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

The EU proposes strengthening bans on compensating donors of Substances of Human Origin (SoHOs)--op-ed in VoxEU by Ockenfels and Roth

 The EU has proposed a strengthening of European prohibitions against compensating donors of "substances of human origin" (SoHOs).  Here's an op-ed in VoxEU considering how that might effect their supply.

Consequences of unpaid blood plasma donations, by Axel Ockenfels and  Alvin Roth / 4 Nov 2023

"The European Commission is considering new ways to regulate the ‘substances of human origin’ – including blood, plasma, and cells – used in medical procedures from transfusions and transplants to assisted reproduction. This column argues that such legislation jeopardises the interests of both donors and recipients. While sympathetic to the intentions behind the proposals – which aim to ensure that donations are voluntary and to protect financially disadvantaged donors – the authors believe such rules overlook the effects on donors, on the supply of such substances, and on the health of those who need them.

"Largely unnoticed by the general public, the European Commission and the European Parliament’s Health Committee have been drafting new rules to regulate the use of ‘substances of human origin’ (SoHO), such as blood, plasma, and cells (Iraola 2023, European Parliament 2023). These substances are used in life-saving medical procedures ranging from transfusions and transplants to assisted reproduction. Central to this legislative initiative is the proposal to ban financial incentives for donors and to limit compensation to covering the actual costs incurred during the donation process. The goal is to ensure that donations are voluntary and altruistic. The initiative aims to protect the financially disadvantaged from undue pressure and prevent potential misrepresentation of medical histories due to financial incentives. While the intention is noble, the proposal warrants critical analysis as it may overlook the detrimental effects on donors themselves, on the overall supply of SoHOs, and consequently on the health, wellbeing, and even the lives of those who need them. We illustrate this in the context of blood plasma donation.

"Over half a century ago, Richard Titmuss (1971) conjectured that financial incentives to donate blood could compromise the safety and overall supply. This made sense in the 1970s, when tests for pathogens in the blood supply were not yet developed. But Titmuss’ conjecture permeated policy guidelines worldwide, despite mounting evidence to the contrary. Although more evidence is needed, a review published by Science (Lacetera et al. 2013; see also Macis and Lacetera 2008, Bowles 2016), which looked at the evidence available more than 40 years after Titmuss’ conjecture, concluded that the statistically sound, field-based evidence from large, representative samples is largely inconsistent with his predictions.

"Getting the facts right is important because, at least where blood plasma is concerned, the volunteer system has failed to meet demand (Slonim et al. 2014). There is a severe and growing global shortage of blood plasma. While many countries are unwilling to pay donors at home, they are willing to pay for blood plasma obtained from donors abroad. The US, which allows payment to plasma donors, is responsible for 70% of the world’s plasma supply and is also a major supplier to the EU, which must import about 40% of its total plasma needs. Together with other countries that allow some form of payment for plasma donations – including EU member states Germany, Austria, Hungary, and the Czech Republic – they account for nearly 90% of the total supply (Jaworski 2020, 2023). Based on what we know from controlled studies and from experiences with previous policy changes, a ban on paid donation in the EU will reduce the amount of plasma supplied from EU members, prompting further attempts to circumvent the regulation by importing even more plasma from countries where payment is legal. At the same time, a ban will contribute to the global shortage of plasma, further driving up the price and making it increasingly unaffordable for low-income countries (Asamoah-Akuoko et al. 2023). In the 1970s, it may have been reasonable to worry that encouraging paid donation would lead to a flow of blood plasma from poor nations to rich ones. That is not what we are in fact seeing. Instead, plasma supplies from the US and Europe save lives around the world.

"In other areas, society generally recognises the need for fair compensation for services provided, especially when they involve discomfort or risk. After all, it is no fun having someone stick a needle in your arm to extract blood. This consensus cuts across a range of services and professions – including nursing, firefighting, and mining – occupations, most people would agree, that should be well rewarded for the risk involved and value to society. To rely solely on altruism in such areas would be exploitative and would eventually lead to a collapse in provision. Indeed, to protect individuals from exploitation, labour laws around the world have introduced minimum compensation requirements rather than caps on earnings. In addition, payment bans on donors, even if they’re intended to protect against undue inducements, raise concerns about price-fixing to the benefit of non-donors in the blood plasma market. In a related case, limits on payment to egg donors have been successfully challenged in US courts. 1

"In addition, policy decisions affecting vital supplies such as blood plasma should be based on a broad discourse that includes diverse perspectives and motivations. Ethical judgements often differ, both among experts and between professionals and the general public, so communication is essential (e.g. Roth and Wang 2020, Ambuehl and Ockenfels 2017). Payment for blood plasma donations is an example. We (the authors of this article) are from the US and Germany, countries that currently allow payment for blood plasma donations while most other countries prohibit payment. On the other hand, prostitution is legal in Germany but surrogacy is not, while the opposite is true in most of the US. And while Germany currently prohibits kidney exchange on ethical grounds, other countries – including the US, the UK, and the Netherlands – operate some of the largest kidney exchanges in the world and promote kidney exchange on ethical grounds.

"The general public does not always share the sentiments that health professionals find important (e.g. Lacetera et al. 2016). This tendency is probably not due to professionals being less cognitively biased. In all areas where the question has been studied, experts such as financial advisers, CEOs, elected politicians, economists, philosophers, and doctors are just as susceptible to cognitive bias as ordinary citizens (e.g. Ambuehl et al. 2021, 2023). Recognising the similarities and differences between professional and popular judgements, and how ethical judgements are affected by geography, time, and context, allows for a more constructive and effective search for the best policy options.

"In our view, the dangers of undersupply of critical medical substances, of inequitable compensation (particularly for financially disadvantaged donors), and of circumvention of regulation by sourcing these substances from other countries (where the EU has no influence on the rules for monitoring compensation to protect donors from harm) are at least as significant as those arising from overpayment. Carefully designed transactional mechanisms may also help to respect ethical boundaries while ensuring adequate supply. Advances in medical and communication technologies, such as viral detection tests, can effectively monitor blood quality and ensure the safety and integrity of the entire donation process – including the deferral of high-risk donors and those for whom donating is a risk to their health – without prohibiting payment to donors. Even if it is ultimately decided that payments should be banned, there are innovations in the rules governing blood donation that have been proposed, implemented, and tested that would improve the balance between blood supply and demand within the constraints of volunteerism; non-price signals, for instance, can work within current social and ethical constraints.

"As the EU deliberates on this legislation, it is imperative to adopt a balanced, empirically sound, and research-backed approach that considers multiple effects and promotes policies to safeguard the interests of both donors and recipients.

References

Asamoah-Akuoko, L et al. (2023), “The status of blood supply in sub-Saharan Africa: barriers and health impact”, The Lancet 402(10398): 274–76.

Ambuehl, S and A Ockenfels (2017), “The ethics of incentivizing the uninformed: A vignette study”, American Economic Review Papers & Proceedings 107(5), 91–95.

Ambuehl, S, A Ockenfels and A E Roth (2020), “Payment in challenge studies from an economics perspective”, Journal of Medical Ethics 46(12): 831–32.

Ambuehl, S, S Blesse, P Doerrenberg, C Feldhaus and A Ockenfels (2023), “Politicians’ social welfare criteria: An experiment with German legislators”, University of Cologne, working paper.

Ambuehl, S, D Bernheim and A Ockenfels (2021), “What motivates paternalism? An experimental study”, American Economic Review 111(3): 787–830.

Bowles S (2016), “Moral sentiments and material interests: When economic incentives crowd in social preferences”, VoxEU.org, 26 May.

European Parliament (2023), “Donations and treatments: new safety rules for substances of human origin”, press release, 12 September.

Iraola, M (2023), “EU Parliament approves text on donation of substances of human origin”, Euractiv, 12 September.

Jaworski, P (2020), “Bloody well pay them. The case for Voluntary Remunerated Plasma Collections”, Niskanen Center.

Jaworski, P (2023), “The E.U. Doesn’t Want People To Sell Their Plasma, and It Doesn’t Care How Many Patients That Hurts”, Reason, 20 September.

Lacetera, N, M Macis and R Slonim (2013), “Economic rewards to motivate blood donation”, Science 340(6135): 927–28.

Lacetera, N, M Macis and J Elias (2016), “Understanding moral repugnance: The case of the US market for kidney transplantation”, VoxEU.org, 15 October.

Macis M and N Lacetera (2008), “Incentives for altruism? The case of blood donations”, VoxEU.org, 4 November.

Roth, A E (2007), “Repugnance as a constraint on markets”, Journal of Economic Perspectives 21(3): 37–58.

Roth A E and S W Wang (2020), “Popular repugnance contrasts with legal bans on controversial markets”, Proc Natl Acad Sci USA 117(33): 19792–8.

Slonim R, C Wang and E Garbarino (2014), “The Market for Blood”, Journal of Economic Perspectives 28(2): 177–96.

Titmuss, R M (1971), The Gift Relationship, London: Allen and Unwin.

Footnotes: 1. Kamakahi v. American Society for Reproductive Medicine, US District Court Northern District of California, Case 3:11-cv-01781-JCS, 2016.

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."

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.

Plasma in Canada: payments and protests

 The local newspaper in Niagara on the Lake, a town in Ontario, Canada, covers the proposed opening next year of plasma collection centers that will pay for plasma.

Pay-for-plasma centre draws criticism from Health Coalition. The centre, which will pay residents to donate their blood plasma, is scheduled to open on Hespeler Road by early 2025, by Matt Betts

"The chair of the Waterloo Region Health Coalition is raising concerns about a pay-for-plasma centre slated to open on Hespeler Road in Cambridge by early 2025.

"Just as it sounds, residents can be compensated for donating their blood plasma.

"It's all part of an agreement between Spanish global healthcare company, Grifols, and the Canadian Blood Services.

"In September 2022, Canadian Blood Services announced our action plan in response to a global shortage of medications called immunoglobulins and plasma needed to make them," CBS said in an email to CambridgeToday.

"With funding from governments, Canadian Blood Services is opening 11 plasma donor centres in Canada and collecting more plasma ourselves. Our agreement with Grifols, a global healthcare company and leader in producing plasma medicines, is another part of that plan."

...

"paying for donations is banned in Ontario, Quebec and British Columbia. 

"However, CBS said its been in close discussions with the government and has an exemption.

...

"The agreement also complies with Ontario’s Voluntary Blood Donations Act, which has always contained an exemption for Canadian Blood Services, with implicit consideration of our agents, given our role as the national blood operator and supplier of blood products in Canada. Through our agreement, Grifols will operate under the Act as an agent of Canadian Blood Services."

"Per the agreement, Grifols must use plasma they collect in Canada to make immunoglobulins exclusively for patients in Canada, which reduces reliance on the global market, CBS said.

"But the whole operation doesn't sit right with Waterloo Region Health Coalition chair, Jim Stewart.

"It's a repugnant example of profit driven healthcare," Stewart said, questioning who's profiting in the end.

"What's next, paying people for their organs or embryos? This is just another example of Premier Doug Ford’s drive to privatize our healthcare system."

...

""These pay-for-donations centres really impact the homeless, people with low incomes and those with high levels of unemployment. This is going to dismantle the voluntary donor base and the sustainability of blood supply could be in jeopardy."

...

"While not confirmed by Grifols, Canadian Blood Resources and giveplasma.ca states qualified donors can earn up to $70 per donation and can donate twice in a seven day period."

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HT: Frank McCormick

Earlier:

Sunday, September 18, 2022

Canadian Blood Services to start paying Canadian plasma donors

Convalescent plasma: the picture is getting clearer

 Slowly, there is evidence accumulating that convalescent plasma is helpful in treating patients with severe Covid, if it is administered early.  There is also evidence that it doesn't help much once the disease has become well established, particularly when the primary symptoms become due to the body's own immune reaction.  These caveats help explain why early reports did not find an effect of convalescent plasma--i.e. it helped only a subset of the patients to whom it was administered. But for those it was sometimes life saving. Here is a recent paper from the New England Journal of Medicine.

Convalescent Plasma for Covid-19–Induced ARDS in Mechanically Ventilated Patients by Benoît Misset, M.D., Michael Piagnerelli, M.D., Ph.D., Eric Hoste, M.D., Ph.D., Nadia Dardenne, M.Sc., David Grimaldi, M.D., Ph.D., Isabelle Michaux, M.D., Ph.D., Elisabeth De Waele, M.D., Ph.D., Alexander Dumoulin, M.D., Philippe G. Jorens, M.D., Ph.D., Emmanuel van der Hauwaert, M.D., Frédéric Vallot, M.D., Stoffel Lamote, M.D., et al., October 26, 2023, N Engl J Med 2023; 389:1590-1600 DOI: 10.1056/NEJMoa2209502

"Abstract

BACKGROUND

Passive immunization with plasma collected from convalescent patients has been regularly used to treat coronavirus disease 2019 (Covid-19). Minimal data are available regarding the use of convalescent plasma in patients with Covid-19–induced acute respiratory distress syndrome (ARDS).

METHODS

In this open-label trial, we randomly assigned adult patients with Covid-19–induced ARDS who had been receiving invasive mechanical ventilation for less than 5 days in a 1:1 ratio to receive either convalescent plasma with a neutralizing antibody titer of at least 1:320 or standard care alone. Randomization was stratified according to the time from tracheal intubation to inclusion. The primary outcome was death by day 28.

RESULTS

A total of 475 patients underwent randomization from September 2020 through March 2022. Overall, 237 patients were assigned to receive convalescent plasma and 238 to receive standard care. Owing to a shortage of convalescent plasma, a neutralizing antibody titer of 1:160 was administered to 17.7% of the patients in the convalescent-plasma group. Glucocorticoids were administered to 466 patients (98.1%). At day 28, mortality was 35.4% in the convalescent-plasma group and 45.0% in the standard-care group (P=0.03). In a prespecified analysis, this effect was observed mainly in patients who underwent randomization 48 hours or less after the initiation of invasive mechanical ventilation. Serious adverse events did not differ substantially between the two groups.

CONCLUSIONS

The administration of plasma collected from convalescent donors with a neutralizing antibody titer of at least 1:160 to patients with Covid-19–induced ARDS within 5 days after the initiation of invasive mechanical ventilation significantly reduced mortality at day 28. This effect was mainly observed in patients who underwent randomization 48 hours or less after ventilation initiation."

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Here are my posts on convalescent plasma, and the confusing initial reports about its effects.

Plasma donations at the border

Here's a WSJ story about the confluence of two controversial transactions, immigration and compensation for plasma donors.

Block on Blood-Plasma Donors From Mexico Threatens Supplies. U.S. officials say crossing border to donate for a fee isn’t allowed with a visitor visa  By Mike Cherney,  Renée Onque and Daniela Hernandez

"Pharmaceutical companies and U.S. officials are fighting over whether to allow people to cross the border from Mexico to be paid for giving blood plasma, a critical ingredient in treatments for some neurological and autoimmune diseases.

"Up to 10% of plasma collected in the U.S. usually comes from Mexican nationals who enter on visitor visas and are paid about $50 to donate, according to legal filings from pharmaceutical companies. Last June, U.S. border officials indicated they would stop the roughly 30-year practice because they viewed it as labor for hire, which isn’t allowed under a visitor visa.

"The pharmaceutical companies that collect plasma have asked federal courts in Washington, D.C., to overturn the decision, which came just as U.S. plasma donations were disrupted by the Covid-19 pandemic. Some companies have argued that the payment compensates donors for their time and commitment rather than for the plasma itself, and isn’t in exchange for any actual work.

...

"The U.S., which provides much of the global plasma supply, is one of the few countries that allows payments to plasma donors, and supporters of the policy say that helps to ensure enough plasma is collected. Two big plasma companies, Australia-based CSL Ltd. and Spain-based Grifols SA, have invested millions of dollars in collection centers near the U.S.-Mexican border.

...

"A spokesperson for U.S. Customs and Border Protection declined to discuss the litigation.

...

"The agency said pharmaceutical companies could increase payments to attract more domestic supply and that Mexicans could still donate plasma without getting paid."

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

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

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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."

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 rise and fall of convalescent plasma as a treatment for Covid

 The NY Times follows the story:

The Covid-19 Plasma Boom Is Over. What Did We Learn From It?  The U.S. government invested $800 million in plasma when the country was desperate for Covid-19 treatments. A year later, the program has fizzled.  By Katie Thomas and Noah Weiland

"In those terrifying early months of the pandemic, the idea that antibody-rich plasma could save lives took on a life of its own before there was evidence that it worked. The Trump administration, buoyed by proponents at elite medical institutions, seized on plasma as a good-news story at a time when there weren’t many others. It awarded more than $800 million to entities involved in its collection and administration, and put Dr. Anthony S. Fauci’s face on billboards promoting the treatment.

"A coalition of companies and nonprofit groups, including the Mayo Clinic, Red Cross and Microsoft, mobilized to urge donations from people who had recovered from Covid-19, enlisting celebrities like Samuel L. Jackson and Dwayne Johnson, the actor known as the Rock. Volunteers, some dressed in superhero capes, showed up to blood banks in droves.

...

"But by the end of the year, good evidence for convalescent plasma had not materialized, prompting many prestigious medical centers to quietly abandon it. By February, with cases and hospitalizations dropping, demand dipped below what blood banks had stockpiled.

...

"All told, more than 722,000 units of plasma were distributed to hospitals thanks to the federal program, which ends this month."

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There were also parallel private efforts that mobilized convalescent plasma donation through social media, and via faith based organizations.  I followed some of the science in a series of posts on plasma and plasma donation more generally.  I should note that, although convalescent plasma hasn't emerged as a treatment for Covid-19, it continues to have many very well documented life-saving uses.

Plasma donation in the EU: compensated and uncompensated

 Here's a commentary on the EU Parliament's current efforts to ban compensation to plasma donors in the EU, published today.

 Julio J Elias, Nicola Lacetera, Mario Macis, Axel Ockenfels, Alvin E Roth, "Quality and safety for substances of human origins: scientific evidence and the new EU regulations," BMJ Global Health, Volume 9, Issue 4 (21 April, 2024) https://doi.org/10.1136/bmjgh-2024-015122

"Summary box

The new European Union (EU) ‘Regulation on standards of quality and safety for substances of human origin (SoHOs) intended for human application’ is based on a long-standing diffidence towards offering compensation to donors of SoHOs.

We point to recent, growing empirical evidence indicating that carefully designed compensation can increase the supply of SoHOs without negatively affecting quality and safety. We also elaborate arguments that address some of the moral concerns that motivate the aversion to payments.

As member states proceed to adopt the new EU regulation, our article may provide insights on how to achieve both self-sufficiency and safety"

...

"At least where plasma for fractionation is concerned, the unpaid-donor system has failed to meet demand. Table 1 indicates that in Europe, countries allowing monetary compensation for donors are the only ones achieving self-sufficiency in plasma collection for the production of immunoglobulin. The plasma sector in countries that compensate plasma donors, notably the USA, serves as supplier to many countries experiencing chronic shortages. The USA alone collects about 70% of the world’s plasma supply.10 A combination of a favourable regulatory environment, an extensive collection network and advanced technological infrastructure contributed to establishing the US position.11

Table 1

Plasma self-reliance and models of plasma collection15–19

Country	Reliance on domestic supply (% of total national need)	Monetary payments allowed	Current payment amount	Other incentives
Austria (2020)	100	Yes	€30–40	–
Czech Republic (2020)	100	Yes	€30–35	–
Germany (2020)	100	Yes	€25	–
Hungary (2020)	100	Yes	€30	–
Latvia (2018)	100	Yes	€17	–
Italy (2018)	76	No	–	Paid leave of absence from work
Slovenia (2017)	54	No	–	Paid leave of absence from work
Belgium (2019)	50	No	–	Paid leave of absence from work
France (2020)	50	No	–	–
Netherlands (2020)	45	No	–	–
Slovakia (2018)	41	No	–	–
Denmark (2018)	34	No	–	–
Spain (2020)	34	No	–	–
Portugal (2018)	22	No	–	Exemption from National Health Service user fees

• The table shows, for each country, the percentage of plasma needed for immunoglobulin (Ig) production that is collected domestically. The year in parenthesis is the one to which the data on self-reliance refer. The table then reports whether monetary payments are allowed, the current range of payments per donation and any other incentives in use in each country. In countries that allow payments, plasma collectors offer, in addition to monetary compensation for each donation, additional monetary or in-kind rewards, for example, when a donor reaches a certain number of donations (eg, 5, 10,…), or to first-time donors. The figures reported above do not include these additional rewards.