It’s been a year since Hurricane Maria made landfall in Puerto Rico. In the aftermath of the devastation it wrought, FDA Commissioner Scott Gottlieb, tweeted, “Our immediate actions [are] focused on saving life and people of #PR. @US_FDA also working to help secure critical drug plants to avert shortages.”

I replied, “If our CMO members can help avert shortages, let us know.” A day later, the FDA’s Incident Management Group reached out to the Pharma & Biopharma Outsourcing Association (PBOA) to find out how CDMOs would be affected by the damage in Puerto Rico.

I surveyed our members, expecting that the responses would be from CDMOs with sites on the island. It turned out to be more complicated than that: less of a supply chain and more of a supply network. Some of our members manufacture product on the mainland U.S. and ship it to their customers’ sites in PR for packaging and distribution. Another told me that certain components used for bioprocessing came from sites on the island and if there was no second supply, the supply of certain biologics would be curtailed.

For our members with operations in PR, as well as one not-yet-member, we helped connect them with the FDA to identify which products they were making, where they fell on FDA’s crisis list, and how to prioritize power restoration to prevent drug shortages.

A number of shortages did occur in the wake of Hurricane Maria. The lack of IV saline bags briefly reached near-crisis levels during the particularly bad flu season in the U.S. While manufacturers in PR worked to rebuild their operations and restore supply, FDA had to bring in emergency imports from foreign sites.

PBOA had already looked into how CDMOs can help alleviate drug shortages, but the nightmare in Puerto Rico inspired us to push those efforts and work with legislators and regulators to provide a backstop against natural disasters and other situations.

Not every drug shortage is due to finished dosage form (FDF) manufacturing facility issues; many arise from API supply problems and economic disincentives. Those latter factors are outside of our scope (for the most part), but we are certain that CDMOs can help restore dosage manufacturing capacity for key drugs.

Currently, if a shortage occurs due to a manufacturing failure, such as a plant being taken “offline” due to inspectional issues or a natural disaster like Hurricane Maria, the license holder of a drug can engage a new facility such as a CDMO or another in-house facility of its own to manufacture the product. But this process is time-consuming, and necessitates that the new facility and the license holder conduct extensive validation requirements, stability testing, and potentially be subject to a facility inspection by the relevant regulator, typically the FDA. While this process is unfolding, the delivery of needed medications to patients may be disrupted.

One solution that PBOA has developed and worked on with Congress would be for FDA to create a new designation—Shortage Manufacturing Establishments (SME)—wherein FDF manufacturing facilities that have potential excess capacity, and that satisfy certain criteria, could seek a “pre-shortage certification” to produce certain types of products in shortage for their customers. The agency would regularly publish a list of the qualifying sites broken out by dosage form, easing the process for license holders to find a potential manufacturing partner.

In other words, if a license holder were to face a potential disruption in its ability to manufacture a product, it would know in advance where it could turn: namely, a facility designated as an SME by the FDA in that dosage form.

To expedite availability of supply from reliable entities, Shortage Manufacturing Establishments would be eligible for a number of regulatory efficiencies and limited exemptions related to pre-approval inspections and manufacturing change submissions, so long as they qualified, and were designated by FDA, to be an SME. To be certified, a facility would have to have an acceptable compliance history, recent experience in manufacturing FDF products in the relevant dosage form class, and available capacity.

Our goal is to create a bench of well-qualified manufacturing sites that are pre-designated and ready to work with license holders in the event of a potential shortage. We believe that this program will help to avoid pending shortages, provide a network of rapid-response manufacturers in case of emergency, and help license holders develop ready backup suppliers of critical drugs.

We should never forget that 3,000 people lost their lives in the wake of last year’s hurricane. For PBOA, we want to make sure that the next natural disaster doesn’t lead to shortages that can cost the lives of those thousands of miles away from the storm.

---

Gil Roth
President, Pharma & Biopharma Outsourcing Association

Gil Roth is the President of the Pharma & Biopharma Outsourcing Association (www.pharma-bio.org). He can be reached at gil.roth@pharma-bio.org.