Generic drugmakers get cannabidiol bioequivalence guidance from FDA
Manufacturers who seek to produce generic versions of cannabidiol oral solution received guidance from the US Food and Drug Administration (FDA) on establishing bioequivalence with the reference listed drug.The guidance follows the June 2018 approval of Epidiolex (cannabidiol) oral solution to treat seizures associated with two rare and serious types of childhood epilepsy. Epidiolex was also approved to treat a third seizure condition, tuberous sclerosis complex, in July 2020. (RELATED: Update on the regulatory status of cannabidiol in food and dietary supplements and future prospects, Regulatory Focus 12 June 2019)
Generic versions of cannabidiol oral solution 100 mg/ml must have “the same active drug ingredient in the same concentration and dosage form as the reference listed drug” in order to qualify for a waiver that exempts the drugmaker from conducting the otherwise-required in vivo bioequivalence study.
Also, the guidance specifies that the tested drug product cannot contain more than 0.10% tetrahydrocannabinol (THC) by weight.
To assure identity of the botanical raw material (BRM), cannabis used to manufacture generic cannabidiol should be of the same species –Cannabis sativa L. -- as that used to manufacture the reference listed drug. The analytic methods used to identify and authenticate the species may include macroscopic and microscopic analysis as well as DNA bar-coding methods, according to the draft guidance.
“Due to the many cultivars within this species, identification and authentication of plant species should be conducted at the cultivar(s) level if the potential cultivar(s) will be used as a natural source of the BRM,” says FDA in the draft guidance.
The assessment should also define which parts of the plant will be used for the BRM. Plant material used for BRM should be collected using good agricultural and collection practices to optimize batch-to-batch consistency. The agency refers drugmakers to two existing guidances for further direction; one addresses botanical drug development and the other details quality considerations for clinical research in cannabis and cannabis-derived compounds.
The cannabidiol-specific guidance regarding demonstration of bioequivalence is one of a suite of product-specific bioequivalence guidances the agency has issued. Comment on the draft guidance is open for 60 days from the 22 September date of publication in the Federal Register.
FDA