What was presented to the committee on safety of devices (MHRA)?

COMMITTEE ON SAFETY OF DEVICES – 20 NOVEMBER 2003 MEETING POLYURETHANE-COATED BREAST IMPLANTS

Background
Conventional breast implants consist of a silicone shell surrounding a silicone gel filling. The silicone shell can be smooth or textured. Silicone gel filled breast implants covered with a polyurethane foam coating were introduced to clinical use by an American manufacturer in the 1980s with the aim of reducing the risks of capsular contracture compared with those seen in conventional breast implants. They were withdrawn from the market in 1991 following concern that the coating might release a carcinogenic breakdown product. An equivalent product was subsequently reintroduced outside the USA and is currently authorised for marketing throughout Europe and is on sale in several European and South American countries. However, the product has not been available in the UK since 1993 and MDA issued advisory notices to draw attention to this in 1994 and 1996 (Annex 1).

In 2001, MDA responded to approaches from a European manufacturer and plastic surgeons on the anomalous position in the UK, compared with the rest of Europe, by preparing an updated analysis of the biological safety of the implants. This found that earlier conclusions on the carcinogenic risk still stood, but the benefits claimed of the polyurethane coating could not be substantiated by the evidence available. There was therefore no basis for altering the advice given in 1994 and 1996.

In July 2003, in response to the MDA report, the European manufacturer provided MHRA with a literature review, which concluded that the superiority of polyurethane-coated breast implants, in terms of capsular contracture rates, had been demonstrated.

Review of carcinogenicity
The carcinogenic risk arising from polyurethane-coated breast implants was assessed by the Committee on Carcinogenicity (COC) in 1991 and 1994. The COC concluded that the breakdown of the polyurethane coating over a number of years leads to the release of small amounts of the probable genotoxic carcinogen, 2,4-toluenediamine (2,4-TDA) into the tissues surrounding the implant. This gives rise to a small, unquantifiable carcinogenic risk.

No evidence has emerged since 1994 that would alter the COC’s conclusions, although MDA noted recent evidence for the in vivo genotoxicity of 2,4-TDA and for its presence in the tissue of implanted women.

The 2001 MDA Review of the biological safety of polyurethane-coated breast implants (Annex 2) summarised the relevant data, reported the opinions of the COC and presented a discussion of the various factors relevant to the carcinogenic risk assessment and their public policy implications.

Review of capsular contracture

The 2001 MDA review noted that there were some reports of a reduction in capsular contracture with polyurethane-coated breast implants but insufficient evidence was available to demonstrate conclusively their long-term benefits over other products. In addition, MDA noted that the necessity of using the particular polyesterurethane foam that gave rise to the release of 2,4-TDA had not been demonstrated. MDA had reviewed evidence published up to 2000, including that considered by Lübbers (2000) (Annex 3) and the case series by Vázquez (1999) which is appended to Annex 4.

The report provided by Polytech Silimed to MHRA in July 2003 (Annex 4) presented evidence for a lower, quantifiable rate of capsular contracture with polyurethane-coated breast implants. This report summarised data previously considered by MDA and reviewed two additional case series (Hester et al, 2001 (appended to Annex 4) and Brunnert, 2003 (Annex 5)).

Questions for the CSD
The CSD is invited to consider the following questions:

1. Are the benefits from polyurethane-coated breast implants substantial in terms of clinical outcome in respect of:
   1. capsular contraction rates;
   2. aesthetic results?
2. Do the demonstrated benefits of polyurethane-coated breast implants outweigh the remote but unquantifiable carcinogenic risk, which has already been identified by the COC?
3. If polyurethane-coated breast implants were to be re-introduced to clinical use in the UK, what information on the risks and benefits should be available to:
   1. surgeons;
   2. women considering implantation;
   3. and what measures would be appropriate to provide this information?