API Source Change Evaluation Checklist

Category Parameter Checkpoints Status (✔/✘) Remarks

Physicochemical Particle Size Compare D10, ☐
Properties Distribution D50, D90
(PSD)
Polymorphism Verify same ☐
polymorphic
form
Crystallinity & Check ☐
Morphology crystalline vs.
amorphous
nature
Hygroscopicity Assess ☐
& Moisture moisture
Sensitivity absorption
properties
Melting Point & Evaluate for ☐
Thermal thermal
Behavior processes
Solubility & pH Compare ☐
Profile solubility in
different media
Compatibility Conduct DSC & ☐
with Excipients FTIR for
interactions
Dissolution & In-vitro Compare ☐
Bioavailability Dissolution dissolution in
Impact Profile different media
f2 Similarity Ensure f2 > 50 ☐
Factor
BCS Identify if API is ☐
Classification BCS II or IV
Intrinsic Compare ☐
Dissolution Rate dissolution rate
(IDR) limitations
Permeability & Check if ☐
Absorption absorption
parameters are
impacted
Stability Forced Evaluate ☐
Considerations Degradation stability under
Studies stress
conditions
API Stability Compare ☐
Profile impurity and
degradation
products
 Shelf-life Conduct ☐
Implications accelerated
stability testing
Packaging Ensure ☐
Suitability compatibility
with packaging
Regulatory & Pharmacopeial Confirm ☐
Compliance Compliance compliance
Aspects with USP, BP,
EP, IP, JP
Impurity Profile Ensure ☐
compliance
with ICH
Q3A/B
Genotoxic & Evaluate for ☐
Elemental new genotoxic
Impurities impurities
Regulatory Determine if ☐
Filing DMF update or
Requirements ANDA variation
is required
Supplier GMP Verify GMP ☐
Compliance status and
documentation
Manufacturing Flowability & Assess impact ☐
& Process Compressibility on granulation
Considerations and
compression
Granulation Check wet/dry ☐
Suitability granulation
behavior
Bulk & Tapped Compare with ☐
Density existing API
Blending & Conduct blend ☐
Homogeneity uniformity
study
Scale-up & Ensure process ☐
Manufacturing robustness and
Impact yield
consistency
In-vivo Bioequivalence Conduct if ☐
Considerations (BE) Studies dissolution
(If Required) profiles differ
Pharmacokinetic Check ☐
(PK) Studies absorption and
metabolism
impact
Clinical & Assess safety ☐
Therapeutic and efficacy
 Impact
Risk Comparability Summarize ☐
Assessment & Protocol differences and
Final establish
Justification equivalence
ICH Q12 Ensure ☐
Lifecycle regulatory
Management compliance
Final Decision & Proceed with ☐
Implementation regulatory
filing &
validation

Final Review & Approval

Parameter Status (✔/✘) Remarks

Physicochemical Properties ☐ Completed

Dissolution & ☐ Completed
Bioavailability
Stability Considerations ☐ Completed
Regulatory Compliance ☐ Completed
Manufacturing Impact ☐ Completed
In-vivo Considerations (if ☐ Completed
applicable)
Risk Assessment & ☐ Completed
Justification
Final Approval ☐ Approved ☐ Not
Approved