Because resources are usually limited, it is important to take steps that will make the most of them. Several options are listed below, and a regulatory authority could benefit from some or all of these suggestions.
Establish mechanisms to regularly receive technical support from other institutions and individuals
In several countries, one or more technical advisory groups or committees are established to provide technical advice to the DRA. Such advisory groups may consist of national experts in clinical pharmacology, pharmacology, pharmaceutical sciences, clinical medicine, and other areas. The group or theme-specific subgroups could meet once or twice a month to provide advice on specific issues. The group could also define a list of basic criteria, e.g., which fixed-dose combinations are acceptable, a common basic data sheet for drugs of the same profile (as in the WHO Model Prescribing Information, the British National Formulary, the Guide National de Prescription, the American Medical Association’s Drug Evaluations, and other publications), labeling criteria, a “positive” list of active principles (e.g., all accepted benzodiazepines, systemic corticosteroids, etc.), or acceptable excipients. On the basis of these documents the regulatory authority will be able to process registration applications for widely used drugs more expeditiously.
Establish effective and meaningful communications with other regulatory authorities
Regulatory authorities with limited resources (both human and material) may wish to proceed cautiously in licensing drugs containing active ingredients that have not been widely used. When facilities or resources do not allow for analysing a large amount of technical documentation or for conducting appropriate studies (e.g., sufficiently large clinical trials, laboratory analysis, and post-marketing surveillance), ad hoc connections with more advanced regulatory authorities in other countries could be established. This would allow the DRAs to learn from each other’s experience and to have a reasonably solid basis for a decision about licensing active ingredients.
A simplified approach that regulatory authorities with limited resources may adopt is the establishment of continuous working relations with two or three highly evolved drug regulatory authorities of countries with a sizeable pharmaceutical market. The DRA could then exclude from registration all active ingredients not registered in at least one of the reference countries, unless exceptional circumstances demonstrated a local need.
In addition, the evaluation, for registration purposes, of manufacturers based abroad is not an easy task for many regulatory authorities. Foreign manufacturers’ premises can be visited only sporadically (if at all), and such visits may not be sufficient to allow sound judgements to be made, or have any legal impact. The most practical approach seems to be to establish connections with the regulatory authorities of the countries where manufacturers are based. This would ascertain whether there is a regulatory authority, what task it performs, and on the basis of which criteria it grants manufacturing licences and monitors production meant for national use and for export.
The WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce is an administrative tool for the exchange of information among regulatory authorities. Its regular and proper utilization may contribute to a significant reduction in the risk of being confronted with substandard or spurious drugs. However, the value of certifications issued pursuant to the Scheme is determined by the credibility of the issuing DRA.
Create simplified and meaningful procedures and documentation analysis
This may significantly contribute to the efficiency and the reliability of the evaluation of applications. In all cases where the safety and efficacy profile of the product for which registration is sought is well established, and the licensing authority is satisfied with the available information showing that this item meets recognized therapeutic needs, quality becomes the most important concern in evaluating an application. If regulatory authorities with limited human and material resources limit most of their licensing activities to well-established drugs, they will be better able to evaluate the manufacturing process and its controls, the specifications of the medicinal product and its regulatory status in other countries, and the GMP profile of the manufacturer.
Example: Assessing marketing applications in a very small, yet computerized, regulatory authority
In this example, a “very small” regulatory authority is one that does not have enough staff to carry out its own assessment for all applications for marketing authorizations that it may receive. Apart from situations of war or long-lasting civil unrest, there are two situations where “very small” regulatory authorities can be found:
• Countries where the market size is sufficiently large and the political situation is sufficiently stable to motivate domestic and foreign companies to engage in drug manufacturing and trade. In this situation, the DRA should try to build the necessary political support to establish a full fledged regulatory body. However, until this is achieved, the approach described here may be considered.
• Small countries with a very small market, often with communication or transportation difficulties. In these situations, the market size for many drugs is so small that the number of potential suppliers is also small. Virtually no manufacturer submits applications for marketing authorizations, and only a few importers ensure regular supply and, if required, submit applications for import permits.
Very small DRAs need to establish priorities to ensure that the best outcome is achieved. In most cases, local production is very small, therefore the priority of regulatory work is to ensure reliable quality and a regular flow of imported supplies. To achieve this, collaboration with importers in both the public and private sectors is crucial. Such collaboration should aim at identifying the most favourable balance among these options:
• Too many regulatory/administrative requirements may overburden small companies, causing a negative impact on drug prices, and reducing the number of companies willing to do business in or with the country.
• Too little regulatory control would put consumers in the hands of importers --who are not necessarily properly qualified-- without sufficient protection from the state.
• Limiting the sourcing of pharmaceuticals to a predefined number of countries with effective regulatory capacity, and making regular use of the WHO-type product certificate may significantly reduce the risk of being confronted with substandard or spurious drugs, but may yield satisfactory results for a limited list of drugs in terms of price and accessibility.
With limited staff and resources, computerization of information can be helpful. However, with limited resources it may be impossible to include every piece of data about an application or MA. An example of the minimum information that a very small regulatory authority may consider is:
• application number and date
• drug name
• dosage form
• primary container
• active ingredients & their amounts by dosage unit
• indications for use
• manufacturer responsible for releasing final dosage form for marketing
• dispensing category
• therapeutic classification
Access to this basic information on authorized products and efficient handling of import permits are crucial elements that permit sound management of the regulatory aspects of drug supply and guarantee credibility for the DRA, even when the institution is very small.
In an African country with three manufacturing units producing only oral solid and liquid forms, two pharmacists and a secretary have been assigned to drug registration activities, and one chemist and three laboratory technicians for the QC laboratory. No GMP inspectors are available.
In this situation, it has been decided that:
→ Since no thorough assessment of applications for marketing authorization can be carried out, authorizations will be given only to products accompanied by a reliable WHO-type product certificate.
→ A list of reference countries whose certificates are accepted is established and kept up to date.
→ Drugs that are not included in the national drug formulary are registered only under exceptional circumstances of documented high public interest and after the decision of a specialized committee.
→ QC lab activities should focus on domestic products, and on imported products that are manufactured in reference countries, have acceptable certification, but are not identical to those marketed in the exporting country.
→ Resources will be made available to permit the two pharmacists engaged in drug registration to visit other regulatory authorities and receive ad hoc training in order to improve their skills and knowledge.