Lucy Reynolds publishes this original paper on the government's proposed sale of the UK's state-owned blood plasma supplier. In their drive to dismantle the last vestiges of the state, the government appear to be exposing the British public to serious - and sometimes fatal - risks, including HIV and hepatitis.
The open market in plasma products creates incentives to exploit all sources of plasma, to operate lax donor selection standards and cut corners on infection control. This allows patients to be infected with lethal diseases.
Following the generation of the new fatal disease vCJD through reduced UK regulation of cattle feed processing which transmitted a brain disease of sheep to cows from where it proved transmissible to humans, it was no longer safe to make plasma products from UK donors. So in 2002 the government purchased a US plasma source to be a protected supply for UK patients. The government now intends to privatise this supply, leaving the country to rely wholly on the open market for supplies.
Competition law was first used by profit-making blood harvesters to force risky blood on US hospitals in 1956: competition law narratives are always framed around “the best interests of patients” but in practice they are no friends of those patients. HIV and blood-borne hepatitis have infected the majority of US clotting factor users in older age cohorts.
Nowadays the stakes are even higher, with more fatal blood-borne infections in the blood supply and new diseases emerging every few years.
Meanwhile, a boom in new and in some cases ill-advised new immune-based treatments is putting huge stress on world supplies of plasma, given that most developed countries and many developing countries make plasma buying illegal. This will result in more and more marginal sources of plasma supply coming into the plasma products market, jeopardising the patients to whom they are administered.
By the sale of Plasma Resources UK, our government commits us to buying all plasma products for UK patients from market suppliers who almost all have a track record of avoidable quality problems, in many cases resulting in deaths or serious chronic illness such as HIV.
This paper sets out the interlocking epidemiological, behavioural and economic basis of the plasma trade to show why the UK government should follow the example of most developed countries and protect patients from the dangerous products regularly circulating on the open market.
Alongside the wholesale privatisation of the NHS which the government are trying to force through against the wishes of the country, there is another sly privatisation of a much smaller national treasure.
While most medicines are extracted from plants or other animals, or synthesised, some life-saving medications are extracted from human blood plasma. While some of these can now be factory-made through genetic engineering solutions, others cannot, especially the new “magic bullet” mixed antibody preparation, intravenous immunoglobulin (IVIG).
In 1975, following problems with exploitative and unsafe collection of plasma, the World Health Assembly passed a resolution to protect the health of donors and recipients. It included recommendations that nations try to become self-sufficient in blood and blood products; and nations enact legislation to regulate collection, processing, distribution, export and import of blood and blood products.1 Ensuring compliance with these precautions requires tight control of the production process from start to finish. This was previously the case in the UK.
Unlike other countries, we can no longer make plasma products from a safe domestic supply because the fatal disease vCJD was created by infection control failures in the British meat supply following reduced regulation. The disease agent has entered the general population but cannot be reliably detected prior to death. Thus in 2002, to minimise the need to buy plasma products from the open market, the government purchased a US plasma collector which the country could regulate to protect patients. The current government have put this company, Plasma Resources UK, up for privatisation.
The present government has already commenced to sell off the blood products made from our protected source of plasma abroad: at the same time as exporting from it in bulk, they already buy two-thirds of these medications for the NHS on the open market, exposing patients to the risk of the kind of disease outbreaks which have repeatedly been traced to malpractice in the global plasma trade. Over and over again this has results in thousands of deaths in countries remote from the plasma source whose governments were unaware the supplies could be infected until patients started to sicken and die with AIDS, liver failure or liver cancer, the last two being the consequences of contracting Hepatitis B or Hepatitis C, both blood-borne infections.
Payment for plasma is still permitted in China and the US, the two main sources of the global supply. It is banned in Western Europe (except Germany), Canada and Australia for ethical reasons and in order to assure the safest supply possible. If payment is permitted particularly stringent care must be taken to ensure that people likely to have transmissible infections are excluded from selling plasma, as they may give despite knowing they could be infected in the interests of acquiring money they badly need.
The day after Lord David Owen MD learnt of the plan to sell PR UK, he wrote to David Cameron, as follows (15 March 2013):
“I am writing to you personally because I believe only you can intervene quickly to stop the pending sale by Lazards of Plasma Resources UK Ltd. The reason I am writing to you to stop this sale in its tracks is that in 1975, against some resistance from those guarding the finances of the DHSS budget, I decided as Minister of Health to invest in self-sufficiency in the UK for blood and blood products.
I now believe this country is on the point of making exactly the same mistake again. I cannot stress enough that we simply do not know everything about the mutation of genes and the spread of as yet unidentified infections to be anywhere near certain of relying exclusively on purchasing plasma supplies on world markets. The world plasma supply line has been in the past contaminated and I fear it will almost certainly continue to be contaminated.”
That decision was, sadly, over the years allowed to lapse and insufficient money allocated for self-sufficiency. This meant that subsequently the Department of Health felt it necessary to make available financial compensation for people infected by contaminated blood supplies, namely, but not exclusively, haemophiliacs. Many other countries were also heavily criticised for not investing in self-sufficiency.
His concerns are well founded: this piece aims to explain why to those with no knowledge of the grubby global industry which produces the latest high-tech medicine, as now being promoted by the UK government under the rubric of “medical innovation.”
This article will provide an overview of the reasons why there is serious concern about the unnecessary risks involved in selling this company and committing to buy all plasma products through the global marketplace.
Plasma is the watery fluid in blood, in which the red and white cells move. It contains many bioactive proteins, some of which can be extracted and used as medication, such as antibodies and clotting factors.
While whole plasma is usually a by-product from donated blood, plasma products are produced through a different process called plasmapheresis from a different set of donors. Plasma donors are not permitted to contribute to the blood supply, and cannot give plasma if they have recently given blood. During plasmapheresis, the blood cells are returned to the body while the plasma is drained off.
Plasma contributions from many people are then pooled together and the different proteins separated by fractionation (by centrifuging) and purified out. Commercially viable products are separated from the rest, packaged and sold.
This process may take place in a state-controlled organisation or a single company which take care of the whole process, or split between different companies each of which deals with only part of the process. For example processors often buy plasma from unconnected harvesters rather than operating their own collection facilities.
Plasma products consisting of purified proteins (also referred to as blood products) are used in the treatment of many conditions. Albumin is needed for burns, shock and serious injury. The mixed antibody preparation IVIG is used for immune disorders, neurological conditions and a fast-expanding range of other conditions. Single antibody preparations are used for many therapies, including protecting unborn children from haemolytic disease resulting from Rhesus incompatibility, and for producing vaccinations. The best known and longest established are the clotting factors needed to treat and protect haemophilia patients who lack the genes to make them.
Because all of these blood proteins except albumin are present only in very small amounts in the blood, many contributions from must be pooled together, and then separated out by fractionation. IVIG products are prepared from plasma pooled from at least 3000 to 10,000 contributors.2
There are three categories of serious infection which can be passed through blood products.
(Parvovirus B19V has recently been identified in more than half of plasma pools at two of the 24 Chinese plasma products manufacturers.5 This virus is associated with encephalitis, liver inflammation and anaemia, especially in immunosuppressed people (such as transplant patients and HIV-infected haemophiliacs) and foetuses, killing some of the latter before birth. Other research demonstrated that 60% to 100% of plasma pools were contaminated, depending on the manufacturer (85% overall), all Factor VIII, 20% of IVIG, and 75% of intramuscular immunoglobulin preparations (IMIG) containing traces of B19V.6 A third reported finding B19V DNA in more than 60% of clotting factor products and plasma pools.7
Parvovirus PARV4 was discovered in 2005 in an injecting drug user, and is found at 2% among Los Angeles blood donors and at 6% among injecting drug users. In haemophiliacs, the transition from a negative to a positive antibody test for exposure to PARV4 is sometimes accompanied by acute liver inflammation and skin rashes. PARV4 has been found inside the cerebrospinal fluid of encephalitis patients and in stillborn babies. It is not inactivated by heat, detergent or solvent treatments.8 Given its resistance to sterilisation procedures, its ready transmission through injecting drug use, and its multiple appearance in haemophiliacs on treatment, it seems likely to be transmissible through plasma products, though it is too early for conclusive evidence demonstrating or disproving this to be available.
Other newly discovered human blood-borne parvoviruses, the bocaviruses, are known to be related to dog and cattle viruses;8 these have been detected in 5.5% of Italian blood donors.
We can expect more and more emergent diseases, as because of expanding population and degradation of land, people live closer and closer to both livestock and wildlife. The latter contact has already brought us blood-borne HIV-1 (from the Central African Congo basin, via chimpanzees killed as bushmeat), the earlier acquisition of HIV-2 from sooty mangabey monkeys in Western Africa, and SARS (from the Chinese taste for eating exotic wildlife). Intensive farming of livestock represents another forcing ground for emergent disease.
Prevention for all of these infections can be done to varying degrees by donor screening. That screening depends on knowing what characteristics of donors are statistically associated with them having each infection: infection routes vary. So avoiding contamination with HIV and blood-borne hepatitis (HBV and HCV) and other blood-borne disease is largely a matter of excluding from the plasma supply those who have been exposed to possibly-contaminated skin-penetrating procedures such as tattoos or injections of recreational drugs, or to sex with members of groups especially likely to be infected. For West Nile Virus the main risk factor for donor exclusion is residence in an infected zone. For vCJD it is consumption of UK processed meat products between the relaxation of safety controls on cattle feed processing and the re-imposition of those controls some years later. Receipt of blood transfusions permanently excludes donors from eligibility to give because they can transmit blood-borne disease.
Despite screening, antibody-based tests may pass a patient with primary infection from a very recent risk as negative, allowing the infected donation to enter the transfusion supply. Thus HIV, HBV, HCV and other diseases can though false negative tests enter the supply. Quarantine protocols offer some protection against known diseases by catching false negatives in the case of plasma donations, but this only assists in the case of the diseases for which tests are both available and used. There have been persistent problems with substandard screening tests used in China, creating another system weakness which can cause contamination to pass into the plasma products.
Plasma products can be subjected to viral inactivation techniques, but these cannot destroy all known pathogens.9
A combination of all of these techniques, carefully executed and independently regulated on a no-notice basis, should be used to ensure the safest supply.
In plasma processing, screening of sellers and of their plasma contribution for known serious blood-borne disease (usually at least HIV and HBV) is useful, but we lack tests for many blood-borne infections, especially emerging diseases. Van Dam et al10 highlight the risks inherent in relying on blood testing alone to manage risk from blood-borne disease, stressing the need to harvest only from the least contaminated donor pools.
Thus all safe blood strategies rely on donor selection strategies which attempt to avoid collection from people who are more likely to have infections that can pass to patients. Potential plasma contributors are told about behaviour and circumstances which could have put them at high risk, and those affected are asked to withdraw from donating. It is known that paying donors discourages such withdrawal from the supply, so the average infection burden of the blood rises when donors are paid.
Furthermore, low cash payments tend to attract, not people with healthy lifestyles (for whom a few dollars is no incentive to take a day off work), but those living in precarious circumstances. It is especially suited to those with a frequent and urgent need to produce small amounts of cash. This profile of course fits the situation of an addicted injecting heroin user, and offers to buy blood or plasma tend to attract them particularly. If they are bled shortly after contracting HBV, HCV or HIV, the standard antibody-based tests will miss these very early infections. Unfortunately it is during very early infection that viral loads are typically at their highest. Quarantine protocols can be used to eject such donations, but these require three-month plasma storage and follow-up of every seller. They are thus expensive to run; producers omitting them can be considerably more competitive in the market.
In a New Zealand study11 of options for increasing blood supply, only 75% of donors said that they would definitely continue giving if they were paid for their blood, while 11% said that they would definitely cease donating if payment were made.
41% of current donors said that they would definitely discontinue donating if profits were to be made from their blood; another 11% said that they might discontinue. The 1993 partial privatisation of New Zealand health services saw higher than normal rates of donor drop-outs in that year.
These findings suggest that safe and unsafe donor bases are to some degree mutually exclusive, so that paying for blood can deter safer donors from contributing to the blood supply. A UK study of the responses of active donors, lapsed donors and non-donors to the question:
“If I were paid enough I would be less/equally/more likely to donate blood”,
found that pay would incentivise 16.4% to give, while deterring 14.7%12. Comparing answers to that question with the following one:
“If you needed blood, would you be content if the donor had been paid: yes/no”,
exposed significant statistical associations between being willing to accept blood from paid donors and being encouraged to give blood by payment, and conversely between being unwilling to accept purchased blood and being deterred from giving by payment. Thus pay for blood may expand the blood supply at the cost of shifting its composition to include more of those least aware of the possible health risks posed by blood-borne disease and fewer of the most health-conscious people.
These studies confirm the 1972 conclusions of Richard Titmuss13, who compared the paid American and the unpaid British blood donor systems finding that the unpaid system increases blood quality and reduces shortages. He linked this with the altruistic motivation of the unpaid donors, who have less reason not to follow guidelines to avoid donating if at risk of blood-borne disease.
A modelling study using evolutionary game theory also suggests that the existence of paid donation tends to destroy the social norm of donation as altruistic, discouraging unpaid donation. It confirms Titmuss’ assertion that once incentives have removed the idea of altruistic donation, withdrawing them makes matters worse in the short-term, as paid donors are lost but insufficient voluntary donors replace them.14
The plasma harvested from many people is pooled to make extracting minority proteins economically viable, with processing most profitable when the pools are huge. Although contaminated units are rare in most populations, risks to blood product recipients may be significant because the pooling of contributions from thousands of donors15 before fractionation distributes the pathogen content of a single unit across multiple recipients of the many different plasma products made from that process batch. If equipment is not properly cleaned, it could contaminate subsequent batches as well.
To explain the multiplication of infection risks caused by plasma pooling we can use a more familiar analogy from another mode of HIV transmission. A blood transfusion or a transfusion of fresh-frozen plasma is like having sex with several people. Receiving a single dose of a plasma product is like having sex with up to 10,000 people.
If the plasma is from an open market source then those thousands of people may well include many injecting drug users and others at high risk of carrying transmissible infections, because the incentives in the market promote acceptance of the highest possible number of donors and their payment at the lowest possible price. Furthermore some or all of the sex might have been unprotected.
Even with all mandated safety procedures followed in full, the US government calculates a residual risk of HIV, HBV or HCV infection of 1/15,662 for a unit of plasma from a voluntary unpaid donor, and 1/10,959 from a paid donor. The 43% higher risk associated with payment of donors arises because of higher incidence of blood-borne disease among paid donors. The fact that payment for blood was associated with increased risk of infection compared to volunteer blood was established in 1959.16
This risk profile is not ideal but is arguably acceptable for a patient with a life-threatening condition. The problem is that the precautions are too often not observed in product made for the open market, because skimping on them or neglecting them entirely keeps costs low.
The government regulator of the US plasma industry stated in 1998 that
“instances of companies’ non-compliance with good manufacturing practices have
“shortcuts, shoddy practices, the pursuit of the bottom line and a lack of oversight can have devastating outcomes”20.
The demand for plasma products has been increasing by about 10% per year, 14% for some products. The range of uses continues to expand, with not only purification of new therapeutic proteins, but identification of new uses for existing product lines such as IVIG.
IVIG has proven uses in replacing absent antibodies in immune failure and immune deficiency disorders. It is now used, at much higher doses, in situations where doctors believe that anti-inflammatory action by IVIG averts damage from the patient’s own immune response, as in septicaemia, transplantation reactions, and a number of autoimmune conditions.
According to the International Patient Organisation for Primary Immunodeficiencies:
“Despite the high cost of plasma products therapies, the demand for these products has increased in every region, and it is expected to continue to grow in the years to come. As a result, higher volumes of plasma will be required in the future.”21
The first product license for IVIG was obtained by Cutter Biological in 1981.22 IVIG, is in particularly high demand and already sells for more, weight for weight, than the price of gold, while being inexpensive to produce. This profit profile is not lost on investors, hence the plasma production market is constrained not by availability of capital but by availability of safe plasma. IVIG can be produced only from human blood.
The 14% growth figure is used below to extrapolate the global consumption of IVIG from 1984 to 2008 into demand up to 2014: this suggests the supply is likely to become seriously constrained by the availability of plasma, with a great deal of unmet demand.
This growth pattern is linked to the fact that IVIG is now widely used in developed countries for "off-label” applications, most of which lack evidence of effectiveness to justify their use. A plasma industry-sponsored 2003 study in Canadian hospitals found 53% by volume of off-label use of IVIG in treating adults, and 38% in paediatric treatment. Of the 90 different uses identified, 84 were “off-label”, that is, not evidence-based.
In a 2008 review of the academic literature identifying more than 150 unlabeled uses of IVIG, the authors warned:
“An examination of IVIG guidelines by specialty society, payer, and other review organizations revealed that the biomedical evidence supporting off-label uses is being interpreted in different ways. Health care institutions are strongly urged to approve and closely monitor specific uses of IVIG to reserve dwindling supplies for the “best-evidence” uses.
Clinicians should be aware of the limits of knowledge in many off-label uses and exercise restraint in prescribing for unproven indications.”23
The use of plasma products to treat ever wider groups of patients also means that any future contamination could threaten far more patients than ever before. For instance IVIG is now being used for childhood asthma, and a new IVIG trial is underway for reducing obsessive-compulsive disorder (OCD) symptoms in children.26 Other recent research suggests use of IVIG for neuropathic pain,27 which is unpleasant but not life-threatening and for which other, safer, treatments exist.
Despite consisting of antibodies, infection transmitted through IVIG has been documented: though it does not transmit HIV or HBV easily, HCV may survive the production process, for instance:
A notorious investigation involved Gammagard, manufactured by Baxter. This product was temporarily withdrawn from the market in 1994, after reports of over 200 cases worldwide of HCV transmission related to multiple lots. The risk of transmission to recipients (11%) was striking.
Baxter was screening donors using an, at the time, new second-generation HCV antibody test, and the loss of donors with neutralizing and complexing antibodies to HCV could have resulted in a higher load of virus. In addition, all implicated IVIG preparations were lyophilized [freeze-dried], which might have allowed greater stability of HCV virions.
Finally, the source of donor (paid for Gammagard vs. volunteer for Polygam) might have affected HCV infectivity in the pools.28
As well as infections passing through IVIG, severe adverse events can be associated with its infusion, including aseptic meningitis, stroke, heart attack, and death from anaphylactic shock. These outcomes are more common with products that are freeze-dried or contain high levels of sugar or salt.
The Australian government prioritises child patients for IVIG made from its own national volunteer programme, on the grounds that products acquired on the open market are less safe.29
Williams et al highlight the fact that pooled antibodies from one person may attack antibodies from another, recognising them as unfamiliar. This can trigger the clotting cascade, resulting in aggregates forming which have been connected with clot formation leading to potentially fatal anaphylactic shock, strokes and heart attacks. The probability of a bad reaction in the patient is related to the quantity of such aggregates found in the IVIG injected, which were measured to be from 5% to 18% of the antibody content.31
Despite these considerable medical risks attached to each dose of IVIG administered, writers in the field have noted that not only are new applications for IVIG continually being suggested, the case definition of some conditions treated with IVIG seems to be widening dramatically. For instance, patients diagnosed with Primary Immune Deficiency (PID) used to have “life-threatening osteomyelitis, meningitis, and lobar pneumonia” but nowadays often have only quite minor problems such as ear and sinus infections, mild pneumonia, or diarrhoea.32
It should be noted that access legislation in the USA has been passed to entitle people over 65 diagnosed with this new expanded definition of PID to have federally-funded IVIG therapy:
“(December 20, 2012) — The Plasma Protein Therapeutics Association (PPTA) applauds the House of Representatives on yesterday’s passage of the Medicare IVIG Access Act (H.R. 1845), which gives Medicare patients who suffer from primary immunodeficiency disease (PID) better access to lifesaving intravenous immune globulin (IVIG) therapy at home. “House passage of this bill is a victory for patient access to lifesaving IVIG and a testament to the steadfast commitment of the Immune Deficiency Foundation,” according to Julie Birkofer, Senior Vice President, North America.
The bill introduced by Representatives Kevin Brady (R-TX) and Doris Matsui (D-CA) establishes a three-year Medicare demonstration project that provides reimbursement for the services required for home infusion of IVIG by PID patients.”33
It is worth noting that this affects only Medicare-funded patients, all of whom are over 65 and thus in the high risk group for dangerous reactions to IVIG.
It is also significant that the Immune Deficiency Foundation, the patient association credited above with successful lobbying for this legally enforceable guarantee, is funded by plasma processors. The Immune Deficiency Foundation website mentions funding from Baxter Healthcare Corporation, CSL Behring, Grifols, Biotest Pharmaceuticals, lgG America/ASD Healthcare/US Bioservices, Octapharma, Kedrion Biopharma, Vidara Therapeutics, and Walgreens IG Therapy Program.34
Rising international demand for plasma products, due to new medical uses and intensive of cutting-edge immune therapies, is likely to outstrip supply and lead to increased shortages. For many there was by 2012 already an increasing shortfall.35 This creates incentives to exploit all sources of plasma, and to operate lax donor selections standards.
Only a few developed countries allow the purchase of plasma which is essential to enable commercial exploitation, so there is great demand for their output. Many studies36,37,38,39,40,41 suggest that voluntary unremunerated donors show lower blood-borne infection rates than do paid donors. Other research42,43 demonstrates that paid donors are more likely to suppress information about high-risk practices which would exclude them from the donor pool if disclosed. The offer of payment thus results in an increase in unsuitable donors drawn by the money who are reluctant to drop out if requested to do so for health reasons because that requires reducing their income.
China’s plasma seller HIV outbreak caused its government to take action against breaches of good manufacturing practice in this industry. The consequent contraction in supply has resulted in insufficient plasma to meet China’s own ever-rising demand and the global commercial appetite for its plasma product exports. In August 2007, the state press reported supply interruptions for albumin at a Shanghai hospital. Available supplies met only half the demand, and were rationed to those patients in greatest medical need.
One major supplier, Shanghai Institute of Biological Products, repeatedly sold out of the limited production that it could make from the output of those plasma collection stations which survived the recent closures on public health grounds. The 2007 raw materials supply of this manufacturer was only a quarter of its 2006 supply, suggesting that in 2006 three-quarters of its supply may have been unsafe44.
The plasma shortage has already hit China’s haemophiliac population of 60,000-100,000. Previously around a quarter of this group were able to afford Factor VIII to prolong their lives (China has market-based national healthcare so it is up to patients to fund their own treatment). Some of those haemophiliacs who had been able to afford treatment have died since July 2007 because of Factor VIII supply interruptions45.
Black and grey markets thrive where supply and demand in regulated markets are unbalanced, as commercial suppliers can profit by sourcing illicit supplies. So this excess demand in the market is not good news for patients.
In theory the failings of a market can be compensated by regulation. However if there are significant commercial incentives to break the rules, watertight regulatory control becomes prohibitively expensive and finally unachievable. The imposition of any significant penalties, or even a requirement to desist from unsafe practice, sets up potential for corruption among the inspectorate, as the companies have incentive to pay the inspectors not to inspect up to the amount that it would cost them to comply with good practice. In other words, the market directly incentivises corruption.
Thus the inspectors themselves need independent regulation to ensure that they are not paid to turn a blind eye, and so on. When even the late head of the Chinese State Food and Drug Administration46 found it impossible to resist payments from pharmaceutical companies to pass substandard medications, it seems unwise to rely on the incorruptibility of blood safety inspectors to protect us when the profits to be made from the plasma trade create such strong incentives to break the rules.
Many tens of thousands of people in many countries have been killed by fatal diseases transmitted through plasma due to inappropriate donor selection, collection and processing arrangements. Markets in raw plasma and in plasma products systematically and inevitably create perverse incentives contrary to patients’ interests.
A US journalist reported the 2007 financial incentives in the plasma industry in a province of China47:
Thus everyone concerned has a financial interest in maximising the quantity of plasma collected. The corollary of this is that everyone has a financial interest in concealing information on substandard plasma and known or suspected infections.
A seller of his or her own plasma, and any middleman, wants to sell the maximum amount of plasma for the maximum price. At every stage in the supply chain, a buyer of plasma wants to buy the maximum amount for the minimum price. Both agree on maximizing the amount which is sold. This creates an incentive for both to suppress information exchange about possible infections and to avoid screening: both stand to gain by putting potentially unsafe raw material into the system.
The bigger the plasma pools are, the cheaper they are to process, but the riskier they are for patients for both infection and for death through stroke, heart attack or anaphylaxis. Use of larger pools multiplies the risks attached to collection methods which are vulnerable to including infected plasma.
Maintenance of infection control in relation to equipment generates risks to patients in a similar way; cleaning takes time, and reusing disposables saves time. Hiring appropriately qualified staff and training them properly takes time. In business, time is money, and money saved is money made.
In a competitive market, the lowest price producer will find it easy to sell all of its production, but competitors offering product at a slightly higher price may attract little custom at times of low demand. Blood products have limited shelf -life, so if they are not sold they cannot be stockpiled to await higher prices but must be discarded. A few pence reduction in the selling price can be the difference between many sales and having to throw away most of the production because it has passed its sell-by date. It may be far cheaper to cut corners on screening and processing then bribe the inspectors than to carry out the procedures properly.
There are thus intrinsic dangers in allowing commercial interests into blood processing. The first duty of a commercial company is to make profits for its shareholders from their invested capital. Minimising costs is the easiest way to maximise short-term profits; while this promotes “economic efficiency”, in this sensitive context it can threaten safety.
Market models assume that everyone involved has “perfect information”, full knowledge of all relevant information. This is one of several reasons why market economics is generally irrelevant to healthcare. Market advocates insist on assuming away the fact that the ultimate consumer of a plasma product is entirely unaware of whether the vial in his hand may be infected with dangerous viruses or not. The patient carries all the risks created by the incentives for producers to increase their incomes by reducing expenditure on infection control and good manufacturing practice.
Thus use of markets in producing and supplying plasma products directly puts patients at risk of life-threatening infections and medical emergencies.
There is an alarming history of incidents showing the dangers of trusting the international commercial plasma market, with diseases being spread to patients on the other side of the world from the plasma source, and unsafe practices sometimes continuing for years after their risks were well understood.
Thousands of people in many countries have been killed by fatal diseases in plasma due to inappropriate donor selection, collection and processing arrangements. Most of the major corporations involved in plasma processing have been implicated at one time or another in scandal due to alleged failures in quality control.48
A brief review follows, explaining relevant events and arrangements in four countries, all of which themselves consume plasma products. The first three countries, Germany, China and the USA all allow plasma purchase and are major plasma products exporters. Canada provides a case study of the workings of plasma brokers and the potential consequences of relying on imports. These are a few illustrative examples: unfortunately the catalogue of catastrophes which follows covers only a small part of the history of problems arising from the plasma trade.
Germany permits purchase of plasma and thus has a commercial plasma products industry.
From the 1970s there have been accusations that doctors with private commercial interests in clotting factor production were over-treating and under-supervising their haemophiliac patients, greatly increasing their risks of contracting infection. One German hospital alone used more Factor VIII than the whole USA, and an average German haemophiliac received up to four times as much donated clotting factor as the typical American haemophiliac. A single patient cost the German state more than $4 million per year to pay for his clotting factors, purchased by the government from his treatment centre on a for-profit basis in a major conflict of interest.49 This high level of prescription was lucrative to the plasma processors but multiplied the infection risk to patients.
In Germany unsafe practice at harvester UB Plasma over some years resulted in HIV infections:
“At least 60 hospitals and clinics across Germany received blood products from UB Plasma or several intermediary firms, according to health officials. Some products also were exported to Austria, Saudi Arabia and Greece.
According to health officials and German press accounts, UB Plasma apparently failed to test two-thirds of its donated blood supply in some cases.
A spokesman for the Social Affairs Ministry in the western German state of Lower Saxony said yesterday that "we operate on 120,000 people a year. Over 10 years that means up to 1.2 million people are potentially affected by the call to be screened. Further complicating matters is the discovery by some hospitals that many - perhaps most - patient files do not indicate whether the blood products originated with UB Plasma.”50
“The Koblenz-based firm UB Plasma was closed down two weeks ago and four workers were arrested over allegations of improper testing, and there are fears that tainted plasma may have been sold to about 80 hospitals in Germany and elsewhere in Europe.
The first two cases of patients infected with HIV due to the use of UB Plasma products were confirmed yesterday, officials said in Koblenz.”51
The four employees were “accused of knowingly using unreliable testing methods on blood to save money”,52 then ignoring information that some donors were HIV+.53 In addition, UB Plasma collected one and half tonnes of plasma in Romania which was impounded by the Romanian government because no screening at all was used. A subsequent government released it and UB Plasma sold it into the global supply chain.54
In 1995, the German authorities shut UB Plasma down and imprisoned its senior managers. One possible purchaser of PR UK, Biotest, was drawn into the scandal, which resulted in its licence being withdrawn:
"German Firm Ordered to Pay AIDS Compensation" Reuters (05/02/94)
A Bonn court yesterday ordered German pharmaceutical firm Biotest to pay more than $150,000 to a 13-year-old boy who became infected with HIV through contaminated blood products distributed by the company.
That amount, in addition to compensation arising from the firm's medical liability, placed the total award at about $240,000, according to a Biotest spokesperson.
The pharmaceutical company was linked to a national scandal that surfaced last year when another company, UB Plasma, was found to have distributed unscreened blood products that were given to millions of people nationwide for more than a decade.
Biotest, as one of the distributors who bought blood from UB Plasma, had its license to make the blood products suspended. The court ruled that the company did not prove that it had not shown lack of due diligence when the hemophiliac youth was infected during routine treatment in 1989 with a preparation derived from HIV-tainted blood.
Biotest has already settled out of court with 10 other patients who were infected through the same batch of blood.55
Poor infection control in the Chinese plasma industry caused a huge scandal which still affects China’s new Premier Li Keqiang.56 Lack of plasma seller screening and other infection control breaches in “entrepreneurial” plasma collection centres led to an enormous outbreak of blood-borne disease which infected tens of thousands of plasma donors and recipients with HIV, HBV, HCV or some combination.
Over the years, various methods have been used to ensure collection of sufficient blood to meet China’s demand, commencing with cash payments to donors who were often homeless migrants. Blood station staff organised middlemen ("blood-heads") to liaise between the blood bank and professional donors of no fixed abode.57 Similar arrangements were used in post-war Japan, until a syphilis-infected transfusion caused a national scandal and the government set up a safe supply chain.
A self-perpetuating commercial system resulted from the Chinese blood-head initiative which soon turned to supplying the lucrative plasma trade with raw material. Its influence saw the quality of plasma fall as the quantity harvested in total and from each individual rose, the blood-heads maximising their incomes by administering medicines to plasma sellers to increase blood volume and conceal disqualifying medical conditions so as to maximise the amounts sold.58
In 1994 and 1995, Chinese media reported children and destitute adults abducted and bled of plasma daily against their will by criminal gangs.59 Plasma donation should not be more than fortnightly for the health of the seller and the quality of the product.60 Too-frequent harvesting can cause malnutrition from protein depletion, and kidney damage.
Plasma sellers were repeatedly bled and given a mix of pooled cell fraction from donors of the same blood type instead of receiving their own cells back. Injecting drug users were transported by middlemen around the country to wherever the middlemen could make the most money by supplying the donors to collection stations. Since their blood entered the pool, other plasma sellers became infected with blood-borne infections mixed with the returned cells.
Even outside plasma-selling areas, 10% of the PRC’s population carry HBV. An additional 50% have been acutely infected and recovered without developing a carrier state, but these cases would be infectious if their plasma were harvested just after initial infection before jaundiced eyes and skin became apparent. That could also be during the initial test window period so that infection could pass undetected into the blood supply despite correctly executed screening protocols.
In China, illicit collection continues in some areas, driven by profit opportunities and enabled by the expense and difficulties of watertight regulation. In September 2006, the Guangdong Bioyee Pharmaceutical Company was found to be running an illegal collection facility65,66 despite passing routine inspections by the Guangdong health department. Hepatitis C was diagnosed among patients treated with the company’s “human gamma globulin” IVIG preparation.67,68 The State Food and Drug Administration (SFDA) has since revoked its operating licence and certificate of Good Manufacturing Practice,12 as the virus would have been destroyed if correct procedures had been followed.
Tighter government controls were applied to purification of antibodies from June 2007 and to albumin from January 2008, following an investigation of the widespread sale of fake albumin.69 The SFDA announced that provincial authorities have assigned 84 quality supervisors to cover China’s 33 blood products manufacturers and also 32 vaccine makers.70 This will constrain the global plasma supply if enforcement is effective, and will make it more hazardous if supervision fails and “entrepreneurs” are able to boost the plasma supply once again to responds to the perverse incentives inherent in a commercial system for producing plasma products.
Blood products made from Chinese plasma now supply the global market71; for instance, the Sino-American joint venture Shanghai RAAS72 exports to English- and Spanish-speaking markets. Other foreign plasma fractionation companies also seek to undertake production in China, to serve both Chinese and global markets.73
Following a spate of “thromboembolic events” (strokes, heart attacks and clots on the lung) in users of Octapharma’s IVIG product Octagam,74 a 2011 exchange75 from the staff blog of a US plasma products manufacturer illustrates the implications of the risk-promoting perverse incentives inherent in any market for infection-transmitting human tissues:
“Re: thromboembolic events, recalls and Noncompliance - oh my
Regardless of what happens with the Grifols/Talecris merger - at least the plasma supply will be cleaner without Octapharma. Bad OPI plasma and drug could bring the whole industry down a notch. Is anyone really looking at how long that stuff is out of the freezer during morning packing?”
“Re: thromboembolic events, recalls and Noncompliance - oh my
“Nope no time record. The FDA will see that. It could be out for more than an hour and no one would notice. For that
matter, no one really keeps track of how long it is sedentary after it's collected. Some of the centers don't use timers so who knows how long before it's frozen. It gets shipped hemolyzed, icteric, and lipemic just the same.” 76
These postings appear to imply that Octapharma did not comply with adequate infection control systems, good manufacturing practice, or quality control of output. They also seem to suggest that the company had omitted even to set up the mechanisms needed to achieve acceptable standards, such as timers to monitor the time that plasma spends outside the freezer. The titling shows that the company’s staff link these failings with serious adverse events found at elevated rates among Octagam users.
Further compliance problems at Octapharma are identified in this staff blog,77 including misrepresentation investigated by US regulators:
CBER's Office of Compliance and Biologics Quality reviewed a card file and dosage guide for Octagam 5% [Immune Globulin Intravenous (Human)], which were disseminated at the Octapharma booth at the American Academy of Allergy, Asthma and Immunology meeting in San Antonio March 18-22. The agency also reviewed the company's website and determined the file card, dosage guide and website were misleading because they failed to reveal the risks and contained unsubstantiated safety, effectiveness and/or superiority claims.71
Some excerpts from the history of the US plasma trade will illustrate the frequency and seriousness of the problems.
Cutter continued to export remaining stocks of unsafe product to haemophiliacs in Latin America and Asia after it started its own safer production line in February 1984. It has been alleged that into 1985 it continued parallel production without the new safety protocol in order to service fixed price contracts at lower cost to the company, causing more than a hundred deaths in Hong Kong and Taiwan and an unknown number in Malaysia, Singapore, Indonesia, Japan and Argentina.
The President of Alpha Therapeutics resigned in 1983 because he believed that the company’s products were unsafe but Alpha’s parent corporation were not addressing the problem.80
Following the 1974 warning of the International Red Cross Inter-American Conference about
“this new modality of exploitation of the most needy, a dangerous, scandalous and unfitting traffic” ,
the World Health Organization asked developing countries about their involvement in plasma harvesting. Eleven of the twelve replies they received recorded approaches by commercial firms.81
Most developing countries eventually evicted the plasma industry as exploitative and dangerous. Even Haiti’s dictator Baby Doc Duvalier felt that these plasma harvesting operations breached the limits of acceptable conduct and ejected them.
In Nicaragua, abuse of the population by plasma harvesters triggered the 1978 revolution.
Further, prison populations tend to have much higher rates of blood-borne diseases than the general population due to both the characteristics of their intake (proportion of injecting drug users, for instance) and behaviour inside prison such as tattooing, injecting with shared equipment, and forced sex.
It has been known since a published study in 1966 since that HBV rates in the USA are roughly proportional to the proportion of the plasma supply derived from prison populations.83 A 1958 study showed that prison donors were about ten times more likely to carry HBV than volunteer donors, but its results were attacked by the plasma industry who correctly perceived that if the findings of this study were taken to their obvious conclusion in the USA, the government would set up the volunteer-only non-commercial blood supply that most developed countries aspire to and their profit stream would vanish overnight. The US Food and Drug Administration met representatives of US fractionators in December 1982 and told them not to use prison plasma.84
Plasma harvesting in Arkansas prisons from the 1960s to 1994 was responsible for thousands of deaths in at least ten developed countries and unknown numbers elsewhere. The prison programme in poverty-stricken, drug-addicted Grady, Arkansas harvested plasma from hundreds of inmates. Cutter Biological ran the collections from 1963, then from 1979 a local company, Health Management Associates Inc. (HMA) took over. HMA sold the plasma to brokers on the open market who resold it to plasma processers.85
The FDA first noted infringements by HMA at Grady in July 1982: prisoners were “over-bled” and there was no evidence that HBV+ contributions were being destroyed as required.86
In 1984 the prison’s output was banned for use in the USA because the FDA found blood-borne hepatitis in HMA plasma and linked it to twelve HBV+ donors. Investigation revealed that an inmate had been put in charge of infection screening. Predictably, he took advantage of his position to earn extra money by selling a screening test bypass to prisoners banned from donating because they had previously tested positive for HBV, to allow them to continue to receive an income from selling their plasma.79 HMA Inc lost its licence temporarily but was then permitted to restart “for the good of the inmates and the prison” (according to Francis Henderson MD, paediatrician who started HMA) when the corrupt clerk was moved on.
HMA continued exporting until it lost the prison contract and consequently shut down in 1986 after a critical 1985 report by the Institute for Law and Policy Planning. By that time HMA had lost its licence three times, but the Arkansas Bureau of Corrections continued to give it the plasma collection contract for the prison despite bids from more reputable companies.
“There is this whole thing about the high-risk population. I disagree with that. There’s no scientific proof to that.”
His comment on precautions taken against HIV appears to indicate lack of knowledge of the role of injecting drug use and other skin-breaching practices in spreading HIV, or the high prevalence of injecting drug use among both the local population and inmates:
“If anyone got caught in a homosexual act, we took them off the roster,”
Plasma collection in Arkansas prisons continued until 1991 under the control of this company, then was run by a third company until no customers at all could be found in 1994.79
Products made from these prisoners’ plasma were implicated in Hepatitis C outbreaks in Canada, 87 France, Iran, Iraq, Ireland, Italy, Japan, Portugal, Spain, Scotland, Switzerland and the USA88,89, all resulting from market purchases of plasma products. The Clintons were part of the Arkansas administration for much of this period, and it has been alleged that they interceded to protect the plasma collection facility.80.
Prisoners in Arkansas were banned from earning money from the labour they undertake (this is the only US state to have such a ban) but were permitted to sell plasma for $5-$10 a pint. The prison sold it on for $50 a pint, earning over half a million dollars a year in some years.80
A selection of comments from those involved in this programme illustrates how it was run79:
“I could see [prisoners] were being given illegal narcotics — several indicated that this was how they were being paid for their plasma.” [Inmates] “appeared jaundiced and very sick. When I would ask if they had just had a blood test, they would say, ‘No, I’ve just given plasma.’ It was clear they were sick.” “I assumed, stupidly, that our people selling this plasma had some process of cleaning it up.”
(Mike Galster MD, Cummins plasma collection center clinician 1979-1983)
“ [People in HMA] management positions…initiated or condoned the destruction or alteration of records concerning these activities.”
(US Federal Drug Administration Report, 1984)
“The prison program they had was pretty shoddy, they had inmates doing things they shouldn’t have been doing. They would let people who was sick bleed … ain’t no telling what they had. They didn’t check all the time.” “I am damn sure I got it [hepatitis C] in the prison, I didn’t have it before I went in. I have never had needles stuck in my arm that wasn’t supposed to be there. I have never interacted with homosexuals. I love women too much. I didn’t get it those ways.”
(John Schock, regular seller while incarcerated at Grady and subsequent liver transplant recipient due to HCV infection)
“After a promotion, an inmate who became my clerk told stories of events that took place when he was assigned to the plasma center, including things like the refrigeration going out for hours and the plasma being refrozen later and shipped.”
(Ex-prison guard, Grady)90
“There was a mentality that we didn’t have any AIDS in the central part of the country. The department (of corrections) said for years we didn’t have any AIDS cases. There was a subconsciousness that we just didn’t want to think we had those people around us. Historically, this [was] the worst possible time to [sell plasma – because prison plasma was now banned in the USA and most buyers no longer wanted it]. I called all over the world and finally got one group in Canada who would take the contract.”
(Henderson, about the creation of HMA’s plasma supply contract with Continental Pharma Cryosan Ltd, Canada’s biggest blood broker).76
"I'd say 70 to 80 percent is going overseas. There's a good market for it over there, and they don't ask where it came from."
“We plan to stick with it till the last day…to the last drop we’re able to sell.”
(John Byus, medical director of the Arkansas Corrections Department, 1991)92
[A] significant burden of responsibility [for tainted blood provided to British hemophiliacs] rests on American suppliers of Factor VIII concentrate. Long after alarms had been sounded about the risks of obtaining paid-for blood donations from communities with an increased incidence of relevant infections, such as prison inmates, this practice continued.
It is difficult to avoid the conclusion that commercial interests took precedence over public health concerns.93
Lord Robert Winston called this episode
“the worst treatment disaster in the history of the NHS.”94
In Canada, the government was nearly brought down97 when it became plain that at least 30,000 patients caught hepatitis C and 1000 contracted HIV during the late 1970s or 1980s from transfusions and blood products.98
The Canadian Red Cross did not know that clotting factor preparations it bought through recently privatised Toronto-based Connaught Laboratories were made from HMA’s Arkansas prison plasma. Canada had itself stopped collecting from prisons in 1971 because of the infection risks. Montreal commercial plasma broker Continental Pharma Cryosan was the source of the HMA plasma used by Connaught Laboratories.
Connaught had ceased doing its own checks on plasma in favour of relying on US Food and Drug Administration reports. The 1997 Krever Commission which investigated the outbreak among Canadian haemophiliacs discovered that Connaught had accepted consignments of blood rejected by the US authorities:
"The Food and Drug Administration inspection reports were obtained, but they were not reviewed....According to Magnin [Dr. Anthony Magnin, former director of plasma fractionation at Connaught], it didn't register with Connaught that it was using blood from the Arkansas Department of Corrections until August,1983 - six months after the company was informed. Magnin, who testified that collecting blood from prisoners "was not considered inherently a problem" by Connaught, admitted that "either the documents were not read" when they were received "or they were read and not acted upon." 79
“Evidence has indicated that checks to safeguard Connaught's blood products against AIDS or hepatitis infection appear to have been almost entirely absent during the early 1980s.”
According to the Commission:
"There was a greater than average risk that the 38 units of plasma from the four inmates [identified as HBV+ in 1983] could transmit AIDS. Four of the units ended up in Canada, the others were sold to corporations in Switzerland, Spain, Japan, and Italy [by Cryosan]."99
“The shipping papers accompanying the plasma had not revealed that the centre was located in a prison. They had simply referred to the source as the ‘ADC Plasma Center, Grady, Arkansas,’ without any indication that ‘ADC’ stood for ‘Arkansas Department of Corrections.’
“In a letter to the Red Cross in March, 1983, a senior Connaught official assured the blood agency that that none of its plasma suppliers was "located in population centres in the U.S. shown to bear high risk for AIDS."
However, a month earlier, Connaught's quality control department had received documents that clearly showed plasma was being collected from prisons in Oklahoma, Texas and Arkansas and sold to Connaught through various brokers.
Further evidence yesterday indicated that, when the developed world began turning to heat-treated blood products, Connaught began eyeing less developed countries as likely markets for its non heat-treated ones.
In confidential Connaught memos from October, 1983, Iran and Spain are mentioned as possible markets, and there is speculation the laboratory "could be in a position to sell 6 million units to France." In a later memo, however, Connaught apparently decides against selling to France, specifying that "current product should not be offered for sale to developed countries."100
Former Canadian Prime Minister Paul Martin has been touched by the scandal because of his role in the Canadian Development Corporation which was supposed to oversee the activities of Connaught once it started to be run for profit.101
In September 1983 Connaught reviewed its records and determined that twelve of its US sources were never approved. Among them were the Grady prison and four Louisiana prisons. The Canadian Red Cross cancelled its contract with Connaught on discovering this, but too late for many haemophiliacs and their wives, already infected by contaminated clotting factors.
Continental Pharma Cryosan had a prior record of unacceptable practice which should have been grounds for Connaught to reject it as a supplier. Following a Canadian police investigation, in 1980 the company entered a guilty plea for labelling blood as sourced from Swedish donors which had in fact been extracted from Russian corpses.102
In the early 1990's The “Committee of Ten Thousand” activists claimed compensation of up to $100,000 apiece with a total settlement of $1 billion sought in 1999.103 The companies they were suing (Baxter, Bayer AG, the US subsidiary of French Rhone-Poulenc, and Japanese-owned Alpha Therapeutic Corporation) announced a settlement for Japanese haemophiliacs infected by Arkansas plasma that dwarfed the numbers being discussed in Canada: $420,000 for each victim, with $235,000 coming from industry and the rest from the Japanese government. 104
In the end Ontario’s settlement alone cost the province $1.2 billion.105
Unfortunately the UK no longer has the option of self-sufficiency in plasma supply, as a consequence of the decision by the Conservative government to deregulate the cattle feed industry. The producers stopped heat-sterilising the sheep remains they were putting into cattle feed, and British cattle developed a never-before seen disease, bovine spongiform encephalitis (BSE or “mad cow disease”) which turned out to be derived from the long-known sheep brain disease scrapie. The meat from infected cattle went into the UK food supply and the disease leaped a second species barrier: it turns out that scrapie is not directly infectious to humans but once the infectious agent passes through cows at least some people who eat it develop an incurable, untestable, untreatable disease. This turned out to be a new variant of Creutzfeldt-Jakob Disease (vCJD), which kills following a decline into madness as brain tissue disintegrates over several years.
So far 175 people have contracted it in the UK and 49 elsewhere (diagnosed between October 1996 and March 2011).106 It was declared unsafe to use UK plasma in 1998 because of the risk of it being contaminated with vCJD, for which no screening test is available. The World Health Organization has this to say on the challenge of determining the risk from vCJD in an infected population:
The maximum duration of infectivity in blood of persons with pre-clinical/sub-clinical vCJD as well as the prevalence of pre-clinical/sub-clinical vCJD in various countries is not known. Consequently, the long-term risk of transfusion-transmitted vCJD for donors exposed to BSE agents in various countries is not known.107
In 1994 a US blood donor died of vCJD and all UK-derived plasma products in the USA were recalled. In 1998, the UK government stopped using UK plasma and started buying plasma on the US open market.108
The Australian government limits vCJD risk within its national plasma supply by opting to
“exclude people from donating who have resided in the UK between 1 January 1980 and 31 December 1996 for a total (cumulative) time of 6 months or more, or [who] have received blood transfusions in the UK since 1 January 1980. Because of the extensive time period covered by the deferral and the possibility of unknowing exposure to beef or beef products, it is not possible to exempt vegetarians who have resided in the UK for a cumulative period of 6 months or more during the risk years. The Blood Service is monitoring progress in the development of a reliable blood screening test for vCJD.”109
In order to secure a sustainable and reliable safe supply of plasma and blood products for the UK’s government-owned plasma processor Bio Products Laboratory (BPL), in 2002 the Department of Health purchased the largest remaining independent US plasma collector.110 At the time commercial plasma processors were buying up plasma harvesters and so the open market supply of plasma in the US was shrinking. The company is now known as Plasma Resources UK; its current market products include blood-clotting factors for haemophiliacs and ingredients for vaccines for rabies and hepatitis.111
This was a wise and sustainable solution to the problem, though far inferior to having the safe pool of UK donors denied to us by BSE.
Eleven years later the uses for plasma have multiplied, the amounts used in the UK and around the world are soaring, and the second largest source nation, China, has been forced to reduce exports because of repeated infection breaches among producers. Thus the reasons are stronger than ever to keep this government-controlled producer and reserve its production for the British people.
The government seems to be ignoring both this quantity-based argument for maintaining a nationally controlled supply of safe plasma, and the more fundamental quality issue that profit-led open market plasma producers inevitably devote themselves to buying cheap and selling dear in an environment where the final user has no protection from abuse by the supplier.
The Health and Social Care Act 2012 explicitly permits the privatisation of our national supply of blood, plasma products, tissues and organs.
In October 2011, the Health Service Journal reported that part-privatisation plans for UK blood and transplant services had been dropped. NHS Blood and Transplant was temporarily reprieved because of protests about a hovering would-be provider, Netcare, a South African company implicated in illegal kidney transplants from minors.
The government are keen to pass the second of these categories, plasma products, over to a commercial plasma producer. PR UK was turned into a limited company by this government in 2012 and now been moved out of NHS Blood and Transplant to be run directly by the Department of Health (DH). This facilitates its sale to the highest bidder and allows the government to continue to claim that none of the functions of NHS Blood and Transplant will be privatised.
Health Minister Simon Burns last July announced that PR UK would be privatised,113 and appointed Lazards, an investment bank chaired by Lord Peter Mandelson, to oversee the privatisation. International companies are currently placing their bids and a deal is likely to be finalised by June114. It emerged in January 2013 that the Spanish plasma producer Grifols SA was the UK government’s preferred bidder for PR UK, but Grifols has declined to purchase, on the grounds that PR UK’s US market presence added to its own would be of sufficient size to trigger a competition law (anti-trust) dispute in the USA.115
Reportedly116 American companies including scandal-hit Baxter International and private equity firm Bain Capital have submitted bids, and the German company Biotest AG117 is said to be interested. In 2002 Biotest was forced to compensate a 13 year old boy for infecting him with HIV, and its licence was revoked for selling contaminated products which had never been screened for infectious disease.
This licence has since been reinstated.118 In January 2013 Biotest launched a new liquid IVIG product called Bivigam,119 but there was a recall of this new intravenous preparation at the start of April because one batch inspected contained visible particles which if injected could trigger stroke or heart attack.120
The planned sale of PRUK is largely a result of the 2010 Government Spending Review which aimed to identify all public sector assets that could be privatised. The sale of PRUK is expected to raise a significant amount of revenue (estimates vary from £100-£300 million, with the most recent at “over £200 million” from the FT on 21 April 2013121) and the Department of Health say private investment is required to enable the growth and development of PRUK so it can better compete internationally. DH officials said that when the government purchased the US plasma supply company in 2002 there was an assumption that vCJD would spread throughout Europe, creating a global shortage of plasma. This threat never materialised and the majority of mainland European countries still use their own population for plasma. As a result, the DH is officially unconcerned about UK plasma product supply.
None of the DH spokespeople that our researchers spoke to seemed to understand the purpose or the importance of the company for the safety of patients, and none seemed aware of the gamble involved in buying these products on the open market given the track record of repeated infections caused by profit-led economising on safety procedures. Instead, bizarrely, our health officials seemed to focus entirely on the profit potential of the company and not on its essential function for our health.
They also stressed that BPL only currently provides around 30% of the UK’s plasma products, so the majority already come from the open market, in which BPL itself competes. These statements show that we are already being exposed to unnecessary risks by misguided pro-market policy, an error about to be greatly compounded by disposing of our means to achieve a safe national plasma supply.
The DH told us that safeguards are provided by the regulated safety and quality standards in the plasma product market. However there is copious evidence from the infections that continue to occur in users of open-market sourced plasma products that these are insufficient, such as the 2008 Baxter heparin scandal that killed 81 patients122, or the 2007 Hepatitis C infections traced to illegal plasma collection in China123.
The DH and our government mentioned only vCJD in relation to the sale of PR UK and none of the many other infection risks. This represents an astonishing lack of grasp of the health risks associated with plasma products, given that new blood-borne diseases emerge every few years globally, through changes in existing diseases or human infection with animal diseases.
While the social incentives to organise a safe and protected supply are plain, use of a market to distribute blood products has from the 1950s been linked with restraint of trade principles being invoked to force acceptance of blood products known to be unsafe.
In 1955, unqualified husband and wife entrepreneurs, Francis and Margaret Bass, spotted a new business opportunity. They started to purchase and supply blood to hospitals in Kansas.124 Their lack of medical training and exclusive focus on keeping costs low and sales high resulted in inappropriate donor selection and processing, aggressive marketing, and attempts to foist substandard blood on to junior hospital staff. They once sent a consignment of three bottles of blood to a hospital: two were visibly clotted (thus unusable) and the third returned a positive test for syphilis. The doctor in charge was threatened when he rejected them.
Local doctors were horrified by the prospect of having to accept blood collected by the Basses and together they formed a non-profit community blood bank to provide their patients with safe supplies from screened volunteer donors. The Basses reacted to this as a threat to their livelihood.
They hired a telemarketer to sell blood insurance plans: a former barman whom they also allowed to screen blood sellers and draw their blood. They complained to the Kansas City Better Business Bureau, via the county medical society accused the doctors of “most severe, unfair and unwarranted persecution” due to their “special interests”, and commenced a campaign of legal harassment.
An investigator arrived from the Federal Trade Commission to investigate the Basses’ complaint. The doctors were tried before the Commission, accused of violating the Federal Trade Commission Act “by mounting a commercial boycott against the Basses to put them out of business”. The verdict:
“the Community Blood Bank of Kansas City should cease and desist from boycotting the Basses”
This decision was upheld on appeal. The penalty for non-compliance was $5000 a day ($42,836 has the same purchasing power today as $5000 in 1956125).
Finally in 1969, after a fourteen year battle, the Federal Court of Appeal ruled that the Federal Trade Commission had exceeded its remit in bringing a trade law action against a non-profit blood bank. Trade law applies only to commodities provided through markets.
We have seen what “exclusive focus on keeping costs low” did to patients at Stafford Hospital under the control of the man who now heads the NHS.126 The UK government is now intent on dragging all of our healthcare into the trade and competition law net127 that reproduces the US trade laws that the Basses used to force their bad blood into patients’ veins.
Concern now focuses on how UK patients can be confident of a safe and secure supply of plasma for plasma products in the future, if the government sells off the national asset acquired to provide and protect that security.
In early February, Lord Philip Hunt asked the government how they will ensure a secure supply of plasma products for the NHS after selling PRUK. Health Minister Earl Howe responded,
“Security of supply of products to patients is of paramount importance to this Government and is one of the key objectives integral to all the options being considered as part of the sale process. [PR UK subunit] Bio Products Laboratory Ltd's supply to National Health Service trusts will continue to be governed by existing supply agreements, and the department will continue to ensure that effective legal and commercial structures are in place to ensure that ongoing security of supply from all suppliers is maintained.”128
Lord Hunt was not reassured by this ministerial response, which invites us to place our trust in fixed term contracts with a commercial supplier which has already shown itself lacking in terms of both quality and ethical conduct:
“I don’t see how in reality the government can guarantee supplies after a sale. When I was a minister we were anxious to secure the future of these supplies for patients because they are critically important. I’m not convinced that the government have got a hold of this issue. What happens if the company that we sell to later runs into financial problems? Contracts can be unreliable. There are so many uncertainties that come with pursuing this plan which make it incredibly risky.”
Biotest will be trying to increase demand for its scarce products and there will be no way for us to control this demand inflation so as to protect an adequate quantity of supply to us at adequate quality. Indeed the company already has a tie-up on albumin with China.129 In 2011, 180 tonnes of human albumin were sold in China, more than 40% of which were imported. Biotest has already doubled its output of albumin to 40 tonnes annually130. If we are to rely on Biotest for albumin, their strategy to concentrate on Chinese growth might make it hard to deliver to us should we have, for example, a serious fire with many people burned, an increasingly likely occurrence given the closure of many fire stations around the country.
Biotest was the first pharmaceutical company to stop selling medicines to Greece in its present economic crisis when ven Price Waterhouse said that there was a moral duty to do so. In combination with this company’s safety record, this lack of concern for patient welfare highlights clearly that we should not seek to rely on this company for secure access to safe supplies131.
The Archer report termed UK infections of haemophiliacs by infected clotting factors a "horrific human tragedy" but did not name any specific medical workers or pharmaceutical companies as being responsible for the deaths of around 2,000 hemophiliacs since the 1970s and for infecting roughly 5,700 haemophiliacs with HIV, Hepatitis C or both:
"It is difficult to avoid the conclusion that commercial interests took precedence over public health concerns," said Archer, who conducted an independent inquiry with the help of legal and medical professionals.”132
MPs have laid an Early Day Motion133 calling on the government to “cancel immediately the instruction to sell PRUK and guarantee that this company will instead be held in perpetuity to protect the health of the people of the UK”. Labour MP Grahame Morris, member of the Health Select Committee, commented,
"This is another step too far in the privatisation of the NHS."
Geoff Dunbar, a retired Methodist minister, has started a 38 Degrees petition134 calling on Health Minister Dr Dan Poulter to “save our blood plasma service” by scrapping the plan to sell off PRUK.
Ernst and Young reportedly advised the government upon the sale in an independent strategic review of PRUK for the Department of Health, but this review is not in the public domain. The commercial sensitivity of the sale restricts information being made available and leaves parliament and the public with insufficient information to scrutinise the rationale for the sale and its potential implications for public health. An informed public debate about the safety and wisdom of this sale is urgently required.
The Coalition is in the process of selling an asset vital for national welfare without making any arrangements to replace it. The privatisation of PR UK is wholly against the UK’s national interest given the market shortages of plasma and the fact that we cannot collect plasma in this country because of the impact of the BSE disaster caused by Mrs Thatcher’s ‘liberalisation’ policies. Another crop of privatising politicians are exposing us to the problems that inevitably hit countries which buy plasma products on the open market, in which competition on price leads to pressure on producers to reduce all costs including those of adequate infection control.
Rather than turning sourcing of plasma products over to the open market, we should expand the operations of PR UK, because buying plasma products on the open market involves exposing patients to substantial risks. The market creates perverse incentives to minimise safety procedures, and almost every open market plasma producer has been caught at one time or another in an infection or faulty product scandal. Should infections result from inadequate safety procedures, plasma products manufacturers can just shut down, allowing their owners to evade the legal consequences of their cost-cutting. This arrangement puts all the risks on patients, including for example asthmatic children and cancer patients treated with IVIG.
When we know of such problems, it cannot be responsible to choose to expose British patients to these risks when an alternative is available.
That alternative could be procured with ease now, but it will be hard to achieve thereafter. There are few independent plasma harvesters left: as demand is so high, the big companies are doing all they can to sequester this precious resource in the few countries that allow its purchase. Most other countries strive for self-sufficiency in plasma supply. With a wholly government controlled plasma source we can ensure that only the safest donors contribute to our supply and we are in a position to ensure that the process is as safe as possible at every stage. We are about to throw that security away and expose ourselves to whatever product is put on the open market.
Historically, social costs have attached to failure to take adequate safety precautions in plasma processing:135 deaths, increased treatment costs, permanent disability, orphaning, lawsuits brought by infected recipients, to public unrest over exploitative plasma collection.136 Billions of dollars have been paid in compensation to victims and their families around the world.
Former Secretary of State for Health and medical doctor Lord Owen recommends:
“We in this country should do everything in our power to avoid being reliant on open market tendering procedures where we can never have absolute confidence in the source of the plasma, let alone the strength of the regulations and quality of the inspectorates in the countries from which we purchase. Plasma Resources UK Ltd is an excellent insurance policy for the NHS, the Labour government was wise to make this purchase, and you would be foolish to sell it off. “
PRUK’s activities should be reorientated away from profit-making back to public service, and its supply developed to ensure our 100% ability to meet the UK’s medical need for safe plasma products without recourse to dangerous markets which reward corner-cutting on safety.
For our safety’s sake, David Cameron should heed Lord Owen’s advice and cancel this sale.
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WARNING: Use of Immune Globulin Intravenous (IVIG) products have been associated with renal dysfunction, acute renal failure, osmotic nephropathy, and death.
Thrombotic events have occurred in patients with risk factors including age over 65.
Closely monitor patients for hemolysis and hemolytic anemia. Risk factors for hemolysis include non-O blood group, underlying inflammation, and high doses.
Carefully consider relative risks and benefits before prescribing high-dose regimen in patients at increased risk of thrombosis, hemolysis, acute kidney injury or volume overload.
Monitor patients for pulmonary adverse reactions and signs of transfusion-related acute lung injury (TRALI). Infrequently, aseptic meningitis syndrome (AMS) may occur (most often with high doses and/or rapid IVIG infusion).
IVIG is derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated.
Hansard: Plasma Supplies (excerpts)
Lord Hunt of Kings Heath: On the evening of Monday 16 December, the Department of Health completed its purchase of the largest remaining independent US plasma collector, Life Resources Incorporated. This will secure long-term supplies of non-UK blood plasma for the benefit of NHS patients, and ensure that the current global plasma shortage will not reduce the availability to National Health Service patients of life-saving plasma products.
Without continuing, secure supplies of US plasma, BPL faced shutdown by 2004 with a consequent removal of massive volumes of plasma products from the NHS market. Independent market analysis by KPMG demonstrated that commercial suppliers would not be able to provide sufficient, secure supplies of plasma products to the NHS if BPL closed. Immediate action was therefore needed to secure long-term supplies of high quality, US plasma for BPL.
Life Resources has supplied BPL with plasma since 1999. It has extremely high quality and safety standards overseen by the US Food and Drugs Administration and the UK Medicines Control Agency. All the company's collection centres are inspected by BPL on a rolling two-year programme. BPL's team also inspected every centre prior to the purchase.
An effective corporate governance regime has been established for the ongoing management of Life Resources. The company will be run by its existing US management team and report to a US parent company, DCI Biologicals Incorporated. DCI Biologicals will report to a UK parent company, Plasma Resources Ltd. The board of Plasma Resources Ltd is chaired by Richard Douglas, the Department of Health's director of finance and investment.
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