Convalescent plasma collection and distribution

Efforts to collect and distribute convalescent plasma from recovered Covid-19 patients are ramping up: there are lots of options.

I donate convalescent plasma at the Stanford Blood Center, in their program on
 CONVALESCENT PLASMA FROM RECOVERED COVID-19 PATIENTS
"This exciting initiative involves taking plasma donations from recovered COVID-19 patients and transfusing that plasma into critically ill COVID-19 patients in the hopes that the antibodies present in the donated plasma will help save the lives of the recipients."

Modern plasma collection is a one-arm process: the machine on my right in the photo alternates between taking blood and returning red blood cells through the same needle (in contrast to the old technology which had blood go out of a needle in one arm and red blood cells return through a needle in the other arm).

Collecting convalescent plasma is not regulated as a research activity, it is just ordinary plasma donation. However giving it to patients is done under FDA guidance, either as a research activity or as an emergency intervention for very ill patients:
Recommendations for Investigational COVID-19 Convalescent Plasma
"Because COVID-19 convalescent plasma has not yet been approved for use by FDA, it is regulated as an investigational product."

There are three FDA-approved pathways right now by which convalescent plasma can be administered to patients.
"Pathways for Use of Investigational COVID-19 Convalescent Plasma:
1. Clinical Trials,
2.  Expanded Access "for patients with serious or immediately life-threatening COVID-19 disease"
3. Single Patient Emergency"

Here is a consortium of nonprofit blood centers, there's likely one near you if you're reading this in the States:
America's Blood Centers (association of independent blood centers)

• ABC Resources on COVID-19 and Convalescent Plasma
• America’s Blood Centers Partners with BARDA to Expand Collection of Convalescent Plasma for COVID-19 Patients

Here's the American Red Cross effort: Plasma Donations from Recovered COVID-19 Patients

My impression is that the nonprofit blood centers don't pay donors, but are able to sell plasma to customers, including the commercial plasma industry, as part of the thriving domestic and international market in plasma. (I blogged Monday about U.S. plasma exports, all over the world, including especially countries in which compensating donors is repugnant.)
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The for-profit plasma industry (which compensates plasma donors) is represented by The Plasma Protein Therapeutics Association (PPTA)
Here's an announcement about their plans for Covid-19 antibodies:

1. CoVIg-19 Plasma Alliance Builds Strong Momentum Through Expanded Membership and Clinical Trial Collaboration

"The CoVIg-19 Plasma Alliance, an unprecedented plasma industry collaboration recently established to accelerate the development of a plasma-derived hyperimmune globulin therapy for COVID-19, is rapidly building momentum. Its membership has expanded globally to include 10 plasma companies, and now also includes global organizations from outside the plasma industry who are providing vital support to encourage more people to donate plasma.

"In addition to those announced at its inception - Biotest, BPL, CSL Behring, LFB, Octapharma and Takeda - the Alliance welcomes new industry members ADMA Biologics, BioPharma Plasma, GC Pharma, and Sanquin. Together, these organizations will contribute specialist advisory expertise, technical guidance and/or in-kind support to contribute to the Alliance goal of accelerating development and distribution of a potential treatment option for COVID-19."

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Here's an NPR story: Market For Blood Plasma From COVID-19 Survivors Heats Up
May 11, 2020

"In Minnesota, a program coordinated by the Mayo Clinic has collected plasma from more than 12,000 COVID survivors for transfusion into more than 7,000 gravely ill patients, the result of a massive public appeal led by government leaders and nonprofit groups such as the Red Cross.

"Meanwhile, for-profit companies that typically pay $50 per donation of plasma used in other lifesaving therapies are advertising aggressively — and significantly bumping up their rates for COVID donors.

"In Utah, John and Melanie Haering, who contracted COVID-19 aboard the ill-fated Diamond Princess cruise ship, received gift cards worth $800 after making two donations apiece at a Takeda Pharmaceuticals' BioLife Plasma Services center. BioLife runs several of the more than 800 paid-plasma collection sites in the U.S., part of an industry that produces plasma protein therapies used to treat rare, chronic conditions such as hemophilia and in medical emergencies."

Plasma and plasma products (such as antibodies) are a big business (and the U.S. dominates the international market)

These days I'm thinking about corona virus covid-19 convalescent blood plasma, which I blogged about yesterday, and about which I hope to say more soon. But that has gotten me to think again about blood plasma generally, which is a source of many therapies, including antibodies, immunoglobulins, that defend against a large variety of diseases.

The U.S. is the Saudi Arabia of blood plasma and plasma products, with both a large domestic commercial market and annual exports valued in the billions of dollars. The reason is largely that it is legal in the U.S. to pay plasma donors, so there's ample supply through a big network of hundreds of  for-profit and nonprofit blood and plasma centers (the nonprofits mostly don't pay donors, I think). In many countries, paying their residents for plasma is repugnant and illegal. Fortunately for their citizens, they mostly don't also suffer from severe shortages of life-saving plasma medicines, because it can be bought from the U.S. (See e.g. my posts on Canada's plasma policies.)

Here are some relevant export figures. They make clear that the U.S. exports billions of dollars of plasma, and tens of billions of dollars of plasma products.

For those who would like to study these data, let me explain where they come from.  (They  include some things that aren't plasma products, and may miss some that are...) It's not so easy to find the U.S exports of exactly blood plasma and plasma products (I needed some help).

In Chapter 30 of the U.S. International Trade Commission (USITC) Harmonized Tariff Schedule (HTS),is the code:
HTS 3002: "Human blood; animal blood prepared for therapeutic, prophylactic or diagnostic uses; antisera, other blood fractions and immunological products, whether or not modified or obtained by means of biotechnological processes; vaccines, toxins, cultures of micro-organisms (excluding yeasts) and similar products:
 Antisera, other blood fractions and immunological products, whether or not modified or obtained by means of biotechnological processes"

That sounds good, but it includes (aside from plasma products) things that I don't want to include e.g. Malaria diagnostic test kits, and Fetal Bovine Serum.

On the other hand the subcategory 3002.12.00  is for "Antisera and other blood fractions" which includes sub-subcategories for things I do want to include:
3002.12.10 Human blood plasma.
3002.12.20 Normal human blood sera, whether or not freeze-dried
3002.12.30 Human immune blood sera

And then there are are codes 3002.13.00, 14.00, and 15.00 which cover the promising (very similar) categories in which most of the immunoglobulins are probably found, but maybe some other things too:

Immunological products, unmixed, not put up in measured doses or in forms or packings for retail sale
Immunological products, mixed, not put up in measured doses or in forms or packings for retail sale
and
 Immunological products, put up in measured doses or in forms or packings for retail sale.

The place to go to turn these numbers into export figures is dataweb.usitc.gov  (But getting data there isn't completely straightforward, and I got help from Julia Fabens.)  The table above shows that whole plasma itself has over $2 billion of annual exports from the U.S., and together with plasma products, including those involving antibodies (immunological products) there are almost $20 billion of exports from the U.S.

So, I'm guessing that soon, if clinical trials show that antibodies against covid-19, are useful, they will become readily available, commercially, in plasma and in pharmaceuticals.  A year ago, those human antibodies didn't exist, and so there was no way to use it to help patient zero or the next many thousands.  But now there's a lot of it, more each day, in the blood of recovered patients.  And there's a whole industry devoted to collecting it and purifying the antibodies into "immunological products." 

I hope human antibodies against covid-19 are clinically useful, to help mitigate and cure the disease if not to prevent it, because my sense is that a vaccine is (at least) many months away.

102,597,746 2,627,504 1,586,634	102,597,746	2,627,504	1,586,634

Cascades of convalescent plasma for Covid-19, and chains of exchanges, by Kominers, Pathak, Sönmez, and Ünver

Covid-19 convalescent plasma is a new thing in the world, that came into existence only when the first human was infected and recovered from the Covid-19 disease that is now pandemic. It isn't clear yet whether it will be clinically valuable, but recovered antibodies have been valuable for some other diseases, so there's excellent reason to hope that will be the case now too.  And as the number of people grows who have recovered from Covid-19, it is likely that the supply of antibodies is growing much faster, since antibody-containing plasma can be donated once a month or so. (There are  ongoing studies of antibody production by recovered patients, examining how long the antibodies remain at high levels, post-recovery). Of course, most of that supply is sequestered in the blood of recovered patients, so there's a non-trivial issue of collection and distribution.

As readers of this blog know, many countries prohibit the sale of plasma. Will Americans continue to support a commercial market for Covid-19 convalescent plasma in the current pandemic?  A distinguished group of market designers has written a paper considering how to apply techniques developed for kidney exchange to the task of collecting convalescent plasma from recovered Covid-19 patients, if it becomes impossible to buy and sell it. In particular, they consider how to create chains of donations, without using money, to overcome the shortages they anticipate.

Here's an easy to read account by Scott Kominers, one of the authors.

How to End the Plasma Shortage for Coranavirus Patients

Scott Duke Kominers, Bloomberg News  May 11, 2020

"convalescent plasma is in short supply: although it’s hard to estimate precisely, some statistics suggest the U.S. may need twice as much as we have on hand.

"In a new paper, Parag A. Pathak, Tayfun Sonmez, M. Utku Unver and I propose a market design strategy that could help close the gap. Our approach makes use of two special features of the way plasma donation works.

"First, convalescent plasma is collected from recently recovered patients, which means that today’s patients become tomorrow’s prospective donors, assuming they manage to beat the virus. ... That suggests the shortage isn’t from lack of potential supply.

"Second, plasma donation is more than one-for-one: the typical donor can give enough plasma at one time for multiple treatments, and they can potentially donate more than once. As a result, assuming plasma therapy does help patients recover, there is a so-called flywheel effect: the more we use the treatment, the more plasma is available -- provided enough recovered patients are willing to donate.

"Many people would like to donate plasma to help a loved one, but can’t for various reasons:  Their blood types might be incompatible or they might live far away and be unable to travel. To address these sorts of obstacles, my collaborators and I suggest that each plasma donor could receive a voucher that can be used to give a family member or friend priority for plasma treatment. Because donation is more than one-for-one, it’s possible to honor vouchers while still increasing the pool of plasma available to treat other patients.

...

"A similar analysis suggests a role for a pay-it-forward system, where we make a point of treating patients who pledge to donate plasma, assuming they recover and are medically able to do so. Because recovered patients can typically donate more plasma than was needed for their own treatment, this again can help increase the plasma supply in the long run. As a result, my collaborators and I show that, somewhat paradoxically, prioritizing patients who pledge to donate can still end up expanding treatment for the patients who are unable to pledge, or just choose not to.

"Both of these policies are similar to systems we’ve used to expand kidney donation in the U.S.: Priority vouchers are sometimes granted when a living donor gives a kidney to a third-party before one of their family members needs a transplant. And pay-it-forward incentives are used in kidney exchange chains, where a patient with a medically incompatible prospective donor receives a kidney from a third-party donor, and then their donor later gives a kidney to some other patient."
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Here is the paper itself:

Paying It Backward and Forward: Expanding Access to Convalescent Plasma Therapy Through Market Design
Scott Duke Kominers, Parag A. Pathak, Tayfun Sönmez, M. Utku Ünver
NBER Working Paper No. 27143
Issued in May 2020

Abstract: COVID-19 convalescent plasma (CCP) therapy is currently a leading treatment for COVID19. At present, there is a shortage of CCP relative to demand. We develop and analyze a model of centralized CCP allocation that incorporates both donation and distribution. In order to increase CCP supply, we introduce a mechanism that utilizes two incentive schemes, respectively based on principles of “paying it backward” and “paying it forward.” Under the first scheme, CCP donors obtain treatment vouchers that can be transferred to patients of their choosing. Under the latter scheme, patients obtain priority for CCP therapy in exchange for a future pledge to donate CCP if possible. We show that in steady-state, both principles generally increase overall treatment rates for all patients—not just those who are voucher-prioritized or pledged to donate. Our results also hold under certain conditions if a fraction of CCP is reserved for patients who participate in clinical trials. Finally, we examine the implications of pooling blood types on the efficiency and equity of CCP distribution.

Here's some of the motivation for their model:

"There is an active debate in economics and philosophy on the appropriate role of market-based

mechanisms with compensation for human products used in medicine or medical research like kidneys, blood, blood products, sperm, breast milk, bone marrow, and other.11 Since, as far as we know, there is no current market where infected patients can buy CCP or where recovered patients can sell CCP, we do not consider this possibility as part of our model.

...

"Because CCP is a form of plasma, a natural question is whether a compensated market for CCP will develop. In our model, there is no option to pay to receive CCP or be paid for donating CCP, but a donor can designate the voucher in our model to particular patient in need. As a result, our model of CCP falls between the two extremes described above. We expect that in a crisis moment, there is unlikely to be an active compensated market for CCP (even though it may be impossible to fully prohibit resale of vouchers). If a price-based market does develop, society may deem it unacceptable."

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I am more optimistic than they are about the likely available supply of convalescent plasma if it proves useful, through existing commercial channels. My optimism is based on the large thriving commercial market for plasma and plasma-derived antibodies in the U.S., and around the world.  I'll try to blog about the general plasma and antibody (immunoglobulin) market tomorrow, and perhaps more on Covid-19 antibodies later this week.

Buying and selling blood plasma, with focus on Canada, continued

Peter Jaworski writes:

"I had a video with Big Think come out recently where I defend paying for plasma against a number of objections. It’s a bit on the long side (17 minutes), but I thought you might be interested in posting it to your blog: https://bigthink.com/videos/paid-plasma-ethics

"I also had an opinion piece on the same topic published in the National Post (with Kate Vander Meer, who is a patient that used plasma therapies): https://nationalpost.com/opinion/opinion-on-covid-19-canada-needs-to-pay-plasma-donors-to-protect-its-domestic-supply?video_autoplay=true"

From the video transcript:

"Out of all the countries in the world only the ones that pay people to make that donation are self-sufficient in plasma therapies. And even the ones that pay not all of them are, in fact, sufficient. So there are only seven countries in the world that legally permit paying people for plasma donations – Germany, Austria, Hungary, Czechia or the Czech Republic, parts of Canada. And I'll talk about Canada in a second. The United States, of course, and China. Those are the seven countries in the world that permit payment. Every other country that does not allow payment for plasma donations imports plasma therapies that make use of plasma primarily from Americans. Germans as well, but primarily Americans. "
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And here's the op-ed:

Opinion on COVID-19: Canada needs to pay plasma donors to protect its domestic supply
Kate Vander Meer and Peter Jaworski: In order to ensure that enough people are willing to give plasma to meet the ever-expanding need, we must urgently adopt a pay-for-plasma model here at home

"There’s no evidence that anything other than paying for plasma will work. According to an expert panel formed by Health Canada in 2018, paid donors in countries that permit payment are responsible for providing 89 per cent of the plasma used to make therapies, with the United States alone providing 70 per cent of the global supply. The panel also revealed that no country in the world that forbids paid donations collects enough plasma to meet its needs — not one!"

Plasma donation, "convalescent plasma" and Covid-19 antibodies

Blood plasma is a big source of antibodies for people who don't make their own, and in these days of Covid-19 pandemic, antibodies are again in the news. As the number of recovering patients grows, can the antibodies they produce be of help in stemming the spread of the disease, or in curbing its intensity?

Here's a just published report of a quite preliminary study from China, in the PNAS:

Effectiveness of convalescent plasma therapy in severe COVID-19 patients
by Kai Duan, ... Xiaoming Yang (46 authors)
PNAS first published April 6, 2020 https://doi.org/10.1073/pnas.2004168117
Contributed by Zhu Chen, March 18, 2020 (sent for review March 5, 2020; reviewed by W. Ian Lipkin and Fusheng Wang)


"Significance: COVID-19 is currently a big threat to global health. However, no specific antiviral agents are available for its treatment. In this work, we explore the feasibility of convalescent plasma (CP) transfusion to rescue severe patients. The results from 10 severe adult cases showed that one dose (200 mL) of CP was well tolerated and could significantly increase or maintain the neutralizing antibodies at a high level, leading to disappearance of viremia in 7 d. Meanwhile, clinical symptoms and paraclinical criteria rapidly improved within 3 d. Radiological examination showed varying degrees of absorption of lung lesions within 7 d. These results indicate that CP can serve as a promising rescue option for severe COVID-19, while the randomized trial is warranted."
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Here's a story from the WSJ:

Coronavirus Survivors Keep Up the Fight, Donate Blood Plasma to Others
National Covid-19 project seeks volunteers to aid the seriously ill; ‘I feel obligated to help’
By Amy Dockser Marcus

"The Mount Sinai Hospital in New York, where Mr. Sherman volunteered to donate plasma, is one of 34 institutions around the country participating in the National Covid-19 Convalescent Plasma Project, which is seeking blood-plasma donations from recovered patients who have a confirmed Covid-positive test and are at least 21 days out from the onset of symptoms.
...
“The biggest problem is not the lack of donors,” said Arturo Casadevall, a professor at the Johns Hopkins Bloomberg School of Public Health, in Baltimore, and one of the organizers of the national project. “It is the logistics of figuring out how people who want to participate can actually donate.”

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And here's a plasma industry press release:

Global Plasma Leaders Collaborate to Accelerate Development of Potential COVID-19 Hyperimmune Therapy

"Osaka, JAPAN, and King of Prussia, PA, USA – April 6, 2020 –  Biotest, BPL, LFB, and Octapharma have joined an alliance formed by CSL Behring (ASX:CSL/USOTC:CSLLY) and Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) to develop a potential plasma-derived therapy for treating COVID-19. The alliance will begin immediately with the investigational development of one, unbranded anti-SARS-CoV-2 polyclonal hyperimmune immunoglobulin medicine with the potential to treat individuals with serious complications from COVID-19.
...
"Developing a hyperimmune will require plasma donation from many individuals who have fully recovered from COVID-19, and whose blood contains antibodies that can fight the novel coronavirus. Once collected, the “convalescent” plasma would then be transported to manufacturing facilities where it undergoes proprietary processing, including effective virus inactivation and removal processes, and then is purified into the product."

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My other posts on plasma, mostly focused on repugnance to compensation for donors. Here's one that explains some of the underlying medical issues:

Thursday, July 11, 2019

Plasma shortage alert from the IDF--the Immune Deficiency Foundation

Poll: majority of Canadians approve of paying plasma donors

New survey results from Peter Jaworski
Canadians think that pay-for-plasma is “morally appropriate.”

"A significant majority of Canadians (63%) believed that paying Canadians for plasma donations was “morally appropriate.”

By age, 18-34 year-olds were most likely to think that pay-for-plasma was “morally appropriate,” with 75% saying so. 70% of 35-54 year-olds, and 49% of those 55 or older thought pay-for-plasma was morally appropriate.

By region, 64% of Atlantic Canada, 69% in Quebec, 61% in Ontario, 70% in the Prairies, 65% in Alberta, and 56% in British Columbia held that opinion.

The provinces of Ontario (2014), Alberta (2017), and British Columbia (2018) have all recently banned pay-for-plasma citing moral objections as part of the motivation behind the prohibitions"

Peter Jaworski on paid and unpaid plasma donation in Canada

Peter Jaworski in the Globe and Mail:
There’s a way to avoid blood plasma shortages: pay donors

and on the radio in Calgary (it isn't Peter in the picture:)


Some quotes from the Globe and Mail article:
" Canada collects only about 17 per cent of the plasma necessary to meet domestic demand for immune globulin. Paid donors in the United States are how we meet (and exceed) our country’s demand."

"Only countries that pay donors are self-sufficient in plasma. The rest have to import it from countries that pay. Paid donors in the United States are responsible for more than 60 per cent of the entire world’s plasma used to make plasma medicine."

"In terms of safety, a Health Canada Expert Panel report from May of last year noted that paid plasma is not less safe than unpaid plasma and it is less expensive than trying to recruit and retain unpaid donors. Paying donors is also the most likely way of ensuring security of supply. Paid donations having a negative effect on unpaid blood donations is also unlikely. The United States has more than 800 paid plasma centres, and still has higher blood donation rates than Canada."

"Claims that paid plasma exploits the poor are also mistaken. Pay is about $30 an hour in Canada (it takes 1.5 hours to donate plasma), and represents about 30 per cent of the total revenue from a litre of plasma (a much larger share than profits, which are less than 3 per cent of revenue). That’s a fair deal."

"Opponents also like to point out that plasma collected in the paid plasma centres in Canada is exported, with none of it staying in Canada. That’s true, but it’s true because Canadian Blood Services choose not to buy Canadian plasma in spite of its lower price and domestic origins."

Plasma shortage alert from the IDF--the Immune Deficiency Foundation

Patients with primary immunodeficiencies don't produce antibodies, and depend on immunoglobulin, one of the primary plasma products produced by donated plasma (the other is albumin, and there are other life-saving and life-improving pharmaceuticals as well).  The IDF is a foundation dedicated to this complex of diseases:

Immune Deficiency Foundation
Dedicated to improving the diagnosis, treatment and quality of life of persons with primary immunodeficiencies

In recent years immunoglobulin has been used around the world to treat other immune deficiency diseases also, as well as to modulate the immune systems of people with auto-immune diseases.

But shortages occur, because the U.S. remains the primary supplier of donated plasma (since it is legal to compensate plasma donors in the U.S., but not everywhere...)

Here's a blog post from John Boyle, the IDF president

Immunoglobulin Product Availability Issues: The Sky Is Not Falling but the World Needs More Plasma
"IDF is working with those who are seeking to increase yields of Ig from plasma, introduce new fractionation technologies, grow plasma donations at collection centers, and more, but those are long term solutions.

"Ultimately, the issue is that the world needs more plasma, and the only good way to make that happen is to collect more plasma. The one thing that we can all do right now is to encourage people to become regular plasma donors if there’s a collection center anywhere near them."
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"Biologic" medicines are regulated by the Food and Drug Administration's
Center for Biologics Evaluation and Research (CBER)

"CBER is the Center within FDA that regulates biological products for human use under applicable federal laws, including the Public Health Service Act and the Federal Food, Drug and Cosmetic Act. CBER protects and advances the public health by ensuring that biological products are safe and effective and available to those who need them. CBER also provides the public with information to promote the safe and appropriate use of biological products."

Here is their list of CBER-Regulated Products: Current Shortages
"GAMMAGARD LIQUID® Immune Globulin Infusion (Human) is currently available, though patient shipping schedules may be impacted as continued high demand exceeds production plans and available inventory."
which they attribute to: "Demand increase in the drug or biological product."

The case for compensating Australian plasma donors, by Bob Slonim

Here's Bob Slonim, explaining the current situation in Australia, of unpaid Australian plasma donors, and big imports of plasma products from countries in which donors are paid:

How Australia can fix the market for plasma and save millions

"The National Blood Authority’s 2016-2017 annual report indicates Australian imports of immunoglobulin, a plasma component, provide 44% of domestic demand. This costs A$120 million while the remaining 56% comes from domestic supply costing A$413 million.

"This implies the domestic supply of immunoglobulin costs over three times more per unit than what is imported, despite domestic donors not being compensated."

Societal Support for Paying Plasma Donors in Canada By Nicola Lacetera and Mario Macis

Here's a concise summary of recent work by Lacetera and Macis, as a Cato Institute Research Brief:

Societal Support for Paying Plasma Donors in Canada
By Nicola Lacetera and Mario Macis

They begin with a concise statement of why repugnance is important for economics:

"The legal status and regulation of economic transactions do not depend only on considerations regarding their economic efficiency, but also on whether a society supports the occurrence of trades through a price mechanism (if at all). Concerns that individuals engaging in certain transactions may be exploited or unduly influenced, that the terms of trade may not be fair, or that some transactions violate human dignity, the sanctity of life, or traditional institutions may lead a society to prohibit certain trades. These principles may take priority over material considerations and may contribute to defining common identities or a collective conscience that allows complex societies to be tied together. "

The article is "based on and includes excerpts from Nicola Lacetera and Mario Macis, “Moral NIMBY-ism? Understanding Societal Support for Monetary Compensation to Plasma Donors in Canada,” Law and Contemporary Problems 81 (2018): 83–105, https://scholarship.law.duke.edu/lcp/vol81/iss3/5.

Compensation for plasma donors--calls for a ban in Canada

At the same time as there are calls for decriminalizing drug use in Canada (see yesterday's post), there are calls for bans on compensating plasma donors. (Repugnance is a big topic..)

This post collects some thoughts on compensation for plasma donors, following my participation in the recent Plasma Protein Forum.

Much discussed there is the rash of recent legislation and proposed legislation in Canada to ban compensation for donors (a sort of repugnance event...).

E.g.
B.C. joins 3 other provinces in banning payment for blood and plasma
Alberta, Ontario and Quebec already have laws prohibiting profit from blood donations

Senator introducing bill to ban payments for blood donation
"“The point of this bill is better safe than sorry,” Wallin said.

“Canadian blood donors are not meant to be a revenue stream.”

Time to end for-profit plasma donations

Canada must never allow another tainted blood crisis and must put an end to cash-for-blood clinics. by (Senator) PAMELA WALLIN

***************

One perplexing feature of this debate is that Canada already buys lots of plasma from the U.S., where it is supplied by paid donors. No one seems to be suggesting that should be changed.

(Here are my posts to date on plasma in Canada.)

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In related notes, China seems to be ramping up it's "source" plasma collection (obtained at the source via plasmapheresis, as distinct from "recovered" plasma obtained from whole blood donations), with collection of about 7 million liters in 2017.  My understanding is that Chinese law forbids the importation of blood products except for albumin.

See this Lancet editorial from 2017:

The big business of blood plasma

"China,  a  country  that  holds  the  questionable  honour  of  being a world leader in liver disease, is now also the highest consumer  of  serum  albumin,  using  300  tonnes  annually,  roughly  half  of  the  worldwide  total  use,  according  to  an  article  in  the  Financial  Times. 

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In Brazil, compensation of plasma donors is forbidden (along with compensation of organ donors) in the Constitution, article 199

"(4) The law establishes the conditions and requirements to allow the removal of human organs, tissues, and substances intended for transplantation, research, and treatment, as well as the collection, processing, and transfusion of blood and its by products, all kinds of sale being forbidden."

Explaining plasma donation

In recent posts I've commented on the repugnance (in Canada and elsewhere) to paid plasma donation, which is legal in the U.S.. (The U.S. consequently supplies much of the world's plasma needs.)  One question facing the plasma industry is how to defend against compensated plasma donation being seen as a repugnant transaction.

I think they are already very well equipped to communicate the need for plasma proteins, which provide treatments for a host of diseases, and which are used around the world.  But to the extent that (paid or unpaid) donation needs to be defended and encouraged, I would expect to see more stories like this one, from Australia.

This man's blood has saved 2.4 million babies
'I'd keep going if they let me,' says 81-year-old with magical plasma.

"The man with the golden arm

"Harrison's blood is valuable because he naturally produces Rh-negative blood, which contains Rh-positive antibodies. His blood has been used to create anti-D in Australia since 1967.

"Every ampule of Anti-D ever made in Australia has James in it," Robyn Barlow, the Rh program coordinator who recruited Harrison, told the Sydney Morning Herald. "Since the very first mother received her dose at Royal Prince Alfred Hospital in 1967."

Harrison was the program's first donor.

"It's an enormous thing ... He has saved millions of babies. I cry just thinking about it."

Since then, Harrison has donated between 500 and 800 milliliters of blood almost every week. He's made 1,162 donations from his right arm and 10 from his left.

...

Harrison's retirement is a blow to the Rh treatment program in Australia. Only 160 donors support the program, and finding new donors has proven to be difficult. Additionally, attempts to create a synthetic version of anti-D have failed."

The market for blood plasma: different tissues, same issues

I'll be speaking at The Plasma Protein Forum, June 12-13 in Washington D.C., on "REPUGNANT TRANSACTIONS AND FORBIDDEN MARKETS: DIFFERENT TISSUES, SAME ISSUES"

Here's the whole program:

DAY ONE:    JUNE 12, 2018

7:00 am–5:30 pm	Registration and Exhibit Hall Open
7:00–8:30 am	Breakfast—Available in Exhibit Halls 1 & 2
8:30–8:45 am	WELCOME & “How Is Your Day?”Jan M. Bult, President & CEO, PPTA
8:45–9:00 am	CHAIRMAN'S MESSAGE David Bell, Chair, PPTA Global Board of Directors; Executive Vice President & General Counsel, Grifols
9:00–10:30 am	PERSPECTIVES: ACCESS TO CARE Moderator:  Larisa Cervenakova, M.D., Ph.D., Medical Director, PPTA
	Speakers:  Tony Castaldo, President, US Hereditary Angioedema AssociationHAE perspective Joanna Chorostowska-Wynimko M.D., Ph.D., D.Sc., Professor, Scientific Director National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland Alpha-1 perspective Professor Paolo Caraceni, Associate Professor, Department of Medical and Surgical Sciences, University of Bologna, Bologna, ItalyANSWER: Long term albumin administration improves survival in patients with decompensated cirrhosis
10:30–11:00 am	BREAK
11:00 am–12:30 pm	CURRENT INDUSTRY AND REGULATORY INITIATIVES IN THE AREAS OF INSPECTIONS AND DONOR HEALTH Moderator:  John Delacourt, Vice President Legal Affairs & Global Operations, PPTA
	Speakers: Ginette Y. Michaud, M.D., Director, Office of Biological Products Operations, U.S. Food & Drug AdministrationFDA’s Office of Biological Products Operations – Form Follows Function Toby L. Simon, M.D., Senior Medical Director, Plasma & Plasma Safety, CSL PlasmaDonor health perspectives: Insights from industry plasma vigilance data and future safety initiatives George B. Schreiber, Sc.D., Director, Epidemiology, PPTA Iron depletion in Source plasma donors; A non sequitur.
12:30–2:00 pm	LUNCH—Buffet Available in Exhibit Halls 1 & 2    Sponsored by:
2:00–4:00 pm	INTERNATIONAL ACCESS TO CARE LANDSCAPE Moderator:  Jan M. Bult, President & CEO, PPTA
	Speakers: P. Martin van Hagen, M.D., Ph.D., Professor, Head, Clinical Immunology Unit Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands Is personalized medicine a national or cross border issue? Dr. Ranjeet S. Ajmani, CEO, PlasmaGen BioSciences Pvt Ltd. Initiatives to improve access to care in India Antonio Condino-Neto, M.D., Ph.D., President, Latin American Society for Immunodeficiencies (LASID)What needs to be done to improve access to Immunoglobulin therapy in Brazil? Diagnosis, Access, Supply
4:00 pm	BREAK – Ice cream social
4:30 pm	Otto Schwarz Award presentation
5:00 pm	REPUGNANT TRANSACTIONS AND FORBIDDEN MARKETS: DIFFERENT TISSUES, SAME ISSUES Alvin E. Roth, Craig and Susan McCaw Professor of Economics, Stanford University; George Gund Professor of Economics and Business Administration, Emeritus, Harvard University; and 2012 recipient of the Nobel Memorial Prize in Economic Sciences
5:45 pm	DAY 1 CLOSING ANNOUNCEMENTS
5:45–7:30 pm	Reception

DAY TWO:    JUNE 13, 2018

7:30 am–1:00 pm	Registration and Exhibit Hall open
7:30–8:30 am	Breakfast—Available in Exhibit Halls 1 & 2
8:30–8:35 am	WELCOME Joshua Penrod, J.D., Ph.D., Vice President, Source & International Affairs, PPTA
8:35–8:50 am	SOURCE DIVISION OUTLOOK Roger Brinser, ‎Chair, PPTA Source Board of Directors; Director, Regulatory, BioLife Plasma Services/Shire
8:50–11:00 am	CURRENT CHALLENGES  Moderator: Joshua Penrod, J.D., Ph.D., Vice President, Source & International Affairs, PPTA
	Speakers: Nicola Lacetera, Ph.D., Associate Professor at the University of Toronto Crowding Out Prof Dr. Liu Zhong, Vice President, Institute of Blood Transfusion, Chinese Academy of Medical Sciences (CAMS)Which is safer source plasma for manufacturing in China: apheresis plasma or recovered plasma? Chen Bin, Deputy Director, Medical Safety and Transfusion Division, Department of Medical Regulatory and Management, National Health CommissionThe current situation and challenge of the Chinese plasma management
11:00–11:30 am	BREAK
11:30 am–1:00 pm	CAN COUNTRIES DELIVER ON THEIR OWN? Moderator:  Julia Fabens, Senior Manager International Affairs, PPTA
	Speakers: Bill Bees, Vice President, Plasma Technologies, Prometic Plasma ResourcesCanada–Debunking the Krever Commission Report Peter Jaworski, Ph.D., Professor, Georgetown University, Washington, D.C. Ethics of Compensation Joshua Penrod, J.D., Ph.D., Vice President, Source & International Affairs, PPTAGlobal sufficiency: Obstacles and opportunities

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Here are my blog posts on plasma, sorted by date (most recent first), going back to one from 2009.

The Economist on blood plasma

The Economist comments on Canada's repugnance towards paying Canadians to donate blood plasma (when you can buy as much as you need from U.S. donors..see previous posts.)

Vital fluids
America’s booming blood-plasma industry
Paid-for plasma is both less exploitative than often recognised, and invaluable

"The World Health Organisation lists immunoglobulins and coagulation factors—both plasma-derived products—as essential medicines. Yet poor countries are often desperate for them and rich countries rely on American imports. Without financial incentives, supplies are hard to come by. “It’s not in people’s nature”, says Mr From, “to let a phlebotomist poke a needle in your arm and suck your blood out.”
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Vein attempts
Bans on paying for human blood distort a vital global market
The market in life-saving blood-plasma products depends on Americans who are paid for it

"The global demand for plasma is growing, and cannot be met through altruistic donations alone. Global plasma exports were worth $126bn in 2016—more than exports of aeroplanes. But paid plasma raises ethical, social and medical concerns: that it will lead to health catastrophes, as in the 1980s when tainted blood spread HIV and hepatitis; that it exploits the poor; and that it reduces the supply of “whole” blood, which is almost all donated voluntarily.

"None of these worries is well-founded. But Canadian reservations about paid plasma are shared across most of the world. America, China, parts of Canada and some European countries are among the few places that permit it. Those countries are extremely effective in securing supplies: three-quarters are collected in America alone, and another 10% in China, Germany, Hungary and Austria, where payment is also allowed. Of over 1,000 plasma-collection centres worldwide, 700 are in America. Jan Bult, head of a trade association representing companies that manufacture more than half of the world’s plasma products, says none collects plasma in countries that have banned compensation.

"Only countries that pay for plasma are self-sufficient in it. (Italy, where donors are given time off work, is close to self-sufficiency.) Half of America’s plasma is shipped to Europe—20m contributions-worth. Canada imports 80% of its plasma products from America. Australia imports 40% of its plasma products, too.

"Drug firms from countries that have banned pay-for-plasma do much of their collection in America. Three of the largest collection companies are European: Grifols of Spain, Shire of Ireland and Octapharma of Switzerland. The parent company of another big collector, CSL Behring, is Australian. Together these four firms run nearly eight out of ten plasma-collection centres. Some of their manufacturing capacity is in America, but much is located elsewhere. Switzerland, which collects very little plasma, exported $26bn-worth of plasma products in 2016.

...

It remains legal to pay for whole-blood donation in America today. But hospitals refuse to accept it. Today’s plasma, however, is safe from the contamination risks of the past. Modern screening and sanitisation are extremely effective. Graham Sher, chief executive of Canadian Blood Services, a non-profit, says plasma products from paid donors are “as safe as those from our unpaid donors”.

Other prejudices against pay-for-plasma are equally deep-seated. Some data, for example, lend weight to the suspicion that it preys on the poor. American plasma centres are concentrated in less well-off bits of the country. Typically they are in postal districts where 27.4% of the population are poor, according to The Economist’s analysis of census data. This is much higher than the average American poverty rate of 16.5%.

The other worry, shared by Dr Sher, is that paying for plasma may lead to a reduction in whole-blood donation. But, if that were true, the problem would be intensifying, as pay-for-plasma centres have nearly doubled worldwide in the past five years. But Peter Jaworski, of Georgetown University, is sceptical, suggesting that, anecdotes aside, the evidence shows paid plasma donation “does not crowd out voluntary blood-donation”. Americans, for example, continue to donate as much voluntary blood per head as do Canadians.

The aversion to paid-for plasma carries its own risks. According to Grifols, the geographic imbalance puts supplies of plasma products at risk. At the plasma industry’s main annual conference, held this year in Budapest in March, over-reliance on imports from America was a hot topic. Representatives from several countries (including Canada) recognised they must do more to diversify their supplies. Making it legal to pay for plasma is an obvious first step."

This article appeared in the International section of the print edition under the headline "Thicker than water"
 Print edition | International
May 10th 2018
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And here's a letter to the editor https://www.economist.com/letters/2018/06/02/letters-to-the-editor. (The highlighted sentence seems to reflect that the editor who decides what letters to publish is a different person than the economics editor  who writes that I study repugnance only to dismiss it, and whose views I remarked on here and here.)

"In your series of articles advocating for payments to plasma donors, you stress the positive supply effects that payments may have. Appeals to increased efficiency, however important, are unlikely to persuade politicians and the public when the opposition to payments resides in deep-rooted ethical concerns. Starting with the seminal work of Nobel laureate Alvin Roth, economists have begun to seriously consider how to design effective market mechanisms while respecting moral beliefs, in order to reach a virtuous balance in the trade-offs between morality and efficiency.

"Based also on our own research on ethically contentious transactions, we would suggest that policymakers collect two types of evidence before adopting extreme policies such as outright bans. First, pilot projects would help assessing the impact of various policy options. Second, policymakers should inform the public about this evidence, and take into account the ensuing prevailing opinions and ethical concerns in the population, instead of being based on pressures (in one direction or the other) from vocal but often scarcely representative groups.

NICOLA LACETERA
University of Toronto
MARIO MACIS
Johns Hopkins University
Baltimore, Maryland 

Blood plasma in Canada: should compensation for donors be banned?

I am one of the signatories of a long letter arguing that Canada (which imports most of it's blood plasma products from the U.S.) should not ban the compensation of Canadian plasma donors.

Here's the letter:
Ethicists and Economists express concerns about banning compensation for plasma donors with regards to ensuring the security of a safe Immune Globulin Product Supply.
Submission to the Expert Panel on Immune Globulin Product Supply and Related Impacts in Canada

Here's the press release:
Ethicists and economists express concerns about banning compensation for plasma donations

Bleeding (and more) for Canada

Peter Jaworski in USA today discusses Canadian repugnance for paying for blood or sperm.

If it weren’t for America's free-market ways, more Canadians would have trouble getting pregnant.

"Canada used to have a sufficient supply of domestic sperm donors. But in 2004, we passed the Assisted Human Reproduction Act, which made it illegal to compensate donors for their sperm. Shortly thereafter, the number of willing donors plummeted, and sperm donor clinics were shuttered. Now, there is basically just one sperm donor clinic in Canada, and 30-70 Canadian men who donate sperm. Since demand far outstrips supply, we turn to you. We import sperm from for-profit companies in the U.S., where compensating sperm donors is both legal and normal.
...
"Canada has never had enough domestic blood plasma for plasma-protein products, such as immune globulin. Our demand for those products, however, is increasing. Last year, we collected only enough blood plasma from unremunerated donors to manufacture 17% of the immune globulin demanded. The rest we imported from you, in exchange for $623 million, or $512 million U.S.

Reliance on your blood plasma looked like it might change a little bit when, in 2012, a company called Canadian Plasma Resources announced plans to open clinics in Ontario dedicated to collecting blood plasma. The trouble is that its business model included compensating donors. Almost immediately, groups such as the Canadian Union of Public Employees and the Canadian Health Coalition began to lobby the Ontario government to pass a law to stop CPR from opening clinics. Ontario obliged in 2014, passing the Safeguarding Health Care Integrity Act, which among other things made compensation illegal.

When CPR shifted attention to Alberta, so did the groups opposing them. Just this year, the Alberta government introduced the Voluntary Blood Donation Act, which would prohibit compensation.

British Columbia’s government is just now looking at options to ban it as well.

What persuaded these governments? The anti-compensation groups argued that blood plasma from compensated donors was less safe, that people should donate blood plasma for free rather than for money, and that there is something wrong with having a for-profit business model in health care.

The latter two concerns are strangely specific. They don’t seem to apply to you Americans. If they did, the groups would have lobbied to make importation of anything other than products made from unremunerated donors also illegal. But they didn’t.

Instead, they object to a Canadian for-profit company compensating Canadian blood plasma donors in Canada, but American for-profit companies compensating American donors in America does not appear to register on their moral radar. Like the importation of sperm from for-profit U.S. companies that compensate donors, it has all the appearance of moral NIMBYism. It’s fine if it happens in your backyard, and we’ll happily buy the products, but we object to it happening in our backyard."

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And here, in Canada's National Post:

Peter Jaworski: Canada needs blood plasma. We should pay donors to get it

Canada buys the vast majority of its plasma-protein products from American companies that attract plasma donors by paying them. Yet we ban the same practice here

Bleeding for Canada: plasma exports from the US to Canada

In the HuffPo:, Peter Jaworski begins his rant about the blood supply with a good line about food:  Commodifying Blood Donation Could Solve Canada's Shortfall

"Many people think blood is special in a way that means it shouldn't be "commodified," or bought and sold on a market. It is a basic human need. It's not like the latest gadget or a pair of shoes; it is to be revered, not remunerated.

"I'm glad we don't think food is special in this way. If we did, imagine how many people would die of starvation, or would suffer from hunger.

This past December, the Ontario legislature preserved the sanctity of the exchange of blood through Bill 21, entitled the "Safeguarding Health Care Integrity Act." Schedule 1 included provisions from Bill 178, the Voluntary Blood Donations Act", which prohibits paying and receiving payment for blood, either directly or indirectly. With this bill, the legislature has made the giving and receiving of blood a sacrament.

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Of course Canadians don't have to pay other Canadians for blood plasma. If you look at the Harmonized Tariff Schedule (HTS) administered by the U.S. International Trade Commission (USITC), you find that HTS number 3002100210 stands for Human Blood Plasma, and in 2013 Canada had imports $29,274,584 worth from the U.S., where of course we compensate plasma donors.

HT: Josh Penrod