FDA Works to Resolve Amino Acids Shortage

Travasol Dosage Information for Pediatric Patients

Baxter Healthcare Corporation has notified ASPEN that Travasol Package Labelling now includes dosage information for pediatric patients. This information can assist clinicians in assessing which infants and children are candidates for Travasol. Additionally, Baxter has developed a comparison chartof Premasol and Travasol. This important new information can be instrumental in assisting the clinician in maximizing the conservation of the specialized amino acid products that should be reserved for neonates who require these products. 

FDA Works to Address Amino Acids Shortage

On November 30th, Dr. Scott Gottlieb, FDA Commissioner issued an update on the Puerto Rico-related drug shortages that included this information about the amino acids shortages:

“In addition to our ongoing concerns related to IV saline products, we also are particularly focused on the shortage of amino acids for injection. This product is of critical need for patients, including children and infants, who are not able to eat and need to receive their nutrition intravenously. Like with saline, an ongoing amino acid short supply situation was worsened by Hurricane Maria’s impact on Puerto Rican drug manufacturing facilities that manufacture this product.

Most notably, the hurricane disrupted Baxter’s amino acids production facilities in Puerto Rico; Baxter is one of the largest manufacturers of this product serving the U.S. market. In order to help mitigate this shortage, the FDA has worked with Baxter to facilitate the temporary importation of amino acids for pediatric and adult formulations of IV amino acids from Baxter facilities in the United Kingdom and Italy. We’re also working with other manufacturers of amino acids to increase supplies to address the shortage, including ICU Medical and B. Braun. ICU Medical had experienced manufacturing delays, but now plans to return to the market soon, which will further help address the shortage.” Read the full statement here

What is Temporary Importation?

When United States (U.S.) pharmaceutical manufacturers are unable to resolve a critical drug shortage, the U.S. Food and Drug Administration (FDA) may look for a manufacturer in another country that makes the drug, can increase capacity and is willing to send the drug to the U.S. Sometimes, U.S. manufacturers also have facilities in other countries that are a potential source for the drug or a therapeutic equivalent to the drug that is in short supply.  The FDA considers a list of criteria to evaluate the product to ensure efficacy and safety and will not pose undue to risk to U.S. patients. These criteria include:

  • the formulation and other attributes of the drug including
    • how does it compare to the drug it is replacing?
    • are all ingredients approved for use in the U.S. and if not, what safety data is available?
    • drug safety data?
  • the quality of the manufacturing site where the drug is made
  • manufacturing practices at the facility and of the facility where the active pharmaceutical ingredient is produced,
  • history of inspection of those facilities from the U.S. FDA or the foreign regulatory counterpart, and
  • sterilization methods used for injectable drugs to ensure they meet the FDA standards. 

Once this thorough review is completed the FDA works with the foreign manufacturer to develop:

  • a distribution and shipping plan,
  • how adverse events will be reported to FDA,
  • a Dear Healthcare Professional (HCP) letter, which highlights important dosing and safety information, and
  • product labeling (preferably in English).

Only after these processes have been successfully completed will the FDA permit the temporary importation of the drug from the foreign manufacturing facility. 

However, like U.S. pharmaceutical manufacturers, facilities in other countries are usually running at full capacity, and do not have idle manufacturing lines or hold excess inventory. This means foreign manufacturers are unable to immediately fill orders for the U.S. market. It may take several weeks for the foreign manufacturer to produce enough drug to send to the U.S. Initial shipments of the foreign-sourced drug may be of limited quantities. They also need to create special product labeling and place the Dear HCP letter in the drug shipping cartons.

Shipping the drug to the U.S. takes time, especially if it is sent by sea. Sometimes air shipment is used, but this is often limited due to the high cost. Once the drug arrives in the U.S. it must clear Customs and be released by the FDA to the distributor and the FDA expedites this process.

As there may be limited quantities of the drug, especially in the early phase of the import, the U.S. distributor may establish an allocation system for fair distribution of the drug to pharmacies and healthcare institutions. Once temporary importation of a drug is established, FDA will continue to support the importation until the approved manufacturers can meet all U.S. patient needs.

The manufacturer of the foreign-source product is not allowed to market the drug, as it is not an approved product in the U.S., thus there is a reliance on the distributors to notify pharmacies/healthcare institutions that the product is available for purchase.

This process from identifying a foreign source of a drug in short supply and getting the drug into the supply chain may take a minimum of 6-8 weeks. While this seems like a long and tedious process towards resolving a shortage, it is an important process to protect the health of patients during a shortage and to ensure that a new product, albeit a replacement for a similar product, is used safely.