This document discusses supplemental new drug applications (SNDA) which are submitted to the FDA for approval of changes to approved drugs. It outlines the types of post-approval changes that require an SNDA including manufacturing process or formulation changes. Major changes with potential safety or efficacy impacts require prior approval, while moderate changes require 30 days notice and minor changes are reported annually. The guidance provides categories and examples to help classify different variation types.

1. Department of Pharmaceutical Sciences,
Maharshi DayanandUniversity
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

4. 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.

5. 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.

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

7.  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

8. 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”.

9. 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 .

10. 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

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.