12.1.1 Regulatory gaps

If the purpose of drug regulation is to promote public health and protect the public from harmful and dubious drugs, it should cover all products for which medicinal claims are made and all activities associated with the manufacture, importation, distribution, dispensing and promotion of drugs.

This study has found that drug regulation does not meet these requirements in all the countries studied. In some countries, legislation omits or exempts certain areas of pharmaceutical activity from the scope of control. In Australia, Malaysia and the Netherlands, legislation requires traditional/herbal medicines to be assessed and registered. But this is not the case in Cyprus, Uganda or Zimbabwe. As a result of such gaps, drug regulation provides only partial protection for consumers.

Since legal structures form the foundation of drug regulation, regulatory gaps should be addressed by modifying or extending existing legislation or introducing new legislation. Drug legislation should be comprehensive, covering all products with a medicinal claim and all relevant pharmaceutical activities, whether carried out by the public or the private sector. It should be updated when necessary in order to meet new challenges. Important factors determining the effectiveness of drug legislation include the extent to which the legislative framework is consistent with national policies and the degree of regulation the government considers it desirable and practicable to exercise. In general, drug legislation must:

• define the categories of medicinal products and activities to be regulated;

• state the missions and goals of drug regulation;

• create the administrative bodies necessary for implementing drug regulation, and define their structural and functional relationships;

• state the roles, responsibilities, rights and functions of all parties involved in drug regulation, including those of the regulators and the regulated;

• define the qualifications and standards required for those handling drugs;

• create mechanisms to ensure that all responsible parties are licensed and inspected and ensure compliance with drug legislation and with the standards and specifications laid down for persons, premises and practices;

• define the norms, standards and specifications necessary for ensuring the safety, efficacy, and quality of drug products, as well as the appropriateness and accuracy of product information;

• state the terms and conditions for suspending, revoking or cancelling licences to import, manufacture, export, distribute, sell, supply or promote drugs;

• establish the administrative measures and legal sanctions that will be applied if drug legislation provisions are violated;

• create mechanisms for ensuring the transparency and accountability of drug regulatory authorities to the government, the public and consumers;

• create mechanisms for ensuring government oversight.

12.1.2 Overall accountability of the DRA

In some countries, all drug regulatory functions fall under the jurisdiction of a single agency, which possesses full authority to command and control these functions, as well as responsibility for ensuring the effectiveness of drug regulation. In other countries, drug regulatory functions are assigned to two or more agencies, at the same or different levels of government. Two phenomena, in particular, which may impede regulatory effectiveness were observed among the 10 countries.

Fragmentation and delegation of responsibilities

In some countries, drug regulatory functions are assigned to more than one agency. For example, in Venezuela, the National Institute of Health and the DDC are each responsible for a number of drug regulatory functions. Similarly, in the Netherlands, the MEB, the Healthcare Inspectorate of the Ministry of Health, the National Institute of Public Health and Environment (RIVM) and the National Registration and Evaluation of Adverse Drug Events (LAREB) are independent agencies, each regulating a different pharmaceutical area. In Tunisia, the National Medicines Control Laboratory, the Pharmaceutical Affairs Department, the Pharmaceutical Inspection Department and the National Pharmacovigilance Centre are independent agencies, each of which is responsible for different areas of drug legislation. When drug regulatory responsibility is dispersed, however, coordination amongst all the agencies is crucial if regulation is to be effective. Yet ensuring such coordination is generally difficult. In the absence of good coordination, lapses in implementation often occur. The risk of duplication of efforts, wastage of resources and even confrontation is increased too. Moreover, no single agency is, or can be, held accountable for overall drug regulatory effectiveness.

Problems relating to delegation of drug regulatory powers generally take one of two forms: a) delegation without authority and accountability; and b) delegation with full authority, but without coordination. The way in which inspections of distribution channels in Uganda are delegated by the NDA to the district assistant drug inspectors is an example of the first type. In this case, the district assistant drug inspectors are given the additional responsibility of inspecting drug distribution channels in their area, but without sufficient authority to enforce the law. Neither are they held accountable for failure to carry out inspections.

While delegation of regulatory authority is found in all types of government, it is most far-reaching in countries with a federal system. Usually, full authority is delegated from the federal or central level to the states. If this is not properly coordinated, there will be problems of accountability. Such arrangements can also affect the national authority’s ability to ensure the effectiveness of overall drug regulation. In Australia, the TGA regulates the supply of therapeutic goods by incorporated bodies, and those manufactured and traded across state boundaries. The states and territories have control over drug distribution. The National Coordination Committee for Therapeutic Goods and the National Drugs and Poisons Schedule Committee coordinate the activities of the Commonwealth with those of the states and territories. But it is unclear whether this system enables the TGA to monitor Australia’s overall drug situation.

Such a problem is not necessarily inevitable in federal-state delegation of authority. Mechanisms exist in some countries which can provide a link in the line of command and control. In Malaysia, the chief officer of the state regulatory authority is also a member of the federal-level organization. Policy communications between the federal and state levels, such as reporting, thereby become a routine.

It may not be easy to achieve and maintain effective coordination between different regulatory bodies. The missing links resulting from fragmentation and delegation can undermine the overall effectiveness of regulation. Ideally, drug regulatory structures should be designed in such a way that a central coordinating body has overall responsibility and is accountable for all aspects of drug regulation for the entire country. The responsibilities of all agencies involved should be clearly demarcated. However, restructuring of the entire DRA will require a substantial amount of time and effort. There may be a need for intermediate options that allow improvements in the existing divided structure. Another solution is to establish official structures for coordination and information systems within existing organizations in order to overcome their failings. A system with formal channels of coordination and information flow should be created to support drug regulatory decision-making at the national level.

Multiple functions and conflicts of interest

The study has shown that some drug regulatory authorities have been assigned multiple functions and are therefore unable to focus solely on drug regulation. If the authority responsible for drug regulation is also assigned other non-regulatory functions, such as manufacturing, procurement and/or delivery of services, conflicts of interest may occur in respect of mandates and resource allocation. In Cyprus, for example, the Pharmaceutical Services Division is responsible for drug regulation, procurement, supply and dispensing, as well as manufacturing. Distribution of human and other resources to cover all these functions has a significant impact on the adequacy of support for regulatory activities. In Venezuela, the National Institute of Health is not only responsible for assessment, registration and QC of pharmaceuticals, but also manufactures biological products. In Cuba, drug regulation, manufacturing, distribution and sales are all undertaken by the State. Although the DRA is not directly involved in the management of the companies carrying out manufacturing, distribution and sales, implementing drug legislation becomes more difficult.

Regulatory double standards

Not all drug regulatory requirements are applied equally. Exemptions are sometimes made, depending on where the drug comes from, who manufactured or imported it, where the drug is distributed or whether it is sold on domestic or overseas markets. For example, in Cyprus, drugs manufactured or imported by State agencies do not have to be registered, whereas those from private businesses do. Assurance of product quality, efficacy and safety in the case of government-manufactured products rests solely with the agency that manufactured the product, which may not conform to the standards set by the DRA. Such double standards raise questions regarding the DRA’s ability to ensure the quality of all drugs distributed.

In Australia, therapeutic goods manufactured for export are not subject to the same standards as those consumed locally. Moreover, therapeutic goods that are manufactured by an unincorporated individual, and goods that are not traded across a state boundary, are exempt goods and not subject to control or registration. Use of double standards in the case of exported products raises questions of fairness in international public health.

Regulatory tools

Drug legislation is the basis of drug regulation, and defines the standards and specifications to be applied. Regulatory tools, such as standards and guidelines, equip drug regulatory authorities with the practical means of implementing this legislation. This study has revealed that not all drug regulatory authorities in the 10 countries make available documented SOPs for registration, and that even fewer countries have documented guidelines and checklists for inspection. When such tools are lacking, application of the legislation may become erratic and even lead to questions about the transparency of law enforcement.

Standards and guidelines should be established in written form for all drug regulatory functions. These tools should then be used to guide regulation practice, as well as being made publicly available in order to ensure the transparency of the drug regulatory process.

Resources

Human and financial resources are critical for successful drug regulation.

Governments should employ people with the specialized knowledge and skills required to ensure effective drug regulation. Employees must be individuals of integrity and should be well remunerated, particularly since drug regulation involves various stakeholders with commercial interests who may try to exert pressure on the authority in order to secure decisions favourable to themselves. Adequate and sustainable financing mechanisms are clearly crucial.

The study has shown that shortage of qualified personnel is the main problem faced by drug regulatory authorities. This is partly due to the lower salaries offered to DRA employees, which makes attracting and retaining staff difficult. The limited pool of pharmaceutical professionals in some countries owing to a shortage of institutions for pharmaceutical education may be another factor.

With regard to the financing of drug regulatory authorities, the study showed that the government budget is the main means of financing for eight out of the 10 countries. In each of the 10 countries, the drug regulatory authorities charge fees for their services. Countries vary both in the type of service for which fees are charged and in the level of the fee. Only two drug regulatory authorities in the group are entirely self-financed from fees. Fees collected by government-financed authorities are transferred to the government treasury. The fees charged by these authorities are almost always much lower than the actual cost of performing the regulatory function. Fees charged by the drug regulatory authorities of Australia and the Netherlands are much higher than fees charged by the developing countries.

Clearly, government resources alone are not sufficient to promote effective drug regulation in most of the countries. The drug regulatory authorities in these countries should set fees at a level that reflects the real cost of drug regulatory services, and should be allowed to retain the fees. The fee system should cover all services provided, including licensing, of establishments registration of products, inspection, QC and control of promotion and advertising. That said, the DRA should not be entirely dependent upon the fees charged for its services. The government should be fully committed to ensuring the sustainability of drug regulation. Financing for the authority should therefore be structured so that a balance is struck between a sufficiently high fee to cover the cost of services and provision of government support. Also, the salaries of DRA employees and the remuneration of expert committee members performing reviews should not be directly linked to specific fees or to the agency’s overall earnings. This will help to ensure that regulatory decisions are not influenced by payment of fees.

Other ways of overcoming human resources problems include the following.

• Coordination may be established, where appropriate, between the DRA and the country’s educational institutions, to provide the number and types of pharmaceutical competency which are needed. The aim is not merely to increase the number of professionals, but also to develop skills through short training courses. A coherent, module-based educational package may be developed by collaboration between countries. The individual modules may be “housed” in institutions with the relevant expertise. The DRA may then choose where to send its personnel for the training they most require.

• The information and knowledge needed for the regulation of a specific area or a specific drug product are usually available in countries where more advanced technologies can be acquired more easily. This information could be made available more widely to developing countries, and the resulting pooling of information resources may help to reduce the regulatory workload. Networks of information sources and users may be built up to facilitate the transfer of information and technologies.

• Drug regulatory authorities in various countries, WHO and other international bodies may collaborate to identify QC laboratories with sufficient capacity which adhere strictly to good laboratory practice. Standards may be set for accreditation of these laboratories. Drug regulatory authorities and other organizations in countries with fewer resources may then send products to them for testing. Pooled resources and division of labour among countries may also be applied to the production of secondary reference substances.

• Where salary rates are low, some way of increasing them, or providing other incentives such as transport or housing allowances and health insurance, must be sought. Good salaries and benefits not only help to attract and retain employees, they also help to minimize corruption.

• To reduce its workload while not compromising on quality, a DRA may identify countries with strong drug regulation and waive some procedures for products imported from those countries. Alternatively, it may decide to consider functions certified in those countries as legally valid in its own country. In Cyprus, foreign manufacturers exporting pharmaceuticals to Cyprus must normally submit documents certifying that GMP standards have been met, but manufacturers in Australia, Canada, the European Union, Japan and the USA are exempted from this requirement. In addition, a number of “reputable” authorities have been identified, and documents certified by these authorities are recognized under the Cypriot regulations. For example, inspections of a foreign manufacturer conducted by the United Kingdom Medicines Control Agency or the United States FDA are considered as equivalent to those made by Cypriot inspectors.

The assumption underlying this approach is that the same high standards apply to all products and all drug regulatory functions. But for countries where double standards are applied to regulatory requirements, and different sets of standards are applied to pharmaceutical products depending on whether they are marketed within the country or exported, this approach may mean that products of lower standard are accepted. The “trusted authority” system may also give some legal leeway for manufacturers exporting pharmaceutical products not registered in the country. In other words, the burden of drug evaluation is shifted to the importing country.

• Prioritization and streamlining of work processes are used by the Australian TGA to enhance efficiency. Using this method, each product or facility is classified according to its “risk”. High-risk products or facilities receive a more intensive review. Thus prescription drugs are higher-risk than non-prescription drugs, and facilities for manufacturing sterile products are higher-risk than packaging facilities. Under this scheme, products and facilities classified as low-risk receive less intense scrutiny, freeing up human resources for high-risk targets.

• Job enlargement and job enrichment methods may also be employed. The multi-skilling approach used in Zimbabwe is one such strategy. The MCAZ streamlines its procedures and uses teamwork in the performance of drug regulatory functions. Staff are trained to handle multiple functions.