Scale up Process and Post Approval Changes

Introduction to Scale up and post approval changes.
SUPAC Guidelines :
1.In component and composition
2.The site of manufacture
3.The scale up batch of manufacture
4.The manufacturing( equipment and process)

1. WELCOME

2. Shri Balasaheb Mane Shikshan Prasarak Mandal Ambap’s
ASHOKRAO MANE COLLEGE OF PHARMACY,PETH VADGAON
TITLE OF SEMINAR:SCALE UP PROCESS AND POST APPROVAL
CHANGES.
SUBJECT:RA (REGULATORY AFFAIRS)
Academic Year 2023-24
Presented by: Guided by:
Miss.Prajakta.R.Patil Dr Sachin.S.Mali
M.pharm First Year Professor and Head,
Department of Pharmaceutics
Roll no:11
Department of Pharmaceutics

3. CONTENT:
INTRODUCTION
SUPAC Guidelines
1.In component and composition
2.The site of manufacture
3.The scale up batch of manufacture
4.The manufacturing( equipment and process)

4. SUPAC
The scale up process and the change made after the approval in
the composition,mfg process,mfg equipment and change of site
together known as scale up and post approval changes
Control of changes in process,method,machineand system is
important part of GMP.
Sometimes we need to change the information given to FDA in
approved application.
These changes done after the FDA approval is called post
approval changes.

5. SUPAC
The FDA issued various guidance for SUPAC changes designated as
Supac-IR(immediate release solid oral dosage
form)
Supac-MR ( for modified release solid oral dosage
form)
Supac–SS ( for non sterile semisolid dosage form
including creams,ointments,gels and lotions)

6. 1.SUPAC GUIDELINE DEFINES
1 Level of changes:
Minor changes
Moderate changes
Major changes
2. Filing:
Annual report
Changes being affected supplement
Prior approval supplement
3.Tests:
Application
In vitro dissolution/release
In vivo

7. Level 1( Unlikely to have detectable impact)
These changes that are unlikely to have any detectable impact on formulation
quality and performance
E.g. changes in the colour, changes in excipients
Level 2( could have significant impact)
Changes are those that could have significant impact on the formulation quality
and performance
E.g. Changes in technical grade of excipient
Level 3( likely to have significant impact)
Changes are those that are likely to have significant impact on formulation quality
and performance
E.g. Ay qualitative and quantitative excipient changes a narrow therapeutic drug
beyond the range for level 1 and all other drugs not meeting the dissolution
criteria as level 2

8. Guideline recommendation for post
approval changes
The component or composition
The site of manufacture
The scale up of manufacture
The manufacturing (process and equipment)

9. COMPONENT AND COMPOSITION
Focus on change in amount of excipient in drug and not on changing the
drug substance
Level 1 :
Test documentation
1.Chemistry documentation
✓Application/compendialrelease requirement stability testing
2.Dissolution document
✓Not beyond compendial requirement
3.In vivo bioequivalence documentation-None
4.Filling documentation
✓Annual report

10. Level 2
Test documentation
1.Chemistry documentation
Level 1+1 batch with 3 month accelerated stability study
2.Dissolution documentation
Case A –High permeability ,High solubility
Case B –Low permeability, High solubility
Case C-High permeability, Low solubility drugs in vivo
3.Bio equivalence documentation-None
4. Filling documentation-As level 1+ Accelerated stability study

11. Level 3
•Test documentation
1.Chemistry documentation-level1 + 1 month accelerated stability
of 1 batch or 3 batches
2.Dissolution documents-Case B
3.In vivo bioequivalence-Full bioequivalence study, except IVIVC
verified
4.Filling documentation-prior approval supplement, annual report

12. SITE CHANGES
It includes the changes in location of site of mfg facilities for both
company owned and contract manufacturer.
Level 1:
Site change within facility where same equipment, SOP,
environment condition are common.
Test document-Chemistry, dissolution are according to compendial
and in vivo BE not required.
Filing the annual report

13. Level 2:
Site change within a contiguous campus,orbetween facilities in adjacent
city blocks
Test documentation-Level1+ one batch long term stability in chemistry
documentation
Filing documentation-annual report.
Level 3:
Site change in different campus
Test documentation
Chemistry documentation-One batch for long term stability or 3 batches
for accelerated or long term stability.
Dissolution testing –Case B
No BE
Filing documentation-Annual report

14. CHANGE IN BATCH SIZE
Post approval changes in size of batch from pilot scale batch to larger
or smaller production.
Scale down below1,00,000 dosage units is not covered by this
guideline.
Level 1:
Changes in batch size up to and including factor of 10 times the size of
pilot batch where,
▪The equipment is of same design and principle
▪Both manufacturer, according to GMP compliance
▪Same SOP’s followed
Testing and filing documents are same as of the level 2 of site changes
requirement

15. Level 2
Changes in batch size beyond factor of 10
Test documentation –As per level1 + one batch for 3 month
accelerated stability+ Case B dissolution testing.

16. MANUFACTURING CHANGES
A.EQUIPMENT
Level 1:
Change from non-automated to automated or vice versa
Change to alternative equipment of same design and operating
principle of same or different capacity
Test and filing documentation as per level 1 of batch size
Level 2:
Change in equipment to different design
Test and filling documentation-As per level 3 of site change except
case C instead of case B.

17. B. PROCESS CHANGES
Level 1
This changes includes process changes like mixing time and operating speed
within application/validation range.
Testing and filing document as per level 1 of site change.
Level 2
This change includes process changes like mixing time and operating speed
outside application/validation range
Testing and filing documentation as per level 2 changes in site.
Level 3
Change in type of process use for manufacture of product, such as change in
from wet granulation to direct compression of dry powder.
Documentation –As per the level 3 changes of component and composition
changes

18. THANK YOU!