Victor Woolf (Royal College of Surgeons Examinations Assessor)
Yolanda Woolf (Risk and Governance Consultant, Ret. NHS Associate Director, Governance, Risk and Compliance)
It has long been recognised that there is a significant group of patients that would benefit from direct to bladder delivery of medication. This ranges from antibiotics for acute and chronic bladder infections, to chemotherapy for bladder tumours, to bladder overactivity/hypersensitivity in patients with spinal cord injury/Multiple Sclerosis/Motor Neuron Disease etc.
With no other alternative, Foley and 3-way catheters are currently being used to instil direct to bladder medication through a channel intended for urine drainage or bladder irrigation. This practice began because there is currently no single universal device designed and MHRA/FDA approved to accommodate safe instillations/medication direct to bladder, drainage and irrigation.
Instillation via a contaminated catheter channel increases risk of introducing infection and inaccurate medication dosage reaching the target. Clinicians that use unapproved and untested off-licence medical devices are required by the MHRA to proactively assess and balance the risks and benefits of off-licence catheter use for each patient, consider the ethical and legal implications, review the risks and gain approval from the MHRA to use the device off-licence for direct to bladder instillation.
The potential for litigation is real and increasing, as the use of catheters off-licence for direct to bladder instillation with associated risks, become more widespread without clinicians following MHRA guidance.
The only alternative to direct to bladder medication delivery, is systemic drug administration either orally or intravascularly. These indirect routes require the medication to circulate around the body, arriving at the bladder through the blood or urine with known risks of systemic side effects such as diarrhoea, toxicity and alteration of the drug, as well as unpredictability of drug dose received at the target.
The Uropharma direct to bladder universal drug delivery device addresses the off-licence use of catheters and systemic drug administration risks yet keeps the basic familiarity of a catheter with a drainage channel and balloon to retain the device in the bladder. The fundamental design change introduces a revolutionary dedicated drug delivery channel with non-return valve and the facility to close the drainage channel at the catheter tip, making this a safe and effective universal medication direct to bladder, drainage, irrigation and drug delivery technology. During extensive background research and development of the direct to bladder technology, several previously accepted (micro)anatomical, physiological and pharmacological principles have been challenged and updated as well as potential new / novel compounds for instillation encountered and are being developed. Absorption systemically from the bladder for the compounds being considered for direct to bladder instillation have so far, proved to be minimal, reducing side effects.
The direct to bladder drug delivery technology has far reaching potential to improve quality of life, reduce risk and open new opportunities/markets for alternative instillations for the treatment of a wide range of bladder conditions. This expected to be ‘game-changing’ technology, bringing fringe methods safely into mainstream effective practices.
With a dedicated, approved device available for delivery of compounds direct to bladder, new treatment options will be developed with the benefit of knowing that they are being delivered appropriately and safely. We expect that the pharmaceutical industry, clinicians and patients will welcome the opportunities that this new drug delivery technology and new treatments will offer.
Laurence Stewart MD FRCSEd FRCS(urol)Ed (Consultant Urological Surgeon)
Prior to 1971 the very idea of placing a urinary catheter into the bladder without using an aseptic technique was considered not only dangerous but an act of medical malpractice. But following the pioneering work of Jack Lapides this all changed and patients were actively encouraged to self catheterise to empty their own bladders if they were unable to void spontaneously. This new freedom of access to the bladder led to the introduction of delivering drug therapies directly into the bladder to treat bladder cancer, interstitial cystitis and in some off label studies anticholinergic drugs to treat overactive bladder.
These agents were all instilled into the bladder using the simple single lumen catheters available at that time. This meant that following drainage of urine from the bladder, sterility was broken and the same, now contaminated, channel was used to instil the agent of choice. Also as the volume of the catheter channel is by necessity relatively large to facilitate urine drainage, a significant volume of the instilled agent does not reach the bladder and the dosage delivered is imprecise. As there was no alternative, little or no consideration was given to these problems.
But with the introduction of Uropharma’s intravesicle drug delivery system all this has changed. This catheter allows for bladder emptying via a large drainage channel, which is then closed off prior to drug instillation via a second small lumen (small volume) channel without breaching sterility or instilling via a contaminated channel. The small volume channel (of known volume) also allows for accurate dosage of the drug delivered.
When this intravesicle drug delivery system becomes commercially available it will no longer be acceptable to use single lumen catheters for this purpose and I would expect that the regulatory authorities would rapidly move to outlaw their use.
Dr Edmund Bonikowski FRCP MRCGP MPhil (Cantab)
Consultant in Rehabilitation Medicine & Chairman
UroPharma's drug-delivery technologies undoubtedly will enable urological medicine to advance more effectively than is possible with standard oral and systemic treatments.
This is because targets for treatment will be hit directly, and the technologies provide the means for doing so. By fulfilling all the relevant criteria for medical devices intimately used with and by patients you assure the comfort of regulatory agency approval.
With your platform technologies, it appears you are well positioned to solve many different urological problems. From my own clinical experience, it is clear that many millions of people will benefit greatly.
I anticipate that both drug discovery and generic provider pharmaceutical companies, in order to add value to drugs in their own portfolios, will embrace your approach and therefore your business. This will be achieved through repurposing as direct-to-bladder instillations.
The commercial potential of many such drugs could be very substantial to many companies. However, the commercial potential to UroPharma in providing the technologies to all of them must be enormous.
Your innovative approach and progress to date in advancing urological medicine in such systematic, scientifically sound and commercially sensible ways deserves hearty congratulations. Therefore, I am pleased to provide this testimonial to UroPharma and you.
Dr Govind Chavada
Consultant Neurologist with Special Interest in MS and Inflammatory Neuropathies
NHS Practice: Queen Elizabeth University Hospital, Glasgow
I offer this as testimonial to the vitally important work UroPharma’s team have undertaken to bring intravesical therapeutics into general use. I expect it to bring wide-ranging benefits, but as a specialist neurologist in multiple sclerosis (MS) I offer comments on particular benefits I see for MS patients.
For people who use catheters, so common in MS, directly targeting the relevant receptors that account for urinary urgency offers safe, effective and side-effect free treatments that can be easily delivered with your devices. The unreliable, side-effects rich oral antimuscarinic treatments (OADs), may finally be consignable to the dustbin of history.
OADs, so long the first-line recommended drug class for treatment of neurogenic lower urinary tract symptoms (NLUTS), have been shown to cause cognitive impairments in MS as well as in the elderly. Prior to the research this had been poorly appreciated, because progressive cognitive decline is a common feature of the disease itself, with the causes indistinguishable clinically. The intravesical approach, by utilising the bladder’s barrier features, can enable effective symptom relief while avoiding this iatrogenic complication.
Symptoms and disabilities worsen in people with MS when their bodies become heated. This is called Uhtoff’s phenomenon. The OADs impair sweating, so predispose people to this condition. Your approach also should eliminate this problem with their bladder treatments.
In MS, the effects of urinary tract infections (UTI) typically are generalised. A UTI can produce e.g. weakness and mobility loss, blurred vision, overwhelming fatigue and slurred speech. These temporary effects can be protracted even long after the infection has resolved. UTI also predispose to disease progression.
Unfortunately, MS makes UTI common. They are the commonest cause of acute hospital admissions of MS patients.
Over the years oral antibiotics generally have become less effective with treatment failure and recurrent infection rates increasing. For MS patients both can be devastating. Your direct approach to tackling catheter associated UTI with intravesical gentamicin, already seen to be working well with recurrent UTI, should be a great contribution to reducing their suffering. Patients as well as my colleagues will wholeheartedly welcome this innovation.
Your intention to bring these innovations to clinical medicine through the specials route is a superb initiative.
That should start to raise treatment success rates quickly for both NLUTS and UTI. With your follow-on plans to obtain market authorisations for both intravesical trospium and gentamicin, in time it also should do so very substantially.
I wish you all strength in pursuit of these developments and best of luck to the company.