M-15: Global Supply Chain Issues Affecting Biopharmaceutical Manufacturers: An Analysis of FDA Warning Letters from 2013-2018
Poster Presenter
Sean Kerns
Graduate Researcher
University of Southern California United States
Objectives
Identify common problems and current trends in quality issues affecting the biopharmaceutical supply chain by reviewing US Food and Drug Administration (FDA) warning letters issued to manufacturers of active pharmaceutical ingredients (APIs) and finished products (FPs).
Method
A ProQuest literature review was conducted to understand the landscape of supply chain quality issues affecting the pharmaceutical industry. FDA Warning Letters from 2013 to 2017 issued to API and FP companies were reviewed for supply chain issues.
Results
Previous research showed that from 2013 to 2018, 22 companies from China, 19 companies from India, and 3 companies from US received warning letters regarding issues related to APIs . In that same period, 19, 24, and 41 warning letters were issued to China, India and US respectively for FPs . Although not all warning letters specifically identified supply chain management issues, many pointed to problems that could impact the supply chain. For example, there were failures to perform tests on incoming materials, to validate that APIs met quality/purity standards, to identify the API manufacturer and qualify the raw materials, and to confirm that the product met specifications upon entering US.
This research examined the warning letters from above that specifically identified quality issues associated with the API and FP suppliers. Of the 44 Warning Letters issued to API suppliers, 11 indicated supplier-related quality issues, including a lack of a proper internal supplier Quality Department. These types of deficiencies led to supplier-related quality breaches like failing to adequately investigate out-of-specification batch results, approving the use of adulterated materials in drug manufacturing, sourcing materials from companies on the FDA Import Alert, and falsifying results of product quality testing.
Of the 36 Warning Letters issued to FP suppliers, 7 did not adequately test incoming APIs to validate product quality. Consequently, tainted APIs could be introduced into the finished products and potentially to the patients. These deficiencies pose serious risks to the integrity of the supply chain.
Conclusion
Because 80% of APIs and 40% of FPs are manufactured outside of the US, the FDA maintains offices and conducts inspections in many regions of the world. Despite this FDA oversight, there are still numerous quality issues resulting from these complex supply chains.
The findings from this study may inform firms sourcing their products from foreign suppliers of the potential adverse quality issues that can impact their products. Firms could incorporate strategies to strengthen their supply chain and ensure the quality of their supplier’s materials. A common theme among the analyzed Warning Letters was the lack of an internal supplier Quality Unit, which provides a strong starting point for firms seeking to ensure product quality. Implementing increased monitoring and review procedures for their suppliers can help ensure they are maintaining a Quality Unit following best practice guidelines. In addition, FP companies should ensure that their own quality and testing departments are given the necessary resources to verify incoming API quality and prevent contamination of their FPS.
A case study illustrating the importance of ensuring API and FP suppliers meet the highest quality standards is the recent recalls of some angiotensin receptor blockers (ARBs) products due to contamination with carcinogenic materials. Although investigation is still underway, the FDA believes the source of this contamination originated with overseas API suppliers. A more robust quality oversight program for the ARB API suppliers, along with strengthened incoming API testing and validation for the FP companies, may have helped prevent these tainted products from reaching patients.
Although issues related to API supplier quality and FP verification were present in 25% or less of the warning letters analyzed, outcomes from these issues may be severe. Due to these serious outcomes, companies and regulators should pay keen attention to ensuring the prevention of these issues.
