Dealing with product supply risks
With limited resources of people, money, time, and facilities, it is not possible to mitigate all risks. A key first step
to addressing risks is to comprehensively identify and document risks, and rank them based on the severity of the disruption
and its probability of occurrence. How and when a company addresses these risks depends on the company's tolerance for risk.
Critical or high risks should be addressed, while the low or medium risks could be accepted and dealt with in a reactionary
mode if and when they occur. Although many of these mitigation projects may have a negative return on investment, they should
be considered as the insurance premium that a company is willing to pay to mitigate the risk.
Once the decision is made to deal with a risk, the team can consider several mitigation strategies, as shown in Figure 1.
Figure 1: Four strategies can be used to mitigate product supply risk. (ALL FIGURES ARE COURTESY OF THE AUTHOR)
- preventive and analytical technology
- inventory control
Infrastructure can be designed to mitigate the effects of natural disaster. For example, buildings can be constructed with
seismic controls or fire-proofing.
Technology can be used to help prevent the risk of adventitious agents (e.g., viruses, mycoplasma, or prions). For example,
media can be treated with high-temperature, short-time (HTST) or ultra-violet C (UVC) radiation or viral filtration, or a
manufacturer can use raw materials that are animal-free, recombinant, or gamma-irradiated. In addition, analytical methods
for early and rapid detection should be considered. Analytical tools that enable early detection (e.g., quantitative polymerase
chain reaction assays for mycoplasma/viral contamination) might allow a manufacturer to isolate the problem and take corrective
action before the contamination spreads through a facility.
Using inventory control, the combined shelf-life of drug substance intermediate (DSI), drug substance (DS) and drug product
(DP) can be leveraged to minimize product shortfalls. By maintaining sufficient levels of DSI and DS, the impact of a sudden
DP shortage could be mitigated by converting the DSI into DS, and then forward processing to DP. In addition, multisite storage
of the DSI, DS and DP should be considered to avoid a stock-out situation in case of a disruption at the storage facility
or with the transportation lanes. However, this needs to be balanced with the cost of inventory.
Finally, diversification by implementing backup manufacturing is an effective mitigation strategy. Diversification can be
achieved using an in-house manufacturing network, partnership, or contract manufacturing organization (CMO) manufacturing
capability. Recent industry surveys suggest that microbial and mammalian manufacturing networks are not fully utilized, which
shows that diversification remains a viable option for companies to pursue to ensure robust product supply. Manufacturers
should consider which products should be diversified and when this should be implemented, whether at late-stage clinical development
or postcommercial approval of the product. Before employing diversification, a company should first consider whether the impact
of disruption can be mitigated effectively using other options and if the company has the resources required for the desired