Grouping Supplements for CMC Changes: FDA Outlines New Policy
Posted 20 April 2016 | By
The US Food and Drug Administration’s (FDA) Office of Pharmaceutical Quality (OPQ) on Tuesday released a new document outlining how supplements can be grouped together and submitted concurrently for the same chemistry, manufacturing and controls (CMC) changes to multiple approved new drug applications (NDAs), abbreviated new drug applications (ANDAs) and biological license applications (BLAs) submitted by the same applicant.
The agency says the goal of its new policy is to make the process more efficient and consistent when reviewing grouped supplements.
The term “grouped supplements” is used to describe two or more supplements reviewed and processed using the procedures set forth in the new document, though FDA makes clear that supplements cannot be grouped if submitted by a different applicant or if the supplements provide for different CMC changes.
“The supporting data necessary for the review of the CMC changes should be the same for each of the grouped supplements,” FDA says. “Any supplement that provides for the same CMC changes but necessitates the review of data that is unique to that supplement (e.g., product-specific data) should not be grouped.”
Supplements can, however, be grouped when the following criteria are met:
- The cover letter for the supplements clearly states the purpose of the proposed CMC changes and indicates that the supplement is one of multiple submissions for the same change.
- Each supplement includes a list of the application numbers (NDA, BLA, and ANDA, as appropriate) and identifies the drug products that will be covered by the CMC changes.
- The supplements have the same submission date on Form FDA 356h.
“On a case-by-case basis, the Center may also group supplements that do not meet some or any of the criteria described above, if grouping the supplements is advantageous to the review process,” FDA says.
Circumstances where this may occur include cases when an applicant submits a group of supplements for the same CMC change and then, at a later date, submits additional supplements for the same change and requests FDA officials include the second set of supplements in the group.
The Regulatory Business Project Manager (RBPM) and Branch Chief (BC) of the relevant review division will decide on a case-by-case basis whether such changes will be allowed, though FDA notes that “consideration will be given to whether the goal date for the original group of supplements could still be met if the second set of supplements is added to the review.”
The seven new procedures were also outlined by FDA in the MAPP and include:
- The Office of Programs and Regulatory Operations (OPRO) RBPMs triage the incoming supplements and confirm that the initial grouping is accurate, and subsequently, identify the proposed lead application and assigned review division
- The BC (or designee) for the assigned review division within OPQ re-confirms the grouping and decides whether an application does not belong within the initial group and informs the RBPM that there is an application that needs to be removed from the group.
- Upon re-confirmation that the supplements can be grouped, the review team is identified and assigned to the group by the BC or designee. Reviewer assignments are made by the supervisors of the team members. In some cases, this determination may be driven by resource issues or a need for specific review expertise.
- If the initial grouping cannot be re-confirmed, the supplements will be ungrouped and each application may be reviewed separately or grouped in a separate manner.
- After the review is complete, the OPRO/RBPM prepares one action letter for the BC (or designee) which includes all the sNDAs and sANDAs. For a group that includes sBLAs, the decision whether to include the sBLA in the action letter will be determined on a case-by-case basis.
- If the grouped supplements include sANDAs, the RBPM forwards a copy of the final review and action letter to the Office of Lifecycle Drug Products’ Division of Post-Marketing Activities II for informational purposes. The RBPM is also responsible for updating the relevant metadata for all supplements in the group and for closing out all projects for the group.
- If the action taken on the supplements is a complete response, subsequent submissions to address the complete response issues will be appropriately grouped as the original supplement submissions.
OFFICE OF PHARMACEUTICAL QUALITY Review of Grouped Product Quality Supplements