Problems related to the safety and quality of drugs exist in many places around the world today, in developing and developed countries alike. Some incidents have ended in tragedy, often with children as the victims. They are caused by the use of drugs containing toxic substances or impurities, drugs whose claims have not been verified, drugs with unknown and severe adverse reactions, substandard preparations, or outright fake and counterfeit drugs. Effective drug regulation is required to ensure the safety, efficacy and quality of drugs, as well as the accuracy and appropriateness of the drug information available to the public.

This document forms part of the World Health Organization (WHO) project “A multicountry study on effective drug regulation”. Its aim was to examine and document the experience of selected countries which have drug regulation in place and identify their strengths and weaknesses and the reasons for them. The 10 countries participating in this study were: Australia, Cuba, Cyprus, Estonia, Malaysia, Netherlands, Tunisia, Uganda, Venezuela and Zimbabwe. Data collection in all the countries was based on a standardized guide developed by WHO and refined by the participating investigators and research advisers.

The objective of this review is to synthesize lessons in drug regulation from the 10 country reports, by comparing and contrasting country experiences. The analyses presented are based on data collected in 1998-1999. The current system of drug regulation in some of the participating countries may be different from that at the time the data were collected. This work does not aim to rank the countries under study against any criteria. Rather, its purpose is to synthesize their experiences and draw generic conclusions from which the participating countries and others may learn. A systematic examination of drug regulation and its environment across countries may shed new light on a country situation, provide a new perspective on the constraints facing it, and provide options for improving the way the system works. The specific aims of this review are to:

• provide simple conceptual frameworks for drug regulation, which policy-makers may use as a basis for designing drug regulatory systems and adapting strategies appropriate to different contexts

• present key features of drug regulatory systems in different countries, compare and contrast them, and highlight and synthesize the generic lessons to be learned

• propose strategies drawn from the experience of countries and from the comparative analyses.

Historical development of drug regulation

The structures of drug regulation that exist today - drug laws, drug regulatory agencies, drug evaluation boards, quality control (QC) laboratories, drug information centres, etc. - have evolved over time. During this process, the scope of legislative and regulatory powers has been gradually expanded, in response both to the ever-increasing complexity of an increasingly sophisticated pharmaceutical sector, and to the perceived needs of society. In some countries, the enactment of comprehensive drug laws was a result of crisis-led change, when public demand led to the adoption of more restrictive legislation to provide stronger safeguards for the public. Drug regulation is therefore a public policy response to the perceived problems or perceived needs of society. Consequently, drug laws need to be updated to keep pace with changes and new challenges in their environment.

Drug laws, norms and standards

Legal structures form the foundation of drug regulation. Some drug laws traditionally omit or exempt certain areas of pharmaceutical activity from their scope of control, thus resulting in a regulatory gap. For instance, some countries do not require registration of herbal and/or homeopathic drugs while, in others, legal mandates are not imposed on the importation of drugs. To protect the public from harmful and dubious drugs and practices, drug laws should be comprehensive enough to cover all areas of pharmaceutical activity in the country.

While drug laws provide the basis for drug regulation, regulatory tools such as standards and guidelines equip drug regulatory authorities with the practical means of implementing those laws. Not all drug regulatory authorities provide documented standard procedures for registration, and even fewer provide documented guidelines and checklists for inspection. The absence of regulatory tools may lead to variations in the implementation of the law, or even lead to questions about the transparency of law enforcement. Standards and guidelines should be established in a written form for all drug regulatory functions. These tools should then be used to guide regulatory practice, as well as being made publicly available to all the parties involved in order to bring transparency to the drug regulatory process.

Structure of drug regulatory authorities

Regulation of drugs encompasses a variety of functions. Key functions include licensing, inspection of manufacturing facilities and distribution channels, product assessment and registration, adverse drug reaction (ADR) monitoring, QC, control of drug promotion and advertising, and control of clinical drug trials. Each of these functions targets a different aspect of pharmaceutical activity. All of these functions must act in concert for effective consumer protection.

In some countries, all functions related to drug regulation come under the jurisdiction of a single agency, which has full authority in the command and control of these functions, as well as bearing the responsibility for their effectiveness. In other countries, drug regulatory functions are assigned to two or more agencies, at either the same or different levels of government. Two phenomena are found in the structural design of drug regulatory authorities which can present problems in regulatory effectiveness - fragmentation and uncoordinated delegation.

When drug laws assign different responsibilities to different regulatory bodies, the exercise of drug regulation is fragmented. Under this type of organizational structure, command and control of drug regulatory functions must be exerted across different government agencies; it is an enormous task to coordinate the multitude of functions to ensure that the overall objectives are achieved. In the absence of effective coordination, there can be no effective drug regulation. In countries with a federal system of government, some drug regulatory activities are delegated to the State. Implementing a public policy through multiple levels of government with autonomous authority requires concerted effort between the agencies at all levels in order to attain the same regulatory objectives for the entire country.

When drug regulatory responsibilities are divided, there is no unity of command over drug regulatory functions. The missing links resulting from fragmentation and delegation can undermine the overall effectiveness of regulation. Drug regulatory structures should be designed in such a way that there is a central coordinating body with overall responsibility and accountability for all aspects of drug regulation for the entire country. An acceptable alternative would be to establish official routes for coordination and information flow to support decision-making in all aspects of drug regulation at the national level, in order to overcome shortcomings in existing organizational structure. In addition, interagency standard operating procedures (SOPs) should be set up. These SOPs should be designed with the ultimate goals of quality, efficacy and safety as the focus, rather than the relative power or existing routines of the agencies involved.

Not all drug regulatory authorities have drug regulation as their sole mission. Drug regulatory agencies in some countries are given non-regulatory functions - such as drug manufacturing, procurement and/or delivery of services. Conflicts of interest in mandates and resource allocation can occur among these multiple functions. Changes in priority among the various functions may be due to political considerations or shortage of resources, and may lead to shifts of personnel and budget resources from one function to another. The consequences of such a change will be to compromise performance in one functional area to the benefit of another. When needed resources are shifted away from drug regulatory functions, overall effectiveness can be undermined.

Resources for drug regulation

The financial sustainability of the drug regulatory authority (DRA) is a critical factor in the continued implementation of the various drug regulatory functions.

Government support in the form of a budget is the method of financing employed in most countries. In only a few countries is the DRA entirely self-financed by fees. The fees charged by drug regulatory authorities financed by a government budget are almost always much lower than the real costs of the regulatory function. In effect, this results in a public subsidy of private interests, by diverting tax revenue to fund functions such as product assessment for registration and assessment of advertisements for the drug industry. Fees should therefore be charged at a level which adequately reflects the real cost of drug regulatory services. However, arrangements should be made so that the financial sustainability of the DRA is not entirely dependent on the fees charged for its services. The government must be fully committed to ensuring the sustainability of drug regulation. Moreover, in order to ensure that fees do not influence regulatory decisions, the salaries of DRA staff and the remuneration of expert committee members who conduct reviews should not be directly linked to specific fees or to the authority’s overall earnings.

A shortage of qualified personnel was cited as a major problem facing the drug regulatory authorities. A number of strategies can be considered in order to alleviate the shortage of human resources: better human resource planning; sharing and pooling of international resources on education and training, on information, and on QC; instituting incentives, prioritizing and streamlining work processes, job enlargement and job enrichment.

Implementing drug regulation

Several areas in drug regulation receive relatively little attention in the implementation process. The informal sector, post-marketing surveillance and control of drug information were the most important of these.

Counterfeit products, products of dubious quality and faulty information - especially exaggerated claims of efficacy - are often found to be widespread in the informal sector. Unlicensed manufacturers, importers, wholesalers, retailers and even persons engaged in the pharmaceutical business pose difficult challenges to drug regulation. The DRA should not allow the informal sector to remain a loophole in regulation. Monitoring of pharmaceutical activities should cover the informal as well as the formal sector.

Drug regulatory systems in most countries expend far more time and effort on pre-marketing than on post-marketing activities. No matter how thoroughly pre-marketing assessment is conducted, it is only one of the functions needed if the efficacy and, especially, the safety of drugs are to be assured. Post-marketing surveillance functions, such as ADR monitoring, QC testing and re-evaluation of registered products, should also be priority areas in drug regulation.

Drug information received by both the consumers and the providers of medicines has a significant influence on rational drug use. Drug information is distributed as widely as drug products themselves. Systems of regulating drug information include pre-approval and self-regulation. However, monitoring of the accuracy and appropriateness of information is generally inadequate, and the effectiveness of existing systems of regulation is unknown.

Monitoring and evaluation

The regulatory process should be routinely and systematically monitored in order to identify problems in the process and determine whether the activities actually carried out are consistent with the intended course of action. Several approaches may be employed for assessing the performance of drug regulatory authorities: self-review, supervisory body review and peer review. These approaches can complement one another in appraising the performance of the DRA, as well as assisting it to identify areas for improvement.

Conclusion

This review synthesizes experience with drug regulation in 10 countries in order to draw generic conclusions from the strengths and weaknesses of different systems and identify features affecting the performance of drug regulation.

In drug regulation, the government acts as the guardian of the public by controlling private powers for public purposes. Ensuring the safety, efficacy and quality of drugs available to the public is the main aim of drug regulation. If regulatory goals are to be achieved, appropriate structures must be established and appropriate activities carried out to achieve the desired goals. Comprehensive and up-to-date laws, unified but independent organization, competent human resources, freedom from political and commercial influence, adequate and sustainable financial resources, clear and transparent standards and procedures, outcome-oriented implementation and systematic monitoring and evaluation are critical components contributing to effective drug regulation.