supplemental new drug application

1. SUPPLIMENT NEW DRUG
APPLICATION
• PRESENTD BY :-
• PATIL PRANJAY SADASHIV.
• FIRST YEAR M.PHARM.
• DEPARTMENT OF QUALITY ASSURANCE.
H. R. Patel Institute of Pharmaceutical Education
and Research, Shirpur

2.  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).
 CDER(Center for Drug Evaluation and Research)must
approve all important NDA changes (in packaging
or ingredients, for instance) to ensure the conditions
originally set for the product are still met.
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3.  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.
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4.  Supplement Type 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). The supplement type refers to
the kind of change that was approved by FDA.
 This includes changes in manufacturing, patient
population, and formulation.
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5.  Why change is required:
 May wish to alter / improve the product or
to introduce additional safeguard
 To meet the market requirements--
scale up, add manufactuing site.
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6. Post approval changes include:
 (1) components and composition, (2)
 manufacturing sites, (3) manufacturing process, (4)
specifications, (5) container closure system, and (6)
labeling, as well as (7) miscellaneous changes and
(8) multiple related changes.
 An applicant should consider all relevant CDER
guidance documents & submit all necessary
information to support a given change.
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7. 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.
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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 as these factors may relate to the
safety or effectiveness of the drug product.
 These are labelled as Prior Approval
Supplement.
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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.
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10.  If FDA disapproves may cease
distribution.
 FDA say prior approval suppliment is
required.
 Information is missing: distribution is
delayed untill amendment is made.
 Minor changes:has minimal potential to have
an adverse effect.The applicant must
describe minor changes in its next Annual
Report
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11. 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

12. APPENDIX I – MINOR CHANGES
 Only few types of variation
predominantly occur Change
in batch size of FPP
Additional new API source
Extension shelf life of FPP
Addition of FPP manufacturing site
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13. APPENDIX II – MAJOR CHANGES
 Major changes
Exceed the scope of minor changes—doesn't
fulfil the conditions
 Do not yet reach the scope of Appendix III—
new application necessary
 Examples:
 Change in the manufacturing process
of the API
 Change in the composition of the FPP
 Change to the immediate primary
packaging of the FPP
 Applicant's responsibility to provide the relevant
documentation to prove that the intended change
will not affect the quality of the prequalified product
negatively
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14. APPENDIX III – CHANGES MAKING A NEW
APPLICATION /EXTENSION APPLICATION
NECESSARY
 Changes to the API
Change of the API to a different API, e.g. different
salt/ester/derivative, different isomer
 Changes to the pharmaceutical form/
dosage form
Change from an immediate-release product to a
modified release dosage form or vice versa
Change from a liquid to a powder for
reconstitution, or vice versa
 Change or addition of a new route of
administration.
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15. APPENDIX IV - STABILITY REQUIREMENTS
FOR VARIATIONS TO PRE-QUALIFIED FPPS
Responsibility of the pre-qualified supplier to
investigate whether or not the intended change
will have an impact on the quality characteristics
of APIs and /or FPPs and consequently on
their stability.
 Based on the knowledge and experience
acquired on APIs and FPPs (Stress testing,
supportive data, accelerated and long- term
testing)
 At the time of submission, 3 or 6 months
stability data should be provided according
to the nature of the change, stability of the
API, dosage form of the FPP,etc 15

16. CHANGES IN MANUFACTURING SITE:-
 Major changes eg:-
 Move to new site never inspected by FDA or
cGMP.
 Transfer of aseptically processed sterile
drug substance eg lyophilized drug.
 Finished drug product sterilized by
terminal process.
 Manufacture of primery package when it
control doge delivered eg aerosols
 Moderate changes
 eg:-Manufacture of drug product that is not. 16

17.  otherwise provided for in this guidence.
 Minor changes eg:-
for secondary packaging
 For labelling.
 Manufacture of drug substance
intermediate other then the final
intermediate.
 Ink imprinting of solid oral dogage form
drug product.
 Sterilization site for packaging component
when process is same.
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18. CHANGES IN MANUFACTURING PROCESS
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50%
.
 Major changes eg:-
 When it effect release of drug eg modified
release or controlled release.
 Change in sterility method.
 Addition or deletion of sterilization
procedure.
 Replacing sterilizer with other of different
principle.
 Addition of new equipment.
 Replace Class 100 aseptic fill area with
barrier system.
 Change to aseptic process methed beyond

19.  Replacing lyophilization equipment of different
size.
 Change in sterilizer load limit from pre validated
load limit.
 Change in pore size of filter.
 For natural product:-change in source
material eg microbe,cell,plant.
 Change in process:-
 from dry to wet granulation.
 One type of drying to another.
 Change in route of synthesis of drug
substance.
 Synthesis of drug substance that may effect
impurity.
 Addition of ink cod imprint not currently
used in CDER. 19

20.  Moderate changes:-
 In drug substance or product except as
identity, strength, quality, purity.
otherwise provided for in this guidance.
 Change in filteration parameters flow
rate, pressure, time.
 change from single to dual sterilizing
filters.
 increase the bulk solution storage time by
more than 50%
 Supplement - Changes Being Effected.
 A change in methods that provides
increased assurance that the drug
substance will have the characteristics of
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21.  Minor changes:-
 changes to equipment of the same design
design.
 minor change in an existing code imprint
 Addition or change in ink imprint when the
ink is currently used on CDER- approved
drug product.
 change in the order of addition of
ingredients.
 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
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22.  Specifications (i.e., tests, analytical
procedures, and acceptance criteria) are
 From single dose to multiple dose.
the quality standards.
 acceptance criteria are numerical
limits, ranges, or other criteria for the
tests described.
 regulatory analytical procedure i.e
specified in USP/NF.
 CONTAINER CLOSURE SYSTEM
 Major Changes:-
 Change from ampule to vial.
 Change that may effect drug product
sterility assurance. 22

23.  change to a flexible container system.
 change to a prefilled syringe dosage.
 Change from metal to plastic.
 Change in size of sterile container.
 Deletion of 2ndary package when it
provide light,moisture protection.
 Addition of secondary package when it
may effect impurity.
 Moderate changes:-
 Change in container size no of units in
unit dosage form.
 Change in label amount.
 Addiion deletion of desiccant.
 Minor changes:- 23

24.  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.
 A change in or addition of a seal.
 LABELING:-
 Major Changes:-
 Changes based on data from preclinical
studies.
 Changes to the clinical pharmacology.
 Claims of superiority to another drug
product.
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25.  Changes based on postmarketing study
results with new indication use.
 Revision of population based on data.
 Change in the labeled storage conditions.
 Moderate Changes:-
 Addition of an adverse event.
 Addition of a
precaution,warning,contraindication
arising out of a postmarketing study,
 adds about drug abuse,
dependence,psycological effect.
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26.  Minor Changes:-
 Editorial changes eg distributer name
add.
 Foreign language versions of the labeling.
 Changes in the layout of the package
label.
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27. CONCLUSION
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 Any change to the content of the pre-qualified
dossier should be reported
 The change should not adversely affect the
quality, safety and efficacy of the pre-qualified
product
 Position correctly the variation and submit
necessary data
 Contact prequalification for assistance in classifying
an unforeseen change pre-submission.

28. THANK YOU
Thank You
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