Supply Chain Matters has highlighted a number of supply risk and potential ingredient safety challenges impacting pharmaceutical and drug supply chains of life-critical medications and yet such challenges seem to persist, often in the same dimensions. A recent Bloomberg published article highlights the latest involving cancer-drug shortages with supply chain ingredients continuing to be sourced from banned Chinese producers. The open question is why the industry continues to foster such sourcing practices.
When we launched Supply Chain Matters back in 2008, one of our first series of commentaries concerned supply chain risk management, specifically the issue of the tainted pharmaceutical drug heparin that originated from Chinese based suppliers. At the time, tainted batches of the prime API compound that produces heparin, a key life-saving drug utilized as a blood thinner, were found to later contain over sulfated chondroitin, an altered version of the required chondroitin sulfate. Instead of sourcing this active API from designated pig intestines, the tainted API apparently came from shark cartilage. This specific incident was directly attributed to the death of 80 persons and many others became seriously ill. Our 2008 commentary, Will FDA Inspectors in China Solve Product Safety Issues?, questioned whether regulatory agencies were ill equipped to keep up with the pace of global outsourcing of pharmaceutical compounds and specifically getting a handle on the increasing occurrence of counterfeit or non-conforming products.
In 2012, the pendulum shifted towards global-wide shortages of life-saving drugs due to a number of domestic and global-based API suppliers either unable to produce required quantities or having to temporarily suspend production operations because regulatory inspections citing lapses in good manufacturing practices. Agencies subsequently had to alert doctors and healthcare providers that in the light of severe shortages of hundreds of drugs, there were clear signs that unauthorized or counterfeit versions of these drugs had infiltrated global supply chains. The U.S. FDA alerted to the appearance of “non-FDA approved injectable cancer medications” and later, patients and drug companies were subjected to counterfeit versions of the drug Avastin, widely prescribed to treat brain, colon, lung and kidney cancers. Swiss drug maker Roche, and its Genetech unit, the global producers of Avastin later indicated that counterfeit versions of its top-selling cancer drug, ones without any active ingredient, were being circulated in the U.S. Patients receiving this counterfeit version would thus not have received required therapy, or worse, could suffer potential harm.
The latest iteration outlined in a recent Bloomberg Businessweek article cites data from the National Academy of Medicine indicating that more than 80 percent of ingredients used in drug manufacturing are now produced externally, primarily in China and India. Further cited is an incident where the U.S. FDA inspected a Chinese production facility in early 2015 and uncovered what was termed “broad data manipulation” resulting in a warning letter to plant owner Zhejiang Hisun Pharmaceutical. That subsequently led to an indefinite ban for this facility in September 2015, a first for one of China’s leading exporters of pharmaceuticals. However, according to this report: “…to avoid possible drug shortages, the regulatory agency allowed the Hisun facility to continue to export about 15 ingredients used for drugs produced in the U.S., including nine components of cancer medicines.” The report goes on to explain the delicate balancing act regulators currently face in insuring adequate supplies of life-saving drugs while de-facto transferring the burden of assuring safety and quality inspections to end-item drug manufacturers themselves. End-item drug producers are therefore asked to perform additional inbound testing, hire independent auditors or take other mitigative actions. Overall, Bloomberg indicates that the FDA has for the current year added 13 plants to its listing of banned plants, with a cumulative total of 52 classified banned plants.
We found that statistic to be staggering and alarming. Once more, we wonder aloud about the strategies that have led to increased outsourcing to lower-cost production regions, especially for drugs that are held to such high specification standards and currently sold for staggering margins in developed countries. One has to wonder aloud as to why.
According to the Bloomberg report, among the 15 API’s from the subject Hisun Taizhou plant that can be exported by exception, most are widely used for producing chemotherapy treatments for leukemia, breast and ovarian cancers. One would surmise that these drugs are expensive. A former FDA official who once was responsible for domestic and international investigations indicated to Bloomberg of his belief that not all U.S. companies are ensuring the safety of ingredients purchased from known banned factories.
Regulators such as the U.S. FDA are indeed placed in a rather difficult position in trying to assure that life-saving drugs remain in adequate supply in the light of an overall industry trend to source compound ingredients from lower-cost production regions. Critical drug shortages of expensive drugs lead to the creation and distribution of counterfeits which obviously adds to overall safety concerns.
Yes, drug markets serving China and India should come with government controls that require far lower costs to healthcare providers and patients. Drug companies continue to extract far higher end-item drug costs for distribution among highly developed countries and economies. Ingredient sourcing and quality conformance strategies should align.
The pharmaceutical and drug industry has often been in media headlines portrayed as profit-grubbing villains. In some cases, that may be underserved, since research, development and production costs for life-saving drugs are rather expensive. However, when the industry continues to pursue supply chain sourcing strategies that are driven more by lower-cost and do not insure adequate safeguards, than they need to be called out. Armies of FDA inspectors chasing endless foreign producers are a Band-Aid to a broader challenge of supply chain sourcing.