Whatever the nature of the problem, substandard drugs:

• Do not provide the desired health intervention and may actually jeopardize health
• Waste scare resources
• Erode the public confidence in the health care delivery system and procedures for drug approval and inspection

In developing nations, commerce in pharmaceuticals poses a double liability-those who have the least purchasing power also have the least protection from exploitation. In order to help ensure product quality in the marketplace, some product testing is required to identify substandard and fake products and remove them from the distribution system. In turn, this means that drug product testing and marketplace removal must be an integral part of a broader overall strategy for ensuring drug product quality in each country and must include:

• Drug product testing, both at the time of approval and subsequent to approval
• Comprehensive inspection in the marketplace, to take samples and to remove substandard products from the supply line
• Regular inspection of approved manufacturing plants with detection and closure of illegal plants
• Suppression of illegal cross-border trade (smuggling)
• Back-up of the control and inspection system by police activity and efficient prosecution of criminal and civil cases

Methods of analysis to assess product quality attributes generally are published in pharmacopoeias. However, the drug product quality testing methods that appear in the United States Pharmacopeia (USP) and British Pharmacopoeia (BP)-the European Pharmacopoeia (EP) has few drug product monographs-generally are based on methods submitted by the innovator firms. Furthermore, the USP and BP have few drug product quality attribute assessment methods available for products that have patent protection in their market zones and have only a limited number of published standards for drug products for diseases that are not endemic in their market zones. From a technological perspective, the pharmacopoeial methods for drug products found in the USP and BP usually employ relatively high-technology equipment along with expensive reference standards materials to assess the required product quality attributes. This poses a product quality assessment barrier to developing markets. Furthermore, many of these high-technology methods require trained personnel and have relatively high maintenance costs. To further compound the problem, there are thousands of drug products available that would need to be covered by a comprehensive quality assurance initiative. The resources required to do this are out of the reach of most, if not all, countries. As new products are marketed, this situation will likely continue to get worse.

Discussion Points

1. How can product quality assurance most efficiently and effectively be built into the product regulatory models in developing countries? How does product testing fit into the overall drug product quality and distribution system?
2. What is the role of bioequivalence testing in ensuring drug product quality?
3. What kinds and amounts of resources realistically are available for product inspection, collection, testing, and enforcement in developing countries? How can one ensure that sufficient resources are made available to handle this activity? What options exist for generating increased funding?
4. What criteria might be used by country authorities to identify priority drugs for periodic monitoring and testing (e.g., drugs for priority health problems, drugs that are very costly, drugs with a narrow therapeutic index, drugs used in certain age groups)?
5. What are the highest-priority sampling locations?
6. What recourse should be available when fake and substandard products are discovered?
7. What activities are currently underway to identify substandard and fake products in the marketplace that address-
   • Inspectional resources?
   • Testing resources?
   • Compliance activities?
   • Communication infrastructure?

Background Materials

Center for Pharmaceutical Management. November 2001 (draft). Drug Product Quality Assurance Framework. Arlington, VA: CPM, Management Sciences for Health.

Layloff, T.P. The importance of analytical procedures in regulatory control. WHO Drug Bulletin, 1997, 11:128-30.