The document discusses scale up and post approval changes (SUPAC) for generic drug applications. It defines SUPAC as changes made to a drug's composition, manufacturing process, equipment, or site after approval. The FDA modernization act of 1997 established four categories for reporting post-approval changes - prior approval, 30-day notice, immediate implementation, and annual report. The FDA has issued SUPAC guidance documents that describe what types of changes require validation studies or prior approval versus those allowable without notice. Post-marketing surveillance is also required to monitor adverse drug events after approval.

1. SCALE UP AND POST APPROVAL
CHANGES (SUPAC)
Submitted by:Gaurav
(M.pharma pharmaceutics)
Jamia hamdard
Submitted to:- Dr.Sanjula Baboota & Dr.Javed Ali

2. CONTENT
1. Introduction
2. What is SUPAC
3. History and background
4. SUPAC documents
5. Requirements for post approval changes
6. Comparability protocols
7. Post marketing surveillance

3. INTRODUCTION
 Technology transfer of a pharmaceutical product
from research to the production with simultaneous
increase in production output is commonly known
as scale up.
 Generic drug approval started from approval of
ANDA (abbreviated new drug application)
 The manufacturer may change.
Drug formulation, batch size, process, equipment, manufacturing
site
Identity, strength, quality, purity and potency

4. WHAT IS SUPAC
 The scale up and the change made after approval
in the composition manufacturing process
manufacturing equipment and change of site have
become known as scale up and post approval
change

5. HISTORY AND BACKGROUND
 On november 21,1997 the food and drug administration
modernization act (FDAMA) was signed into law.
 The FDAMA initiative was directed at providing more
definite language to the current food and cosmatic act.
 FDAMA added section 506A (21U.S.c 365a) to the
FD&C act, which provided specific language for
manufacturing changes to an approved application and
reporting requirement for those changes.

6. FDAMA PROVIDED FOR FOUR REPORTING
CATEGORIES:
1. Prior approval changes: Major changes that require
FDA approval before implementation
2. Supplement changes being effected(30 days):
Moderate changes that require 30 day’s notice before
implementation
3. Supplement changes being effected (0 days):
Moderate changes that can be implemented
immediately
4. Annual report: Minor changes that can be
implemented immediately and filed in the next periodic
report.

7. SUPAC DOCUMENTS
 List of document issued by FDA for help applicant with
post approval changes.
 Documents are divided into IR(immediate release),
MR(modified release), SS (non sterile semisolid dosage
form like cream, ointment and etc)
 Various types are changes are required
a) Components and compositions of drug product
b) Manufacturing equipment
c) Batch size
d) Manufacturing site change

8. LEVEL OF CHANGES DESCRIBE BY FDA

9. REQUIREMENTS FOR POST APPROVAL CHANGES
 Components and composition of drug product
In general, mainly focus on change in ingredents in
drug products. Change in adding or deleting an
excipent are describe in level 3. Adding or deleting
of ingredients must be filled as prioe approval
supplement. The exception to this applied to
colours, which can be removed or reduce from
formulation and filled in an annual report

12.  Change in batch size
Change in batch size from pivotal/pilot scale bio batch
to larger or smaller production batches tends to
change the operating parameter. Therefore, all the
parameters, such as mixing time, speed, etc., are
adjusted according to the equipment (large or
small) used in the process.
Bellow 100,000
dosage unit are not
covered by this
guidance

14. MANUFACTURING EQUIPMENT CHANGE
 Any change in manufacturing equipment other than that used in
the approved application requires appropriate validation studies
to demonstrate that the new equipment is similar to the original
equipment. Equipment should be same design and operating
principal according to SUPAC IR
Example:
Change in V-blender from one manufacturer to another
manufacturer would not represent a change in operating
principle, and hence be considered to be the same under
SUPAC-IR, whereas a change in equipment from one class (V-
blender) to a different class (ribbon blender) would be considered
a change in design and operating principle and would be
considered different under SUPAC-IR.

17. MANUFACTURING SITE CHANGE
 The sponsor of an ANDA must include in its
application the site of manufacture, where the drug
product will be produced, tested, packaged, or
labelled. A change in any of these sites can
adversely affect the identity, strength, quality,
purity, or potency of the finished product.
Therefore, any site change under SUPAC-IR calls
for the new site to be in compliance with good
manufacturing practice (cGMP) regulations.

19. COMPARABILITY PROTOCOLS
According to the guidance, “A comparability protocol
is well defined, detailed, written plan for assessing
the effect of specific cmc changes in the identity,
strength, quality, purity and potency of a specific
drug product as these factors relate to the safety
and effectiveness of the product.

20. POST MARKETING SURVEILLANCE
• Once the FDA approves a generic drug product,
manufacturers are responsible for conducting
post-marketing surveillance.
• Post-marketing reporting requirements for an
approved ANDA are set forth in the US Federal
Code of Regulations.
• Post-marketing report in requirements for an
approved ANDA are set forth in the US Federal
Code of Regulations, 21 CFR 314.80 (5) and
314.98

21. “According to 21 CFR 314.80(a), an adverse drug
experience is de¢ned as ‘‘any adverse event
associated with the use of a drug in human,
whether or not considered drug related”

22. REFERENCE
1. Shargel.L, Kanfer.I, Generic drug product
development (solid dosage form), Scale up, post-
approval changes and post-marketing surveillance
page no.281