asked questions

No long-term complications have been reported from over 70,000 women treated with Bulkamid since its introduction in 20031. As with any procedure, short-term complications may occur. However, these normally resolve within a couple of days after treatment. These can include post-operative pain, difficulty voiding, urgency, urinary infection, mild burning or bleeding during urination.

Due to the low rate of acute urinary retention following the Bulkamid procedure (0-5.7%)1, the majority of patients do not require self-catheterisation. When self-catheterisation is required it is only temporary (usually less than 24 hours).

There are no studies which specifically look at the use of Bulkamid in patients with a hypermobile urethra. However, no clinical trials have excluded these patients suggesting that a large proportion of patients with a hypermobile urethra are most likely included in existing studies and have shown good outcomes.

Patients can normally return to normal activities within 24 hours of the procedure, although heavy lifting, hard physical exercise and sexual intercourse should be avoided for up to 2-3 weeks.

The rate of de novo urgency has reportedly occurred in 0–3.6% of patients. The majority of publications report an incidence of between 0–1.5%, with the higher rate of 3.6% being reported in patients who had undergone a previous sling procedure prior to receiving Bulkamid.1

Plastics are synthetic materials (usually solid) made from a wide range of organic polymers such as polyethylene, polypropylene, PVC, nylon, etc., that can be molded into shape while soft, and then set into mostly rigid objects. Plastics possess a significant resistance to deformation, which in turn can cause stress in the interface between the solid plastic and the surrounding soft tissue, thus inducing  deformations of the native tissue. It is this rigidity that is thought in some cases to cause problems with mid-urethral tapes in terms of tape erosion and possibly pain.

Bulkamid is a hydrogel. Hydrogels are soft materials composed of one or more polymers consisting mostly of water. The Bulkamid Hydrogel consists of 97.5% water and 2.5% cross-linked polyacrylamide. All plastics are polymers, but not all polymers are necessarily plastic. Obvious examples of polymers not being plastic are polysaccharides and polypeptides. Hydrogels are easy to deform with practically no resistance to deformation with body movements, and their mechanical properties are compatible with native soft tissues and organs.

In short the answer is no there are no health risks linked to acrylamide with treatment with Bulkamid. Some animal studies have shown acrylamide to be carcinogenic and it is thought to possibly also be carcinogenic in humans, although this has not yet been evidenced. A recent report indicates that acrylamide found in the everyday diet does not pose a risk to most common cancers (Int J Cancer. 2015 Jun 15;136(12):2912-22). The debate is still open on whether there may be an association for some particular cancers.

By way of background, the US Environmental Protection Agency (EPA) indicated that for a general population the daily exposure to acrylamide is approximately 0.5-1 µg/kg/day (EPA/635/R-07/009F). Many common foods contain relatively high amounts of acrylamide, e.g. 1 g of fried potato chips contains 0.5 µg of acrylamide.

The Bulkamid Hydrogel consists of approximately 2.5% polyacrylamide and 97.5% water. Over the last 18 years, Contura has extensively studied and evaluated the safety of its hydrogel, in accordance with numerous international regulatory authorities. It is worth noting that the US FDA classify Bulkamid as a Class III device which puts it under a high level of regulatory scrutiny, unlike a polypropylene mid-urethral tape which is a Class II device and consequently requires a much lower level of regulatory testing.

The polyacrylamide in Bulkamid is a polymer made of distinct repeat units of acrylamide, where the monomers are bonded covalently by strong single bonds and cross linked to further strengthen its structural integrity. The polymerisation process being rigorously controlled and is based on many years of extensive engineering design and manufacturing practice. The cross-linked polyacrylamide is highly stable and is not cleaved back to monomers even under high mechanical or chemical stress. We have demonstrated this through well controlled studies. Mechanical stability studies have demonstrated the structural integrity of the Bulkamid Hydrogel to be able to withstand shear stress, when different levels of forces are applied, forces beyond what would be considered reasonable within the human body and particularly the normal sites of injection. An equivalent of a food blender was ultimately needed to break the Bulkamid Hydrogel to smaller, non-toxic constituents and even under this level of extreme physical force no increase in monomers of acrylamide were detectable. Chemical stability in highly oxidative (up to 20% hydrogen peroxide) and hydrolytic environments (as low as pH 2) have shown that the Bulkamid Hydrogel is chemically stable in vivo, i.e. that the Bulkamid Hydrogel withstands oxidative and hydrolytic stress well beyond normal physiological conditions.

Therefore, the only possible source of any acrylamide monomer in the Bulkamid Hydrogel would be residual monomer that remain following the manufacturing process. As part of the routine Quality Assurance release for every batch of Hydrogel produced, levels of acrylamide monomer are tested. The release specification for residual acrylamide monomer in Contura’s polyacrylamide hydrogels, as approved by EU and US FDA authorities, has been set at 1.5 µg/mL. Typically, the acrylamide levels in batch testing are < 0.6 µg/mL. Thus when considering an injected Bulkamid Hydrogel volume of 16 mL, a volume much higher than the 2 mL typically used in clinical practice, a maximum of 24 µg of acrylamide could theoretically have been injected into a single patient. Assuming a woman with a body weight of 58 kg, 16 mL injected would equate to a dose of 0.4 µg/kg. The EPA/Minnesota Department for Health cancer risk lifetime dose limit is 0.01 µg/kg/day. The total quantity of acrylamide in the 16 mL dose must be translated into a lifetime average daily dose (LADD). This is achieved by taking the dose of 16 mL and dividing it by the total days in a 70 year lifetime (~25,500). The LADD for the 16 mL residual acrylamide is 0.000016 µg/kg/day lifetime dose. Clearly, the LADD from residual acrylamide in 16 mL of Bulkamid is almost 1000 times lower than the lifetime daily cancer risk dose limit of 0.01 µg/kg/day. It is therefore reasonable to conclude that the maximum possible residual acrylamide exposure will not pose a toxicological risk to clinical subjects.

Thus, the amount of residual acrylamide in Bulkamid is negligible in comparison with daily environmental exposure and hence implantation of Bulkamid gives no increased health risk.

A variety of materials are commonly and safely used in medicine. Their safety and effectiveness depend on many factors which include quantity, intended use, placement as well as their physico-chemical characteristics and manufacturing process. Each of these parameters has a significant effect on safety and performance. Polyacrylamides differ considerably in their chemical and physical structure and hence their use cannot be commonly considered as the same.

Bulkamid is a hydrogel consisting of 97.5% water and 2.5% cross linked polyacrylamide. Manufactured at our facilities in Copenhagen, the process has been established over 20 years and inspections from international regulatory authorities take place regularly to ensure compliance and robust standards are maintained.

Safety in the body has been established through comprehensive biocompatibility and clinical testing in accordance with international and national regulations (EU and US) that are relevant for this class of device. Bulkamid is a Class III device in the US that is subject to a rigorous premarket clinical investigation and regulatory approval pathway. In comparison mesh products for urinary incontinence surgery are Class II devices in the US and undergo a less rigorous regulatory process.

Given the standards and testing that has been in place and the clinical experience over the last two decades, Bulkamid’s safety has been well established.

For a detailed list of biocompatibility testing requirements, see FDA guidance document Use of International Standard ISO 10993-1, “Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process”.

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