This document provides information on modified release oral solid dosage forms, including definitions and examples of different types of modified release formulations. It discusses how modified release formulations can improve drug efficacy, safety, and patient compliance by targeting drug delivery or releasing the drug over an extended period of time. The document also outlines a three-level scale for classifying changes to modified release formulations based on their potential impact on drug quality and performance. Level 1 changes are minor, level 2 changes could have a significant impact, and level 3 changes are likely to have major effects and require additional testing, including bioequivalence studies.

1. SUPAC
Scale-Up and Post approval
Changes (Part-4)
MODIFIED RELEASE ORAL
SOLID DOSAGE FORMS
For B.Pharmacy (VII Semester)
BP 702 T: INDUSTRIAL PHARMACYII
DR. KAVITA BAHMANI
ASSISTANT PROFESSOR
DEPARTMENT OF PHARMACEUTICAL SCIENCES
GURU JAMBHESHWAR UNIVERSITY OF SCIENCE &
TECHNOLOGY, HISAR, HARYANA, INDIA

2. What are modified release oral solid
dosage forms
• Modified-release dosage forms can also improve the efficacy and
safety of a drug and/or reduce adverse events.
• This is because drugs targeted to reach a specific region or to be
released in smaller doses over time may improve efficacy and/or
help reduce or diminish unwanted side effects for certain class of
drugs. Different delivery systems can help mask unpleasant taste or
odor, or, for example, ease nausea or irritation by delaying release
until after passing through the stomach.
• Improves patient compliance and outcomes.
• The different MR dosage forms can also increase selectivity of drug
activity, or be used to treat new indications – e.g., the management
of neuropathic pain in addition to severe or chronic pain -- or
provide new therapeutic benefits – e.g., improving tolerability.

3. Modified release drug product are those that
alter the timing and/or the rate of release of
drug substances

4. Modified Release
Formulations
Controlled Release
Delayed Release
Sustained Release Extended Release Prolonged Release

5. • guidance focuses on changes in non release controlling
excepients in the drug product.
• For modified release solid oral dosage forms, consideration
should be given as to whether the excepients is critical or not
critical to drug release. The sponsor should provide appropriate
justifications for claiming any excepients(s) as a non release
controlling excepients in the formulation of the modified release
solid oral dosage form.
• The functionality of each excepients should be identified.
Changes in the amount of the drug substance are not addressed
by this guidance.
• Changes in components or composition that have the effect of
adding a new excepients or deleting an excepients are defined at
level 3 (defined below), except as described below in Section
III.A.1.a. Waiver of bioequivalence testing for a change in
composition which involves only a different color, flavor or
preservative may be permissible as described in 21 CFR
320.22(d)(4)

6. Level 1 Change
Level 1 changes are those that are unlikely to have any
detectable impact on formulation quality and
performance.
Examples:
a. 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.
b. Changes in non release controlling excepients, expressed as
percentage (w/w) of total formulation, less than or equal to the
following percent ranges: .The total additive effect of all non
release controlling excepients changes should not be more than 5%.

7. TEST DOCUMENT
a. Chemistry documentation
• Application/compendial product release requirements.
• Stability: First production batch on long-term stability data reported
in annual report.
b. Dissolution documentation
None beyond application/compendial requirements
c. Bioequivalence documentation-None.
Filing Documentation
Annual report (all information including long-term stability data).

8. Level 2 Change
Level 2 changes are those that could have a significant
impact on formulation quality and performance.
Example: Avicel PH102 vs. Avicel PH200
Examples:
a. A change in the technical grade and/or specifications of a non release
controlling excepients.
b. Changes in non release controlling excepients, expressed as percentage
(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): The total additive
effect of all non release controlling excepients changes should not change
by more than 10%.

9. Test documentation
a. Chemistry documentation
• Application/compendial product release
requirements and updated executed batch
records.
Stability:
One batch with three months accelerated
stability data reported in prior approval
supplement and long-term stability data of
first production batch reported in annual
report.

11. Dissolution Documentation
Extended
release
Delayed
release
Bioequivalence documentation-None.
Filing Documentation
Prior approval supplement (all information including
accelerated stability data); annual report (long-term
stability data).

12. Level 3 Change
Level 3 changes are those that are likely to
have a significant impact on formulation
quality and performance.
Example:
• Changes in the non release controlling
excepients range beyond those Listed.
• total weight of the dosage form may be
within or outside the approved original
application range.

13. Test Documentation
a. Chemistry documentation
• Application/compendial product release
requirements and updated executed batch
records.
Stability:
• Significant body of information available: One
batch with three months' accelerated stability
data reported in prior approval supplement
and long term stability data of first three
production batches reported in annual report.

14. Dissolution documentation
Extended
release
Delayed
release

15. Bioequivalence documentation
• A single-dose bioequivalence study. The
bioequivalence study may be waived in the
presence of an established in vitro/in vivo
correlation .
Filing Documentation
• Prior approval supplement (all information
including accelerated stability data); annual
report (long-term stability data).

16. THANK YOU