The now-defunct Poly Implant Prothesis (PIP) company was issued a warning letter by the US Food and Drug Administration (FDA) in June 2000 following an inspection of a plant run by the manufacturer at La Seyne-sur-Mer in southeastern France. The letter cited at least 11 deviations from 'good manufacturing practices', which the FDA said "may be symptomatic of serious underlying problems in [the] firm's manu-facturing and quality assurance systems".
Although the letter concerned only the saline implants made by PIP and not the silicone ones that have recently sparked worldwide alarm, the plant inspected by the FDA was responsible for making both types.
The FDA stated that the saline implants being made at the plant were "adulterated", meaning that "the methods used in, or the facilities or controls used for manufacturing, packing, storage, or installation, are not in confor-mance with the Good Manufac-turing Practice (GMP) for Medical Devices Regulation".
Some of the specific violations identified in the letter included failing to report any complaints related to saline implants to the FDA, failing to have procedures in place to analyze data from the defective implants and failing to ensure that all staff were adequately trained. Because of the severity of these violations, the FDA said it would be detaining all PIP implants imported into the US until permanent corrective actions are made.
The key question that is now being asked is why the FDA's warning did not trigger greater scrutiny of PIP's activities by regulators in France and else-where.
The letter was made public in 2000, but the French health authority Agence Francaise de S'ecurit'e Sanitaire des Produits de Sant'e (AFSSAPS; French Agency for the Safety of Health Products) has said that it had not been informed of the warning's existence.
An FDA spokeswoman said she could not confirm if the results of the PIP inspection were also relayed to the French health authorities. But she did explain that "generally speaking, when the FDA conducts inspections in foreign countries of foreign facilities, they are aware of our presence in [the] country".
News of the FDA warning to PIP more than a decade ago will no doubt anger the hundreds of thousands of women who have since been fitted with PIP silicone implants, now known to contain industrial-grade silicone never authorized for medical use. The company went into liquidation in 2010 after the AFSSAPS recalled the implants, but the practice of using unapproved material had been going on since 2001. Why was this not discovered sooner?
The UK's Medicines and Health-care Products Regulatory Agency (MHRA) first noted concerns about the PIP implants in 2008, but it wasn't until 2010 that they issued a 'Medical Device Alert' on the products, advising UK clinic-ians not to implant them, and commissioned testing to evaluate the implants' safety. More worrying, as early as 2006, surgeons had begun publically reporting their own anxieties about the implants, yet no action was taken by the MHRA.
Richard Horton, editor-in-chief of the prestigious medical journal The Lancet, asked in a recent editorial whether the MHRA had read one such report, which spoke of a "massive failure" involving a three-year-old implant. R.B. Berry wrote in 2007 that "not only had silicone migrated to a regional lymph node, but the exposed silicone gel appears to have provoked an inflammatory response with the production of a significant quantity of serous exudate. In view of these two reports, the reliability of PIP implants must be questioned and, for myself, I intend to discontinue their use in favour of implants from other manufacturers."
If the MHRA did not read this report, Horton says, "then what is the point of an agency that does not keep up with safety signals reported in the medical litera-ture?" If it did read the report, then why did it not order an urgent safety review, he asks. The only reasonable conclusion, he states, is that "the MHRA failed to do the job the public expects of it-to protect it from harm".
Horton also criticizes the MHRA's response on 23 December last year to France's decision to advise women to have the implants removed. He says that its decision not to follow suit was "hasty, cavalier, and completely counter to ongoing concerns about PIP implants".
He is equally critical of the Chief Medical Officer's advice to women who had received PIP implants, which was "not [to] be unduly worried". As Horton writes, "that view was quite literally incredible given that women had received implants containing an industrial-grade silicone gel that was not approved for human use" (Lancet, 2012; 379: 106).
Indeed, the British Association of Aesthetic Plastic Surgeons (BAAPS)-a not-for-profit organi-zation set up for the advancement of education and the practice of aesthetic plastic surgery for the public benefit-is steadfastly recommending "precautionary removal" of the defective implants. According to consultant plastic surgeon and BAAPS President Fazel Fatah, "Although there is no immediate health risk, the gel within these implants is simply not meant to be inside the human body."
Passing the buck
Fortunately, the UK government has now stated that the NHS will pick up the tab for the removal and replacement of the PIP implants in concerned women who received their implants through the NHS-although it is not recommending their routine removal. As for the vast majority of women who had the PIP implants fitted privately, the government said it expects the clinics involved to offer the same deal. If the clinic no longer exists or refuses to help, the NHS will cover the costs of removal of the PIP implants, but will not replace the implants unless it is "clinically necessary".
One clinic-or, rather, group of clinics-that is refusing to replace the PIP implants free of charge is the Harley Medical Group (HMG), which fitted nearly 14,000 women with the implants between September 2001 and March 2010. Its chairman Mel Braham said the company had neither the resources, the surgeons nor the operating facilities necessary to do the surgery, adding that the government must accept "moral responsibility" for replacing the PIP implants.
"We're only sitting here today because the MHRA, their own regulatory authority, has approved these implants and obviously hasn't done their proper check-ing," Braham said. "We can't take on this whole thing on our own, especially when it wasn't our fault." Instead, he said the HMG would supply the NHS with the replacement implants.
Similarly, Nigel Robertson, head of the cosmetic surgery firm Transform, has said: "Private sector providers with large volumes of patients do not have the resources to ensure the removal and reaugmentation of all PIP implants free of charge." He called the government plans "unwork-able" and blamed the MHRA for "a catastrophic failure" of regulation.
The MHRA has officially responded to these attacks by saying that it did everything by the book: "The manufacturer PIP gave these products a European CE Mark indicating that it complied with the relevant EU regulations. This was overseen by TUV Rheinland-a German commercial organization responsible for undertaking the necessary safety and regulatory checks required for a CE Mark. Once a medical device has a CE Mark, it can be placed on the market in any EU member state. Under these circumstances, our responsibility here was to investigate adverse incidents as part of our post-market surveill-ance role. We did this and we have continually monitored the safety
of these breast implants."
In other words, the MHRA is saying that it's not to blame-a position UK Independence Party MEP Paul Nuttall agrees with: "The real responsibility lies in a combination of regulatory failure in France and then European Union laws that prevent British authorities from protecting UK consumers," he says. Under EU law, he explains, the national regulatory authorities can grant their own companies and products a CE Mark-which is supposed to provide a guarantee of quality. European law then forbids the MHRA from conducting further checks, as all products that carry a CE Mark are given free passage within the combined marketplace.
Change is needed
Ultimately, the blame game that's going on in the media at the moment is doing nothing to help the thousands of women worried about the risks associated with their PIP implants. Preliminary reports suggest that these implants may be more prone to rupture and leakage, but the real worry is that we don't know the extent of the risks, as the silicone used in them has never been tested for human use.
Whoever's to blame, the fiasco highlights the gaping holes in the double safety net that's supposed to protect public health in the UK and Europe. Tighter controls are urgently needed to avoid such disasters in the future.
WDDTY VOL 22 NO 11, February 2012