The document presents the SUPAC (Scale-Up and Post Approval Changes) guidelines, which regulate changes in drug manufacturing post-approval, encompassing aspects like composition, manufacturing site, batch size, and processes. It details the historical background, categorization of changes (minor to major), and necessary documentation and testing procedures involved in the scale-up process. Additionally, the document highlights the advantages and disadvantages of these guidelines, emphasizing the importance of maintaining product quality during transitions.

1. SUPAC GUIDELINES
Scale-Up and post approval changes
Geethanjali College of Pharmacy, Hyd.
Presented by:
Gundlapally Yokshita
Jagati Saketh
K Vaishnav
Karamtod Devika
Kavali Sri Lakshmi
Kethavath Shashikala
Under the guidance:
P. NAGA CHANDRIKA, M.Pharm, (Ph.D)

2. INTRODUCTION
1
SUPAC GUIDELINES -HISTORY
4
SUPAC GUIDELINES
5
ADVANTAGES AND
DISADVANTAGES
16
REFERENCE
18

3. INTRODUCTION:
• SUPAC, which stands for scale-up and post approval changes, refers to
guidelines that govern changes made during the post-approval phase
of drug manufacturing.
• In pharmaceutical technology, the transfer of a pharmaceuticals
product from small scale to the production scale is termed as scale-up
with an increase in simultaneous production outputs.
• These guidelines apply when there are changes :
 In composition or components,
 In Manufacturing site,
 In Scale-up or scale-down of batch size,
 In Manufacturing procedures or equipment .
• It is important to make sure that the applied process is capable
enough to manufacture an appropriate quality product and as well as
to know that the product after scale-up doesn’t suffer any changes in
the physical and chemical properties of the product.
3

4. SUPAC GUIDELINES-HISTORY:
 Two workshops were held in 1991 and 1992 by the APPS , FDA and
UPS . The purpose is to discuss the fundamentals of modifying the
procedure or composition of drug products after they have been
approved by the appropriate authorities.
 In the end, these adjustments included adjustments to the
formulation or composition of the product, alteration to the
processes, modification to the size of the processes and
adaptation to the site or campus where the operations were
performed.
The contents of the workshop were finally made public by the
FDA in the form of a guidelines paper titled “scale-up post
approval changes”.

5. 5
SUPAC Guidelines- Define:
• Level of changes- Minor change,
Moderate change,
Major change.
• Tests - Application/ compendial tests,
In vitro dissolution/ releases,
In vivo.
• Filing - Annual report,
Changes being effected
supplement,
Prior approval supplement.

6. 6
LEVELS OF CHANGES:
• Level 1: Unlikely to have
detectable impact.
• Level 2: Could have significant
impact.
• Level 3: likely to have significant
impact.

7. 7
1) Changes in components or composition:
This section focuses on changes in excipients in the drug product.
SUPAC-IR : Changes made for immediate – release solid oral dosage forms.
SUPAC-MR: Changes made for modified – release solid oral dosage form.
SUPAC-SS : Changes made for non-sterile semisolid dosage forms.
SUPAC-IR:
LEVELS CLASSIFICATION EXCIPIENT
RANGE
TEST
DOCUMENTATION
FILING
DOCUMENTATIO
N
LEVEL-1 - Delition or partial
delition of an
ingredient.
- Changes in
excipients,
expressed as %
(w/w) of total
formulation, less
than or equal to
Filler ±5
Disintegrant
Starch ±3
Other ±1
Blinder ±0.5
Lubricant
Ca or mg
stearate± 0.25
Other ±1
- Stability
- application/
compendial
requirement.
-Annual report.

8. 8
.
LEVEL-2 -Change in technical
grade of excipients.
-Change in excipients
expressed as (W/W)of
total formulation
greater than level-1
changes.
Filter 1.0
Disintegrant
Starch 6
Other 1
Binder 1
Lubricant
Ca or mg
stearate 0.5
Others 1
Glidant
Talc 2
Other 0.2
Film coat 2
-stability application/
compendial requirement
-dissolution data depends
on solubility TR’s and
permeability
CASE-A : high
permeability, high
solubility drugs (single
point dissolution)
CASE-B : low permeability,
high solubility(drugs
multiple point)
CASE-C : high
permeability, low
solubility(drugs multi
point and multi media
dissolution profile).
-prior approval,
-annual report.
LEVEL-3 Higher than SUPAC-
IR level 1 and 2
-stability application,
CASE B dissolution profile
-prior approval
supplement,

9. 9
SUPAC – MR:
LEVELS CLASSIFICATION TEST DOCUMENTATION FILING
LEVEL-1 Deletion of ingredients upto
SUPAC –IR level -1 excipient
ranges.
-stability
-application/ compendial
requirements.
-annual report
LEVEL- 2 -changes in technical grade
of excipients
-upto SUPAC –IR level 2
excipient range.
-stability
-multipoint dissolution
profile(15,30,45,60and 120
min)
-USP buffer media at 4.5-
7.5 three media (eg:
water,0.1Hcl)
-USP buffer media at PH
4.5-6.8 for delayed
release.
-Prior approval
supplement
-annual report.
LEVEL-3 Higher than SUPAC-IR level -stability -prior approval

10. 10
SUPAC-SS
LEVELS CLASSIFICATION TEST DOCUMENTATION FILING
LEVEL -1 Quantity 10% or less change in
approved amount of
preservative.
-application / compendial
requirement.
-preservative effectiveness
test at low specified levels.
-annual report.
LEVEL-2 10%-20% change in approved
amount of preservative.
-application requirement.
-preservative effectiveness.
-changes being
effected.
-annual report.
LEVEL-3 >20% change in approved
amount of preservative.
-application requirement.
-excecuted batch records.
-prior approval
supplement.
-annual report.

11. 11
2) MANUFACTURING SITE CHANGES:
LEVELS CLASSIFICATION TEST
DOCUMENTATION
FILING
LEVEL-1 -Site change within a
single facility,
-No change in SOP,
-Common personnel.
-Application/
compendial
requirement.
-Annual report.
LEVEL-2 -Same continuous
campus,
-Common personnel,
-No other changes.
-Application/
compendial
requirement
-Notification of
location of new site--
Updated batch
records
-Annual report.
-Changes being
effected
supplement.
LEVEL-3 -Different campus, -Application/ -Annual report

12. 12
3) BATCH SIZE CHANGE(SCALE UP):
LEVELS CLASSIFICATION TEST DOCUMENTATION FILING
LEVELS-1 Change in batch size, upto
and including a factor of
10 times the size of pilot/
biobatch..
-Updated batch records .
-Application / compendial
requirement stability.
-Annual report.
LEVELS-2 Change in batch beyond a
factor of 10 times the size
of the pilot or biobatch ,
no other changes
-Updated batch records
- Application/ compendial
requirement
- Stability
- SUPAC-IR (multipoint
dissolution profile)
- SUPAC-MR : multipoint
dissolution profile(eg:
USP buffer)
- Three other media.
- -SUPAC-SS: invitro
-Annual report.
-Changes being
affected supplement.

13. 13
4)MANUFACTURING CHANGES : Manufacturing changes may affected both
equipment used in the manufacturing process and the process itself.
- Appropriate validation studies are conducted.
EQUIPMENT:
LEVELS CLLASSIFICATION TEST DOCUMENTATION FILING
LEVEL-1 -Alternate equipment of
same design and principles
automated equipment
-Updated batch records
-Application/ compendial
requirements
-stability
-annual report
LEVEL-2 Change to equipment of
different design and
principle
-Updated batch records
-application/ compendial
requirement
-stability.
SUPAC-IR: multi-point
dissolution profiles in
multiple medias
SUPAC-MR: multi-point
-annual report
-changes being
effected supplement

14. 14
MANUFACTURING CHANGES- PROCESS:
LEVELS CLASSIFICATION TEST DOCUENT FILING
LEVEL-1 -Adjustment of equipment
operating
conditions(operating speeds,
mixing times)
-Updated batch
records
-application /
compendial
requirement.
-stability
-SUPAC-IR(multi-point
dissolution profile)
-Annual report
-changes being
effected supplement
LEVEL-2 Beyond approved application
ranges
-SUPAC-SS: change in the process
of combining two phases
-SUPAC-MR: multi- point
dissolution profiles in
multiple medias (eg: USP
buffer media at PH 4.5-
7.5 for extended release)
-three media(eg: water,
0.1Hcl and USP buffer
media at PH 4.5 and 6.8
for delayed release
-SUPAC-SS: In vitro
-Annual report
-Changes being effected
supplement

15. 15
.
LEVELS CLASSIFICATION TEST DOCUMENTATION FILING
LEVEL-3
(SUPAC-IR
SUPAC-MR)
Changes in this type
of process used(eg:
wet granulation to
direct compression)
-Updated batch records
-Application/ compendial
requirements
-Stability
-Biostudy or IVIVC
-SUPAC-IR: Multi –point
dissolution profile
-SUPAC-MR : Multi-point
dissolution profile in multiple
media(eg: USP buffer media at
PH 4.5-7.5 for extended
release)
Three other media(water, 0.1N
Hcl and USP buffer media at PH
4.5 and 6.8 for delayed release)
-Prior approval
supplement
-annual report

16. 16
ADVANTAGES:
- Easy scale-up running is
observed in both production
and quality assurance
- More capacious workspaces of
the production division..
- -Installation, maintenance, and
repair of equipment becomes
attainable with the assistance
of expert from the engineering
department.
DISADVANTAGES:
-It does not discuss multiple
changes.
- It does not cover modified
equipment.
- It must be used in conjunction
with other reference.
- It has no been updated.

17. REFERENCE:
1) Lachman leon and schwartz. B joseph pharmaceuticals dosage form: tablet. Vol 3
edition-2 .
2) SUPAC Slideshare by Rohit
3)Savant D.A Pharma Pthway Industry and Applied pharmacy8th Edition.
4)Nash R.A Wachter A.H Pharmaceutical process validation; 3rd
Edition.

18. Thank you