The PIP scandal: an analysis of the process of quality control that failed to safeguard women from the health risks

Introduction

Plastic surgery is a sector of medicine that continues to show strong trends in growth. In 2011, women accounted for 90% of all procedures, with breast augmentation being the most common.¹ There are estimated to be a total of 130,000 women in the UK who have received breast implants and around 47,000 of these were silicone implants manufactured by the French-based company Poly Implant Prothèse (PIP).² Following the misuse by PIP of industrial grade silicone, an expert panel, chaired by Sir Bruce Keogh, was appointed by the Department of Health to investigate the consequences of this scandal. They concluded in their final report of June 2012 that ‘PIP implants have not shown any evidence of significant risk to human health’.³

We disagree with their conclusion. Here we aim to share our concerns on the regulatory and quality control procedures that failed to safeguard thousands of women from the health risks associated with PIP breast implants. In light of the current ongoing review into cosmetic surgery which is also being led by Sir Bruce Keogh, it is vital that such failings are identified and tightened to ensure such a scandal is not repeated.

What is a breast implant?

• A medical prosthesis used to augment, reconstruct, or create the physical form of breasts

• Modern (so-called fifth generation) breast implants usually contain either saline or a viscous silicone gel

• The outer casing, or shell, is composed of durable elastic silicone manufactured through a chemical process called vulcanization in which sulphur is added to the silicone to increase durability

The PIP breast implant story

The Medicines and Healthcare Products Regulatory Authority (MHRA) began to receive reports of potential problems with PIP implants in 2002, nearly a decade before the scandal broke in March 2010. In total, they received 269 adverse incident reports relating to PIP silicone implants between 2001 and 2009, including a case of premature rupture of both implants in the same patient.

From 2003 onwards it began to relay this information back to the French manufacturer. Following an inspection of the French-based company by national health authorities, a ban on PIP implants was announced in March 2010 due to concerns over the use of an unapproved filler. While the French government subsequently recommended all women with PIP implants have them removed as a precaution, the MHRA announced that there was no need for their routine removal.

In July 2010, the MHRA commissioned a limited number of analyses intended to provide a preliminary evaluation of the filler material used in PIP silicone gel implants. The analysis revealed the presence of silicone compounds in addition to traces of organic and inorganic impurities (Keogh report). Based on the subsequent laboratory analysis, the MHRA went on to conclude in June 2012 that these results ‘did not raise any concerns regarding risks to human health’.

Chemical composition of breast implants

The significant component of breast implants is silicone (polydimethylsiloxane), not to be confused with the chemical element silicon. Although silicone does contain silicon, the former does not occur in nature and is entirely synthetic. Due to the production method, commercial silicone products will contain variable concentrations of molecular weights and sizes including a subgroup of small-sized molecules referred to as D4, D5, D6.^4,5

In addition, the normal manufacturing process may result in traces of platinum, used as an essential catalyst. Small traces of platinum may be an acceptable find in medical grade silicone, unlike heavy metals such as tin, zinc, chromium, arsenic, lead, antimony, nickel or copper. In addition to specific health concerns associated with these heavy metals, there is also the risk that they may induce platinum toxicity.^6,7 Traces of lead and zinc were reported in the PIP implants but these were within permitted regulatory levels. A more detailed chemical analysis of the gel is still ongoing.

The PIP implants working group

The working group on PIP breast implants was appointed by the Department of Health to review the potential health risks of PIP breast implants and to advise the Department on policy in relation to women who received these implants. It was chaired by Sir Bruce Keogh, a cardiologist and NHS medical director, and consisted chiefly of plastic surgeons from the British Association of Aesthetic Plastic Surgeons (BAAPS) and one toxicologist, Professor Ian Kimber. The panel produced their final report in June 2012, based upon results of toxicological tests carried out by the MHRA as well as those of other national regulatory bodies, including France and Australia.⁸

The key findings of the working group were that, although PIP implants had double the average rupture rate, the PIP gel material itself did not reveal anything that could cause a long-term threat to human health and was shown to be ‘not toxic and not carcinogenic’.³ The expert group dismissed tests carried out by the French authorities that suggested PIP implants could cause skin irritation in rabbits and instead accepted subsequent tests commissioned by the Australian authorities without gaining independent or any further validation.⁸

The final report acknowledged the conclusion from the European Union's Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) but carried out no further investigations:

‘in the case of PIP implants, when the limited available clinical information is taken together with the findings from tests of the physical and chemical properties of the shell and silicone, and of the in vivo irritancy test, some concerns are raised about the safety of PIP breast implants as the possibility for health effects cannot be ruled out.’

Our concerns

1. The PIP implants were found to contain a higher proportion of small-sized molecules D4, D5, D6 than the norm.⁸ D4 (octamethylcyclotetrasiloxane) was identified as an endocrine disrupting chemical (EDC) of ‘high concern’ in 2007 by a report commissioned by the European Commission entitled ‘Study on enhancing the Endocrine Disrupter priority list with a focus on low-production chemicals’.⁹ The effects of low doses of such chemicals, particularly on the developing fetus, have been well documented.^10–13 While most regulatory levels of impurities in breast implants are considered acceptable in the range of a few parts per million, Le et al.¹⁴ showed that EDCs are capable of affecting developing neurons in vitro at concentrations of less than one part per trillion. Considering these known risks and the fact that most women receiving breast implants were of reproductive age, we would expect the MHRA and the Department of Health to fulfil its duty of care and thoroughly investigate these risks as well as provide full information to patients.

2. The report bases much of its evidence upon animal data rather than readily available human-based methodologies, such as toxicogenomics using human cell lines, which are ideal platforms for studying the effects of trace quantities of impurities on gene expression levels.^15,16 This is of some surprise given the current level of knowledge of the human genome and the chair's acknowledgment that the toxicological data cited in the report was ‘based upon the availability of methods’ despite his acceptance of the clear ‘advantages’ of human based ones. Furthermore, the report is inconsistent with its reliance upon animal-based data, accepting some results while dismissing others without providing human-based support tests as back up. For example, it dismisses the effects attributed to D4 on the reproductive system that occur in rodent tests on the basis that it is thought to be independent of any estrogenic activity (estrogen receptor binding activity) of D4 without proving the human effects of this.

3. The MHRA is the UK government agency responsible for regulating all medicines and medical devices in the UK by ensuring they work and are acceptably safe, see http://www.mhra.gov.uk/Aboutus/index.htm. Yet the MHRA and review panel both relied upon the findings of other non-UK bodies for the basis of its policy-making. It was the French regulator (Agence Francaise de Securite Sanitaire des Produits de Sante [AFSSAPS]) who was responsible for certifying the PIP implants and they delegated the task to a private German company (TUV Rheinland). The visits were announced 10 days in advance which allowed the factory staff sufficient time to conceal evidence of the cheaper PIP silicones being used.¹⁷ Additional gaps in the regulations mean that no unannounced checks of the implants' contents took place, nor did the chemical composition of the implants, once approved, require re-testing. This meant that a person with no scientific training commercially manufactured a substandard medical product without detection by European safety regulators for many years. Given that breast implants are categorized as ‘higher risk medical devices’ one would expect a rigorous quality control system in place for all such products imported into the UK. This is certainly true for another popular medical product with cosmetic applications, namely ‘Botox’ (botulinum toxin). The National Institute for Biological Standards and Control (NIBSC) is the UK's Official Medicines Control Laboratory, where every batch of botulinum toxin used in the UK is independently evaluated for potency using recognized in-vitro methods.¹⁸ Had one of the PIP implants been subjected to rigorous NIBSC-style quality control when these products were originally imported into the UK for marketing in 2001, their defective characteristics would have been flagged up from the start.

4. There have been many developments in the field of molecular toxicology over the past decades including the 2007 report referred to above on EDCs, yet the current MHRA website advice to women (as of August 2012) remains largely based on a report published in 1998 (Silicone Gel Breast Implants by the Independent Review Group [IRG]) which fails to provide women with the latest relevant health risks associated with EDCs.

5. The expert panel contained just one toxicologist, Professor Ian Kimber. A panel appointed to investigate a scandal of this nature is expected to contain more than one toxicologist. Ironically, the IRG of 1998 contained no toxicologist at all.

Conclusion

Based upon the evidence presented here we feel that the PIP breast implant scare is an example of regulatory and quality control failure that urgently requires addressing as an integral part of the ongoing review of plastic surgery.

We recommend the following:

1. The MHRA implements its own quality control process of all prosthetic materials, in this case breast implant materials, independent of other agencies, including EU agencies.

2. The EU requirements for biological evaluation of ‘higher risk’ medical devices such as breast implants (e.g. ISO 10993-1) undergo urgent revision in order to include modern toxicology testing methods, based on human genomic cell data and other methods that are directly relevant to the species in question, namely humans.

3. Effective quality control should keep in step with scientific progress as well as technical specifications, such as those described for ISO, HACCP and GLP. This is especially relevant with respect to implanting devices into the body, whose contents may leach or leak regionally or systemically over time. Several scientific studies, confirmed by magnetic resonance imaging, have indicated that many women have lived for a long period with ruptured implants without knowledge thereof.^19,20 In these situations, the leaked chemicals could not only invade surrounding tissues but also spread systemically either via the lymph or the blood.

4. A programme of biomonitoring of women with breast implants should be implemented as part of an overall epidemiological health monitoring scheme. This should include the periodic analysis of blood and urine samples, using ‘omics’ technologies to detect biomarkers of early pathology, well before the manifestation of clinical disease. It would be advantageous to consider the cost effectiveness of such a programme.

5. Any review panel or body should uphold transparency and public accountability and be free of conflicts of interest. Its composition therefore should include more than one toxicologist and those who are without conflicts of interest. Greater transparency would also reduce the impact of conflicting messages to the public.

DECLARATIONS

Competing interests

None declared

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors

Ethical approval

Not applicable

Guarantor

VM

Acknowledgements

None

Reviewers

Shreelata Datta and Michael Coleman