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PIP - the tip of a regulatory iceberg

Total reform of the MHRA is essential if professional and public confidence
in the safety of medical devices and drugs is to be restored.

Douglas Cross CBiol, FSB
29th January 2012

Summary

This review of the failure of the Medicines and Healthcare Products Regulatory Agency (MHRA) to exercise adequate vigilance in its regulation of both medical devices and medicines examines two examples, one in each field. These demonstrate that the Agency is vulnerable to both external commercial fraud and to internal improper political influences that have serious repercussions on the health and safety of the public.

The regulatory process that applies to medical devices and medicines is subject to Community law, but the European Commission has allowed a flawed regulatory system to be put in place that is heavily dependent on misplaced trust and a naive ‘gentleman’s agreement’ that leaves it wide open to deliberate abuse. The reputation of the CE-mark indicating a product’s presumed fitness for purpose is now in crisis. It can only be restored by a critical revision of the legislation and procedures on which its reliability depends. Since the defective legislation under which the Agency carries out its regulatory function derives from European law, any investigation of its role must include an examination of the failure of the European Commission to establish an appropriately robust and enforceable regulatory system covering medical devices and medicines.

Under the existing flawed legislative framework, national regulators have become dangerously out of control. The autonomy of the MHRA is compromised by its financial reliance and intimate staffing links with the industry over which it is required to exert its police powers. Its failure to exercise due diligence in the case of medical devices such as breast implants, and its deliberate refusal to implement its regulatory obligations with respect to the chemicals used in water fluoridation, indicate that it may be subject to improper influence by the vested interests of its industrial paymasters and prepared to pander to domestic political interests rather than protect the public for whose safety it is ultimately responsible.

The MHRA’s negligence and its underlying lack of independence and accountability have exposed the State to severe long-term financial liability. Responsibility for the investigation into its fitness for purpose must now be placed in the hands of entirely independent and qualified specialists, on whose impartiality both Parliament and the public can depend.

The breast implant scandal - PIP’s shady past

An anonymous tip-off in 2010 alerted the French regulator of medical devices (AFSSAPS) that a manufacturer of breast implants, Poly Implant Prosthese (PIP) based near Toulon, had been substituting the approved medical-grade filler with an untested and illegal industrial-grade silicone gel since 2001. AFSSAPS took immediate action to close down the production line and recalled all unused implants already on the market.

But AFSSAPS should have been more diligent in checking the background of PIP and its US partner, Donald McGhan, when breast implants were reclassified as high risk medical devices by the Commission for Health and Consumers in 2003. Had the regulator checked out the backgrounds of those running this production facility before the EC’s respected CE mark of quality was re-issued for their defective product, it would have found imperative reasons to keep a very close watch on the manufacturer of this high-risk product.

PIP had been making implants at its factory at La Seyne sur Mer, near Toulon, France, since 1991 Initially these were filled with either saline solution or Hydrogel, a polysaccharide material. The saline-filled implants were distributed in the USA from 1999 by PIP’s partner Medicor, founded by Donald McGhan, but a year later the US Food and Drug Administration (FDA) ordered their withdrawal because it had discovered that the production process and product were defective on 11 counts. However, Medicor got around the FDA’s official ban for two more years before replacing them with PIP’s latest version of the product. But to cut costs the new version contained an illegal home-brewed sub-standard mixture of industrial grade silicone gel, mixed with only 20% of authorised medical-grade gel.

PIP’s partner, Donald McGhan, had a poor reputation in the field of medical implants. As Tom Hals reported for Reuters,
While McGhan created, sold, bought and merged implants businesses, the industry was rocked by a series of health scares through the 1980s and early 1990s. The devices were found to rupture and leak, and women brought thousands of product liability lawsuits against manufacturers including Dow Corning and 3M. The FDA banned silicone implants for most women from 1992 to 2006 pending additional safety data.

By the time he [McGhan] partnered with France's Jean-Claude Mas, founder of Poly Implant Prothèse (PIP), in 1999, he had been sued by shareholders who accused him of stealing money, was being investigated by the Securities and Exchange Commission for false accounting and had been replaced from his position as chief executive at one of the world's leading implant makers. McGhan has since been jailed for wire fraud for illegally using money from clients in a real estate company in an attempt to build yet another implant business

With a record like this, both AFSSAPS and the MHRA should have carried out careful checks on the product and its makers. PIP’s sub-standard implants were supplied to 300,000 women world-wide, at least 40,000 of them in the UK. They were also rebranded as ‘M-implants’, and were very popular for elective breast enhancement amongst women throughout Europe, so the number of British women at risk may in fact be significantly higher than official estimates suggest.

It has now been revealed that PIP used the same unauthorised industrial-grade silicone filler in male chest implants, and in artificial testicles supplied to replace those removed in cases of male testicular cancer, so both women and men must now be considered to be at risk.

Between 2000 and 2010 the reliability of PIP implants in the UK became increasingly suspect, and the MHRA had plenty of time to subject them to quality assessment. According to Sir Bruce Keogh, head of the NHS Expert Group now investigating the scandal
From about 2006 onwards, concerns began to emerge among cosmetic surgeons about the performance of PIP implants. In 2008 the MHRA noted an increase in the number of reports of ruptures and raised concerns with the manufacturer and the notified body, but this was understood to be the result of an increase in sales and improvements in the manufacturer’s reporting criteria. The MHRA raised further concerns in 2009.

During this period, the French and the British governments successfully petitioned the European Commission to reclassify breast implants as high-risk medical devices in 2003. But for seven more years they continued to rely for quality assurance on inspections of the manufacturing process and the product carried out by the German Notified Body (inspection company) TUV Rheinland, in compliance with the Directive. So how did PIP manage to deceive the regulators and the inspection company for so long?

Hobbling the regulators - the defective European Directives on Medical Devices.

As the Reuter’s report reveals, the records of PIP and its American associate Donald McGhan should have alerted both regulators at least a decade ago. That they did not was at least in part due to the astonishing incompetence of the European Commission itself, in its drafting the Directives on medical devices, since this was the body that set the rules with which regulators must carry out their responsibility to ensure that all medical devices are fit for purpose.

The original Directive (93/42/EEC) aimed to establish a rigorous ‘quality assurance system’ that permitted inspections of facilities where medical devices are manufactured. The Directive authorises inspection companies to visit manufacturers’ premises without notice if there were grounds to suspect a manufacturer was producing a sub-standard product. But the bungling Commission then inserted an astonishing ‘get-out’ clause into the Directive - one that effectively pulled the teeth of the watchdog regulators in all Member states of the Community. It recommended that inspectors should give manufacturers two weeks notice of any impending inspection.

It seems that, in the abstracted political circles of the European Commission, the concept that dodgy manufacturers might lie about their products was simply inconceivable. This naive provision ensured that any fraudulent manufacturers would have plenty of time to hide defective material and hoodwink official inspectors with impunity. And in a further obstacle to effective enforcement, national regulators in Member States wishing to check up on a product certified in another State were required to seek information on it either from the relevant inspection company or, incredibly, from the manufacturer himself. To experts on regulatory enforcement this might be considered to imply a certain lack of common sense on the part of the Commission.

The original Directive was updated in 2003 on the initiative of the British and French regulators. Directive 2003/12/EC upgraded the classification of breast implants from moderate risk (Class 2b) to high-risk (Class III) products. Existing CE-marks were to be rescinded, and could only be reinstated on proof that a manufacturer’s production facilities and product met the higher standards demanded for Class III products. The deadline for this was March 2004, but despite this shake-up in the industry, the loophole for fraudulent manufacturers remained open.

As a direct result of the Commission’s incompetence, and the absurd assumption that manufacturers should be presumed to be honest, it took almost ten years to uncover the fraud, and even then only after a tip-off. Without this, the fraud could easily have continued indefinitely. Assuming that this loophole was not deliberately left open, such negligence confirms that the primary liability for the consequences of this regulatory failure rest squarely on the Commission itself.

The MHRA’s failure to exercise due diligence over the PIP implants.

The Agency has a statutory duty to ensure that medical devices used in the UK comply with their original approved specifications. In attempting to defend its position it has protested that it was unable to carry out more detailed scrutiny of this product because its powers of inspection are limited. Instead, as the NHS Expert Group has itself revealed, the Agency relied on unsubstantiated assurances from the inspectors and the PIP management that everything was in order. This is a remarkable admission of the Agency’s gullibility; in fact its protestations that it had no powers to take direct action itself are untrue - the Medicines Act and the Consumer Protection Acts both give the MHRA powers to take spot samples from end-users for analysis.

But rather than admit its liability for the impacts of this regulatory failure it is now blaming private clinics and surgeons for fitting ‘cut-price’ implants, and engages in high-profile public handwringing over calls for the NHS to pay for removing implants from patients from the private sector. Its attempts to de-fuse public concern over the medical implications of ruptured implants are also a matter of concern. Women are particularly apprehensive of breast cancer, and although there is no sound evidence that implants are a causative factor in the development of this disease, the MHRA evasively assures the public that the PIP implants are no more likely than any other brand to be associated with breast cancer,.

This diverts public concern away from another unusual cancer, Anaplastic Large Cell Lymphoma (ALCL, a rare form of Non-Hodgkin’s Lymphoma) that is specifically linked to silicone breast implants. The Agency dismisses ALCL as a risk by deliberately understating its prevalence - 60 cases have been recorded by the US Food and Drugs Administration (FDA) - and assuring the public that no cases have been recorded in Britain. In the world of the MHRA, half truths seem to replace honesty and transparency when its own reputation is at stake.

The CE-mark, a worthless guarantee of the quality assurance process.

These contrived arguments obscure a more significant issue. Like all such products, the PIP implants bore the European CE mark, indicating that it was fully accredited as being ‘fit for purpose’, and professional end-users were absolutely entitled to assume that they could rely on them. But this incident has called the reputation of the CE mark of approval into question, particularly with respect to high-risk products permanently inserted into the human body. The confidence of end-users that certified devices meet the expected standards has been destroyed, and the credibility of the CE-mark is now in severe crisis.

The scale of the regulatory problem.

The regulators are now viewed by medical professionals as having acted without due diligence in protecting patients against fraudulent or sub-standard goods. This is reinforced by emerging public concern over metal-on-metal hip replacement devices that also appear to be of substandard quality. So the public is now entitled to ask, is this regulatory incompetence the full extent of the problem, or does it also affect other activities for which the regulators are responsible?

The PIP incident has shown how an incompetent Commission and lazy regulators can easily be hoodwinked by fraud in the private sector, confirming that at both the Commission and national levels the regulatory system is vulnerable to external fraud. But there is also very strong evidence that the second field for which regulators such as the MHRA have responsibility - the control of medicines - is equally prone to improper regulatory practices.

In this case, the fraud is not confined to misbehaviour within the pharmaceutical industry, itself responsible for promoting the use of numerous medicines whose efficacy, reliability and safety have been cause for considerable concern in the past. In the UK the regulation of what is probably the largest medicinal product by bulk has been deliberately manipulated by internal political interests and professional pressures. The MHRA acts as the keystone on which an astonishing regulatory charade is utterly dependent - the endorsement by both the Commission and the British and Irish governments of the use of fluorosilicic acid as a prophylactic treatment for dental decay.

Water fluoridation - the greatest regulatory failure of all?

The refusal of the MHRA to exercise its regulatory function over the chemical used in water fluoridation has probably caused as much actual physical damage to the public as any other of its past debacles. Whilst the fatality rate from fluoride poisoning is very low, for over 40 years many thousands of new-born children in England each year have been, and continue to be, condemned to develop unsightly disfiguration of their teeth in adolescence as an inevitable result of the government’s obsession with the discredited practice of water fluoridation.

For around 3,000 children annually, dental fluorosis becomes so severe during late childhood and adolescence that for the rest of their lives they need often prohibitively expensive remedial cosmetic dental treatment to conceal the damage. Whilst faulty breast implants can be removed, dental fluorosis cannot be cured, only concealed. Yet it is the declared objective of the Dept of Health to quadruple the number of children who will in the future be at risk of experiencing this otherwise avoidable disfigurement. The MHRA’s support for government policy in this travesty of public health is the single factor that has allowed this unacceptable situation to develop.

The Hazardous Waste used to contaminate public drinking water supplies.

Around 10% public water supplies in England are deliberately contaminated with crude fluorosilicic acid. It is alleged that this chemical provides a low-cost, safe and effective prophylactic treatment for dental caries in children, especially those in socially disadvantaged communities. In fact, the chemical supplied to water treatment works is not of pharmaceutical quality; it is a highly toxic, corrosive, and cumulative systemic poison.

Contrary to claims by proponents of fluoridation, it is not chemically identical to ‘natural fluoride’ once it is dissolved in drinking water. When the chemical products released when the fluorosilicic acid is added to neutral pH water at the water treatment works are converted to dangerous toxins in extremely acidic human stomach, and these have toxic systemic effects throughout the body. Despite this, no appropriate clinical or toxicological trials on the safety of the actual fluoridating chemical used in the UK have even been performed.

The fluorosilicic acid added to public drinking water supplies is actually a scheduled Hazardous Waste, and there are clear and compelling legal reasons why it should not be disposed of in this unauthorised fashion, or used as a prophylactic treatment in the field of public health medicine.

The MHRA’s refusal to regulate fluorosilicic acid.

The status of fluoridated water as a medicine was established as a jurisdictional fact in 1983 by Lord Jauncey in the Scottish Court of Session. In a number of cases the European Court of Justice has ruled that products such as this must be regulated as medicines, and that national regulators have no authority to exercise their discretion on the classification of such products. The MHRA is therefore in contempt of these rulings and repeatedly issues, either directly or through Ministerial statements in Parliament, its improper ‘opinion’ that fluoridated water is a food, and not subject to regulation as a medicine.

The direct result of the Agency’s refusal to comply with the rulings of the Courts is that dental fluorosis, the medical sign confirming chronic fluoride poisoning, is now evident in many hundreds of thousands of children who are compelled to consume this unlawful medicine. The MHRA defies its statutory duty to constrain the use of this substance through the application of medicinal law, as established by the rulings by both the domestic and European judiciary.

Protecting commercial vested interests in the ‘Fluoride’ brand

The underlying motive for the collaboration of the MHRA with the Dept of Health in this contempt of law appears to be to protect the commercial interests in the globally important brand image ‘Fluoride’ that is so relentlessly promoted to the public. Fluorine is a key ingredient in many highly lucrative commercial pharmaceutical products, and any threat to its wholesome image would be regarded as a commercial disaster. The MHRA’s refusal to accept that fluorosilicic acid as a medicine has a protective effect on the commercial interests from which the Agency derives the majority of its revenue.

As a Government Trading Fund, the MHRA is an independent business operation, and is required to make a profit. Around 90% of the Agency’s annual income of about £120 million comes from the pharmaceutical industry. The rest is provided by the Treasury, to pay for its work in regulating medical devices. With its overwhelming financial dependence on the industry, and the intimate staffing links between the Agency and the sector on which it depends for its income, there is a marked potential for a very serious conflict of interest in this relationship. It may be argued that the MHRA’s apparent protection of the reputation of fluoride in drinking water may arise from commercial pressures aimed at supporting its commercial clients’ interests in the marketing of other products containing fluorine or fluoride.

If the use of fluoride in drinking water were to be prohibited, then this would undoubtedly send an unwelcome and potentially damaging message to the public, casting doubt on the benign image of ‘Fluoride’ in other products. The MHRA’s insistence that it does not regard fluoridated water as a medicinal product provides a contrived and spurious ‘authority’ to the Department of Health’s that supports its illegal policy of water fluoridation. It is also the sole prop allowing governmental dental public health advocates of fluoridation to present this practice to the general public in the guise of a benevolent, harmless and, most importantly, a legitimate public health intervention.

The public health consequences of the MHRA’s refusal to regulate fluoridated water.

The Dept of Health’s fluoridation policy relies absolutely on misleading propaganda fabricated by the dental public health sector. Much of this promotional hype is based on unsound research funded by companies manufacturing fluoridated dental health-care products. Yet through intensive Parliamentary lobbying by powerful industrial interests, gullible (and invariably unqualified) Members of both Houses in Parliament have been persuaded to endorse the spurious claim that fluoridated water prevents children’s teeth from rotting.

With manifest ignorance these unwitting apologists assure Parliament and the public that the practice of fluoridation is ‘Safe and effective’. When challenged more specifically, they cite the MHRA’s highly idiosyncratic versions of which judgments they claim support their unique interpretation of their legal position. If the inevitable side effect of fluoridating public water supplies, dental fluorosis, is referred to at all it is simply dismissed as being of no social significance. Indeed, in a parody of ethical professional behaviour, the dental public health sector’s most recent promotional strategy relies on spurious ‘research’ specifically targeting young children, and aimed at persuading them that having chalky white teeth, the unique biomarker of chronic fluoride poisoning, is actually more socially desirable than having normal teeth. In fluoridated parts of the Republic of Ireland, less than half the population now has teeth with ‘normal’ enamel.

This improper relationship between the pharmaceutical industry, the MHRA and the Dept of Health has had a disastrous effect on tens of thousands of British children. Recent independent high-level scientific reviews of fluoridation have thoroughly discredited its alleged efficacy and safety. These studies have also confirmed that, in every country where water supplies are deliberately contaminated with this and related fluoridating chemicals, innumerable children are being disfigured every year by dental fluorosis.

Water fluoridation is the primary causative factor in the increased prevalence and severity of dental fluorosis in all fluoridating countries. In many cases it forces young adults to seek cosmetic dental treatment for a condition from which the vast majority of those affected would otherwise be almost entirely free. The Dept of Health’s own Committee on Toxicity reported in 1997 that 3 to 4% of children growing up in fluoridated water areas in England - representing around 3,000 new cases annually - suffer from moderate or worse fluorosis. Yet every year thousands of tonnes of waste fluorosilicic acid continue to be added to public drinking water supplies in direct violation of the Medicines and Waste Framework Directives.

The costs of regulatory failure.

The induced epidemic of dental fluorosis that accompanies water fluoridation indicates how the MHRA’s apparent willingness to pander to political and commercial pressure has resulted in unforeseen consequences within the cosmetic medical sector. It has provided a very substantial windfall for the cosmetic dentistry industry by stimulating demand, and even greater need, for remedial cosmetic dental treatment for those whose teeth have been disfigured by the very practice that the Dept of Health and the profession so enthusiastically endorse.

Whilst dental public health consultants deceive the public by claiming that children’s teeth are in a dreadful state (they are actually far better now than ever), many dentists profit from the jealously-guarded monopoly that allows them the exclusive right to provide remedial cosmetic dental treatment to those who can afford the high costs of remedial cosmetic dental treatment to conceal fluorosis. So since both the defective breast implant fiasco and the induced inflation of the need for remedial treatment for fluorosis involve cosmetic medical procedures, it is relevant to compare the relative costs of the MHRA’s regulatory failings in the two quite different parts of the cosmetic medical sector.

In an evident damage-limitation tactic, the MHRA has diverted debate over its own regulatory responsibilities - and therefore its liability - for the PIP scandal into an acrimonious and newsworthy argument over how much it might cost if the NHS were to remove implants supplied in both elective breast enhancement and after clinical mastectomy related to breast cancer. Removing suspect breast implants surgically, with or without replacement, is a one-off and relatively permanent solution to the problems raised by the use of the defective implants. At a rough estimate, the costs for removing all of the PIP implants supplied to 40,000 British women would be in the region of £100 million. (There are no data on which it is possible to estimate the relatively modest overall costs of removing male implants supplied by PIP.)

In comparison, the remedial costs of treating the dental fluorosis resulting directly from the Agency’s refusal to regulate fluoridated water are of an entirely different nature and scale. Fluorosis visibly and permanently disfigures the teeth of its victims. Veneering the visible damaged front teeth is the most commonly used procedure, but veneers have a limited life, and must be replaced whenever they break or fall off. Over a lifetime the cost of veneering a person’s teeth to conceal moderate or severe fluorosis averages around £30,000. If fluoridation is not abolished and the Dept of Health is permitted to reach its declared target of fluoridating 40% of English water supplies, then the 3,000 children in fluoridated areas of England who now develop fluorosis severe enough to need such treatment every year will increase to approximately 12,000 a year within a decade of this target being reached.

Relying on the most authoritative studies cited above, the cost liability for providing lifetime remedial cosmetic dental treatment to these victims of fluorosis will quadruple, from its present annual incremental increase of around £90 million to, eventually, around £360 million. It is no coincidence that all NHS Feasibility Studies for proposed new fluoridation schemes always deliberately and fraudulently exclude the cost liability for damage remediation in the target population. The reason for this should now be quite apparent.

The social costs of the MHRA’s refusal to regulate fluorosilicic acid.

But even this estimate does not provide a full indication of the social costs that are caused by the MHRA’s regulatory intransigence. The social and economic opportunity costs to victims of fluorosis are entirely ignored in the anxiety of the dental public health sector to attempt to justify its detested policy. Dental fluorosis can be a traumatic condition for both adolescents and older people. As children and adolescents, the psychological and social impacts of peer-group rejection can adversely affect educational performance. When seeking employment, victims may be rejected because employers wrongly assume that their unsightly teeth indicate that they may be negligent with their personal hygiene.

The claim by proponents of fluoridation that the practice selectively benefits the poor and reduces inequalities in oral health due to the effects of social deprivation is deliberately false. Although fluorosis affects children from rich and poor families equally, its social and financial burdens fall far more heavily on the poor, who are less able to afford the repeated cosmetic remedial treatment that is needed to conceal their condition. The high costs involved mean that most children (and especially those from less affluent backgrounds) who are disfigured by fluorosis do not actually seek treatment. But for the assessment of public sector liability, this is irrelevant - the State’s liability for the damage remains, even if the victims cannot themselves actually afford the treatment.

The unceasing attempts within the dental public health sector to persuade communities that fluoride in drinking water is entirely beneficial, in defiance of all reliable evidence to the contrary, suggests that there is justifiable cause for concern over the profession’s refusal to recognise the impropriety of its support for this practice.

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