Feature

A licence to print money?

John Abraham reports on how the ‘Europeanisation’ of regulation and licensing for marketing new medicines is profit-driven, unaccountable and a threat to public health

Before new medicines reach the prescription pad, they must first be approved by the appropriate regulatory authorities, which assess their safety and efficacy.

Recently drug regulation has undergone radical Europeanisation with some worrying implications for drug safety and public health. This is part of a political trend that began 20 years ago. The Thatcher government in the UK started the ball rolling in the early 1980s by reducing the Department of Health’s regulatory requirements for the approval of clinical trials.

In 1989, the government’s Medicines Division became semi-autonomous from the Department of Health and lost its state funding. Unlike its predecessor, the new Medicines Control Agency (MCA) did not receive half its income from the Treasury via taxation, but instead became almost wholly dependent on fees paid by pharmaceutical companies in exchange for regulatory services. Most other EU countries adopted this model to a greater or lesser extent during the 1990s.

To facilitate a single European market in pharmaceuticals, the European Commission established a ‘mutual recognition’ procedure for most drug regulation between EU member states in 1995, and a ‘centralised’ procedure for the regulation of drugs which are based on biotechnology or are highly innovative, such as Viagra.

Under mutual recognition, if a drug company wants to market a drug in more than one member state, the first state to approve the drug becomes known as the reference member state (RMS), which then seeks to obtain agreement of its approval from the other member states in which the company wishes to market the drug. If mutual recognition proves impossible, then there is supranational arbitration by the Committee for Proprietary Medicinal Products (CPMP), which comprises expert regulators from each of the EU countries. The CPMP’s decision is binding.

The lion’s share of licensing fees from the company goes to the RMS and companies favour regulatory agencies which approve drugs quickly because it promises faster market entry. As a result, this mutual recognition procedure has created an internal EU market in which national regulatory agencies compete for the fastest approval times, to maximise their income from pharmaceutical companies.

In 1995, the European Medicines Evaluation Agency (EMEA) was set up to administer the centralised procedure. Marketing approval under this procedure is through a single application to the EMEA. An EU-wide licensing opinion from the CPMP is triggered as soon as a company seeks approval for an appropriate product in one member state. Although the EMEA chooses the rapporteur from the CPMP, whose national regulatory agency undertakes the initial assessment of the application, companies can express a preference which is usually respected. Hence, rapporteur status also provides additional work and income for national regulatory agencies which means they have an incentive to be chosen by companies to be rapporteurs.

To complete this Europeanisation, the possibility of parallel national applications for new drugs was abolished in January 1998, so that national licences for new medicines have disappeared, except for drugs to be used in only one member state (so-called local markets).

A major public health concern regarding these new regulatory systems is that they put pressure on national agencies to ‘sell themselves’ to pharmaceutical companies as the fastest in reviewing and approving drugs. As one regulator at the Swedish Medical Products Agency commented: ‘I’m a bit concerned when I see agencies like the MCA market themselves as being the quickest, 65 days or 54 days. I think it’s a pity if we, as agencies, start running in a race. The industry might like it but we tend to forget why we have agencies: agencies are there to make sure that safe and effective drugs are on the market – as consumer protection.

‘The health care systems are less interested in 56 or 86 days, they’re more interested in the quality of the assessment. Instead of competing, let’s make the best evaluations instead of the quickest ones.’

While the pharmaceutical industry generally welcomes these new competitive pressures on regulatory agencies, some regulators believe that the drive for fast approvals could lead to excessive trust being invested in the manufacturers’ scientific documentation. These concerns have been heightened by the growing emphasis of governments and the EC on increasing consultation between regulators and manufacturers about drug development. Some regulators fear this could compromise their independence.

One German regulator gave the following warning: ‘If you try to assess complicated products in a very short time, in most cases you must believe what is written down by companies. If you have a company working correctly, it’s not a problem, but if you have companies which are not, there will be a problem. To find these companies out you must have time. I think there will be a risk for safety in the future.’

Also of crucial importance to patients is whether mutual recognition and inter-agency competition will create an EU regulatory system based on the lowest common denominator; that is, a ‘levelling down’ in drug safety standards, rather than a ‘levelling up’. Many drug companies claim that the new systems are producing a levelling up, but it is not difficult to find regulators in Germany, Sweden and the UK who disagree.

Some German and Swedish regulators say they have accepted products that would not have met their national safety standards, while others regard EC regulation as an exercise in promoting trade interests, not drug safety.

In the light of such concerns, it is particularly important that regulation of medicines in Europe is transparent and publicly accountable – but it is not. In the UK, the 1911 Official Secrets Act and section 118 of the 1968 Medicines Act prevent regulators in the MCA and all its expert advisory committees, such as the Committee on Safety of Medicines (CSM), from divulging information on medicines licensing applications. A similar cloak of secrecy surrounds medicine licensing in other European countries, apart from Sweden.

Despite the rhetoric of the EC and the EMEA supporting greater freedom of information, European drug regulation remains virtually closed to public scrutiny. Even basic information about mutual recognition applications, such as the names of the member states involved, may be treated on a ‘need to know’ basis.

Nor is there any right of access to CPMP meetings or minutes. Under the EU’s 1994 code of conduct on public access, disclosure is prohibited if it ‘could undermine the protection of commercial and industrial secrecy’ or if ‘confidentiality [is] requested by the source of the information or required by legislation of the member state supplying that information’. So statutory bans, such as that contained in the UK Medicines Act, can be used to refuse access to information at the EU level, if the UK regulatory authorities are the source of the information.

A product can be approved for marketing in Sweden through mutual recognition but, in the event of extensive adverse reactions to the drug, even Swedish patients may not be able to gain access to information about the product’s safety using their domestic freedom of information legislation, because the RMS could refuse its release. The new Europeanised systems may well increase secrecy in drug regulation.

The most conspicuous attempt to improve the transparency of the system is the publication of the European Public Assessment Reports (EPARs) for drug products approved under the centralised procedure. EPARs usually consist of about 30 pages providing reasons why the CPMP has recommended marketing approval of the product, including a summary of scientific discussions about the drug. But again, the information disclosed is at the discretion of the regulators and EPARs are not available for most drugs.

Moreover, the drug companies’ acceptance of EPARs is probably because they are confident that they can influence, if not determine, the information included. There is no consultation with consumer organisations or health professionals about these matters. While EMEA sources insist that the CPMP decides the contents of EPARs and can ignore industrial objections, regulators may be unwilling to permit such an adversarial relationship with industry for the sake of public access to information.

For example, according to one MCA official: ‘The final say [over the contents of EPARs] is with the regulatory authority, although the regulatory authority would need to consider very carefully that if a company had got a difficulty with something being included, then the regulatory authority would need to be much clearer about the basis for publishing that, otherwise they could expect trouble.’

By contrast, Swedish regulators believe that the public have a right to see how new drugs are approved. Even some scientists in the pharmaceutical industry acknowledge that greater public access to existing drug testing data could be beneficial to medical science. They use the US Freedom of Information Act to obtain data on competitors’ products, which can help them to avoid mistakes in toxicology and clinical testing.

So far, the Europeanisation of drug regulation has been a missed opportunity to promote public health and improve accountability in the pharmaceutical sector. Instead, an internal market of regulatory agencies chasing industry fees poses a threat to public health and regulators’ independence. EU regulators have been busy extending their consultation processes with industry and striving to approve medicines ever more rapidly. But progress in establishing greater transparency and public accountability of the new procedures has been pitiful, even though it is widely acknowledged that more open flows of information would enhance drug safety.

Regulators defend the current situation by arguing that companies have a right to protect their commercial secrets from unscrupulous competitors. But the irony of this argument is that, because pharmaceutical companies do not trust each other, EU regulations have been established in which health professionals, patients and the public are expected to trust the entire pharmaceutical industry and its regulators combined. Consequently, the new European medicines licensing systems remain deficient in their capacity to accommodate public scrutiny.