategy, and if our readers were so inclined, I would just put down the initials BPR (brand, provider, route of administration). And this then would be the stimulus for a conversation potentially with your physician. I think that’s a logical order that you might want to approach and become an advocate for yourself. If you can’t get the brand, consider the route of administration. Have a conversation with your physician if the brand you are prescribed cannot be gotten in the site of care where you are getting your IG. Is there another brand that you could have access to if you can’t get a brand in that site of care? If not brand b, is brand c available? Know the brands, and go through a list of those. I’m sure IG Living could provide you with a complete list of all the brands. If a brand is not available in your current provider site, is there an opportunity for you to change provider sites? Could you go from an ambulatory infusion center to your home setting? Could you go from the home setting and your provider who’s providing your home care to a physician office or a hospital? Is there an opportunity for you to move and get your IG in a location that might have better access for you? And then if all of those are still not options, and you’ve been prescribed IVIG, is SCIG an option? So, I think those are maybe just some logical steps to advocate for yourself. Can I change brands? Can I change provider site? And if IVIG isn’t is an option for me, is there potentially another option — an SCIG product? There are pockets of IG available. We are never completely out in this country. Manufacturers are producing millions of grams that are being released in the marketplace every month. And by becoming an advocate for yourself and aggressively pursuing alternatives for your brand or your provider site or route of administration, we think you’ll be successful.

Abbie: Thank you very much. One of the questions that we received a number of times from patients is: When do you think the shortage will end? I was hoping you could share some insight with us on that.

Patrick: Abbie, that’s a question I’m asked often, and one that frankly I dread. And I was afraid you were going to ask it today because it’s very difficult to say. I think the best advice is maybe what we just gave about being able to advocate for yourself. Because of the growing demand for IG that has been consistent year after year, and then manufacturing just behind it trying to catch up, this could be a protracted shortage. That may not be what everybody wants to hear. We’ve also seen prior shortages at FFF through our 31 years of history, and we’ve lived through several of these shortages. So we’re no strangers to them, and we have a lot of experience on how to manage them. But, there is a management component to it that does improve access that probably is not for this podcast, but I think it’s best for our readers to plan for this to be a protracted shortage. Anything other than that will be a win. 

There are new products coming to the marketplace. I think we might have a little bit of time to touch on that. There are new manufacturers, and there are new techniques that are being used to increase the yield from plasma. Everybody’s invested in this, and nobody in the industry — none of the manufacturers, none of the providers — want any of the patients to suffer from IG shortages.

Abbie: Thank you, Patrick. You’re right, I would like to touch on some of the new things that could affect the industry in the future. Before we end today’s podcast, is there anything additional you’d like to share?

Patrick: I would just like you to know again that IG Living and many other organizations are trying to produce some information and understanding for the patient communities that are so dependent on

IG. I had a conversation the other day that really inspired me. It was from an autoimmune patient, and she said for autoimmune patients, once the rogue antibodies realize that the donated IG antibodies are no longer keeping them at bay, the rogue antibodies come back with even a more forceful vengeance than before. And that attitude and characterization should inspire others about what a shortage does and the fear it creates in people who are so dependent on IG therapy. That should inspire all of us to continue to do more. And I applaud IG Living for the work they’re doing. 

And then, there are new manufacturers. There’s a company called ADMA Biologics that has two products coming to the market in the second half of 2019: a new 10% liquid IVIG product, Asceniv, and a second product, Bivigam, which is a reintroduction of a product that was previously on the market that had been withdrawn. And then, there’s a company out of Canada called Evolve Therapeutics that’s working on a very interesting new technique to produce IG that will increase the yield of product. And then, a little more distant out is a company called GC Pharma, or the Korean Green Cross, that’ll probably be in the 2021 to 2022 timeframe. And then, we think in November, we’re predicting Grifols will produce a 20% SCIG product called Xembify. So there’s help on the way, and we’re very hopeful we’ll be able to continue to meet the demand. And when I say we, I mean the entire industry, everybody that’s involved in this, from the plasma collectors to the manufacturers to all the distributors and all the infusion providers, we’re very hopeful we’ll be able to continue to meet the demand for a long time to come. 

Abbie: Patrick, thank you again for joining us today to discuss this important issue. I would also like to thank the readers who wrote in with their questions. Our guest speaker today was Patrick M. Schmidt, chief executive officer of FFF Enterprises Inc. and Nufactor, a Specialty Infusion Company, who discussed the topic of the increased demand for IG products and its effects on patients.

For another resource to monitor IG shortages, please visit www.ashp.org or www.fda.gov. Both websites will be posted on IGliving.com to reference. 

Additional information regarding this podcast can be found on our website at www.igliving.com. If readers have a question that was not answered, please contact me at acornett@igliving.com.

Look for the next IG Living Advocate podcast announcement on our website for the opportunity to submit your questions.

IG Living Advocate is a copyright production of IG Living magazine, published by FFF Enterprises. It is the only magazine for the IG community comprised of patients who suffer from chronic illnesses and their caregivers.