Law and the Regulation of Medicines

Emily Jackson

• Publisher: Hart Publishing
• Year: 2012
• ISBN:
  9781847319098
• Edition: 1
• Topic: Law
• Subtopic: Medical Law
• Index: Law

The principal purpose of this book is to tell the story of a medicine's journey through the regulatory system in the UK, from defining what counts as a medicine, through clinical trials, licensing, pharmacovigilance, marketing and funding. The question of global access to medicines is addressed because of its political importance, and because it offers a particularly stark illustration of the consequences of classifying medicines as a private rather than a public good.
Two further specific challenges to the future of medicine's regulation are examined separately: first, pharmacogenetics, or the genetic targeting of medicines to subgroups of patients, and second, the possibility of using medicines to enhance well-being or performance, rather than treat disease.
Throughout, the emphasis is on the role of regulation in shaping and influencing the operation of the medicines industry, an issue that is of central importance to the promotion of public health and the fair and equitable distribution of healthcare resources.

1

What are Medicines and why are they Special?

OBVIOUSLY, THERE ARE points of similarity between the design and manufacture of pharmaceutical drugs and other products. Computer manufacturers are also under considerable commercial pressure to come up with new and improved computers, and novel technological gadgets. Like drug companies, they must continually innovate in order to remain profitable. The food industry makes products for human ingestion, and, in common with the pharmaceutical industry, its reputation will be badly affected if an unsafe product causes its consumers to become ill.¹ Despite the existence of similarities with other industries, one of the key assumptions underlying this book is that there is something distinctive about medicines which necessitates a special regulatory regime.

This chapter begins by examining, in very general terms, what it is that makes medicines special. Next, it considers how medicines are defined by law, and the difficulties that can sometimes arise in telling the difference between medicines and other products, like vitamin supplements and homeopathic remedies. The line the law attempts to draw between medical and non-medical products depends both upon the claims made for a product’s efficacy, and upon the nature of the substance itself. Complementary and alternative medicines are subject to a special regulatory regime, where the burden of proof of efficacy is different from that which applies to conventional medicines. This chapter will conclude by arguing that the reasons which justify treating medicines differently from other products apply whenever someone claims to be able to cure disease or relieve symptoms, and that, as a result, purveyors of alternative medicines should either have to prove effectiveness in the same way as manufacturers of conventional medicines or stop making medical claims for their products.

I Why Medicines are Special

The claim that medicines are unlike other products has two components. First, there are the intrinsic properties of medicines, which must be powerful enough to alleviate symptoms or alter disease progression. Any compound which is potent enough to have these positive effects may also be potent enough to cause adverse side effects in some users. Even common and generally safe drugs like aspirin are not safe for everybody: in children, aspirin can cause Reye’s disease. And treatments for life-threatening diseases, like cancer, are so toxic that they cause extremely unpleasant side effects in almost everyone. The sort of risk-benefit calculation that makes it acceptable to market a drug which has very serious side effects, even when taken exactly according to instructions, would not make sense in relation to other products for human ingestion. A substance which is inert enough never to cause adverse side effects is also likely to be too inert to cure disease. If every licensed medicine had to be wholly safe for the entire population, there would be few treatment options available. The question then becomes whether a medicine is safe enough to license for use in humans, rather than whether it is 100 per cent safe for everyone.

The second and related aspect of the claim that medicines are special relates to how they are purchased and used. Here there are important differences between medicines depending upon how consumers obtain them. Some medicines require a prescription written by a doctor or a nurse prescriber; others can be purchased, but only in a pharmacy staffed by a qualified pharmacist; others are available for general sale, in pharmacies but also in supermarkets and convenience stores. Chapter three considers this subdivision in more detail. For now, the important point is that general sale medicines, like paracetamol and ibuprofen, are not that different from other consumer products. People can purchase and take them without the intervention of a professional intermediary. Limits on packet size and on how many packets may be purchased simultaneously are intended to discourage overdose, but it is clear that these are ineffective obstacles to someone who is determined to obtain large quantities of, say, paracetamol. The local chemist may only be prepared to sell me two packets of sixteen tablets, but I could very easily visit a number of other shops in order to amass sufficient pills to cause serious harm to myself.

Pharmacy medicines are subject to slightly more control. For example, the sale of a commonly used pharmacy-available sleep-aid will be accompanied by a reminder that it is for occasional use only. Where there is a contraindication to the use of a pharmacy-available medicine, the pharmacist will be able to ask the customer whether they have diabetes, say, or high blood pressure. Of course, the pharmacist is not able to insist upon proof that the person buying the medicine is telling the truth, so this level of control, while more intensive than that which exists in relation to general sale medicines, is still imperfect. This means that where medicines are available for sale in pharmacies, they should not be so unsafe that there are likely to be very serious consequences if they are used either by people with contraindications, or more frequently than is advisable.

It is the category of prescription-only drugs which are sold, purchased and consumed in a wholly different way from any other consumer product. When a medicine is prescribed by a doctor, the person who makes the purchasing decision is not its ultimate consumer. A person may visit their doctor and ask to be prescribed antibiotics or sleeping pills, but they have no right to a prescription. If the doctor believes that antibiotics would be useless, or that sleeping pills might be used in order to take an overdose, the patient is likely to leave the surgery empty-handed.

In addition, in relation to prescription medicines, the medicine is paid for neither by the person who makes the purchasing decision, nor by its ultimate consumer. The vast majority of patients in the United Kingdom pay nothing for their medicines. Prescription charges have been abolished in Wales, Northern Ireland and Scotland, and in England, because children, the elderly and the unemployed are exempt, only a minority of patients actually pay the prescription charge. Even for those English patients who do have to pay £7.40 per prescription, this will commonly be a fraction of the real cost of the drugs, which are funded instead through the NHS budget, and ultimately through general taxation.

Doctors decide which drugs to prescribe, but they do not pay for them. Patients do not decide which drugs they are prescribed, and again, they will rarely pay the full cost. Of course there are other situations when people buy things for others’ consumption, but it must be admitted that in the context of prescription drugs, normal market relationships between manufacturers of products and their ultimate consumers are distorted, to say the least. In chapter five, this issue will be revisited in relation to the implications it has for advertising and marketing.

Doctors act as the gatekeepers to prescription medicines, and this is important in relation to the risk-benefit calculation that must be carried out when deciding whether a medicine is safe enough to be licensed for use in patients. If a medicine is effective in curing a very serious condition, but known to cause terrible side effects in some users, doctors should, in theory, be able to ensure that it is prescribed only to people in whom it can be used safely. An extreme example might be the drug thalidomide, which was withdrawn from use after evidence emerged that it caused extremely serious birth defects. In recent years, there have been indications that thalidomide can be effective in the treatment of leprosy and certain cancers. Its side effects mean that it is unthinkable that thalidomide would ever be available ‘over-the-counter’, but the doctor as intermediary is able to ensure that its use is limited to people who are gravely ill and who are informed in clear and direct terms that they must not expose themselves to even the smallest risk of pregnancy while taking the drug.

Of course, while the prescription system should enable a high level of third-party control over the consumption of medicines, the rise of online pharmacies poses a new challenge to what has been called the ‘learned intermediary’ rule.² If you type ‘buy Valium’ or ‘buy Ritalin’ into Google, there is no shortage of sites, frequently based offshore or with no information about their location,³ offering prescription-only medicines for sale and shipping without a prescription. Indeed, ‘buy Viagra without prescription’ comes up with 20.9 million hits on Google.

Although there are certainly examples of good practice in online pharmacies,⁴ and they may be especially attractive to patients who find their symptoms embarrassing,⁵ one of the principal reasons for a drug being ‘prescription-only’ is precisely that self-medication is inappropriate, usually on safety grounds. There is evidence that some online pharmacies are willing to supply medicines to patients in whom they are clearly contraindicated. Eysenbach, for example, found it remarkably easy to obtain Viagra online, despite pretending to be an obese 69-year-old woman suffering from coronary artery disease and hypertension.⁶ Online pharmacies are also helping to blur the line between illegal drugs and prescription medicines. As discussed further in chapter nine, prescription painkillers are increasingly used for recreational purposes, rather than to treat symptoms.⁷ This trend is undoubtedly facilitated by the existence of websites where it is possible to buy these drugs anonymously, without a prescription.

II The Development of a Special Regulatory Regime for Medicines

The use of plant and animal preparations to treat disease and relieve symptoms has a very long history, dating back (at least) to the fourth century BC, when the Sumerians used plants like liquorice, mustard, myrrh and opium in the treatment of disease. Aspirin, a very commonly used analgesic, is also a very old drug. Two thousand years ago the bark and leaves of the willow tree (which contain salicylic acid, the active ingredient in aspirin) were widely used in Greece in order to alleviate pain and fever.⁸

The regulation of medicines in the UK probably began in the fifteenth century, and was limited to inspecting the premises of apothecaries and their wares in order to ensure that they were not defective or contaminated.⁹ Another early regulatory technique was the publication of a pharmacopoeia, a book which contains a list of pharmaceutical products and sets out their prescribed formulae and methods of preparation. The Pharmacopoeia Londinensis was published in 1618, and the British Pharmacopoeia, now produced by the British Pharmacopoeia Commission Secretariat of the Medicines and Healthcare products Regulatory Agency (MHRA), is still the official collection of standards for UK medicinal products and pharmaceutical substances.¹⁰

More recent regulation of the supply of medicines has taken a number of forms including restrictions on who may supply medicines: the Pharmacy Act 1868 contained a list of drugs, including opium, which could only be sold by pharmaceutical chemists and the Dangerous Drugs Act 1920 further restricted supply, by specifying that some drugs could only be supplied on prescription.

In the 1950s, thalidomide’s UK manufacturers, Distillers, claimed that it could ‘be given with complete safety to pregnant women and nursing mothers without adverse effect on mother or child’.¹¹ Unfortunately, this claim was wrong, and between 1956 and 1961 12,000 children were born in over 30 countries with very severe limb and other birth defects. One-third of these ‘thalidomide’ babies died within a month. Although interest in regulating the safety of medicines existed before the thalidomide tragedy, there is no doubt that in the UK it played an important part in the drive towards the regulation of the safety and efficacy of medicines, in addition to their quality. The Medicines Act 1968 was the result, and, as amended, it continues to apply today. Its role in the licensing of medicines is considered in detail in chapter three.

Before the Medicines Act came into force in 1971, regulation of the supply of medicines was limited to control over their quality, and did not address questions of safety or efficacy.¹² It might be thought that ‘quality’ and ‘safety’ are essentially similar requirements – and hence that the pre-1968 system of regulation went some way to protect patient safety. There can, however, be an important difference between quality and safety, as illustrated by the US experience with Elixir Sulfanilamide. Sulfanilamide had been used successfully to treat streptococcal infections. Responding to demand for the drug in liquid form, in the 1930s its manufacturer’s chief chemist discovered that sulfanilamide would dissolve in diethylene glycol. Raspberry flavouring was added, and the new medicine – Elixir Sulfanilamide – was widely marketed. Unfortunately, while there was no doubt as to the quality of the ingredients, diethylene glycol is poisonous, and Elixir Sulfanilamide killed more than one hundred people, many of them children in whom it had been used to relieve sore throats. This incident prompted the instigation of safety-based medicine requirements in the United States in 1938, and this – along with the stoic refusal of one Food and Drug Administration employee, Frances Kelsey, to approve thalidomide¹³ – helped the US to avoid the thalidomide tragedy which occurred, mainly in Europe, three decades later.

III What is a Medicine?

The Medicines Act 1968, and the series of EU Directives which have been incorporated into UK law since it came into force, apply only to medicinal products, and it is therefore critically important to be able to tell when a substance is and is not a medicine. While there is a clear and obvious difference between a blister pack of antibiotics and a lettuce, sometimes the line between foodstuffs and medicines is much less clear. Dietary supplements often look like medicines – they often come in the form of pills and capsules – and people generally take them because they believe they will have a positive impact upon their health. So how do manufacturers tell whether or not the product they wish to market is a medicine, and hence requires a marketing authorisation based on proof of quality, safety and efficacy, or whether it is a foodstuff, and hence subject to food safety regulations which are concerned only with safety and hygiene?¹⁴

‘Medicinal products’ are defined in the Codified Pharmaceutical Directive, as amended,¹⁵ as follows:

(a) Any substance or combination of substances presented as...

Table of contents

• Cover
• Title
• Copyright
• Acknowledgements
• Table of Contents
• Preface
• 1 What are Medicines and why are they Special?
• 2 Clinical Trials
• 3 Licensing
• 4 Pharmacovigilance and Liability for Dangerous Drugs
• 5 Marketing
• 6 Funding and Access to Medicines in the UK
• 7 Funding and Access to Medicines: A Global Problem
• 8 The Future of Medicines I: Pharmacogenetics
• 9 The Future of Medicines II: Enhancement
• Concluding Remarks
• Bibliography
• Index