Issue link: https://www.e-digitaleditions.com/i/1295512
Tablets & Capsules October 2020 9 streamline and simplify operations more than ever before, which could come at a cost to quality assur- ance. Additionally, high demand for certain ingredients and products are causing shortages, which, in turn, are leading to surges in production of those ingredients or products [7]. While shortages are worrisome, so are surges—materials coming from new suppliers to combat shortages may lack quality. For the same reason, there is increased risk of adulteration by bad actors motivated by economic gain and not dedicated to quality [8]. Country of origin and supply chain complexities are two major external risk factors for manufacturers working to produce quality drug products and ingredients. Other external risk factors include material value and economic motivation for adulteration, the reputation of manufactur- ers and distributors, and transportation practices. Internal factors can also increase risk, including source of material, amount and type of processing, lack of compendial stan- dards, complexity of material, and product variability due to season or temperature conditions. For example, nizatidine capsules were voluntarily recalled in 2020 due to contamination of the API with N-nitrosodimethylamine (NDMA) to prevent any poten- tial adverse events [9]. These risks can also lead to serious consequences. Recently, the excipient, propylene glycol, contained in ColdBest-PC cough syrup, was contami- nated with chemical diethylene glycol (DEG)—causing the death of nine children [10]. Manufacturers must mit- igate these internal and external risks and prevent them from compromising the quality of their products and impacting people's lives. Prioritizing quality With the industry facing so many concerns, many manufacturers are seeking solutions to ensure that con- sumers can trust their products. Quality standards serve as a roadmap for helping to ensure quality and prevent fraud. by the pandemic, compared to only 4,180 inspections through June 11, 2020 [1]. The decrease in on-site inspections has the potential to increase quality risks to the global supply chain and puts more of the burden on manufacturers and suppliers to ensure the quality of their drug products and ingredients. Per a July 10, 2020 FDA statement, the agency "deter- mined that for the foreseeable future, prioritized domes- tic inspections will be pre-announced" [2]. Also, the FDA has been forced to use different tactics for foreign manu- facturers to ensure safety and is relying on methods such as denying entry of unsafe products into the US, con- ducting physical examinations and/or product sampling at US borders, reviewing a firm's previous compliance history, using information sharing from foreign govern- ments as part of mutual recognition and confidentiality agreements, and requesting records "in advance of or in lieu of" on-site drug inspections [3]. The cost of disruption The global drug supply chain is complex and has always been vulnerable to disruptions. In fact, the past 200 years have been defined by a series of disruptions to the industry. The 40 years preceding COVID-19 were characterized by growth, distribution, and consolida- tion—all potential drivers of disruption [4]. Today, more companies manufacture drug products outside the US, and only 28 percent of active pharmaceutical ingredient (API) manufacturing sites are in the US [5]. Many inter- mediaries play a role in a drug products' production, dis- tribution, and delivery. In fact, a 2011 survey showed that 79 percent of manufacturers of pharmaceuticals rely on at least one component, manufacturing material, or finished product from a non-US supplier [6]. The COVID-19 pandemic is a disrupter unlike any the global supply chain has seen, and with increased disruption comes increased risk. Manufacturers must 20_0313_AD_O Tab and Cap Mag.pdf 1 3/13/20 1:50 PM