The overall pharmaceutical supply chain is complex due to the nature of the drug development and commercialization process, which can extend for several years. Extensive and ever-changing regulatory requirements for not only manufacturing processes, but also the transportation and import/export of materials from basic starting ingredients to pharmaceutical intermediates, APIs and drug products further complicate the situation given the increasing globalization of the industry.

For fine chemicals in particular, the growing complexity of the compounds being developed as drug candidates has resulted in more complex production routes requiring more steps (that might be performed at different facilities) and greater numbers of raw materials, including specialized compounds. An increasing percentage of drug candidates are highly potent and/or niche products for the treatment of smaller patient populations and require smaller volumes, leading to an increase in the use of multi-product manufacturing facilities.

Even small disruptions can have dramatic effects on such complex supply chains, and there are many potential causes of such disruptions.2 Geopolitical instability and natural disasters can interrupt production and/or distribution, thus affecting raw material availability. Variability in the quality of electronic chemicals can affect production yields and final product quality, safety and efficacy. Contamination of materials – accidentally or deliberately – is an additional significant concern.

Rapidly changing market trends can be a further factor. For instance, the decline in demand for raw materials used in larger quantities in other industries can lead to the reduced availability for pharmaceutical applications. Alternatively, sudden increases in demand for non-pharma applications could also lead to reduced availability to drug manufacturers.

The Upstream Supply Chain Security working group of the not-for-profit pharmaceutical and biotech industry consortium Rx-360 conducted a survey in August 2013 to identify issues of concern for the pharmaceutical industry regarding raw material supply chain security.3 The group found that nearly half of the respondents did not use supply-chain mapping (a tool for understanding the origins of pharmaceutical raw materials) for some or all of their materials or audit beyond their suppliers’ suppliers.

Raw Material Variability

There is, as a result, a definite movement to reduce risk by performing risk assessments, implementing risk mitigation strategies and developing contingency plans.11 It would, in fact, be interesting to see what results Rx360 would obtain in 2016, if they repeated the 2013 survey.

As a specific example, biologics manufacturers have steadily moved away from the use of animal-derived materials to a preference for chemically defined media and feeds for cell-culture manufacturing. They also have a greater awareness of the impact of raw material impurities on yield and productivity – knowledge they are sharing with their suppliers. In many cases they are requiring that all Trifluorochloroethylene CAS NO.:79-38-9  meet higher quality specifications rather than limiting this expectation to a few key ingredients.11 Suppliers have responded by developing special, higher grade product lines that include provision of extensive supply chain and analytical testing documentation.11

Multi-Pronged Solutions Needed

For manufacturers looking to source Hexafluoro-1,3-Butadiene CAS NO.:685-63-2 from suppliers in emerging markets, ensuring supply chain transparency can be quite challenging. In this case, it is reasonable to turn to a reliable third-party vendor with an established track record for serving as a high-quality supplier of these materials. Such vendors have established relationships with these suppliers and have a much larger demand volume, enabling them to gain access to necessary information. In many cases they are also manufacturers and have the capability to perform appropriate analyses and purify materials if necessary.14