1. Medicines regulation - ensuring effective medicines with acceptable risk

1. Medicines regulation - ensuring effective medicines with acceptable risk

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Medicines constitute one of the most highly regulated areas in modern industries.

• Everybody wants to be able to get treatment if they are ill. Therefore, we need medicines that are effective against the illness.
• We do not want side effects from the medicine. This means that we want the products to be sufficiently safe for normal use.

The use of ineffective, poor quality, unsafe medicines can result in therapeutic failure, worsening of disease, and sometimes death. It also undermines confidence in health systems, health professionals, pharmaceutical industry and distributors. And money spent on ineffective, unsafe and poor-quality medicines is wasted.

Medicines regulation is a safeguard against this. In broad terms the task of medicines regulation is to protect and promote public health and guarantee to the largest possible extent the availability of efficient, safe medicines.

1.1. The development of medicines regulation

Creating regulations for medicines started as a reactive process following some serious medicines-related disasters that took place during the 20^th century. In the 1930s in the USA, more than 100 children were poisoned by antibiotic syrup. The product contained the toxic substance diethylene glycol instead of sugar. In the late 1950s and early 1960s, thousands of children in Europe were born with malformations due to the use by pregnant women of a medicine containing thalidomide that was promoted for anxiety, trouble sleeping, "tension", and morning sickness. Both incidents caused massive changes in regulatory legislation.

As a result, the whole regulatory system was reshaped in the UK where a Committee on the Safety of Drugs (CSD) was started in 1963 followed by a voluntary adverse drug reaction reporting system (Yellow Card Scheme) in 1964. In the United States the Drug Amendments Act of 1962 required the FDA to approve all new drug applications (NDA) and, for the first time, demanded that a new drug should be proven to be effective and safe. In Europe the EEC Directive 65/65/EEC on the approximation of provisions laid down by law, defining regulation and administrative action relating to medicinal products was also induced by the thalidomide disaster. In subsequent years harmonisation of regulatory activities in the European Community (EC) was further developed.

1.2. Principal medicines regulatory activities

Medicines regulation incorporates several mutually reinforcing activities all aimed at promoting and protecting public health. These activities vary from country to country in scope and implementation, but generally include the following:

• Assessing the safety, efficacy and quality of medicines, and issuing marketing authorisation for individual products

• Licensing of the manufacture, import, export, distribution, promotion and advertising of medicines

• Inspecting and surveillance of manufacturers, importers, wholesalers and dispensers of medicine

• Controlling and monitoring the quality of medicines on the market

• Controlling promotion and advertising of medicines

• Monitoring safety of marketed medicines including collecting and analysing adverse reaction reports

• Providing independent information on medicines to professionals and the public

1.3. What comprises an effective medicines regulation?

Medicines regulation demands the application of sound medical, scientific and technical knowledge and skills, and operates within a legal framework. Regulatory activities involve interactions with various stakeholders (e.g., pharmaceutical industry, traders, consumers, health professionals, researchers and governments) whose economic, social and political motives may differ, making implementation of regulation both politically and technically challenging.

Medicines regulation has an administrative part but far more important is the scientific basis for it. Thus, Governments need to establish strong regulatory authorities (on the national level called National Competent Authorities, NCAs), to ensure that the development, manufacture, trade and use of medicines are regulated effectively.

As already mentioned, all medicines must meet the three criteria of quality, safety and efficacy, and the judgments about these should be based on solid science. There are several general and specific factors contributing to effective regulation by a regulatory authority. They include a clear mission statement, adequate medicines legislation and regulation, appropriate organisational structure and facilities, clearly defined roles and responsibilities, adequate and sustainable financial resources, and appropriate tools, such as standards, guidelines and procedures and internal collaboration with all stakeholders, transparency (making transparent how and based on which information decisions are made) and accountability combined with good management and effective internal quality systems. Minimum functions that a regulatory authority should be able to carry out are laid down in the following:

A regulatory authority should

• Ensure that all medicines manufacturing, importation, exportation, wholesale and distribution establishments are licensed. Activities and premises must comply with Good Manufacturing Practices (GMP) and Good Distribution Practice (GDP) requirements

• Before medicines are marketed, assess their quality, safety and efficacy

• Monitor the quality and safety of medicines on the market to prevent harmful, substandard and counterfeit medicines from reaching the public and to adapt the MA and package leaflet if needed (see also “Pharmacovigilance”).

• Regularly inspect and control the informal market, including e-commerce, to prevent illegal trade of medicines

• Monitor advertising and promotion of medicines, and provide independent information on their rational use to the public and professionals

• Participate in sub-regional and regional regulatory networks and international meetings of drug regulatory authorities to discuss issues of mutual interest and concern, facilitate timely exchange of information and promote collaboration

• Monitor and evaluate performance to assess if perceived regulatory objectives have been met, to identify weaknesses and take corrective action

Source: WHO Policy Perspectives on Medicines no 7, 2003.

1.4. A note on promotion and advertising

Excessive promotion of pharmaceuticals has been associated in many countries with serious problems of irrational drug use. Unethical medicines promotion activities often convey misleading information about medicines to the different target audiences. Misinformation can contain expansion of indications or an exaggeration of efficacy but can also downplay the seriousness or the incidence of side effects. In the EU, the directive 2001/83/EC contains relevant provisions regarding advertising for medicinal products which are reflected in the legislation of the EU member states. For example, advertising of a medicinal product, for which a marketing authorization has not been granted, is prohibited; only product information approved during the authorisation process can be included in the package leaflets or promotional materials; direct to the general public advertising of prescription only medicines is not allowed; the advertising of a medicinal product to the general public shall not contain any statements which are in any way misleading, such as that the effects of taking the medicine are guaranteed, are unaccompanied by adverse reactions or are better than those of another treatment or medicinal product (a more extensive list can be found in the directive (Article 90)).