Despite their higher cost, branded medications are bought in higher quantities than their generic counterparts in low- and middle-income countries (LMICs). This is due to concerns about the safety or forgery of generic drugs, but actions are underway to improve the situation.
Unbranded generic medications account for only 5% of the LMIC pharmaceutical market by volume. That statistic is almost the opposite in the U.S., where unbranded quality-assured generics account for 85% of the market by volume.1
“Unfortunately, LMICs disproportionately purchase expensive branded drugs rather than cheaper unbranded generics. That’s because purchasers in those places don’t trust their regulatory system, and because they have no independent capacity to evaluate or verify the quality of a health product, they gravitate toward familiar brands or are influenced by advertising,” said Javier Guzman, MBBS, MSc, MBA, director of global health policy and senior fellow at the Center for Global Development in Washington, D.C.
Treatment failures occur with both branded, innovative medicines and generic drugs for a range of reasons related to the product, the prescription, or the patient.
“The key issue with generics is ensuring the product is interchangeable with the branded, innovative medicine. This means having the same dosage form, safety, strength, route of administration, quality, performance characteristics, and intended use,” Dr. Guzman said. However, he added that regulators in many LMICs might not have the capacity to guarantee interchangeability, especially in relation to quality.
According to Jayasree K. Iyer, PhD, chief executive officer at the Access to Medicine Foundation in Amsterdam, a generic medicine of poor quality can lead to ineffective treatment and place the patient at severe risk due to contaminants or improper formulations, and even result in death.
“When there is a lack of access to effective and safe medicines due to supply constraints, affordability, or lack of availability for specific patients, patients are left untreated or revert to other treatment options that are suboptimal or cause other major health issues,” Dr. Iyer said.
The Access to Medicine Foundation recently released a report on the steps being taken by the generic drug industry to expand access to medicine in LMICs. The initiatives among the five companies, which include Cipla, Hikma, Sun Pharma, Teva, and Viatris, focus on bolstering local manufacturing capacity in LMICs or facilitating technology transfer to local partners. The report also cited strategies to mitigate the risk of drug shortages and ensure the quality and safety of generics. Research and development projects included adapting generic medicines for use in children, simplifying dosing regimens, and removing the need to refrigerate generics.2
Claudia Martínez, research program manager at the Access to Medicine Foundation, wrote alongside the report that opportunities exist for companies to “ramp up their efforts and to work closely with local implementers, governments, and global health organizations to continue to break down barriers for the millions who either lack adequate access or are forced to go without the medicines they need.”2
Counteracting Questionable Practices
In oncology, patients in LMICs may evade treatment because of the high cost of branded drugs. Although generic medications cost much less, they may be substandard or artificial, or contain questionable ingredients.3 However, countries can take action to counteract the production of these potentially ineffective medications, addressing oversight in safety standards to ensure that quality products reach patients.
Countries should factor in the price and the quality of products when purchasing medicines, according to Dr. Iyer. Regulatory systems should be effective and ensure that companies with quality issues are monitored and that strict enforcement of the standards are implemented.
“Countries should also ensure that manufacturers of products report transparently and early on any unforeseen manufacturing issues faced and on the steps they take in managing risks of ineffective or poor-quality drugs,” she said. “Procurers should only buy from reputable sources and ensure that products available in pharmacies are also of high quality through training, regulation, and effective monitoring.”
Many countries have local regulations, and procurers have expectations on the quality of medicines, but in some countries the regulatory system is weak or shortcuts are taken because of corruption, Dr. Iyer said.
To help combat this, the World Health Organization (WHO) launched the Global Surveillance and Monitoring System for substandard and falsified medical products in 2013.4
“The WHO and countries collaborate on this system for surveillance and monitoring of health products or medicines. The system aims to detect, report, and share information on falsified and substandard medicines and thus protect patients in time,” Dr. Iyer said. “More support and ensuring companies and countries report issues in a timely way helps this.”
Increasing Regulation
Dr. Guzman emphasized that generics and branded, innovative medicines can be substandard, counterfeit, or contain questionable ingredients. “This is not only a problem with generic medications. Countries address these problems with effective regulation; that means appropriate checkpoints along the medicines’ lifecycle — from marketing authorization to post-marketing surveillance,” he said. “Importantly, LMICs have increasingly stronger regulatory systems.”
The WHO’s Global Benchmarking Tool (GBT) is a globally accepted tool for objectively assessing and strengthening regulatory capacity for medicine and vaccines. The WHO began developing the GBT in 2014 in response to the World Health Assembly’s Resolution 67.20 on strengthening the regulatory system for medical products. The GBT Revision VI was released in 2018.5
The number of regulatory agencies with functional systems as per the GBT increased from one in 2017 to 13 in 2022. Those 13 agencies represent about 50% of the world’s population. In addition to this, regional initiatives have built significant regulatory capacity beyond these 13 agencies, Dr. Guzman said.
“In the Americas, for instance, you have eight National Regulatory Agencies of regional reference that have been nominated as such by the PAHO [Pan American Health Organization] after external audits,” he said.
“LMICs should invest in strengthening their regulatory systems. This means having an adequate legal framework as well as appropriate resources — for example, funding, infrastructure, and human resources,” Dr. Guzman added. “The WHO GBT path is clear, and countries should follow it. A good entry point these days is local manufacturing. Regulation is a prerequisite for any local manufacturing initiative to be successful.”
Enforcing Post-Manufacturing Compliance
In a 2022 review, Hamid A. Merchant, PhD, now head of the Department for Bioscience at the University of East London in the U.K., and colleagues highlighted the key considerations to address before legally enforcing generic prescribing in LMICs.6 They focused on the Drug Regulatory Authority of Pakistan’s (DRAP) generic prescribing initiative, which directed health care providers to prescribe medicines with their generic names. The initiative started in response to the public disagreement on increasing medicine prices in the country, partly because prescribers in LMICs often receive incentives from pharmaceutical companies to favor a particular branded medication.
Dr. Merchant and colleagues reported a lack of evidence on bioequivalence and a lack of compendial compliance as difficulties in enforcing generic prescribing in LMICs, including Pakistan. The authors also highlighted that the lack of quality assurance practices in material sourcing and vendor approval processes means that products are subjected to increased inter- and intra-batch variability.
According to Dr. Iyer, companies require batch testing and an effective quality management system. “Procurers can incentivize this by ensuring that they only purchase from those who can demonstrate quality assurance and no issues,” she said.
“Quality can also be affected by improper storage, transportation, and use,” Dr. Iyer explained. Manufacturers can control storage in extreme climates in various ways, including refrigeration, packaging, and temperature-controlled indicators that can monitor when products go through large fluctuations that may affect a medication’s effectiveness or quality. “There are also, in some instances, kits that help pharmacists, health care workers, and others in testing products for quality,” she added.
The Access to Medicine Foundation monitors companies’ promotional behavior. “Companies should look at how sales agents are incentivized. They should be delinked from the volume of sales. Incentives given to doctors, pharmacists, and health care workers by the pharmaceutical industry should be banned,” Dr. Iyer said.
Addressing Varied Attitudes and Definitions
Physicians and pharmacists are aware of the cost- saving function of generic drugs, according to a 2015 systematic review, but attitudes varied worldwide.7 Else-Lydia Toverud, PhD, MScPharm, of the Department of Social Pharmacy at the University of Oslo in Norway, and colleagues found that trust in the quality of generic medications stood higher in Nordic countries than in southern countries. Less mature health care systems reported variation in the perspectives toward bioequivalence requirements and manufacturer standards. In the most developed health care systems, physicians and pharmacists trusted the quality of generic drugs and offered them to all patients regardless of socioeconomic status.
Concerns highlighted by Dr. Toverud and colleagues included the taste, packaging, and appearance of generic drugs, which may affect patients’ acceptance, adherence, and understanding, particularly among vulnerable groups, when switching to generics. In general, pharmacists appeared to have better knowledge of bioequivalence and aspects of generic medications than physicians.
“Knowledge and acceptance of generic drugs is still low amongst doctors,” wrote Jaykaran Charan, MD, of the All India Institute of Medical Sciences in Jodhpur, India, and colleagues in their 2021 study.8 Of the 240 primary care physicians in India that the researchers surveyed, 57% agreed that doctors should only prescribe generic drugs. The primary care physicians cited poor quality and less effectiveness as reasons for the low use of generics. Moreover, only 11.6% of the physicians surveyed could identify all the correct statements about generic drugs.
In principle, “a generic medicine should be marketed without a commercial brand name, under the international non-proprietary name (INN),” wrote Livio Garattini, PhD, and Katelijne van de Vooren, MSC, of the Center for Health Economics at the Mario Negri Institute of Pharmacological Research IRCCS, in Ranica, Italy, in a 2015 editorial.9 However, the authors, who cited a 2015 review, noted that the “definition of generic medicine is not always precise.”10
The definition of generic medicines should include the requirements for bioequivalence to permit the complete interchangeability of generics with originators. Differences in the terms used for generic medications — such as similars, copies, and branded generic products — exist among countries worldwide. “These differences and inconsistencies can challenge the trust of local people and must be addressed and recognized, particularly in developing countries,” Drs. Garattini and van de Vooren wrote.
Dr. Iyer, who also recommended that prescriptions should use the INN, noted that “patients should not be influenced by a drug’s brand, but rather be treated by effective medicines.”
References
- Bonniflield RS, Keller JM, Glassman A, et al. Tackling the triple transition in global health procurement. Center for Global Development. June 17, 2019. Accessed January 4, 2024. https://www.cgdev.org/better-health-procurement.
- Access to Medicine Foundation. Spotlight on the generics industry: new analysis looks at access efforts of 5 major companies. September 16, 2023. Accessed January 4, 2024. https://accesstomedicinefoundation.org/news/is-the-generics-industry-stepping-up-on-access-to-medicine-new-analysis-spotlights-actions-of-5-major-companies.
- Renner L, Nkansah FA, Dodoo AN. The role of generic medicines and biosimilars in oncology in low-income countries. Ann Oncol. 2013;24 (Suppl 5):v29-v32.
- World Health Organization. WHO Global Surveillance and Monitoring System. Accessed December 27, 2003. https://www.who.int/who-global-surveillance-and-monitoring-system.
- Guzman J, O’Connell E, Kikule K, et al. The WHO Global Benchmarking Tool: a game changer for strengthening national regulatory capacity. BMJ Glob Health. 2020;5(8):e003181.
- Merchant HA, Babar ZU, Hussain IM. A leap towards enforcing medicines prescribing by generic names in low- and middle-income countries (LMICs): pitfalls, limitations, and recommendations for local drug regulatory agencies. J Pharm Policy Pract. 2022;15(1):104.
- Toverud EL, Hartmann K, Håkonsen H. A systematic review of physicians’ and pharmacists’ perspectives on generic drug use: what are the global challenges? Appl Health Econ Health Policy. 2015;13(Suppl 1):S35-S45.
- Charan J, Saxena D, Chaudhri M, et al. Opinion of primary care physicians regarding prescription of generic drugs: a cross-sectional study. J Family Med Prim Care. 2021;10(3):1390-1398.
- Garattini L, van de Vooren K. Safety and quality of generic drugs: a never ending debate fostered by economic interests? Appl Health Econ Health Policy. 2015;13(Suppl 1):S3-S4.
- Alfonso-Cristancho R, Andia T, Barbosa T, et al. Definition and classification of generic drugs across the world. Appl Health Econ Health Policy. 2015;13(Suppl 1):S5-S11.