Analytical considerations for administering drugs using food vehicles
by Harley E. Wilcox, Senior Scientific Advisor (CMC Small Molecule), Eurofins BioPharma Product Testing-Columbia
Administration of drugs using foods/liquids as a vehicle is needed for subjects with inadequate swallowing capabilities. This would include pediatric and geriatric patients, and those with physical impairments. Some drugs are specifically formulated for delivery in foods/liquids as sprinkles or small beads. This class of pharmaceutical compounds presents a unique challenge when determining the best analytical methodologies to use.
Historically, evaluation of suitable food types for use as a dosing vehicle included limited stability of a selected matrix where assay was the primary test method. Thus, the drug would be mixed with foods (i.e. apple sauce) and stored for a few hours prior to potency testing. The July 2018 FDA draft guidance, “Use of Liquids and/or Soft Foods as Vehicles for Drug Administration: General Considerations for Selection and In Vitro Methods for Product Quality Assessments” provides specific suggestions for testing of drugs developed to be administered with a food vehicle. The intent of the guidance is to ensure consistency and standardisation for products developed for use with a food vehicle. Analytical recommendations discussed include: in vitro, method validation, stability, integrity, potency, impurity evaluation, and homogeneity.
- Polymorphism and bead integrity are suggested as part of integrity evaluations, but polymorph evaluation can be complex for drug products. If known polymorphisms are soluble in an aqueous environment, this may not be a critical issue. However, appropriate methodology would be developed to support a drug product if significant solubility differences exist between polymorphs.
- Potency Assay requires a validated method and assumes method qualification with food material matrices. Partially dissolved active pharmaceutical ingredients (APIs) in food vehicles will complicate the assay as the API is in two matrices. Homogeneity requires three to six equal portions of the food/DP mixture.
- Stability is evaluated at room and refrigerated temperatures over two hours. If potency testing shows loss of API, an impurity assessment is required using a stability indicating method and may require additional qualification with the prospective matrix.
- Dissolution testing is required if the API does not dissolve in the food matrix and is complicated if the API only partially dissolves.
The Guidance’s decision tree is useful for determining the sample preparation and food vehicle qualifications. Overall, the Guidance adds definition and complexity to drug products for use with food vehicles. Product labeling may require “do not use with” text based on the food vehicle data if the drug product is shown to not be compatible with certain matrices.
With these unique analytical evaluations, a client’s study design can be an important factor to ensure regulatory compliance and study success. Eurofins has experience with complex analytical programmes, including food vehicle administration. If the programme requires custom analytical design, Eurofins has the expertise to guide clients to the right fit for any regulatory and technical needs.
For more information, visit: www.EurofinsUS.com/BPT