FDA has proposed some relief from the component shortages created for parenteral and other products identified in the just released Guidance entitled, COVID-19 Container Closure System and Component Changes: Glass Vials and Stoppers. The Agency has recognized the need to provide some regulatory flexibility regarding the filing type for certain changes that may be necessitated by the shortages in parenteral components that are the result of increased industry demand as necessitated, as the pandemic continues.
The Guidance document, which will remain in effect only until after the National Health Emergency is over, provides a comprehensive discussion of FDA expectations and potential down regulated filing categories. In addition, the document suggests that if multiple potential changes are necessary, then the change with the highest potential to impact drug product quality will dictate the filing type. The document also suggests that industry could consider a Comparability Protocol describing how the firm will document the identified changes should they be necessary, and reminds applicants that such comparability protocols require submission and approval of a prior approval supplement (PAS), after which, a down regulation of other potential PAS supplements for the same change may be permitted.
The Agency is quick to point out that the potential down regulation of filing type does not mean a lessening of the data set necessary to support and approve the proposed changes. That is always the case, so be sure to do your homework in understanding what testing and documentation is necessary to supply in your submissions to support the change, whether it is submitted as a PAS, CBE-30, CBE or annual reportable. There are no shortcuts.
The guidance provides a plethora of examples of changes specific for NDAs, ANDAs, and BLAs and describes the relevant guidance documents upon which the agency relies in making its filing and data recommendations. There is also an Appendix A that provides specific examples of a number of changes specific to the application type and the suggested regulatory submission type based on the proposed change.
The Agency also advises firms to seek FDA advice for products that are related to the COVID emergency and drug shortages if there is a need to propose further regulatory relief. The complete guidance can be found here https://www.fda.gov/media/146428/download. Remember, don’t guess! If there is a unique situation not covered in the guidance document please ask FDA for advice before you stray outside of the guidance recommendations, and in any case be certain to perform the entire comparative body of work prior to proposing or making any changes. When necessary wait for approval or the designated time-period to pass prior to introduction of the changes into the marketplace for PAS and CBE-30 supplements. This advice may keep you from getting caught in a vile situation to make a component change.