The document discusses Scale-Up and Post Approval Changes (SUPAC) guidelines established by the FDA. It defines SUPAC as changes made to the manufacturing process, equipment, batch size, or site after a drug has received FDA approval. The guidelines establish three levels of changes with varying documentation and reporting requirements depending on the level of change. Level 1 changes have the least requirements while level 3 changes require extensive testing data and may need pre-approval before implementation.

1. Scale-Up and Post Approval
Changes (SUPAC)
By:
Prakhar Rai
M.Pharm. (Pharmaceutical quality
assurance)

2. Content
 Introduction
 Process of new drug application
 SUPAC Guidelines
 Site changes
 Changes in batch size
 Changes in manufacturing
 References
2

3. Introduction
Scale-up:
▪ Scale up is the term used to refer to the increase in the batch
size of a product. For example, if a drug is successful, then it
may scale-up multiple times throughout its life cycle to meet
growing demand.
▪ Technology transfer of a pharmaceutical product from
research to the production floor with simultaneous increase
in production outputs is commonly known as scale – up.
Post Approval Changes: Means changes made after approval.
3

4. Conti…
▪ Control of changes in process, method, machine & system is
important part of GMP. Sometimes we need to change the
information’s given to the FDA in approved application. These
changes done after the FDA approval is called Post Approval
Changes.
Definition: The scale-up process and the changes made after
approval in the composition, manufacturing process,
manufacturing equipment, and change of site have become
known as Scale-Up and Post approval Changes, or SUPAC.
4

5. Process of new drug application
5
1. New drug
application
(NDA) Approved
by FDA
Batch Size Increase
ANDA approved
by FDA
2. Generic drug
product
Batch Size Increase
Bioequivalent to the
FDA Reference listed
drug (RLD) Product
SCALE-UP
SCALE-UP

6. SUPAC Guidelines
It defines:
6

7. Site Changes
Site changes consist of changes in location of the site of
manufacture for both company owned and contract
manufacturing facilities and do not include any scale-up
changes:
Level 1 Changes:
Consist of site changes within a single facility.
Test Documentation: None
Filing Documentation: Annual report
Level 2 Changes:
changes consist of site changes within a contiguous campus, or
between facilities in adjacent city blocks.
7

8. Conti…
Test Documentation: Chemistry Documentation Location of
new site and updated batch records.
Filing Documentation: Changes being effected supplement;
annual report (long term stability test data).
Level 3 Changes
Level 3 changes consist of a change in manufacturing site to a
different campus.
Test Documentation: Chemistry Documentation Location of
new site and updated batch records and application/ compendial
release requirements. Stability: Significant body of data
available One batch with three months accelerated stability
8

9. Conti…
data reported in supplement, one batch on long-term stability
data reported in annual report.
Dissolution Documentation Case B: Multipoint dissolution
profile should be performed in the application/compendia
medium at 15, 30, 45, 60 and 120 minutes .The dissolution
profile of the drug product at the current and proposed site
should be similar.
Filing Documentation: Changes being effected supplement;
annual report (long-term stability data).
9

10. Changes in Batch Size
Post-approval changes in the size of a batch from the pilot scale
bio batch material to larger or smaller production batches call for
submission of additional information in the application.
Level 1 Changes
Change in batch size, up to and including a factor of 10 times the
size of the pilot/bio batch.
Test Documentation: Chemistry Documentation Application/
compendial release requirements. Notification of change and
submission of updated batch records in annual report. One batch
on long-term stability reported in annual report.
Filing Documentation-Annual report (long-term stability data).
10

11. Conti…
Level 2 Changes
Level Changes in batch size beyond a factor of ten times the
size of the pilot/bio batch.
Test Documentation: Chemistry Documentation Application/
compendial release requirements. Notification of change and
submission of updated batch records. Stability testing: One
batch with three months accelerated stability data and one batch
on long-term stability.
Dissolution Documentation-Case B testing.
Filing Documentation Changes being effected supplement;
annual report (long-term stability data).
11

12. Changes in Manufacturing
Equipment:
Level 1 Changes
Change from non-automated or nonmechanical equipment to
automated or mechanical equipment and Change to alternative
equipment of the same design and operating principles of the
same or of a different capacity.
Test Documentation: Chemistry documentation application/
compendial release requirements. Notification of change and
submission of updated batch records.
Filing Documentation-Annual report (long-term stability
data).
12

13. Conti…
Level 2 Changes
Change in equipment to a different design and different
operating principles.
Test Documentation: Chemistry Documentation Application/
compendial release requirements. Notification of change and
submission of updated batch records. Stability testing:
Significant body of data available: One batch with three months
accelerated stability data reported in supplement; one batch on
long-term stability data reported in annual report.
Dissolution Documentation-Case C dissolution profile.
Filing Documentation: Prior approval supplement with
justification for change; annual report (long-term stability data).
13

14. Conti…
Process:
Level 1 Changes
This category includes process changes such as mixing times and
operating speeds within application/validation ranges.
Test Documentation: None
Level 2 Changes
This category includes process changes such as mixing times and
operating speeds outside of application/validation ranges.
Test Documentation: Chemistry Documentation Application/
compendial release requirements. Notification of change and
submission of updated batch records.
14

15. Conti…
Stability testing: One batch on long-term stability.
Dissolution Documentation-Case B dissolution profile.
Filing Documentation: Changes being effected supplement;
annual report (long term stability data).
Level 3 Changes
This category includes change in the type of process used in the
manufacture of the product, such as a change from wet
granulation to direct compression of dry powder.
Test Documentation: Chemistry Documentation Application/
compendial release requirements. Notification of change and
submission of updated batch records.
15

16. Conti…
Stability testing: Significant body of data available: One batch
with three months accelerated stability data reported in
supplement; one batch on long-term stability data reported in
annual report.
Dissolution Documentation: Case B dissolution.
In Vivo Bioequivalence Documentation: In vivo
bioequivalence study. The bioequivalence study may be waived
if a suitable in vivo/in vitro correlation has been verified.
Filing Documentation Prior approval supplement with
justification; annual report (long-term stability data).
16

17. References:
▪ https://www.researchgate.net/publication/316021703_SCA
LE_UP_AND_POSTAPPROVAL_CHANGES_SUPAC_
GUIDANCE_FOR_INDUSTRY_A_REGULATORY_NO
TE
▪ https://www.plianced.com/compliance-wiki/supac-scale-up-
and-post-approval-changes/
17