Scribd
Upload
576 views

Scale Up & Post Approval Changes: (Supac)

The document discusses Scale-Up and Post Approval Changes (SUPAC), which are changes made to drug products after approval regarding composition, manufacturing process, equipment, or site. SUPAC guidelines define three levels of changes - minor, moderate, and major - based on their likelihood of impacting drug quality and performance. They provide recommendations for appropriate tests and documentation for filing based on the level of change, focusing on excipient composition changes and dissolution testing requirements.

Uploaded by

Nidhi
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
576 views

Scale Up & Post Approval Changes: (Supac)

The document discusses Scale-Up and Post Approval Changes (SUPAC), which are changes made to drug products after approval regarding composition, manufacturing process, equipment, or site. SUPAC guidelines define three levels of changes - minor, moderate, and major - based on their likelihood of impacting drug quality and performance. They provide recommendations for appropriate tests and documentation for filing based on the level of change, focusing on excipient composition changes and dissolution testing requirements.

Uploaded by

Nidhi
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
You are on page 1/ 15

Scale up & post approval changes

(SUPAC)

1
What is SUPAC

 In the process of developing a new drug product, the batch sizes


used in the earliest human studies are small.

• The size of the batches is gradually increased (Scale- up).

 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.

2
Scientific Rationale

 To expedite the processes of post approval changes of drug


products

 FDA can assure their safety and effectiveness.

 Lower the regulatory burden for industry.

3
SUPAC GUIDELINES - DEFINE

• Minor change
Level of • Moderate change
Changes • Major change

• Application / Compendial Tests


Tests • In Vitro Dissolution / Release
• In Vivo

• Annual Report
Filing • Changes Being Effected Supplement
• Prior Approval Supplement

4
Levels of change:

likelihood of impact on formulation quality and performance

Level 1: unlikely to have detectable impact


Level 2: could have significant impact

Level 3: likely to have significant impact

5
Component and Composition Changes

1)Focus on the changes in amount of excipients in the


drug product

1)Not focus on change in the amount of the drug


substance .

6
LEVEL 1:

Examples:
 Deletion or partial deletion of an ingredient intended to affect
the color or flavor of the drug product; or

Change in the ingredient of the printing ink to another approved


ingredient

Changes in excipients, expressed as percentage (w/w) of total


formulation, less than or equal to the following percent ranges:

7
8
Test documentation
 Chemistry documentation
 Application/compendial release requirements stability testing (One
batch long term)
 Dissolution Documentation
 None beyond the compendial requirements
 In vivo bioequivalence documentation- None

Filling documentation
 Annual report

9
LEVEL 2 CHANGES

• Change in the technical grade of an excipient


(Example: Avicel PH102 vs. Avicel PH200.)

• Changes in excipients, expressed as percent (w/w) of total


formulation, greater than those listed above for a Level 1 change
but less than or equal to the following percent ranges (which
represent a two fold increase over Level 1 changes):

10
11
12
Test Documentation
 Chemistry documentation
 Level 1 + 1 batch with 3 month accelerated stability study

 Dissolution documentation
 Case A – High permeability, High solubility
 Case B – low permeability, High Solubility
 Case C – High permeability, Low Solubility Drugs In vivo

 Bioequivalence documentation –None

Filing documentation

 Prior approval supplement (As level 1 + Accelerated stability study),


Annual report (longterm stability data) 13
LEVEL 3
Examples:
Any qualitative and quantitative excipient changes to a narrow
therapeutic drug beyond the ranges noted in level 1

All other drugs not meeting the dissolution criteria under level 2

Changes in the excipient ranges of low solubility, low permeability


drugs beyond Changes in the excipient ranges of all drugs beyond
2x level 1

14
Test documentation
 Chemistry Documentation – Level 1 + 3 month accelerated stability of
1 batch (SBOIA) or 3 batches (SBOINA)
 Dissolution documentation – Case B
 In vivo Bioequivalence – Full bioequivalence study. Except IVIVC
verified.
Filing documentation –
 Prior approval supplement (all information including accelerated
stability data),
 Annual report (long-term stability data)

15

You might also like

pFad - Phonifier reborn

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.

Note: This service is not intended for secure transactions such as banking, social media, email, or purchasing. Use at your own risk. We assume no liability whatsoever for broken pages.


Alternative Proxies:

Alternative Proxy

pFad Proxy

pFad v3 Proxy

pFad v4 Proxy