4.1. Production of Silicone gel filled breast implantsThe thickness of the silicone elastomer shell (sac) of a breast implant varies, but is typically between 0.5 and 1.0 mm thick. There is a hole at the back of the shell through which the silicones that are later cured to form the gel material are introduced. The hole is sealed using a silicone patch after the shell has been filled.
The raw material silicones that are used to make the silicone gel are a mixture of chemically reactive and un-reactive silicone oils. The gel is produced by curing the silicone raw materials inside the sealed (patched) shell. During the curing process, the reactive silicones form matrix of lightly cross-linked polydimethyl siloxanes (silicones) swollen by the viscous silicone fluid (oil), which is not chemically bonded to the gel and can constitute around 90% of the gel. The cured gel is highly cohesive and has the consistency of a well set jelly.
4.2. Formulations of filler gel and shell used in PIP breast implantsAFSSAPS report that there are at least three different formulations of the filler gel used in PIP breast implants(4). The authorised gel was manufactured using oils supplied and manufactured by the Nusil Corporation. The gel produced using these oils (Nusil MED 3 6300) has been extensively tested to demonstrate that it is biologically safe and suitable for use in medical applications. The unauthorised gels were manufactured using a combination of other brands of silicone raw materials, with two different formulations identified as PIP1 and PIP2. The PIP1 and PIP2 formulations do not appear to have been subjected to the sorts of biological safety tests that the Nusil MED 3 6300 gel has passed. Apparently, PIP1 was manufactured prior to 2008 and PIP2 from the beginning of 2008. It is not clear if or when the Nusil silicones were being used to manufacture the gel used in PIP breast implants.
4.3. Test Results – AFSSAPS, FranceAFSSAPS reports indicate that studies investigating the integrity of the PIP shell found that the tensile set and fatigue resistance tests complied with the requirements of the international standard (ISO 14607:2007), while the tensile elongation of textured PIP breast implants did not comply(4). AFFSAPS also commissioned cytotoxicity tests, a variety of genotoxicity tests and an intradermal irritation test. The tests concluded that the materials used in PIP implants are not cytotoxic or genotoxic, but the intradermal irritation test showed an irritant potential in the PIP gel. Testing of PIP breast implants by AFSSAPS was carried out on samples with an expiry date of 2011 or later.
Physico-chemical analysis has confirmed that different formulations of filler gel had been used and that there was variability in physical and chemical characteristics of the filler gels used in different batches of PIP breast implants. In particular, the different filler gels can be identified by the presence of low molecular weight silicones.
4.4. Testing Program – TGA, AustraliaThe TGA testing program has focused on four key areas:
- physical and mechanical properties
- chemical analysis
- explanted PIP implants.
4.4.1 Samples available for testingThe TGA testing plan is using the broadest cross-section of samples of PIP breast implants available to the TGA, and includes both PIP1 and PIP 2 formulations of the filler gel. To date, samples of the product with an expiry date before 2011 have not been available to the TGA.
The TGA has tested 19 different batches (29 samples) of PIP breast implants available in Australia plus batches of other brands of breast implant for comparison. The TGA has obtained a further five batches (23 samples) of PIP breast implants from overseas for the on-going testing program.
The TGA is investigating explanted PIP breast implants to complement testing being carried out on unused sterile PIP breast implants and to provide further evidence that will assist with determining the overall quality and safety of the product.
4.4.2 Testing regimeThe tests conducted as part of the program are summarised in Table 1 below.
Table 1: TGA Testing Regime
|Testing on explanted PIP implants||
Explanted breast implants are not sterile and contain matter derived from the woman’s tissues, as well as chemicals and materials from the surgical procedure that may confound chemical and toxicological tests. For example, the implant can be contaminated by chemicals from latex gloves and contact with various instruments, as well as cleaning and sterilising fluids used during or after surgery. Furthermore, containers and bags, which are used to store the explants, as well as microbiological organisms from the environment, can contaminate the implants during storage. This means that tests to determine the presence of chemicals that may be toxic could be invalid. Such tests should be carried out on unused sterile breast implants.Top of page
4.4.3 Limitations to testingTesting provides a measure of the compliance of a particular sample with specified quality criteria. The quality of the sample is taken to be reflective of the batch from which the sample is drawn. However, the samples of PIP implants tested may not be representative of other batches of the product due to uncertainty relating to manufacturing quality. Nevertheless, it does provide a very useful support to other measures by providing an immediate assessment of quality of the portion or the sample of the batch tested.
Interpretation of testing results must be made with caution as there are limitations to the testing program, especially relating to a lack of unambiguous controls, presence of multiple gel formulations, lack of manufacturing batch documentation and a lack of samples manufactured prior to 2008.
4.5. Testing results and findingsA specific serious safety concern for PIP breast implants has not been identified from the particular mechanical, toxicology or chemical tests carried out by the TGA to date.
While the AFSSAPS reported a ‘potential irritant’ finding for the filler silicone gel, this is not consistent with testing results from studies commissioned by the TGA. Two different laboratories, one in Australia and one in France (the same laboratory used by AFSSAPS to conduct its dermal irritation tests), carried out tests on behalf of the TGA in accordance with those described in the designated international standard and results from both laboratories showed that the gel and the shell of tested PIP breast implants were non-irritant.
To date, repeated cytotoxicity testing by TGA has confirmed previous findings (from 2010) that the tested PIP gels do not contain chemicals that are toxic to living cells. Similar findings have been reported by AFSSAPS and the regulatory authority in the UK (MHRA)(5). Both those authorities also reported that tests for genotoxicity indicated that the gel was not genotoxic (damaging to DNA).
Questions were raised about the amount of low molecular weight silicones (D4-D6 siloxanes) that may be present in unauthorised gels. To date, chemical testing indicates that the amount of these siloxanes (especially D4) in PIP breast implants is not a safety concern but is a useful test for identifying implants containing unauthorised gel. Further, testing has not identified any metals in the tested PIP breast implants that are at a level of concern.
While testing has not identified a serious quality concern, the TGA has noted that there is variability in the physical and chemical characteristics of different batches of PIP breast implants. The significance of this variability is still being investigated. The TGA testing has not identified problems regarding shell integrity, although AFSSAPS reported failures related to the tensile elongation test. Testing the tensile elongation of further samples of PIP breast implants confirmed the findings of 2010 that all tested samples comply with the requirements of the designated international standard.
To date, the TGA has observed that most filler gels from either unused or explanted PIP breast implants appear to be firm. However, the TGA has noticed that the occasional gel, which was from an implant that has been either explanted or removed from packaging and exposed to the environment over a long period of time, appears relatively less firm and oily. The significance of this observation is being further investigated.
Explanted PIP breast implants with ruptures were found to be associated with a ‘milky’ fluid, which testing showed to be predominantly an emulsion of water and silicone.
The TGA website contains details for the on-going TGA laboratory testing program at http://www.tga.gov.au/safety/alerts-device-breast-implants-pip.htm.
4.6. International cooperationThe TGA established an international testing panel for PIP breast implants (ITPP), which includes representatives from Brazil, Czech Republic, European Commission, Germany, Ireland, Netherlands and the United Kingdom. France has been invited to join in discussions, but has not been available. The role of the ITPP is to discuss laboratory testing of PIP breast implants through teleconferences and on-going email exchange. To date, the TGA has hosted three teleconferences (19 January, 9 February and 8 March 2012). No other country reported, at these meetings, that they have recent laboratory testing results.
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