Presentation for GADA: New API Supplier Information

1. Presentation for GADA:New API Supplier Information Karen Finnegan (HFV-145) Andrea Kerrigan (HFV-145) Laura Moussa (HFV-145)

2. Requirements for Approval of a New API Supplier • Common Information • Dosage Form Specific Information • Type A Medicated Articles and Multiple Ingredient “Multi-use Container” Soluble Powders • Points to Consider

3. Common Information - All Dosage Forms

4. Guidance Information • CVM GFI #5 Stability Guidelines • CVM GFI #73/VICH GL3 Stability Testing of New Veterinary Drug Substances and Medicinal Products • CVM GFI #42 Animal Drug Manufacturing Guidelines – Series of Four Guidelines • CVM GFI #83 Chemistry, Manufacturing and Controls Changes to Approved NADA/ANADA

5. Filing Decision • CBE-30 vs. Prior Approval (GFI 83) • Not dependent on dosage form • Important factors are cGMP and Master File status of the new supplier • If the Master File has never been reviewed, then accepting the submission as a CBE 30 is unlikely

6. Submit: • A reference to the Master File • A Letter of Authorization • The LOA date is not important for a DMF. Firms must be referenced in the DMF holder’s current list of authorized users. • The LOA for a VMF should be more current (2-3 years best). The VMF holder may or may not maintain a current list of authorized users. • Environmental Assessment (EA) or claim for categorical exclusion

7. Submit (Continued): • At least one (1) COA from the new API supplier with vendor qualification* • All tests on the COA should be performed unless a scientific justification is provided as to why the test is not a critical quality attribute • All USP/NF tests must be performed. If the material is not USP grade, then commit to add all necessary tests to the routine testing program • Method validation/verification for new methods may be required (commonly seen with impurity methods) * Your vendor (re)qualification program should be approved by CVM and include procedures for initial testing of 3 lots and annual testing of 1 lot.

8. Dosage Form Specific Information True Solutions All Other Dosage Forms

9. True Solutions (injectables, single-use soluble powders*, etc.) (GFI 42) • Provide the “common information” • Commit to place the first three (3) production batches manufactured with the new supplier’s API on stability (VICH GL3 and GFI 5) * Single-use refers to soluble powder products in which the entire package is dissolved at one time

10. All Other Dosage Forms (tablets, suspensions, etc.) (GFI 42) • Provide the “common information” • Provide a completed batch record for one batch of drug product (at least 10% of full production scale) manufactured under production conditions with the new supplier’s API • For a product with multiple strengths, manufacture of only one (1) strength (e.g., tablet common blend) or a bracket approach may be acceptable

11. All Other Dosage Forms (Continued) • Provide full release data for the pilot lot • Dissolution for tablets, suspensions, etc. • Three months (0, 1, 2, 3) of long-term and accelerated data (VICH GL3) for the pilot lot • Commitment to place the first three (3)* production batches on stability (GFI 5) * If the pilot lot is full production scale, then a commitment to place the next two (2) lots on stability should be provided.

12. Dosage Form Specific Information - Type A Medicated Articles - Multiple Ingredient “Multi-use Container” Soluble Powders

13. Submit: • Common Information • Master file reference • EA or claim for categorical exclusion • Vendor qualification • Completed batch record • Release testing • Stability data • Testing to show that the product manufactured with the proposed API has equivalent uniformity to product manufactured with the approved API may be required

14. What is different about these dosage forms? • These dosage forms should contain uniform product so that each dose contains the same amount of API and excipients • To produce uniform Type A Medicated Articles, the particle size of the finished product should be controlled. Typically, this means controlling the particle size of the API and the excipients. • To produce uniform soluble powders that have multiple ingredients and are stored in multiple-dose containers, the particle size of the API and the excipient(s) should be controlled

15. When will uniformity studies be required? • If there are no particle size specifications for the approved API, then uniformity studies will be required • If the existing raw material specifications for the approved API include a specification for particle size but the proposed API does not meet these specifications, then new uniformity studies will be required • If uniformity studies are not performed, then provide a scientific justification.

16. What type of uniformity studies may be required? • Type A medicated article: • Blend uniformity: uniformity of the bulk batch • Homogeneity: uniformity of the packaged product • Segregation: transportation studies • Soluble powder with multiple ingredients in multiple-use container • Blend uniformity • Homogeneity

17. Points to Consider - All Dosage Forms

18. Points to Consider • Indicate why are you requesting the new supplier – alternate or replacement • Ensure that all COAs are legible and translated into English (if applicable) • Significant differences between the supplier’s COA results and your verification results should be justified

19. Questions?