Challenges of drug manufacturing
Challenges of drug manufacturing
Although the challenges of bringing a new pharmaceutical product to market are well known; what is sometimes surprising is that manufacturing pharmaceutical products at a commercial scale is not always the easy part.
Broadly speaking, there are two categories of pharmaceutical companies: innovator companies and generic companies. Innovator companies generally invest a significant amount of their revenue in research and development in order to discover, develop and bring new pharmaceutical products to the market.1 In terms of the money spent by pharmaceutical companies all along the value chain, for innovators, the largest costs are associated with drug discovery, clinical trials and the costs involved to satisfy regulatory authority requirements. Once the drug is approved, innovative companies then need to actively promote the drug by educating stakeholders about the product and its potential benefits. Generic companies on the other hand generally have lower development and manufacturing costs and their promotional activities tend to focus on incentives to secure large volume orders.1 Although the clinical development of new drugs is widely understood to be time consuming, expensive and financially fraught – with disappointing clinical results leading to the abandonment of new drugs – the challenges associated with the manufacture of pharmaceutical products are legion.2,3 This is important as in recent years new manufacturing and supply chain disruptions have arisen, which have resulted in an increased frequency of drug shortages.4
The manufacturing process of a drug can be summarized in two steps: the manufacturing of the active pharmaceutical ingredient, which involves the processing of the raw ingredients used in medicines; and the manufacturing of the finished pharmaceutical form, which is ready for distribution and sale.1 However, the transition from bench research to final product can be more challenging than expected, and in some cases can be the reason for abandoning the product’s development. For example, in the arena of contrast agents, a number of promising candidates such as Gadomer-17 and Vistarem were abandoned during the clinical development phase for a number of issues that included problems with the industrialization.5-7 Even once the drug is marketed, emergent disruptions in the ingredient supply chain may lead to critical shortages of the drug.8,9
There can be many reasons for drug shortages, for example, issues related the quality of the drug, disruptions in supply of manufacturing components or ingredients, or unanticipated demand, to mention just a few.9 In order to mitigate the potential public health implications caused by shortages of essential medication, the FDA has issued guidance to manufacturers in an attempt to minimize or avoid production and supply chain disruptions.9 These guidelines provide a framework for manufacturer to proactively identify, prioritize, and implement strategies to mitigate hazards that could cause disruptions in the provision of drugs.9
The existence of these guidelines highlights how serious the issue can be and serves as a reminder for manufacturers to expect – and to prepare for – the unexpected.
- Aitken M. Understanding the pharmaceutical value chain. Pharm Policy Law 2016;18:55-66.
- Grangeia HB, Silva C, Simões SP, Reis MS. Quality by design in pharmaceutical manufacturing: A systematic review of current status, challenges and future perspectives. Eur J Pharm Biopharm 2020;147:19-37.
- Yu LX, Kopcha M. The future of pharmaceutical quality and the path to get there. Int J Pharm 2017;528:354-9.
- Cameron EE, Bushell MA. Analysis of drug shortages across two countries during pre-pandemic and pandemic times. Res Social Adm Pharm 2021;17:1570-3.
- Lancelot E, Raynaud JS, Desché P. Current and future MR contrast agents: seeking a better chemical stability and relaxivity for optimal safety and efficacy. Invest Radiol 2020;55:578-88.
- Fries P, Runge VM, Bücker A, Schürholz H, Reith W, Robert P, Jackson C, Lanz T & Schneider G. Brain tumor enhancement in magnetic resonance imaging at 3 tesla: intraindividual comparison of two high relaxivity macromolecular contrast media with a standard extracellular gd-chelate in a rat brain tumor model. Invest Radiol 2009 44 200-206.
- Misselwitz B, Schmitt-Willich H, Ebert W, Frenzel T & Weinmann HJ. Pharmacokinetics of Gadomer-17, a new dendritic magnetic resonance contrast agent. Magma 2001 12 128-134.
- Cundell T, Guilfoyle D, Kreil TR, Sawant A. Controls to minimize disruption of the pharmaceutical supply chain during the COVID-19 pandemic. PDA J Pharm Sci Technol 2020;74:468-94.
- Risk management plans to mitigate the potential for drug shortages. Guidance for Industry. U.S. Department of Health and Human Services, 2022. (Accessed May 2022, at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/risk-management-plans-mitigate-potential-drug-shortages.)