503A Compounders May Get Another Bulk Substance Permitted, But For Now, Enforcement Discretion

In a Federal Register Notice (here) published today, the FDA announced a Compliance Policy which will exercise enforcement discretion relative to 503A compounders using the bulk drug, Oxitriptan, for compounding oral forms of the drug.  Remember, “FDA issued a final rule (84 FR 4696) (“February 19, 2019, final rule”), which established the list of bulk drug substances that can be used to compound drug products under Section 503A of the FD&C Act even though they are not the subject of an applicable USP or NF monograph or a component of an FDA approved drug product (the 503A Bulks List).” Oxtriptan was specifically excluded from that list.

Additionally, since ”Oxitriptan is neither the subject of an applicable USP or NF monograph, nor a component of an FDA approved product, the FD&C Act requires that Oxitriptan be placed on the 503A Bulks List.

Oxitriptan was nominated and evaluated for inclusion on the 503A Bulks List for use in the treatment of insomnia and depression, not BH4 deficiency of an FDA-approved drug.

So why the sudden turnaround?  Shortly after the Notice prohibiting the use of the bulk substance, FDA began hearing “from pharmacists and caregivers regarding the use of Oxitriptan to treat patients with BH4 deficiency.”  “BH4 deficiency is also known as: primary tetrahydrobiopterin deficiency, atypical phenylketonuria (PKU), GTP cyclohydrolase (GTPCH) deficiency, 6-pyruvoyl-tetrahydropterin synthase (6-PTPS) deficiency, and dihydropteridine reductase (DHPR) deficiency.”

FDA notes that, in its initial assessment of Oxtriptan, it did not consider the use of the bulk drug in treating BH4 deficiency when it did not place the bulk drug on the list of bulk substances that could be used to compound drug products by 503A compounders.  Based on this identified use, the FDA will reconsider whether to officially include Oxtriptan on the bulk list of bulk drugs for use by 503A compounders, until it reaches a conclusion that Agency does not intend to take actions against 503A facilities that compound oral versions of Oxtriptan for patients with diagnosed BH4 deficiency.

Enforcement discretion will be exercised so long as:

  • The compounded Oxitriptan-containing drug product is intended only for oral administration;
  • The compounder provides the Oxitriptan-containing oral drug product solely for identified individual patients with BH4 deficiency, after receiving a valid prescription for such identified individual patient indicating the diagnosis;
  • The compounder maintains records documenting that the drug product was compounded for a patient with BH4 deficiency; and
  • All other conditions of Section 503A and other applicable requirements of the FD&C Act and FDA regulations are met.

FDA will take enforcement action if the bulk drug is used for other than the oral route of administration,  or if used to treat other conditions.  This would likely mean that FDA will may evaluate the written prescription to assure there is documentation on the script to show the product dispensed is for BH4 deficiency.  A copy of the Guidance which is for immediate implementation can be found here.

Keep your eye on this issue for future Federal Register Notices that will likely permanently revise the list.