FDA Publishes Draft Guidance Proposing to Establish Standardized Assay Limits for Medicated Feeds

Today, the Food and Drug Administration (FDA) Center for Veterinary Medicine (CVM) published a draft Guidance for Industry (draft guidance) proposing to standardize assay limits for medicated feeds. CVM requests electronic or written comments concerning the draft guidance be submitted to the docket by April 27, 2020.

The draft guidance recommends a standardized set of assay limits for Type B and Type C medicated feeds. It provides that assay limit standardization does not change the current standards for safety and effectiveness or the expectation regarding medicated feed assay methods, method validation, or method transfer studies. Standardization also will not necessitate medicated feed studies beyond those already required in the chemistry, manufacturing and controls (CMC) technical section of the New Animal Drug Application for the Type A medicated article, nor will it result in the tightening of previously approved medicated feed assay limits. Rather, if a pioneer Type A medicated article sponsor so requests, CVM would be willing to consider widening previously approved medicated feed assay limits to match the assay limits in the draft guidance. CVM would also be willing to discuss with sponsors on a case-by-case basis alternative medicated feed assay limits, such as for medicated feeds with drug inclusion rates below 5 ppm, but recommends that this type of discussion occur early in the drug development process.

Medicated feed assay limits are based on Permissible Analytical Variability (PAV), which is calculated from the standard deviation derived from the feed assay method transfer study results for fortified feed samples according to CVM Guidance for Industry 136. Historically, the assay limit range was calculated by adding the PAV to and subtracting it from the percent recovery of the drug derived from the feed assay method transfer study results:

Assay Limits = % Recovery ± PAV.

A major limitation to this approach is that medicated feed assay limits are not finalized until the CMC technical section was complete. This raises the risk that, prior to establishing the medicated feed assay limits, significant work on safety and effectiveness could have been conducted using medicated feed that assayed outside the subsequently-established final assay limits.

The draft guidance recommends a standardized set of PAVs for medicated feeds based on feed type and drug inclusion rate. CVM proposes categorizing medicated feeds into two groups: swine, poultry, and minor avian feeds and cattle and minor ruminant feeds. The feeds within each category are similar with respect to flow and handling characteristics, including particle size, particle size distribution, moisture content, and composition, making it reasonable to assign the same standardized PAVs to feeds within each group. Because feeds for other species, such as fish and exotic animals, can require unique manufacturing processes and may lack historical data, CVM will determine the PAVs for feeds for other species on a case-by-case basis.

CVM recommends the following standardized PAVs:

CVM would calculate the standardized medicated feed assay limits by adding the standard PAV to and subtracting it from 100%, unless the sponsor has data to show that the typical recovery is not 100%. If so, the sponsor could propose that the assay limits be centered on the average percent recovery. There could be more than one set of approved medicated feed assay limits for Type A medicated articles intended for use in multiple species or across inclusion rate ranges that cross 25 or 500 ppm. CVM suggests using the same PAVs listed in the table above for free-choice medicated feeds, but sponsors may discuss with CVM alternative PAVs on a case-by-case basis.

The draft guidance contains an Appendix that discusses CVM’s calculation of standardized PAVs for medicated feeds.

If you have any questions concerning the material discussed in this client alert, please contact the following members of our Animal Food and Drug practice.