The COVID-19 pandemic has highlighted vulnerabilities within the generic drug supply chain. To minimize the effects of antibiotic API supply disruptions, it is important to understand the underlying reasons for shortages to then identify the best-fit manufacturing partners.
The COVID-19 pandemic has disrupted the global drug supply, as manufacturing companies contend with government-mandated or recommended temporary shutdowns, new safety initiatives to ensure employee health and well-being, employee absences due to illness and restrictions for importing/exporting and travel. Antibiotic manufacturing has been particularly affected, and this is not the first time. In the United States alone, there were 148 antibiotic shortages from 2001 to 2013,1 and a recent penicillin shortage affected at least 39 countries throughout Europe, the Americas and Asia.2 As of June 29, /2020, 10.5% of all drug shortages listed by the FDA were antibiotics.3
Gaining an understanding of the underlying reasons for antibiotic shortages can help inform your choice of global active pharmaceutical ingredient (API) suppliers, to help minimize the impact of supply disruptions.
Narrow profit margins
First, the profit margin for antibiotics is narrow – throughout the supply chain – resulting in few manufacturers for a given API. For those manufacturers that remain in operation, constraints on manufacturing capacity force decisions about the best use of their available resources.4 The most profitable choice often wins. This, among other factors, could be contributing to the increasing rate of generic drugs exiting from the market,5 resulting in fewer available generic drug options.
Lack of incentives for quality
The FDA has found that quality issues are the cause of most shortages and suggested that incentives for quality management systems are lacking.6 Older, poorly maintained manufacturing equipment can lead to quality problems and ultimately a shortage in the API supply. But some manufacturers find it difficult to justify the high cost and risk of investing in equipment expansion or upgrades, particularly for older drugs (median time of 35 years since first approval) that represent a large proportion of drugs in shortage.4 With the aging of facilities producing the API for these older drugs, the following factors contribute to quality issues: lack of updates to routine operations to maintain a state of control, older technology and changes in suppliers and scientific expectations.
Logistical and regulatory issues
Finally, disruptions such as an outbreak or natural disaster tend to upend the market due to logistical and regulatory issues. Because there are typically few active suppliers for a given API, when one stops production, output from the remaining suppliers must increase exponentially to meet demand. Significant resources are required not only to increase production but also to get the additional required approvals from multiple regulatory agencies.
To minimize the risk of drug shortages, the FDA and International Council for Harmonisation (ICH)7 have issued or are expected to issue guidelines to improve quality controls and provide reasonable expectations for the level of regulatory review required when scaling production to meet increased demand. In addition, the FDA has suggested that drug manufacturers conduct a risk assessment to identify vulnerabilities in their supply chain, establishing a risk mitigation plan and moving to continuous manufacturing, which is considered more reliable than batch manufacturing.6
Find the right API partners
The COVID-19 pandemic has highlighted the need to ensure a quality, reliable API supply by partnering with the best-fit API manufacturers. To achieve this, it is important to understand the number of available manufacturers for your API, manufacturers’ global experience within and across regulated and less-regulated markets, production and logistical performance capabilities and presence of quality systems. With appropriate planning and the right partners, the effects of API supply disruptions can be minimized.
Understand the generics landscape and find the best API partners with Cortellis Generics Intelligence, to grow your business and rise above the competition.
- Quadri F, Mazer-Amirshahi M, Fox ER, et al. Antibacterial drug shortages From 2001 to 2013: implications for clinical practice. Clin Infect Dis 2015;60:1737–1742.
- Nurse-Findlay S, Taylor MM, Savage M, et al. Shortages of benzathine penicillin for prevention of mother-to-child transmission of syphilis: An evaluation from multi-country surveys and stakeholder interviews. PLOS Med 2017;14:e1002473.
- FDA Drug Shortages. Current and resolved drug shortages and discontinuations reported to FDA. https://www.accessdata.fda.gov/scripts/drugshortages/default.cfm. Accessed 6/29/2020.
- FDA. Drug shortages: Root causes and potential solutions. A report by the Drug Shortages Task Force. 2019. fda.gov/media/131130/download. Accessed 6/29/2020.
- Conti RM, Berndt ER. Four facts concerning competition in US generic prescription drug markets. NBER working paper series. 2019. http://www.nber.org/papers/w26194. Accessed 7/15/2020.
- Dabrowska A. Drug Shortages: Causes, FDA Authority, and Policy Options. December 17, 2018. https://fas.org/sgp/crs/misc/IF11058.pdf. Accessed 7/15/2020.
- International Council for Harmonisation. Technical and regulatory considerations for pharmaceutical product lifecycle management: Q12. November 20, 2019. https://database.ich.org/sites/default/files/Q12_Guideline_Step4_2019_1119.pdf. Accessed on 6/29/2020.