Table 1 Key Country Selection Criteria — SF and MRA information

Africa

▪ One of the countries with the highest reported prevalence of poor quality medicines [10, 35].

▪ Extensive publicity on poor quality medicines circulating as a result of importation and local manufacture [10, 33].

▪ Large local pharmaceutical industries, with references citing that poor quality medicines produced locally have been diverted to other countries[36]

▪ Some STs (Minilab™ and TruScan™) have been deployed domestically [37, 38].

▪ The National Agency for Food and Drug Administration and Control (NAFDAC) has recently made efforts to decrease the amount of poor quality medicines in circulation. However, pharmaceutical regulations in many cases are still not implemented and enforced [38, 39].

▪ Limited public information available about poor quality medicines in country.

▪ In 2003, WHO examined the quality of selected antimalarials and found quality problems with both chloroquine and sulfadoxine pyrimethamine tablets [40].

▪ Widespread poverty and stock outs have forced some people to obtain their medicines from unlicensed vendors selling falsified products [41].

▪ Despite economic challenges, the Medicines Control Authority of Zimbabwe (MCAZ) is one of Africa’s regulatory success stories and has provided technical assistance to neighboring countries. The OMCL is WHO prequalified and ISO 17025 accredited [42].

Americas

▪ Falsification of medicines is cited as a serious, systemic problem in which leaders from various sectors participate: politics, business, and labor [43].

▪ As part of continuing investigations, over 40 raids were recently conducted into falsified and illegal drugs distributed by organized crime. The police in collaboration with the National Administration of Drugs, Foods and Medical Devices (ANMAT) collected samples of primarily cancer, hemophilia, and HIV/AIDS medicines as well as documentation related to their purchase and distribution [44].

▪ The ANMAT is recognized by the Pan American Health Organization as a National Regulatory Authority of Regional Reference [45].

▪ Since 1997 Argentina created the National Research Program of Illegitimate Medicines, to determine the magnitude of SF medicines on the market and limit their circulation and public health consequences [46].

▪ Extensive local production and import of falsified medicines and instances of poor quality medicines were found at US-Mexico border pharmacies [47].

▪ Illicit drug cartels are also involved in the distribution chains of falsified medicines [9].

▪ A recent study analyzed the active pharmaceutical ingredients from local pharmacies of 17 commonly used products, with several units falling outside of U.S. Pharmacopeia standards specifications [48].

▪ Mexico’s Federal Commission for Protection against Sanitary Risks (COFEPRIS) is recognized by the Pan American Health Organization as a National Regulatory Authority of Regional Reference [49].

▪ Mexico’s OMCL is WHO prequalified [42].

▪ Falsified medicines are becoming more prevalent in the United States. Most are “lifestyle” medicines but there are exceptions, notably anti-cancer, anti-depressant and anti-anxiety medicines [3, 50].

▪ Media reports contain several examples of falsified medicines seized at borders, which were imported illegally [3, 50].

▪ Locally produced falsified medicines have been discovered, but medicine seizures indicate that the majority of falsified products are either imported or smuggled in across borders [51].

▪ An estimated 80% of falsified medicines come from overseas [2, 6]

▪ The U.S. Food and Drug Administration (USFDA) regulates over-the-counter and prescription drugs, including biological therapeutics and generic drugs.

▪ USFDA recently established the Office of Pharmaceutical Quality, which is dedicated explicitly and exclusively to product quality.

Eastern Mediterranean

▪ Media reports claim that falsified medicines are now estimated to make up 30% of the Egyptian market; in 2015, a series of raids found counterfeit medicines worth hundreds of millions of dollars and exposed a criminal network feeding consumers across Middle East [52].

▪ This problem is tightly linked to pharmacies with multiple branches whose owners hold huge capital and are close to Egyptian decision makers; they are the ones primarily smuggling and selling falsified medicines.

▪ Egypt serves as a transit hub for falsified medicines destined to other countries [53, 54].

▪ The Egyptian Drug Authority has its own website and is the pharmaceutical regulatory body of the Egyptian Ministry of Health. The Authority is composed of three sub-organizations: Central Administration of Pharmaceutical Affairs, the National Organization for Drug Control and Research (NODCAR) and National Organization for Research & Control of Biologicals.

▪ In 2008, 431 pharmacies were found in violation of law; 14 were shut down for selling counterfeit medicines and 34 were selling smuggled medicines [55].

▪ In 2013, the Jordanian Food and Drug Administration (JFDA) seized USD $307,682 of counterfeit medicines and issued warnings to 21 manufacturers over the course of six months [56].

▪ JFDA’s OMCL is in the process of obtaining ISO 17025 accreditation.

Southeast Asia

▪ Global supplier of generic medicines, although literature exists of local manufacturers producing and exporting substandard and falsified medicines [10, 50].

▪ Reports claim that some local manufacturers have two-tiered production, making substandard drugs for markets with poor regulatory authorities in Africa [36, 57].

▪ Large manufacturer, Ranbaxy, recently pled guilty to felony charges for adulterating medicines [58].

▪ Regulatory functions are decentralized; state and national-level institutions are given different powers [10].

▪ State-level agencies license and monitor drug manufacturing establishments and drug testing laboratories, regulate medicine quality, and approve drug formulations [9].

▪ Overall, the state regulatory authorities are weak and lack adequate quality testing facilities [59].

▪ Large personnel and budget shortages at both levels [60].

Western Pacific

▪ Numerous reports of poor quality medicines, both falsified and substandard [36].

▪ In 2015, the Philippines Food and Drug Administration (FDA) ordered the seizure of 20 different unregistered medicines [61].

▪ In 2015, two customs officials were fired after releasing a shipment of counterfeit medicines worth USD $269,000 [62].

• There is a strong public bias against generic medicines, with people spending large amounts to purchase originator products or ‘higher-quality’ branded generics [63].

• The Cheaper Medicines Act was therefore established by FDA to demonstrate the quality of generics [63].

▪ Production value of domestic pharmaceutical industry increased from 137.1 billion yuan to 667.9 billion yuan from 1997 to 2007 [64].

▪ Along with India and Nigeria, China has reports of SF medical products which can be attributed in some cases to substandard local manufacturing and are sometimes exported [10, 64].

▪ China and India manufacture 70–80% of the active pharmaceutical ingredients for all medicines globally [57, 65].

▪ China has recently been cracking down on poor quality medicines, giving the State FDA additional resources to supervise, implement regulations, and to initiate investigations into and enforce penalties for violations [66, 67].

▪ Recent reforms have emphasized transparency, strict regulatory standards, and enforcement mechanisms and China requires manufacturers to follow WHO’s Good Manufacturing Practices for pharmaceutical active ingredients and finished products [6, 67].