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Chemistry, Manufacturing, and Controls (CMC) Information Submitted to Both CDER and CVM

Contents

Q1. If a CMC package has been approved by CDER, would an identical CMC package submitted to CVM be found acceptable?
Q2. Could the approval of a CMC package submitted to CDER be reversed or negatively impacted by the subsequent review of an identical CMC package submitted to CVM?
Q3. How should post-approval changes to identical CMC information submitted to both CDER and CVM be handled?
Q4. What should an animal drug sponsor who intends to reference an (A)NDA do first?

Q1. If a CMC package has been approved by CDER, would an identical CMC package submitted to CVM be found acceptable?

In general, CVM will concur with the CDER acceptance of an identical CMC package. The legal basis for this approach is based on 21 CFR 514.1(a) ‘Pertinent information may be incorporated in, and will be considered as part of, an application on the basis of specific reference to such information in the files of the Food and Drug Administration; however, the reference must be specific in identifying the information.’ While the typical use for right of reference is to allow a sponsor to reference information without submitting it in their file, in this case the CMC information will be submitted to CVM and the right of reference allows CVM to compare the information to that submitted to CDER as well as to access CDER’s review of the information. Therefore, a prerequisite for an inter-center collaborative review is that the animal drug sponsor must have obtained a Right of Reference/Letter of Authorization (LOA) or be included on the list of authorized users in the New Drug Approval/Abbreviated New Drug Approval ((A)NDA) as well as all referenced Drug Master Files (DMF), thereby providing CVM with the necessary access to the contents of the (A)NDA and DMFs and associated reviews. There may occasionally be differences due to the intended species for the dosage form that would necessitate differences in the CMC information required to support approval of a drug product.

Q2. Could the approval of a CMC package submitted to CDER be reversed or negatively impacted by the subsequent review of an identical CMC package submitted to CVM?

CVM is not aware of such a subsequent withdrawal or reversal.  

Q3. How should post-approval changes to identical CMC information submitted to both CDER and CVM be handled?

Post-approval changes to the CMC information should ideally be submitted to both CDER and CVM, using one of two possible approaches. 

  • The information may be submitted concurrently, in which case the submission to CVM should include a statement that the information has also been submitted to CDER and the Right of Reference/Letter of Authorization to the CDER submission or a statement that the animal drug sponsor is on the list of authorized users in the (A)NDA. 
  • Alternatively, the information may be submitted first to CDER, and following approval, then be submitted to CVM. In this case there may be a reduced filing category for major changes to animal drugs that have identical composition (i.e., formulation), manufacturing processes, and analytical controls to a corresponding approved human drug product. As stated in GFI 83 Section X.B.1.b.(miscellaneous moderate changes as CBE-30): “Changes categorized as major changes, other than changes to the components and composition, that have been approved by FDA in the corresponding human drug product” are allowed as a CBE-30. As part of CVM's 30-day assessment to determine the change's eligibility as a change that can be placed into effect according to 21 CFR 514.8(b)(3)(iv), the sponsor should also submit, along with the requirements in 21 CFR 514.8(b)(2)(iii), a copy of FDA's approval letter for the change in the human drug product and a certification that the animal and human drug products are identical with the exception of labeling.

Q4. What should an animal drug sponsor who intends to reference an (A)NDA do first? 

The animal drug sponsor should talk with the supervisor for the impacted technical section in advance to discuss if information may be required to support the CMC technical section in addition to the LOA, so we can ensure that we can access the specific (A)NDA files.

Key Points:

  • The animal drug sponsor is responsible for the quality, safety and effectiveness of the product approved for animal use. 
  • The animal drug sponsor must still submit the CMC information for which they are referencing the (A)NDA.
  • Open communication between the animal drug sponsor and the (A)NDA holder about any post-approval change is critical as is the reporting of these changes to CVM. 
  • If owners of the (A)NADA or (A)NDA change, new letters of reference/authorization to access the information in the (A)NDA are required. 
  • If at some point the (A)NDA holder withdraws the Right of Reference, the approved animal product can still be marketed (e.g., the original approval is still valid). However, all subsequent changes will be evaluated by CVM independently of any evaluation of similar information in the (A)NDA by CDER. 
  • If the animal drug differs from human drug, e.g., different container, the sponsor needs to submit data supporting that difference directly to the (J)INAD/(A)NADA. 
 
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