Supplemental new drug application

SNDA,: application to make changes in products

1. Department of Pharmaceutical Sciences, Maharshi Dayanand University Presented By… Garima Saini M.Pharm. (SEM-I) Guided By… Dr. ( Mr.) Arun Nanda Professor of Pharmaceutics

2. SUPPLEMENTAL NEW DRUG APPLICATION (SNDA) Include changes in manufacturing and formulation

3. SUPPLEMENTAL NEW DRUG APPLICATION (SNDA) SUPPLEMENT : A supplement is an application to allow a company to make changes in a product that already has an approved new drug application (NDA). Center for Drug Evaluation and Research (CDER) must approve all important NDA changes (in packaging or ingredients, for instance) to ensure the conditions originally set for the product are still met.

4. SUPPLEMENT NUMBER A supplement number is associated with an existing FDA New Drug Application (NDA) number . Companies are allowed to make changes to drugs or their labels after they have been approved. To change a label, market a new dosage or strength of a drug, or change the way it manufactures a drug, a company must submit a supplemental new drug application (SNDA). Each SNDA is assigned a number which is usually, but not always, sequential, starting with 001.

5. POST APPROVAL CHANGES INCLUDE : Components and composition , manufacturing sites , manufacturing process, specifications, container closure system, labeling, miscellaneous changes multiple related changes.

6. An applicant should consider all relevant CDER guidance documents & submit all necessary information to support a given change . CONDITION : Changes may have potential impact on the quality, safety or efficacy of products . Any change to prequalified products are subject to approval by FDA & CDER

7. GUIDANCE ON VARIATION AS PER US FDA Three categories of variations according to their potential impact on pharmaceutical quality Major changes : substantial potential to have an adverse effect on the identity , strength, quality, purity, or potency of a drug product relate to the safety or effectiveness of the drug product . These are labelled as “Prior Approval Supplement” .

8. Moderate changes : moderate potential to have an adverse effect . 2 types: (1) requires the submission of a supplement to FDA at least 30 days before the distribution of drug product . labelled as– “Supplement - Changes Being Effected in 30 Days” . (2) for which distribution can occur when FDA receives the supplement . labelled as - “Supplement - Changes Being Effected” If FDA disapproves may cease distribution. Information is missing: distribution is delayed until amendment is made . Minor changes : has minimal potential to have an adverse effect . The applicant must describe minor changes in its next Annual Report   .

9. GUIDANCE ON VARIATION TO A PREQUALIFIED PRODUCT To facilitate classification of various types of changes, the variation guide is composed of 4 Appendixes : - Appendix I : lists minor changes, including notification (N ). Appendix II : definition and examples of major changes. Appendix III : changes that make a new application /extension application necessary. Appendix IV: stability requirements for variations and changes to Pre-qualified FPPs

10. MAJOR CHANGES: Move to new site never inspected by FDA or cGMP . IN MANUFACTURING PROCESS Change in sterility method. Replacing sterilizer with other of different principle. Addition of new equipment. Change to aseptic process method beyond 50 %. Change in pore size of filter. For natural product:-change in source material e.g. microbe, cell, plant.

11. MAJOR CHANGES(CONT….) Change in process:- from dry to wet granulation. One type of drying to another. Change in route of synthesis of drug substance . IN CONTAINER CLOSURE SYSTEM Change from ampule to vial. Change that may effect drug product sterility assurance. From single dose to multiple dose .

12. MAJOR CHANGES(CONT….) Change to a flexible container system. Change to a prefilled syringe dosage. Change in size of sterile container . IN LABELING Changes based on data from preclinical studies. Changes to the clinical pharmacology. Change in the labeled storage conditions .

13. MODERATE CHANGES: IN MANUFACTURING PROCESS Change in filtration parameters flow rate, pressure, time. Change from single to dual sterilizing filters. Increase the bulk solution storage time by more than 50 % IN CONTAINER CLOSURE SYSTEM Change in container size no of units in unit dosage form . Change in label amount. Addition deletion of desiccant .

14. MODERATE CHANGES(CONT….) IN LABELING Addition of an adverse event. Addition of a precaution ,warning , contraindication arising out of a post marketing study, adds about drug abuse, dependence , psychological effect.

15. MINOR CHANGES: IN MANUFACTURING PROCESS Changes to equipment of the same design Minor change in an existing code imprint Increase the bulk solution storage time by no more than 50 percent. For natural increase or decrease in production. Replacement with equipment of the same design.

16. MINOR CHANGES(CONT….) IN CONTAINER CLOSURE SYSTEM Change in child resistant pack. Increasing the wall thickness. Change in or addition of a cap liner. Change in antioxidant, colorant, stabilizer. Change to new container already in NDA.

17. MINOR CHANGES(CONT….) IN LABELING Editorial changes e.g. distributer name add. Foreign language versions of the labeling. Changes in the layout of the package label.