Dear Dr. Feigal:

I have conducted studies on saline inflatable breast prostheses for more than twenty years and have published on medical devices extensively. I was associated with the Canadian counterpart of the CDRH as Senior Scientific Advisor up to my departure in 1989. I continue to study these products.

At the request of Ms. L. Bodtke of 7938 Pipers Path, Glen Burnie, MD, 21061, the following comments pertinent to the Final Rule on the Requirements for Premarket Approval of the Silicone Inflatable Breast Prosthesis (21 CFR Part 878) are provided. The comments are based on findings from studies I have conducted singly and jointly with other research groups.

The need for mandatory filing of premarket approval applications (PMA) and/or Notice of Completion of a Product Development Protocol (PDP) for this class of product is clearly demonstrated in the light of performance shortfalls and the alarming pattern of adverse reaction.

Field reports on failures and adverse reactions from saline inflatable prostheses are not comprehensive. There is a history of underreporting which has worsened significantly since 1993. Therefore, field report data do not realistically assess the extent or severity of complications.

Published information is sparse and incomplete. There is suppression of information regarding untoward events and service failure of the items. Any committee engaged in review of safety and efficacy of saline inflatable prostheses will not have access to all data; much of it is unpublished. Thus they will not be able to derive informed conclusions and policies without access to implant retrieval programs and independent laboratory studies.

Amongst all commercially made saline inflatable prostheses, there is not one currently in use which could be construed as being substantially equivalent to a product made before May 28, 1976. This view is confirmed in current manufacturer advertisements and promotional material to physicians where the products are claimed to be novel and significantly different from what was made previously.

The most frequently discussed complication of saline inflatables is capsular contracture. Some consider the problem 'normal' and unworthy of special mention in the context of adverse reaction reporting. This distorts the perceived risk of the product.

Saline inflatable implants incorporate filling valves which have been at the center of controversy in FDA Classification Panels and review committees since the late-seventies. Security of these valves and reliability of closure are key problems unresolved to this day. Whereas such a gap in the technology could be perceived as 'accidental' or the result of insufficient research and development, there is emerging evidence that valve leakage was intentionally sought so as to support tenuous claims of control of capsular contracture. This issue appears in the literature and in patents.

The incorporation of a non-secure filling valve which allows unpredictable bidirectional fluid flow in a permanently implanted saline-filled device is a major safety concern. Egress of fluid leads to loss of volume and eventual deflation requiring replacement. Users are therefore compelled to undergo additional surgeries with major attendant risks. Ingress of body fluids within the implant causes accumulation of denatured proteins and adventitious micro-organisms within the filling charge. The unreliable valve subsequently discharges the contaminated fluid exposing users to these substances. The leakage of fluids containing denatured autologous proteins and viable micro-organisms which coexist in the mixture has predictable systemic consequences.

Long term saline inflatable implant use is associated with mineralization of the surrounding tissue. The problem affects at least 30% of users within ten years. In the late part, calcification phenomena affect the elastomeric material which is penetrated, swollen and rendered porous by the process. This has been noted in saline inflatable prostheses for more than twenty years. The mechanism is related to base-initiated hydrolysis of the silicone elastomer at an elevated intracapsular pH which prevails in long term users with calcific deposits.

Mineralization or calcification of tissue around such devices is a fundamental and unavoidable process caused by a combination of trauma from continuous movement of the prosthesis against the surrounding tissue. It is exacerbated by chronic denaturation of intracapsular substances. The effect is progressive and may affect all users of the technology. Formation of abrasive material at the interface between tissue and implant is noted widely. Excoriation of the shell against the mineralized tissue leads inevitably to perforation and leakage. It is not a 'risk' - it is a certainty.

Erosive action from calcified capsules and from mutual contact of shell material at shell folds produces fine particles of silica-rich elastomer with exposed silica. This debris is analogous to that produced by Swanson type joint implants. Fine particles with systemic inflammatory properties disperse in the implanted area and eventually spread throughout the lymphatic chains initiating systemic phenomena, as noted for the finger joint prosthesis (21 CFR 888.3230).

Current devices obtained at explantation show a large ratio of items that incorporate serious manufacturing defects. The defects are obvious and would have been unavoidably noted by competent Quality Assurance services. Widely encountered defects include improperly dimensioned valves which do not mate accurately and where closure is not possible. Such valves are generic commodities and are fitted to different types of saline inflatable implants. Consequently, the same valve defects are encountered in many types of implants made by different facilities. These findings support the need for 'Dear Doctor' letters and related memoranda addressing the valve problem.

Perforated or leaky implants deflate and refill gradually with fluid and biological material from the user. Statistically, microbiological contamination of the fluid is inevitable within several weeks. The protected environment with nutrients makes the fluid ideal for colonization. Thus, a deflated implant is a clear and present danger. Prompt surgical removal of such an entity must be addressed in the context of user safety. It is not a cosmetic or elective issue and is worthy of a 'Dear Doctor' letter.

Product Insert terminology on adverse effects is misleading. Adverse events are presented as rare and random occurrences. Studies on explanted devices reveal otherwise. They confirm that complications result largely from manufacturing defects, design inadequacies and time dependent changes in constituent materials. Thus, with time, adverse events are inevitable. The short service life of some saline inflatable prostheses is therefore predictable. The inevitability of removal and/or replacement as well as risks from a retained deflated implant must be addressed explicitly.

Rupture followed by immediate deflation is not the prevailing mechanism of failure. Instead, it is the slow deterioration of the shell followed by rapid or progressive unprovoked leakage which may appear benign to the user. Medical attention is thus likely to be delayed exposing the user to greater yet more subtle risks such as infective phenomena from the release of colonized saline. Recommendations in accordance with this must appear in the documentation.

Material intended for distribution to prospective users and frequently incorporated in promotional brochures describe the aqueous filling material as a harmless substance which will not adversely affect the user should leakage occur. Such claims are misleading. Sterilization processes used by the implant industry do not support claims that there can be no viable entities within saline inflatable prostheses at the outset. Even if absolute sterility is achieved fortuitously, subsequent handling and intrasurgical filling would lead inevitably to inoculation by viable entities from the surgical field.

Instructions for use allow filling of a device in situ via a cannula-bearing tube. Manual closure of the valve completes the filling procedure. This manipulation is performed within a blood infiltrated surgical field where there can be no reliable control on sterility. Blood and plasma proteins become entrapped within the valve mechanism during decoupling of the filling tube, providing nutrients for viable entities. Most valve mechanisms are incompetent from the outset. Many have no capacity to seal. They rely on bidirectional 'pumping action' to maintain the volume of the prosthesis. These features ensure the presence of inoculae and nutrients in large quantities within the saline charge.

Private plastic surgery clinics with only basic infection control are the usual environment where saline inflatable prostheses are inserted. There is no capacity to achieve the required level of microbiological safety in such an environment. Reliance on antibiotic cover explains the comparative paucity of infective episodes at these facilities when surgeries do not involve implants. However, antibiotics are not well suited to control infective processes where implants are concerned, least of all for micro-organisms dispersed within the protected saline charge.

Extemporaneous use of pharmaceuticals in saline-bearing prostheses continues unabated, antibiotics and anti- inflammatories being the preferred additives. Product Inserts are silent or non-committal on this issue. In peripheral documentation, the practice is presented as a benign risk to shell integrity. Hazards associated with denatured pharmaceuticals colonized by adventitious micro-organisms are not discussed. The practice of extemporaneously medicating the saline charge must be explicitly contraindicated. It is contrary to basic concepts of pharmacology and drug use.

There is a basis to explicitly contraindicate breastfeeding for all saline inflatable implant users. The recommendation is strongly supported by observations that nearly all devices of this kind explanted to date show evidence of colonization of the saline charge after as little as one year of dwell time. With the knowledge that valves are, on average incompetent or leaky by design, it is reasoned that users will suffer sustained low level infections. In turn, the ongoing silent infective processes and colonization of the breast tissue will contribute to drastic diminution of quality of the breast milk. Risk of mastitis will be enhanced and may require supplemental medical treatment.

Risks to infants from breast milk contaminated by low level infective processes are not documented. It is contrary to common logic to assume safety of breast milk derived from bearers of leaky saline inflatable prostheses containing colonized aqueous fluids. Furthermore, breast engorgement followed by lactation has disruptive effects, even on non-augmented breasts. For an unstable augmented breast where severed ligaments and reattached muscles are often present, there are strong risks that the cosmetic effect for which the procedure was done will be lost thus motivating the user to undergo more corrective surgery with attendant risks.

It is acknowledged that radiographic assessment of augmented breasts for tumor detection is subject to false negatives and is of minimal diagnostic value except for users with palpable, highly calcified tumors which would not require the procedure in the first place. Radiodense structural elements of saline prostheses introduce artifacts, reduce contrast and often shield otherwise radiodiscernible tumors. The converse phenomenon is not widely acknowledged.

Calcification of the periprosthetic space after a dwell time of 5-7 years introduces periprosthetic artifacts which can mimic tumors with punctuate or stellated microcalcifications. Thus, the value of radiographic studies for tumor detection is compromised both by false positives and false negatives. Special techniques such as the displacement/compression (Eklund) technique introduce risks of their own. The processes may cause avulsion of valve closures or introduce sufficient stress to propagate shell defects at pleats.

The foregoing information may assist you and FDA staff in the development of PMA guidelines. I believe it is urgent to publicize the requirements that will be demanded of inflatable prostheses that may remain in commerce. It is equally urgent to advise potential users of the hazards that the items pose. Similarly, current users must be made aware regarding the properties and the insidious risks that these devices present after 4-5 years in situ. Users of saline inflatable prostheses must be made aware that they are at significant risk for well-defined simple but difficultly treated systemic disturbances which worsen with time.

The hazards of saline inflatable prostheses result partly from poor manufacturing practices. Some are easily understood from simple mechanical and anatomic considerations. However, these issues are overshadowed by fundamental microbiological considerations. The proliferation of atypical micro-organisms within large intracorporeal fluid-filled cavities subject to rapid discharge is not immediately apparent. In simple terms, the environment created by current saline inflatable prostheses is analogous to that from large volume abscesses. Studies regarding the impact of chronic abscesses predate World War II. Such risks have been hidden for more than thirty years by segments of the industrial and medical communities involved in plastic surgery products.

I will be pleased to provide supplemental briefings if required.