SlideShare a Scribd company logo
Vivek Singh Rathore
Research Scientist
R&D- Formulation
Jubilant Generics Pvt. Ltd.
 PURPOSE OF GUIDANCE
 SUPAC GUIDANCE DEFINES
 COMPONENTS AND COMPOSITION- NON RELEASE
CONTROLLING EXCIPIENTS
 COMPONENTS AND COMPOSITION- RELEASE
CONTROLLING EXCIPIENTS
 SITE CHANGES
 CHANGES IN BATCH SIZE (SCALE-UP/SCALE-DOWN)
 MANUFACTURING EQUIPMENT CHANGES
 MANUFACTURING PROCESS CHANGES
 REFERENCES
 This guidance provides recommendations to sponsors
of new drug applications (NDA's), abbreviated new
drug applications (ANDA's), and abbreviated antibiotic
applications (AADA's) who intend, during the
postapproval period, to change:
 1) the components or composition;
 2) the site of manufacture;
 3) the scale-up/scale-down of manufacture; and/or
 4) the manufacturing (process and equipment) of an
modified release oral formulation.
 1) Levels of change:
 Level I: Unlikely to have any detectable impact
on formulation quality and performance
(Minor Change).
 Level II: That could have a significant impact
on formulation quality and performance
(Moderate Change).
 Level III: That are likely to have a significant
impact on formulation quality and
performance (Major Change).
 2) Test Documentation
 Recommended chemistry, manufacturing, and controls tests
for each level of change.
 In vitro dissolution tests :-
 Extended release: In addition to application/compendial
release requirements, multipoint dissolution profiles should be
obtained in three other media, for example, in water, 0.1N
HCl, and USP buffer media at pH 4.5, and 6.8 for the changed
drug product and the bio-batch or marketed batch (unchanged
drug product). Adequate sampling should be performed, for
example, at 1, 2, and 4 hours and every two hours thereafter
until either 80% of the drug from the drug product is released
or an asymptote is reached. A surfactant may be used with
appropriate justification.
To be continue……
 2) Test Documentation.
 In vitro dissolution tests :-
 Delayed release:
 In addition to application/compendial release
requirements, dissolution tests should be performed in 0.1 N HCl for 2
hours (acid stage) followed by testing in USP buffer media, in the range of
pH 4.5-7.5 (buffer stage) under standard (application/compendial) test
conditions and two additional agitation speeds using the application/
compendial test apparatus (three additional test conditions).
 If the application/compendial test apparatus is the rotating basket method
(Apparatus 1), a rotation speed of 50, 100, and 150 rpm may be used, and
 if the application/compendial test apparatus is the rotating paddle method
(Apparatus 2), a rotation speed of 50, 75, and 100 rpm may be used.
 Multipoint dissolution profiles should be obtained during the buffer stage
of testing. Adequate sampling should be performed, for example, at 15,
30, 45, 60, and 120 minutes (following the time from which the dosage
form is placed in the buffer) until either 80% of the drug from the drug
product is released or an asymptote is reached.
 The above dissolution testing should be performed using the changed drug
product and the biobatch or marketed batch (unchanged drug product).
o 2) Test Documentation
 in vivo bioequivalence tests for each level of change.
 3)Filing Documentation that should support the change.
 Annual Report
 Changes Being Effected Supplement
 Prior Approval Supplement
Level of
Changes
Level I Level II Level III
1. Definition  Unlikely to have any
detectable impact on
formulation quality and
performance.
 That could have a
significant impact on
formulation quality and
performance.
 That are likely to
have a significant
impact on formulation
quality and
performance.
2. 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.
 Change in the
technical grade and/or
specifications
 Changes greater than
those listed above for a
Level 1 change but less
than or equal to the
following percent
Ranges.
 Any qualitative and
quantitative excipient
changes beyond the
ranges noted in Level II
Level of Changes Level I Level II
Non-release Controlling
Excipients
PERCENT EXCIPIENT (w/w) OUT OF TOTAL TARGET DOSAGE
FORM WEIGHT
Filler ±5 ±10
Disintegrant (Starch) ±3 ±6
Disintegrant (Other) ±1 ±2
Binder ±0.5 ±1
Lubricant (Calcium or
Magnesium Stearate)
±0.25 ±0.5
Lubricant (Others) ±1 ±2
Glidant (Talc) ±1 ±2
Glidant (Others) ±0.1 ±0.2
Film Coat ±1 ±2
The total additive effect of
all excipient changes
should not be more than
5%.
The total additive effect of
all excipient changes
should not be more than
10%.
Level of
Changes
Level I Level II Level III
3. Test
Documentation
(a. Chemistry
Documentation)
Application/com
pendial release
requirements.
 Stability testing:
First production
batch on long-
term stability data
reported in annual
report.
Application/compendia
l release requirements
and update executed
batch records.
 Stability testing: 1
batch with 3 months
accelerated stability
data in supplement and
1 batch on long-term
stability, data reported
in annual report.
Application/compendial release
requirements and update executed
batch records.
Significant body of information
available:
One batch with three months
accelerated stability data reported in
supplement; first three production
batch on long-term stability data
reported in annual report.
Significant body of information not
available:
Up to three batches with three months
accelerated stability data reported in
supplement; first three production
batch on long-term stability data
reported in annual report.
3. Test
Documentation
(b. Dissolution
Documentation)
 None beyond
application/compe
ndial
requirements.
Application/compendia
l requirements plus
multipoint dissolution
profiles in 3 other media
(e.g in water, 0.1N HCl,
and USP buffer media at
pH 4.5, and 6.8) until
either 80% of the drug
from the drug product is
released or an
 Application/compendial
(Profiling/Multipoint) dissolution
requirement.
Level of
Changes
Level I Level II Level III
3. Test
Documentation
(c. In Vivo
Bioequivalence
Documentation)
 None.  None  A single-dose BE
study. The BE study
may be waived with an
established in vivo/in
vitro correlation.
4. Filing
Documentation
 Annual report
(all information
including long-
term stability
data).
 Prior approval
supplement (all
information
including
accelerated stability
data); annual report
(long-term stability
data).
 Prior approval
supplement (all
information including
accelerated stability
data); annual report
(long-term stability
data).
Level of
Changes
Level I Level II Level III
1. Definition  Unlikely to have any
detectable impact on
formulation quality and
performance.
 That could have a
significant impact on
formulation quality and
performance.
 That are likely to have
a significant impact on
formulation quality and
performance.
2. Examples
 Changes in the release
controlling excipient(s) in
the formulation less than
or equal to 5% w/w of
total release controlling
excipient (e.g. Controlled
release polymer,
plasticizer) content in the
modified release solid oral
dosage form.
 Change in the technical
grade and/or
specifications
 Changes in the release
controlling excipient(s) in
the formulation less than
or equal to 5% w/w of
total release controlling
excipient (e.g. Controlled
release polymer,
plasticizer) content in the
modified release solid
oral dosage form.
Addition or deletion of
release controlling
excipient(s) (e.g., release
controlling
polymer/plasticizer).
 Changes in the release
controlling excipient(s)
in the formulation less
than or equal to 5% w/w
of total release
controlling excipient
(e.g. Controlled release
polymer, plasticizer)
content in the modified
release solid oral
dosage form.
Level of
Changes
Level I Level II Level III
3. Test
Documentation
(a. Chemistry
Documentation)
Application/com
pendial release
requirements.
 Stability testing:
First production
batch on long-
term stability data
reported in annual
report.
Application/compendial release
requirements and update
executed batch records.
 Stability Non-NTRD: 1 batch
with 3 months accelerated
stability
data in supplement and 1 batch
on long-term stability, data
reported in annual report.
Stability NTRD: Three batch with
3 months accelerated stability
data in supplement and first
three production batch on long-
term stability, data reported in
annual report.
Application/compendial
release requirements and
update executed batch
records.
 Stability Up to three
batches with three months
accelerated stability data
reported in supplement;
first three production batch
on long-term stability data
reported in annual report.
3. Test
Documentation
(b. Dissolution
Documentation)
 None beyond
application/compe
-ndial
requirements.
Nonnarrow therapeutic range
drugs Application/compendial
requirements plus multipoint
dissolution profiles in 3 other
media (e.g in water, 0.1N HCl,
and USP buffer media at pH 4.5,
and 6.8) until either 80% of the
drug from the drug product is
released or an asymptote is
reached.
 Application/compendial
(Profiling/Multipoint)
dissolution requirement.
Level of Changes Level I Level II Level III
3. Test
Documentation
(b. Dissolution
Documentation)
NA Narrow therapeutic
range drugs
Application/compendial
(Profiling/Multipoint)
dissolution requirement.
NA
3. Test
Documentation
(c. Bioequivalence
Documentation)
 None.  Nonnarrow therapeutic
range drugs None
 Narrow therapeutic
range drugs A single-
dose BE study. The BE
study may be waived
with an established in
vivo/in vitro correlation.
 A single-dose BE study.
The BE study may be waived
with an established in
vivo/in vitro correlation.
4. Filing
Documentation
 Annual
report (all
information
including
long-term
stability
data).
 Prior approval
supplement (all
information including
accelerated stability
data); annual report
(long-term stability
data).
 Prior approval supplement
(all information including
accelerated stability data);
annual report (long-term
stability data).
Level of
Changes
Level I Level II Level III
1. Definition  Consist of a site
changes within a single
facility
 Equipment, standard
operating procedures
(SOP's), environmental
conditions (e.g.,
temperature and
humidity)
and controls, and
personnel common to
both manufacturing
sites
Used are same
 And no changes are
made to the
manufacturing batch
records
 Consist of site
changes within a
contiguous
campus, or between
facilities in adjacent city
blocks.
 where the same
equipment, SOP's,
environmental
conditions (e.g.,
temperature and
humidity) and controls,
and personnel common
to both manufacturing
sites are used.
 And no changes are
made to the
manufacturing batch
records
 Consist of a change
in manufacturing site
to a
different campus.
 To qualify as a Level
3 change, the same
equipment, SOP's,
environmental
conditions, and
controls should be
used in the
manufacturing process
at the new site.
 And no changes may
be made to the
manufacturing batch
records
Level of
Changes
Level I Level II Level III
2. Test
Documentation
a. Chemistry
Documentation
 None beyond
application/compe
ndial release
requirements.
 Notification of location
of new site and updated
executed batch records.
 None beyond
application/compendial
release requirements.
 1 batch with 3 months
accelerated stability
data in supplement and 1
batch on long-term
stability, data reported in
annual report.
 Notification of location of
new site and updated batch
records.
Application/compendial
release requirements.
 Stability:
Significant body of information
available:
Significant body of information
not available:
b. Dissolution
Documentation
None beyond
application/compe
ndial release
requirements.
 Application/compendial
requirements plus
multipoint dissolution
profiles in 3 other media
(e.g in water, 0.1N HCl,
and USP buffer media at
pH 4.5, and 6.8) until
either 80% of the drug
from the drug product is
released or an asymptote
is reached.
 Application/compendial
(Profiling/Multipoint)
dissolution requirement.
Level of
Changes
Level I Level II Level III
c. In Vivo
Bioequivalence
Documentation
 None  None  A single-dose BE study.
The BE study may be
waived with an
established in vivo/in vitro
correlation.
3. Filing
Documentation
 Annual
report.
 Changes being
effected supplement;
annual report (long
term stability test
data).
 Prior approval
supplement (all
information including
accelerated stability data);
annual report (long-term
stability data).
Level of Changes Level I Level II
1. Definition
 Change in batch size, up to and
including a factor of 10 times the
size of the pilot/biobatch, where:
 Changes in batch size beyond a
factor of ten times the size of the
pilot/biobatch, where:
1. The equipment used to produce the test batch(es) is of the same
design and operating principles.
2. The batch(es) is (are) manufactured in full compliance with CGMP's
3) the same standard operating procedures (SOP's) and controls, as well
as the same formulation and manufacturing procedures, are used on the
test batch(es) and on the full-scale production batch(es).
2. Test Documentation
a. Chemistry
Documentation
 Application/compendial release
requirements. Notification of
change and submission of updated
batch records in annual report.
 Stability: One production batch
on long-term stability reported in
annual report.
 Application/compendial release
requirements. Notification of
change and submission of updated
batch records.
 Stability testing: One batch with
three months accelerated
stability data and first production
batch on long-term stability data.
Level of Changes Level I Level II
2. Test
Documentation
b. Dissolution
Documentation
 None beyond
application/compendial
release requirements.
 Application/compendial
requirements plus
multipoint dissolution
profiles in 3 other media
(e.g in water, 0.1N HCl, and
USP buffer media at pH 4.5,
and 6.8) until either 80% of
the drug from the drug
product is released or an
asymptote is reached.
2. Test
Documentation
c. In Vivo
Bioequivalence
 None.  None.
3. Filing
Documentation
 Annual report (all
information including long-
term stability data).
 Changes being effected
supplement; annual report
(long-term
stability data).
Level of Changes Level I Level II
1. Definition
 Change from non-automated
or non-mechanical equipment to
automated or mechanical
equipment to move ingredients.
 Change to alternative
equipment of the same design
and operating principles of the
same or of a different capacity.
 Change in equipment to a
different design and different
operating principles.
2. Test Documentation
a. Chemistry
Documentation
 Application/compendial release
requirements. Notification of
change and submission of
updated batch records.
 Stability testing: First
production batch on long-term
stability.
 Application/compendial release
requirements. Notification of
change and submission of updated
batch records.
 Stability testing:
Significant body of information
available:
Significant body of information not
available
Level of Changes Level I Level II
2. Test Documentation
b. Dissolution
Documentation
 None beyond
application/compendial release
requirements.
 Application/compendial
requirements plus multipoint
dissolution profiles in 3 other
media (e.g in water, 0.1N HCl,
and USP buffer media at pH 4.5,
and 6.8) until either 80% of the
drug from the drug product is
released or an asymptote is
reached.
2. Test Documentation
a. In Vivo
Bioequivalence
Documentation
 None.  None.
3. Filing Documentation  Annual report (all
information including long-
term stability data).
 Prior approval supplement
with justification for change;
annual report (long-term
stability data).
Level of
Changes
Level I Level II Level III
1. Definition
 Change in
process such as
mixing times and
operating speeds
within application
or validation
ranges.
 Change in process such
as mixing times and
operating speeds outside of
application/validation
ranges.
 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.
2. Test
Documentation
a. Chemistry
Documentation
None beyond
application/comp
endial release
requirements.
Notification of
the change and
submission of the
updated executed
batch records.
 Application/compendial
release requirements.
Notification of change and
submission of updated
batch records.
 Stability testing: One
batch with three months
accelerated stability data
and first production batch
on long-term stability data.
 Application/compendial
release requirements.
Notification of change and
submission of updated batch
records.
Stability testing: Three
batch with three months
accelerated
stability data and first three
production batch on long-
term stability data.
Level of
Changes
Level I Level II Level III
2. Test
Documentation
b. Dissolution
Documentation
 None beyond
application/compe
ndial release
requirements.
 Application/compendial
requirements plus
multipoint dissolution
profiles in 3 other media
(e.g in water, 0.1N HCl, and
USP buffer media at pH 4.5,
and 6.8) until either 80% of
the drug from the drug
product is released or an
asymptote is reached.
 Application/compendial
(Profiling/Multipoint)
dissolution requirement.
2. Test
Documentation
a.Bioequivalence
Documentation
 None.  None.  A single-dose BE study.
The BE study may be waived
with an established in vivo/in
vitro correlation.
3. Filing
Documentation
 Annual report.  Changes being effected
supplement; annual report
(longterm
stability data).
 Prior approval supplement;
annual report
(long-term stability data).
 Guidance for Industry, SUPAC-MR: Modified
Release Solid Oral Dosage Forms, Scale-Up
and Postapproval Changes: Chemistry,
Manufacturing, and Controls, InVitro
Dissolution Testing, and In Vivo
Bioequivalence Documentation.

More Related Content

What's hot

NEW DRUG APPLICATION ( NDA)
NEW DRUG APPLICATION ( NDA)NEW DRUG APPLICATION ( NDA)
NEW DRUG APPLICATION ( NDA)
Suvarta Maru
 
NDA and ANDA regulatory approval process
NDA and ANDA regulatory approval processNDA and ANDA regulatory approval process
NDA and ANDA regulatory approval process
Nilesh Gawade
 
Pilot plant Techniques and Product consideration for liquid dosage forms.
Pilot plant Techniques and Product consideration for liquid dosage forms.Pilot plant Techniques and Product consideration for liquid dosage forms.
Pilot plant Techniques and Product consideration for liquid dosage forms.
D.R. Chandravanshi
 
Hatch waxman act & amendments ppt
Hatch waxman act & amendments  pptHatch waxman act & amendments  ppt
Hatch waxman act & amendments ppt
Alexa Jacob
 
CTD and eCTD
CTD and eCTDCTD and eCTD
CTD and eCTD
Girish Swami
 
Supac
SupacSupac
hatch-waxman act@amendments
hatch-waxman act@amendmentshatch-waxman act@amendments
Cmc postapproval regulatory affairs (ppt)
Cmc postapproval regulatory affairs (ppt)Cmc postapproval regulatory affairs (ppt)
Cmc postapproval regulatory affairs (ppt)
suresh gautam
 
Drug excipient Compatibility
Drug excipient CompatibilityDrug excipient Compatibility
Drug excipient Compatibility
Suraj Choudhary
 
Supac
SupacSupac
Sr or cr formulations
Sr or cr formulationsSr or cr formulations
Sr or cr formulations
Pratiksha Chandragirivar
 
API, BIOLOGICS,NOVEL,THERAPIES........pptx
API, BIOLOGICS,NOVEL,THERAPIES........pptxAPI, BIOLOGICS,NOVEL,THERAPIES........pptx
API, BIOLOGICS,NOVEL,THERAPIES........pptx
PawanDhamala1
 
Code of Federal Regulations
Code of Federal RegulationsCode of Federal Regulations
Code of Federal Regulations
Swapnil Fernandes
 
Dmf seminar
Dmf seminarDmf seminar
Dmf seminar
Saroj Makwana
 
DRUG PRODUCT PERFORMANCE, IN VITRO
DRUG PRODUCT PERFORMANCE, IN VITRODRUG PRODUCT PERFORMANCE, IN VITRO
DRUG PRODUCT PERFORMANCE, IN VITRO
Ankit Malik
 
Supac and post marketing serveillance
Supac and post marketing serveillanceSupac and post marketing serveillance
Supac and post marketing serveillance
BhavyaJivrajani
 
Supac
SupacSupac
REGULATIONS FOR COMBINATION PRODUCTS AND MEDICAL DEVICES
REGULATIONS FOR COMBINATION PRODUCTS AND MEDICAL DEVICESREGULATIONS FOR COMBINATION PRODUCTS AND MEDICAL DEVICES
REGULATIONS FOR COMBINATION PRODUCTS AND MEDICAL DEVICES
Arunpandiyan59
 
Regulatory affairs cmc , post approval regulatory affairs
Regulatory affairs   cmc , post approval regulatory affairsRegulatory affairs   cmc , post approval regulatory affairs
Regulatory affairs cmc , post approval regulatory affairs
ArjunDhawale
 
Impd
ImpdImpd

What's hot (20)

NEW DRUG APPLICATION ( NDA)
NEW DRUG APPLICATION ( NDA)NEW DRUG APPLICATION ( NDA)
NEW DRUG APPLICATION ( NDA)
 
NDA and ANDA regulatory approval process
NDA and ANDA regulatory approval processNDA and ANDA regulatory approval process
NDA and ANDA regulatory approval process
 
Pilot plant Techniques and Product consideration for liquid dosage forms.
Pilot plant Techniques and Product consideration for liquid dosage forms.Pilot plant Techniques and Product consideration for liquid dosage forms.
Pilot plant Techniques and Product consideration for liquid dosage forms.
 
Hatch waxman act & amendments ppt
Hatch waxman act & amendments  pptHatch waxman act & amendments  ppt
Hatch waxman act & amendments ppt
 
CTD and eCTD
CTD and eCTDCTD and eCTD
CTD and eCTD
 
Supac
SupacSupac
Supac
 
hatch-waxman act@amendments
hatch-waxman act@amendmentshatch-waxman act@amendments
hatch-waxman act@amendments
 
Cmc postapproval regulatory affairs (ppt)
Cmc postapproval regulatory affairs (ppt)Cmc postapproval regulatory affairs (ppt)
Cmc postapproval regulatory affairs (ppt)
 
Drug excipient Compatibility
Drug excipient CompatibilityDrug excipient Compatibility
Drug excipient Compatibility
 
Supac
SupacSupac
Supac
 
Sr or cr formulations
Sr or cr formulationsSr or cr formulations
Sr or cr formulations
 
API, BIOLOGICS,NOVEL,THERAPIES........pptx
API, BIOLOGICS,NOVEL,THERAPIES........pptxAPI, BIOLOGICS,NOVEL,THERAPIES........pptx
API, BIOLOGICS,NOVEL,THERAPIES........pptx
 
Code of Federal Regulations
Code of Federal RegulationsCode of Federal Regulations
Code of Federal Regulations
 
Dmf seminar
Dmf seminarDmf seminar
Dmf seminar
 
DRUG PRODUCT PERFORMANCE, IN VITRO
DRUG PRODUCT PERFORMANCE, IN VITRODRUG PRODUCT PERFORMANCE, IN VITRO
DRUG PRODUCT PERFORMANCE, IN VITRO
 
Supac and post marketing serveillance
Supac and post marketing serveillanceSupac and post marketing serveillance
Supac and post marketing serveillance
 
Supac
SupacSupac
Supac
 
REGULATIONS FOR COMBINATION PRODUCTS AND MEDICAL DEVICES
REGULATIONS FOR COMBINATION PRODUCTS AND MEDICAL DEVICESREGULATIONS FOR COMBINATION PRODUCTS AND MEDICAL DEVICES
REGULATIONS FOR COMBINATION PRODUCTS AND MEDICAL DEVICES
 
Regulatory affairs cmc , post approval regulatory affairs
Regulatory affairs   cmc , post approval regulatory affairsRegulatory affairs   cmc , post approval regulatory affairs
Regulatory affairs cmc , post approval regulatory affairs
 
Impd
ImpdImpd
Impd
 

Similar to Supac - Guidance for Modified Release Dosage Form

SUPAC-IR.ppt
SUPAC-IR.pptSUPAC-IR.ppt
SUPAC-IR.ppt
PavanDhoble1
 
Supac
SupacSupac
Supac
SupacSupac
SUPAC
SUPACSUPAC
SUPAC
sonian22
 
scaleup and post approval modification.pptx
scaleup and post approval modification.pptxscaleup and post approval modification.pptx
scaleup and post approval modification.pptx
PankajSharma446574
 
SUPAC.pptx
SUPAC.pptxSUPAC.pptx
SUPAC.pptx
vinod431496
 
IN VIVO AND SCALE-UP PROCESS APPROVAL CHANGES.pptx
IN VIVO AND  SCALE-UP  PROCESS APPROVAL CHANGES.pptxIN VIVO AND  SCALE-UP  PROCESS APPROVAL CHANGES.pptx
IN VIVO AND SCALE-UP PROCESS APPROVAL CHANGES.pptx
PawanDhamala1
 
SUPAC(Scale Up and Post Approval changes for RA 1st sempptx
SUPAC(Scale Up and Post Approval  changes for RA 1st sempptxSUPAC(Scale Up and Post Approval  changes for RA 1st sempptx
SUPAC(Scale Up and Post Approval changes for RA 1st sempptx
Charmi13
 
(SUPAC PART- 4) (SCALE-UP AND POST APPROVAL CHANGES
(SUPAC PART-  4) (SCALE-UP AND POST APPROVAL CHANGES (SUPAC PART-  4) (SCALE-UP AND POST APPROVAL CHANGES
(SUPAC PART- 4) (SCALE-UP AND POST APPROVAL CHANGES
kavita bahmani
 
Scale up Process and Post Approval Changes
Scale up Process and Post Approval ChangesScale up Process and Post Approval Changes
Scale up Process and Post Approval Changes
PrajaktaPatil890246
 
2. SUPAC.pdf
2. SUPAC.pdf2. SUPAC.pdf
2. SUPAC.pdf
bhagwanyadav12
 
Scale – Up & Post Approval Changes
Scale – Up & Post Approval ChangesScale – Up & Post Approval Changes
Scale – Up & Post Approval Changes
VAIBHAV SHENDE
 
Scale up post approval changes
Scale up post approval changesScale up post approval changes
Scale up post approval changes
ROHIT
 
Supac
Supac Supac
Supac guidelines for mr tablets
Supac guidelines for mr tabletsSupac guidelines for mr tablets
Supac guidelines for mr tablets
AmruthaSanthoshini
 
Chap 1_ SUPAC mpharm quality assurance semester 2
Chap 1_ SUPAC mpharm quality assurance semester 2Chap 1_ SUPAC mpharm quality assurance semester 2
Chap 1_ SUPAC mpharm quality assurance semester 2
christinajohn24
 
Supac
SupacSupac
Scale Up And Post Approval Changes (SUPAC)
Scale Up And Post Approval Changes (SUPAC)Scale Up And Post Approval Changes (SUPAC)
Scale Up And Post Approval Changes (SUPAC)
Prabhjot kaur
 
Scale up and post approval changes
Scale up and post approval changesScale up and post approval changes
Scale up and post approval changes
prakhar rai pk
 
Qualityassurancecontrolinpharmaindustry
QualityassurancecontrolinpharmaindustryQualityassurancecontrolinpharmaindustry
Qualityassurancecontrolinpharmaindustry
Malla Reddy College of Pharmacy
 

Similar to Supac - Guidance for Modified Release Dosage Form (20)

SUPAC-IR.ppt
SUPAC-IR.pptSUPAC-IR.ppt
SUPAC-IR.ppt
 
Supac
SupacSupac
Supac
 
Supac
SupacSupac
Supac
 
SUPAC
SUPACSUPAC
SUPAC
 
scaleup and post approval modification.pptx
scaleup and post approval modification.pptxscaleup and post approval modification.pptx
scaleup and post approval modification.pptx
 
SUPAC.pptx
SUPAC.pptxSUPAC.pptx
SUPAC.pptx
 
IN VIVO AND SCALE-UP PROCESS APPROVAL CHANGES.pptx
IN VIVO AND  SCALE-UP  PROCESS APPROVAL CHANGES.pptxIN VIVO AND  SCALE-UP  PROCESS APPROVAL CHANGES.pptx
IN VIVO AND SCALE-UP PROCESS APPROVAL CHANGES.pptx
 
SUPAC(Scale Up and Post Approval changes for RA 1st sempptx
SUPAC(Scale Up and Post Approval  changes for RA 1st sempptxSUPAC(Scale Up and Post Approval  changes for RA 1st sempptx
SUPAC(Scale Up and Post Approval changes for RA 1st sempptx
 
(SUPAC PART- 4) (SCALE-UP AND POST APPROVAL CHANGES
(SUPAC PART-  4) (SCALE-UP AND POST APPROVAL CHANGES (SUPAC PART-  4) (SCALE-UP AND POST APPROVAL CHANGES
(SUPAC PART- 4) (SCALE-UP AND POST APPROVAL CHANGES
 
Scale up Process and Post Approval Changes
Scale up Process and Post Approval ChangesScale up Process and Post Approval Changes
Scale up Process and Post Approval Changes
 
2. SUPAC.pdf
2. SUPAC.pdf2. SUPAC.pdf
2. SUPAC.pdf
 
Scale – Up & Post Approval Changes
Scale – Up & Post Approval ChangesScale – Up & Post Approval Changes
Scale – Up & Post Approval Changes
 
Scale up post approval changes
Scale up post approval changesScale up post approval changes
Scale up post approval changes
 
Supac
Supac Supac
Supac
 
Supac guidelines for mr tablets
Supac guidelines for mr tabletsSupac guidelines for mr tablets
Supac guidelines for mr tablets
 
Chap 1_ SUPAC mpharm quality assurance semester 2
Chap 1_ SUPAC mpharm quality assurance semester 2Chap 1_ SUPAC mpharm quality assurance semester 2
Chap 1_ SUPAC mpharm quality assurance semester 2
 
Supac
SupacSupac
Supac
 
Scale Up And Post Approval Changes (SUPAC)
Scale Up And Post Approval Changes (SUPAC)Scale Up And Post Approval Changes (SUPAC)
Scale Up And Post Approval Changes (SUPAC)
 
Scale up and post approval changes
Scale up and post approval changesScale up and post approval changes
Scale up and post approval changes
 
Qualityassurancecontrolinpharmaindustry
QualityassurancecontrolinpharmaindustryQualityassurancecontrolinpharmaindustry
Qualityassurancecontrolinpharmaindustry
 

Recently uploaded

RNA AND DNA VIRUSES morphology,chemical composition
RNA AND DNA VIRUSES morphology,chemical compositionRNA AND DNA VIRUSES morphology,chemical composition
RNA AND DNA VIRUSES morphology,chemical composition
BenjaminMutisyaMuimi
 
Girls Call Hyderabad 000XX00000 Provide Best And Top Girl Service And No1 in ...
Girls Call Hyderabad 000XX00000 Provide Best And Top Girl Service And No1 in ...Girls Call Hyderabad 000XX00000 Provide Best And Top Girl Service And No1 in ...
Girls Call Hyderabad 000XX00000 Provide Best And Top Girl Service And No1 in ...
pinkichadda23 #v08
 
High Class Girls Call Mumbai 9910780858 Provide Best And Top Girl Service And...
High Class Girls Call Mumbai 9910780858 Provide Best And Top Girl Service And...High Class Girls Call Mumbai 9910780858 Provide Best And Top Girl Service And...
High Class Girls Call Mumbai 9910780858 Provide Best And Top Girl Service And...
jealousviolet
 
How Virtual Medical Assistants Improve Patient Engagement.pdf
How Virtual Medical Assistants Improve Patient Engagement.pdfHow Virtual Medical Assistants Improve Patient Engagement.pdf
How Virtual Medical Assistants Improve Patient Engagement.pdf
johnmark49490
 
�� د حاتم البيطار القمةاسينمنت فاضية لطلاب القمة كورس مساعد طبيب الاسنان 2�.pdf
�� د حاتم البيطار القمةاسينمنت فاضية لطلاب القمة كورس مساعد طبيب الاسنان 2�.pdf�� د حاتم البيطار القمةاسينمنت فاضية لطلاب القمة كورس مساعد طبيب الاسنان 2�.pdf
�� د حاتم البيطار القمةاسينمنت فاضية لطلاب القمة كورس مساعد طبيب الاسنان 2�.pdf
د حاتم البيطار
 
New Girls Call Navi Mumbai 9930245274 Unlimited Short Providing Girls Service...
New Girls Call Navi Mumbai 9930245274 Unlimited Short Providing Girls Service...New Girls Call Navi Mumbai 9930245274 Unlimited Short Providing Girls Service...
New Girls Call Navi Mumbai 9930245274 Unlimited Short Providing Girls Service...
revolutionary575
 
Girls Call Delhi 000XX00000 Provide Best And Top Girl Service And No1 in City
Girls Call Delhi 000XX00000 Provide Best And Top Girl Service And No1 in CityGirls Call Delhi 000XX00000 Provide Best And Top Girl Service And No1 in City
Girls Call Delhi 000XX00000 Provide Best And Top Girl Service And No1 in City
snehamittal#G05
 
Bronchiectasis and Physiotherapy Management
Bronchiectasis and Physiotherapy ManagementBronchiectasis and Physiotherapy Management
Bronchiectasis and Physiotherapy Management
abdulazeezvpadikkal
 
Ihuman Case Study Help-ihuman case study modules help.pdf
Ihuman Case Study Help-ihuman case study modules help.pdfIhuman Case Study Help-ihuman case study modules help.pdf
Ihuman Case Study Help-ihuman case study modules help.pdf
Reliable Assignments Help
 
Body to Body Massage in Ajman - Malayali Kerala Spa Ajman
Body to Body Massage in Ajman - Malayali Kerala Spa AjmanBody to Body Massage in Ajman - Malayali Kerala Spa Ajman
Body to Body Massage in Ajman - Malayali Kerala Spa Ajman
Malayali Kerala Spa Ajman
 
Girls Call Thane 000XX00000 Provide Best And Top Girl Service And No1 in City
Girls Call Thane 000XX00000 Provide Best And Top Girl Service And No1 in CityGirls Call Thane 000XX00000 Provide Best And Top Girl Service And No1 in City
Girls Call Thane 000XX00000 Provide Best And Top Girl Service And No1 in City
snehamittal#G05
 
Female Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Serv...
Female Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Serv...Female Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Serv...
Female Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Serv...
bellared2
 
Massage Centre Ajman - Malayali Kerala Spa Ajman
Massage Centre Ajman - Malayali Kerala Spa AjmanMassage Centre Ajman - Malayali Kerala Spa Ajman
Massage Centre Ajman - Malayali Kerala Spa Ajman
Malayali Kerala Spa Ajman
 
Premium Girls Call Mumbai 9910780858 Provide Best And Top Girl Service And No...
Premium Girls Call Mumbai 9910780858 Provide Best And Top Girl Service And No...Premium Girls Call Mumbai 9910780858 Provide Best And Top Girl Service And No...
Premium Girls Call Mumbai 9910780858 Provide Best And Top Girl Service And No...
saroni night girls
 
Top Companies Empowering Access to Healthcare 2024.pdf
Top Companies Empowering Access to Healthcare 2024.pdfTop Companies Empowering Access to Healthcare 2024.pdf
Top Companies Empowering Access to Healthcare 2024.pdf
insightscare
 
Respectful Care _Special Patient Care for health science students
Respectful Care _Special Patient Care for health science studentsRespectful Care _Special Patient Care for health science students
Respectful Care _Special Patient Care for health science students
Debre Berhan University
 
Cardiac_Disease-1.ppt in canine & feline
Cardiac_Disease-1.ppt in canine & felineCardiac_Disease-1.ppt in canine & feline
Cardiac_Disease-1.ppt in canine & feline
MadhudarshiKumar2
 
chapter 1- changing trends in physical education.pptx
chapter 1- changing trends in physical education.pptxchapter 1- changing trends in physical education.pptx
chapter 1- changing trends in physical education.pptx
divijsinghrenu10
 
Ruksha Mudra (Dry Mudra) -Mudra will reduce the bladder pressure
Ruksha Mudra (Dry Mudra) -Mudra will reduce the bladder pressureRuksha Mudra (Dry Mudra) -Mudra will reduce the bladder pressure
Ruksha Mudra (Dry Mudra) -Mudra will reduce the bladder pressure
Karuna Yoga Vidya Peetham
 
Welco to PowerPointhihhlljjjllasfafafkkk
Welco to PowerPointhihhlljjjllasfafafkkkWelco to PowerPointhihhlljjjllasfafafkkk
Welco to PowerPointhihhlljjjllasfafafkkk
TngHunh31
 

Recently uploaded (20)

RNA AND DNA VIRUSES morphology,chemical composition
RNA AND DNA VIRUSES morphology,chemical compositionRNA AND DNA VIRUSES morphology,chemical composition
RNA AND DNA VIRUSES morphology,chemical composition
 
Girls Call Hyderabad 000XX00000 Provide Best And Top Girl Service And No1 in ...
Girls Call Hyderabad 000XX00000 Provide Best And Top Girl Service And No1 in ...Girls Call Hyderabad 000XX00000 Provide Best And Top Girl Service And No1 in ...
Girls Call Hyderabad 000XX00000 Provide Best And Top Girl Service And No1 in ...
 
High Class Girls Call Mumbai 9910780858 Provide Best And Top Girl Service And...
High Class Girls Call Mumbai 9910780858 Provide Best And Top Girl Service And...High Class Girls Call Mumbai 9910780858 Provide Best And Top Girl Service And...
High Class Girls Call Mumbai 9910780858 Provide Best And Top Girl Service And...
 
How Virtual Medical Assistants Improve Patient Engagement.pdf
How Virtual Medical Assistants Improve Patient Engagement.pdfHow Virtual Medical Assistants Improve Patient Engagement.pdf
How Virtual Medical Assistants Improve Patient Engagement.pdf
 
�� د حاتم البيطار القمةاسينمنت فاضية لطلاب القمة كورس مساعد طبيب الاسنان 2�.pdf
�� د حاتم البيطار القمةاسينمنت فاضية لطلاب القمة كورس مساعد طبيب الاسنان 2�.pdf�� د حاتم البيطار القمةاسينمنت فاضية لطلاب القمة كورس مساعد طبيب الاسنان 2�.pdf
�� د حاتم البيطار القمةاسينمنت فاضية لطلاب القمة كورس مساعد طبيب الاسنان 2�.pdf
 
New Girls Call Navi Mumbai 9930245274 Unlimited Short Providing Girls Service...
New Girls Call Navi Mumbai 9930245274 Unlimited Short Providing Girls Service...New Girls Call Navi Mumbai 9930245274 Unlimited Short Providing Girls Service...
New Girls Call Navi Mumbai 9930245274 Unlimited Short Providing Girls Service...
 
Girls Call Delhi 000XX00000 Provide Best And Top Girl Service And No1 in City
Girls Call Delhi 000XX00000 Provide Best And Top Girl Service And No1 in CityGirls Call Delhi 000XX00000 Provide Best And Top Girl Service And No1 in City
Girls Call Delhi 000XX00000 Provide Best And Top Girl Service And No1 in City
 
Bronchiectasis and Physiotherapy Management
Bronchiectasis and Physiotherapy ManagementBronchiectasis and Physiotherapy Management
Bronchiectasis and Physiotherapy Management
 
Ihuman Case Study Help-ihuman case study modules help.pdf
Ihuman Case Study Help-ihuman case study modules help.pdfIhuman Case Study Help-ihuman case study modules help.pdf
Ihuman Case Study Help-ihuman case study modules help.pdf
 
Body to Body Massage in Ajman - Malayali Kerala Spa Ajman
Body to Body Massage in Ajman - Malayali Kerala Spa AjmanBody to Body Massage in Ajman - Malayali Kerala Spa Ajman
Body to Body Massage in Ajman - Malayali Kerala Spa Ajman
 
Girls Call Thane 000XX00000 Provide Best And Top Girl Service And No1 in City
Girls Call Thane 000XX00000 Provide Best And Top Girl Service And No1 in CityGirls Call Thane 000XX00000 Provide Best And Top Girl Service And No1 in City
Girls Call Thane 000XX00000 Provide Best And Top Girl Service And No1 in City
 
Female Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Serv...
Female Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Serv...Female Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Serv...
Female Girls Call Navi Mumbai 🎈🔥9920725232 🔥💋🎈 Provide Best And Top Girl Serv...
 
Massage Centre Ajman - Malayali Kerala Spa Ajman
Massage Centre Ajman - Malayali Kerala Spa AjmanMassage Centre Ajman - Malayali Kerala Spa Ajman
Massage Centre Ajman - Malayali Kerala Spa Ajman
 
Premium Girls Call Mumbai 9910780858 Provide Best And Top Girl Service And No...
Premium Girls Call Mumbai 9910780858 Provide Best And Top Girl Service And No...Premium Girls Call Mumbai 9910780858 Provide Best And Top Girl Service And No...
Premium Girls Call Mumbai 9910780858 Provide Best And Top Girl Service And No...
 
Top Companies Empowering Access to Healthcare 2024.pdf
Top Companies Empowering Access to Healthcare 2024.pdfTop Companies Empowering Access to Healthcare 2024.pdf
Top Companies Empowering Access to Healthcare 2024.pdf
 
Respectful Care _Special Patient Care for health science students
Respectful Care _Special Patient Care for health science studentsRespectful Care _Special Patient Care for health science students
Respectful Care _Special Patient Care for health science students
 
Cardiac_Disease-1.ppt in canine & feline
Cardiac_Disease-1.ppt in canine & felineCardiac_Disease-1.ppt in canine & feline
Cardiac_Disease-1.ppt in canine & feline
 
chapter 1- changing trends in physical education.pptx
chapter 1- changing trends in physical education.pptxchapter 1- changing trends in physical education.pptx
chapter 1- changing trends in physical education.pptx
 
Ruksha Mudra (Dry Mudra) -Mudra will reduce the bladder pressure
Ruksha Mudra (Dry Mudra) -Mudra will reduce the bladder pressureRuksha Mudra (Dry Mudra) -Mudra will reduce the bladder pressure
Ruksha Mudra (Dry Mudra) -Mudra will reduce the bladder pressure
 
Welco to PowerPointhihhlljjjllasfafafkkk
Welco to PowerPointhihhlljjjllasfafafkkkWelco to PowerPointhihhlljjjllasfafafkkk
Welco to PowerPointhihhlljjjllasfafafkkk
 

Supac - Guidance for Modified Release Dosage Form

  • 1. Vivek Singh Rathore Research Scientist R&D- Formulation Jubilant Generics Pvt. Ltd.
  • 2.  PURPOSE OF GUIDANCE  SUPAC GUIDANCE DEFINES  COMPONENTS AND COMPOSITION- NON RELEASE CONTROLLING EXCIPIENTS  COMPONENTS AND COMPOSITION- RELEASE CONTROLLING EXCIPIENTS  SITE CHANGES  CHANGES IN BATCH SIZE (SCALE-UP/SCALE-DOWN)  MANUFACTURING EQUIPMENT CHANGES  MANUFACTURING PROCESS CHANGES  REFERENCES
  • 3.  This guidance provides recommendations to sponsors of new drug applications (NDA's), abbreviated new drug applications (ANDA's), and abbreviated antibiotic applications (AADA's) who intend, during the postapproval period, to change:  1) the components or composition;  2) the site of manufacture;  3) the scale-up/scale-down of manufacture; and/or  4) the manufacturing (process and equipment) of an modified release oral formulation.
  • 4.  1) Levels of change:  Level I: Unlikely to have any detectable impact on formulation quality and performance (Minor Change).  Level II: That could have a significant impact on formulation quality and performance (Moderate Change).  Level III: That are likely to have a significant impact on formulation quality and performance (Major Change).
  • 5.  2) Test Documentation  Recommended chemistry, manufacturing, and controls tests for each level of change.  In vitro dissolution tests :-  Extended release: In addition to application/compendial release requirements, multipoint dissolution profiles should be obtained in three other media, for example, in water, 0.1N HCl, and USP buffer media at pH 4.5, and 6.8 for the changed drug product and the bio-batch or marketed batch (unchanged drug product). Adequate sampling should be performed, for example, at 1, 2, and 4 hours and every two hours thereafter until either 80% of the drug from the drug product is released or an asymptote is reached. A surfactant may be used with appropriate justification. To be continue……
  • 6.  2) Test Documentation.  In vitro dissolution tests :-  Delayed release:  In addition to application/compendial release requirements, dissolution tests should be performed in 0.1 N HCl for 2 hours (acid stage) followed by testing in USP buffer media, in the range of pH 4.5-7.5 (buffer stage) under standard (application/compendial) test conditions and two additional agitation speeds using the application/ compendial test apparatus (three additional test conditions).  If the application/compendial test apparatus is the rotating basket method (Apparatus 1), a rotation speed of 50, 100, and 150 rpm may be used, and  if the application/compendial test apparatus is the rotating paddle method (Apparatus 2), a rotation speed of 50, 75, and 100 rpm may be used.  Multipoint dissolution profiles should be obtained during the buffer stage of testing. Adequate sampling should be performed, for example, at 15, 30, 45, 60, and 120 minutes (following the time from which the dosage form is placed in the buffer) until either 80% of the drug from the drug product is released or an asymptote is reached.  The above dissolution testing should be performed using the changed drug product and the biobatch or marketed batch (unchanged drug product).
  • 7. o 2) Test Documentation  in vivo bioequivalence tests for each level of change.  3)Filing Documentation that should support the change.  Annual Report  Changes Being Effected Supplement  Prior Approval Supplement
  • 8. Level of Changes Level I Level II Level III 1. Definition  Unlikely to have any detectable impact on formulation quality and performance.  That could have a significant impact on formulation quality and performance.  That are likely to have a significant impact on formulation quality and performance. 2. 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.  Change in the technical grade and/or specifications  Changes greater than those listed above for a Level 1 change but less than or equal to the following percent Ranges.  Any qualitative and quantitative excipient changes beyond the ranges noted in Level II
  • 9. Level of Changes Level I Level II Non-release Controlling Excipients PERCENT EXCIPIENT (w/w) OUT OF TOTAL TARGET DOSAGE FORM WEIGHT Filler ±5 ±10 Disintegrant (Starch) ±3 ±6 Disintegrant (Other) ±1 ±2 Binder ±0.5 ±1 Lubricant (Calcium or Magnesium Stearate) ±0.25 ±0.5 Lubricant (Others) ±1 ±2 Glidant (Talc) ±1 ±2 Glidant (Others) ±0.1 ±0.2 Film Coat ±1 ±2 The total additive effect of all excipient changes should not be more than 5%. The total additive effect of all excipient changes should not be more than 10%.
  • 10. Level of Changes Level I Level II Level III 3. Test Documentation (a. Chemistry Documentation) Application/com pendial release requirements.  Stability testing: First production batch on long- term stability data reported in annual report. Application/compendia l release requirements and update executed batch records.  Stability testing: 1 batch with 3 months accelerated stability data in supplement and 1 batch on long-term stability, data reported in annual report. Application/compendial release requirements and update executed batch records. Significant body of information available: One batch with three months accelerated stability data reported in supplement; first three production batch on long-term stability data reported in annual report. Significant body of information not available: Up to three batches with three months accelerated stability data reported in supplement; first three production batch on long-term stability data reported in annual report. 3. Test Documentation (b. Dissolution Documentation)  None beyond application/compe ndial requirements. Application/compendia l requirements plus multipoint dissolution profiles in 3 other media (e.g in water, 0.1N HCl, and USP buffer media at pH 4.5, and 6.8) until either 80% of the drug from the drug product is released or an  Application/compendial (Profiling/Multipoint) dissolution requirement.
  • 11. Level of Changes Level I Level II Level III 3. Test Documentation (c. In Vivo Bioequivalence Documentation)  None.  None  A single-dose BE study. The BE study may be waived with an established in vivo/in vitro correlation. 4. Filing Documentation  Annual report (all information including long- term stability data).  Prior approval supplement (all information including accelerated stability data); annual report (long-term stability data).  Prior approval supplement (all information including accelerated stability data); annual report (long-term stability data).
  • 12. Level of Changes Level I Level II Level III 1. Definition  Unlikely to have any detectable impact on formulation quality and performance.  That could have a significant impact on formulation quality and performance.  That are likely to have a significant impact on formulation quality and performance. 2. Examples  Changes in the release controlling excipient(s) in the formulation less than or equal to 5% w/w of total release controlling excipient (e.g. Controlled release polymer, plasticizer) content in the modified release solid oral dosage form.  Change in the technical grade and/or specifications  Changes in the release controlling excipient(s) in the formulation less than or equal to 5% w/w of total release controlling excipient (e.g. Controlled release polymer, plasticizer) content in the modified release solid oral dosage form. Addition or deletion of release controlling excipient(s) (e.g., release controlling polymer/plasticizer).  Changes in the release controlling excipient(s) in the formulation less than or equal to 5% w/w of total release controlling excipient (e.g. Controlled release polymer, plasticizer) content in the modified release solid oral dosage form.
  • 13. Level of Changes Level I Level II Level III 3. Test Documentation (a. Chemistry Documentation) Application/com pendial release requirements.  Stability testing: First production batch on long- term stability data reported in annual report. Application/compendial release requirements and update executed batch records.  Stability Non-NTRD: 1 batch with 3 months accelerated stability data in supplement and 1 batch on long-term stability, data reported in annual report. Stability NTRD: Three batch with 3 months accelerated stability data in supplement and first three production batch on long- term stability, data reported in annual report. Application/compendial release requirements and update executed batch records.  Stability Up to three batches with three months accelerated stability data reported in supplement; first three production batch on long-term stability data reported in annual report. 3. Test Documentation (b. Dissolution Documentation)  None beyond application/compe -ndial requirements. Nonnarrow therapeutic range drugs Application/compendial requirements plus multipoint dissolution profiles in 3 other media (e.g in water, 0.1N HCl, and USP buffer media at pH 4.5, and 6.8) until either 80% of the drug from the drug product is released or an asymptote is reached.  Application/compendial (Profiling/Multipoint) dissolution requirement.
  • 14. Level of Changes Level I Level II Level III 3. Test Documentation (b. Dissolution Documentation) NA Narrow therapeutic range drugs Application/compendial (Profiling/Multipoint) dissolution requirement. NA 3. Test Documentation (c. Bioequivalence Documentation)  None.  Nonnarrow therapeutic range drugs None  Narrow therapeutic range drugs A single- dose BE study. The BE study may be waived with an established in vivo/in vitro correlation.  A single-dose BE study. The BE study may be waived with an established in vivo/in vitro correlation. 4. Filing Documentation  Annual report (all information including long-term stability data).  Prior approval supplement (all information including accelerated stability data); annual report (long-term stability data).  Prior approval supplement (all information including accelerated stability data); annual report (long-term stability data).
  • 15. Level of Changes Level I Level II Level III 1. Definition  Consist of a site changes within a single facility  Equipment, standard operating procedures (SOP's), environmental conditions (e.g., temperature and humidity) and controls, and personnel common to both manufacturing sites Used are same  And no changes are made to the manufacturing batch records  Consist of site changes within a contiguous campus, or between facilities in adjacent city blocks.  where the same equipment, SOP's, environmental conditions (e.g., temperature and humidity) and controls, and personnel common to both manufacturing sites are used.  And no changes are made to the manufacturing batch records  Consist of a change in manufacturing site to a different campus.  To qualify as a Level 3 change, the same equipment, SOP's, environmental conditions, and controls should be used in the manufacturing process at the new site.  And no changes may be made to the manufacturing batch records
  • 16. Level of Changes Level I Level II Level III 2. Test Documentation a. Chemistry Documentation  None beyond application/compe ndial release requirements.  Notification of location of new site and updated executed batch records.  None beyond application/compendial release requirements.  1 batch with 3 months accelerated stability data in supplement and 1 batch on long-term stability, data reported in annual report.  Notification of location of new site and updated batch records. Application/compendial release requirements.  Stability: Significant body of information available: Significant body of information not available: b. Dissolution Documentation None beyond application/compe ndial release requirements.  Application/compendial requirements plus multipoint dissolution profiles in 3 other media (e.g in water, 0.1N HCl, and USP buffer media at pH 4.5, and 6.8) until either 80% of the drug from the drug product is released or an asymptote is reached.  Application/compendial (Profiling/Multipoint) dissolution requirement.
  • 17. Level of Changes Level I Level II Level III c. In Vivo Bioequivalence Documentation  None  None  A single-dose BE study. The BE study may be waived with an established in vivo/in vitro correlation. 3. Filing Documentation  Annual report.  Changes being effected supplement; annual report (long term stability test data).  Prior approval supplement (all information including accelerated stability data); annual report (long-term stability data).
  • 18. Level of Changes Level I Level II 1. Definition  Change in batch size, up to and including a factor of 10 times the size of the pilot/biobatch, where:  Changes in batch size beyond a factor of ten times the size of the pilot/biobatch, where: 1. The equipment used to produce the test batch(es) is of the same design and operating principles. 2. The batch(es) is (are) manufactured in full compliance with CGMP's 3) the same standard operating procedures (SOP's) and controls, as well as the same formulation and manufacturing procedures, are used on the test batch(es) and on the full-scale production batch(es). 2. Test Documentation a. Chemistry Documentation  Application/compendial release requirements. Notification of change and submission of updated batch records in annual report.  Stability: One production batch on long-term stability reported in annual report.  Application/compendial release requirements. Notification of change and submission of updated batch records.  Stability testing: One batch with three months accelerated stability data and first production batch on long-term stability data.
  • 19. Level of Changes Level I Level II 2. Test Documentation b. Dissolution Documentation  None beyond application/compendial release requirements.  Application/compendial requirements plus multipoint dissolution profiles in 3 other media (e.g in water, 0.1N HCl, and USP buffer media at pH 4.5, and 6.8) until either 80% of the drug from the drug product is released or an asymptote is reached. 2. Test Documentation c. In Vivo Bioequivalence  None.  None. 3. Filing Documentation  Annual report (all information including long- term stability data).  Changes being effected supplement; annual report (long-term stability data).
  • 20. Level of Changes Level I Level II 1. Definition  Change from non-automated or non-mechanical equipment to automated or mechanical equipment to move ingredients.  Change to alternative equipment of the same design and operating principles of the same or of a different capacity.  Change in equipment to a different design and different operating principles. 2. Test Documentation a. Chemistry Documentation  Application/compendial release requirements. Notification of change and submission of updated batch records.  Stability testing: First production batch on long-term stability.  Application/compendial release requirements. Notification of change and submission of updated batch records.  Stability testing: Significant body of information available: Significant body of information not available
  • 21. Level of Changes Level I Level II 2. Test Documentation b. Dissolution Documentation  None beyond application/compendial release requirements.  Application/compendial requirements plus multipoint dissolution profiles in 3 other media (e.g in water, 0.1N HCl, and USP buffer media at pH 4.5, and 6.8) until either 80% of the drug from the drug product is released or an asymptote is reached. 2. Test Documentation a. In Vivo Bioequivalence Documentation  None.  None. 3. Filing Documentation  Annual report (all information including long- term stability data).  Prior approval supplement with justification for change; annual report (long-term stability data).
  • 22. Level of Changes Level I Level II Level III 1. Definition  Change in process such as mixing times and operating speeds within application or validation ranges.  Change in process such as mixing times and operating speeds outside of application/validation ranges.  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. 2. Test Documentation a. Chemistry Documentation None beyond application/comp endial release requirements. Notification of the change and submission of the updated executed batch records.  Application/compendial release requirements. Notification of change and submission of updated batch records.  Stability testing: One batch with three months accelerated stability data and first production batch on long-term stability data.  Application/compendial release requirements. Notification of change and submission of updated batch records. Stability testing: Three batch with three months accelerated stability data and first three production batch on long- term stability data.
  • 23. Level of Changes Level I Level II Level III 2. Test Documentation b. Dissolution Documentation  None beyond application/compe ndial release requirements.  Application/compendial requirements plus multipoint dissolution profiles in 3 other media (e.g in water, 0.1N HCl, and USP buffer media at pH 4.5, and 6.8) until either 80% of the drug from the drug product is released or an asymptote is reached.  Application/compendial (Profiling/Multipoint) dissolution requirement. 2. Test Documentation a.Bioequivalence Documentation  None.  None.  A single-dose BE study. The BE study may be waived with an established in vivo/in vitro correlation. 3. Filing Documentation  Annual report.  Changes being effected supplement; annual report (longterm stability data).  Prior approval supplement; annual report (long-term stability data).
  • 24.  Guidance for Industry, SUPAC-MR: Modified Release Solid Oral Dosage Forms, Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls, InVitro Dissolution Testing, and In Vivo Bioequivalence Documentation.