The challenge of clearing the regulatory and procurement hurdles between a bright idea and an innovative product in use may be daunting. However, Martin Goldman argues, it’s a challenge that brings out the best in the medical technologies sector.
I have just finished reading a bulletin from the Health Protection Agency, informing me that we may not witness swine flu Armageddon in the immediate future. While governments and big pharma figure out what to do with the millions of vaccine doses left over, it made me think about the great-grandfather of vaccination – Edward Jenner. Today he would be vilified in the press (well, he actually was then) for the use of unlicensed medicines – but he must have had some kind of device to scarify the skin, and it was probably not designed for that purpose. When I was a student, I met a doctor who told me he had specially grown one of his fingernails so that it could rupture the membranes of pregnant women to induce labour. I never saw him do it, and that was probably for the best.
Today, everything used in the delivery of healthcare is regulated to ensure the safety of patients by conformity to predetermined standards. That starts by defining all healthcare products in terms of their therapeutic or diagnostic purpose. Directive 2007/47/ec of the European Parliament and the council of 5 September, 2007 defines a medical device as “any instrument, apparatus, appliance, software, material or other article, whether used alone or in combination, including the software intended by its manufacturer to be used specifically for diagnostic and/or therapeutic purposes and necessary for its proper application, intended by the manufacturer to be used for human beings.” That may be a mouthful, but it is a useful statement. It is basically a ‘put up or shut up’ if you want to manufacture something and advocate its use for treating patients.
Additionally, it creates an interesting interface between medicines and their delivery systems. With the arrival of devices such as drug-eluting stents, which combine drug delivery and structural device functions, there is a clear need for careful consideration. There have been some well-publicised untoward outcomes with a few devices such as IUDs, prosthetic joints and heart valves, and it is therefore necessary that there should be a regulated process for the development of devices.
Concept to product
For most new devices, there is a process whereby an unmet healthcare need (or an untapped potential profit) is identified – either by an individual or in response to a generally held belief. Often there is an identifiable inventor: an academic or healthcare professional. Given a problem such as the need for a pain-free injection device, where there is an obvious need, a number of possible solutions may come to light in time. Some manufacturers actively court inventive minds, then bring their engineering, electronic and computing skills to bear on a proffered concept. Sometimes the inventor will get into bed with the manufacturer and develop a relationship for the lifetime of a product. The relationship may be driven by financial motives – though if the device bears its inventor’s name, that may be a further incentive.
For an embryonic medical device, the only chance of survival into maturity may be the involvement of organisations with sufficient funds to finance the development, testing and initiation of manufacturing and subsequent commercialisation. Much has been written recently about partnerships for the development and commercialisation of medical devices, and the involvement of academia in refining and validating the role of a device is a valued contribution to the commercial organisations.
If a device is an original concept or uses novel processes, it is very important to protect this intellectual property. Failure to do so will prompt copying and ultimately damage the chances of recouping investment, let alone making a profit. Again, this is a reason why funding is needed, as successfully filing and protecting patents is an expensive activity. Fledgling companies may run out of capital before realising their product; the hard side of the business is that there are always vultures circling for opportunities, and acquisitions are so frequent they are not always news.
Having said that, a company in the USA calls itself ‘Generic Medical Devices’, and its intention is exactly that: to produce cheap facsimiles of products out of patent that represent value for money. If you search on the Internet, a picture of its generic circumcision clamp can be found. Strangely enough, despite its being in the generics market, the company has patents attributed it!
Product to profit
The delivery of healthcare has become a highly regulated activity, especially in the western world. This is true of medicines, devices and the way that services are run (though the latter is regulated more by audit and inspection). For medical devices, unlike medicines, there does not appear to be a legal requirement for appropriately qualified individuals such as physicians and pharmacist to sign off documents and approve processes, so there is a clear need for structured guidance. It can’t be a free for all. Those involved in device development and production must have clearly defined responsibilities, be suitably trained, have knowledge of the regulations and have adequate resources to fulfil the directives.
In the UK, the Medicines and Healthcare Regulatory Agency (MHRA) conducts the regulation of medicines and medical devices (the latter having been added to its remit more recently). Lots of information about the regulation of devices can be found on the MHRA website at www.mhra.gov.uk/Howweregulate/Devices/index.htm. The rules are subject to the European Directive on Medical Devices – but as that is less easy to get your head round than the UK information, we will limit ourselves to the local context.
Many documents, regulations and guidelines are available here, but there is no one place where all the relevant information for developing and registering can be found: it is necessary to wade through many separate documents. There are independent consultancies that can assist device virgins with their first experience of putting a device on the market. The regulatory environment is fluid (because technology advances rapidly), and this means that sections of the guidelines and regulations are constantly being updated. The MHRA has undertaken, in line with the recommendations of the Hampton Report (2005), to keep its guidance documents under constant review.
A good starting point is Bulletin 8, which provides information about the European Medical Devices Directive (from the MHRA viewpoint). It explains the intentions of the directive and covers topics such as the classification of devices, the CE Mark and the competent authority and notified bodies. Bulletin No. 2 covers CE Mark approval, which means that a device may have access to the whole of the European Community market without any further need for compliance with national approval systems. This is leagues away from the complex ways in which medicines are centrally approved and are handled within the community.
Bulletin 10 covers the classification of devices covered by the Directive into 4 areas: Class I (low risk), Classes IIa and IIb (medium risk) and Class III (high risk). The bulletin outlines a number of rules, e.g. that any non-invasive product belongs to Class I if other rules do not apply. For a supplier of devices, being able to claim Class 1 means it is subject to the least obligation for supply of information and documentation. At the other end of the scale, a Class III device may require clinical investigation before marketing. This is the subject of a document, ‘Guidance for manufacturers on clinical investigation to be carried out in the UK’ (updated September 2009).
One of the most useful documents is Bulletin 17, which sets out in broad terms the regulation of specific products and helps to clarify the distinction between medicines and medical devices. A device (such as a drug-eluting stent) whose function involves a medicinal content falls into a more highly-regulated division of devices. The bulletin offers a helpful annex listing areas of doubt and offering guidelines as to whether something is a device or a medicine. This can be confusing to the uninitiated, and the arbitrary-seeming division of dentistry products may serve as an object lesson.
Talking cure
One of the things that make the medtech industry attractive in this country is that a company may make promotional claims about a device and not be subject to the same level of legal restriction as for medicines. That is not to say a company would advertise a new hip prosthesis in the Daily Express – but the relationship with healthcare professionals is less constrained, and there is less need for an approval process that prolongs the time from agency concept to printed materials.
The ABHI Code of Business Practice is like a very watered-down version of the guidelines for medicines, and relies on self-regulation rather than sanctions. For this reason, some companies that have been hindered by legislation and guidelines on medicines are now looking at whether their products could be classified as medical devices. Similarly, the pricing issues and regulatory schemes do not apply in the same way; and for a class I device, arguably, there is no need for the involvement of a healthcare professional if a patient purchase is intended.
A bright future
The role of medical technologies in our healthcare is increasing all the time. Their development and provision need to follow an agreed structure and set of regulations in order to protect the public. There are many regulations, but it is difficult to round them up in one place.
Even so, the regulations are easier to deal with than those governing medicines – and once they are negotiated, the commercial possibilities in Europe are great. The medtech industry has a bright future, as long as its activities transparently reflect the fact that the wellbeing of patients is the highest priority.
Dr Martin Goldman qualified in medicine and practised initially in hospitals. He has worked in the pharmaceutical industry for over 25 years, and has been involved in a wide variety of medical department activities – including the recent development of a dry powder inhalation system to deliver antibiotics to the lungs.
The role of medical technologies in our healthcare is increasing all the time. There are many regulations, but it is difficult to round them up in one place. Once they are negotiated, the commercial possibilities in Europe are great.