How do I determine if my change is Level 1, 2, or 3?

Classify your change by matching it to specific criteria in SUPAC IR guidance sections covering seven change categories: components/composition, site of manufacture, batch size, manufacturing process, equipment, container closure, and dissolution method. Level 1 has minimal impact (minor quantitative changes within narrow ranges), Level 2 has moderate impact (changes requiring dissolution and stability data), and Level 3 has significant impact (major changes requiring prior approval and often bioequivalence studies).

What is the difference between CBE-30 and Prior Approval Supplement?

CBE-30 (Changes Being Effected in 30 days) allows implementation 30 days after FDA receives the supplement, typically for Level 2 changes with moderate risk. Prior Approval Supplement (PAS) requires explicit FDA approval before implementation, required for all Level 3 changes with significant risk to product quality or performance. The key difference is implementation timing: CBE-30 permits change after waiting period, PAS prohibits change until approval letter received.

How long does stability testing take for SUPAC changes?

Minimum 3 months of accelerated stability testing (40°C/75% RH) is required at submission for Level 2 and Level 3 changes. Long-term stability testing (25°C/60% RH or 30°C/65% RH) continues for the duration of the approved shelf life, typically 24-36 months. Level 1 changes require only a stability commitment without data at implementation, with ongoing monitoring per the approved protocol.

Why is SUPAC IR guidance important?

SUPAC IR guidance provides science-based criteria for managing post-approval changes without compromising product quality or patient safety. It enables pharmaceutical manufacturers to improve manufacturing efficiency, respond to supply chain changes, and scale production while maintaining regulatory compliance. Proper SUPAC classification prevents costly delays (wrong filing type), regulatory violations (implementing prior approval changes without approval), and unnecessary studies (over-testing low-risk changes).

Can I implement multiple changes in one supplement?

Yes, multiple related changes can be submitted in a single supplement if they are part of a unified manufacturing improvement. FDA expects a single regulatory pathway: if any change is Level 3, the entire supplement must be filed as Prior Approval Supplement. For example, scaling up batch size (Level 1), changing to larger equipment (Level 2), and moving to a new site (Level 3) should be combined in one PAS rather than separate filings.

What happens if FDA disagrees with my SUPAC classification?

If FDA determines your classification is incorrect during review, they will issue an information request requiring reclassification and additional data. If you submitted as CBE-30 but FDA considers it Level 3, you must stop implementation immediately and convert to Prior Approval Supplement. If you implemented as Annual Report but FDA deems it Level 2 or 3, you may face regulatory action for unapproved manufacturing changes. To avoid this, include detailed justification for your classification in the submission and consider pre-submission meetings for complex changes. ---

SUPAC IR Guidance: Complete FDA Post-Approval Changes Guide for Immediate Release Dosage Forms

Quick Answer

SUPAC IR guidance is FDA's framework for managing post-approval changes to immediate release solid oral dosage forms. Published in November 1995, it categorizes changes into three risk-based levels (Level 1, 2, and 3) and specifies which regulatory filing pathway each requires-from annual reports for low-risk changes to prior approval supplements for high-risk changes. Proper classification is critical because misclassifying a change can delay product availability, trigger regulatory action, or expose the company to GMP violations.

SUPAC IR guidance is FDA's framework for managing post-approval changes to immediate release solid oral dosage forms. Published in November 1995, this guidance establishes science-based requirements for chemistry, manufacturing, and controls (CMC) changes after NDA or ANDA approval.

If you're managing post-approval changes for tablets or capsules, you're navigating one of the most consequential decisions in pharmaceutical manufacturing: determining whether your manufacturing change requires prior FDA approval or can proceed under annual reporting.

A wrong classification can delay product availability, trigger regulatory action, or expose patients to unvalidated formulations. A correct classification saves months of review time while maintaining product quality and safety.

In this guide, you'll learn:

How SUPAC IR guidance categorizes post-approval changes into three risk-based levels
When changes require prior approval supplements versus annual reports
Stability testing protocols for different change categories
Documentation requirements for each regulatory filing pathway
Common CMC changes and their SUPAC classifications

What Is SUPAC IR Guidance?

Definition

SUPAC IR guidance (Scale-Up and Post-Approval Changes: Chemistry, Manufacturing, and Controls; In Vitro Dissolution Testing and In Vivo Bioequivalence Documentation) is FDA's regulatory framework for evaluating post-approval changes to immediate release solid oral dosage forms. It categorizes changes into three risk-based levels and specifies the testing, data, and regulatory filing pathway required for each change type. The guidance applies to NDA, ANDA, and abbreviated antibiotic applications (AADA) for tablets and capsules.

SUPAC IR guidance (Scale-Up and Post-Approval Changes: Chemistry, Manufacturing, and Controls; In Vitro Dissolution Testing and In Vivo Bioequivalence Documentation) is FDA's regulatory framework for evaluating post-approval changes to immediate release solid oral dosage forms. The guidance applies to NDA, ANDA, and abbreviated antibiotic applications (AADA) for tablets and capsules.

Key characteristics of SUPAC IR guidance:

Categorizes changes into three levels (Level 1, 2, 3) based on risk to product quality and performance
Defines when bioequivalence studies, dissolution testing, or stability data are required
Specifies regulatory filing pathways: prior approval supplement (PAS), changes being effected supplement (CBE), changes being effected in 30 days (CBE-30), or annual report (AR)
Covers seven major change categories: components and composition, site of manufacture, batch size, manufacturing process, equipment, container closure, and dissolution test method

Key Statistic

SUPAC IR guidance was published in November 1995 as FDA's first comprehensive framework for science-based post-approval change management. It established a model that FDA later adapted for modified release and transdermal systems.

The Three SUPAC Change Levels Explained

SUPAC IR guidance categorizes every post-approval change into one of three levels based on the change's potential to affect product quality, performance, or bioavailability.

Level 1 Changes: Lowest Risk

Level 1 changes are unlikely to have any detectable impact on formulation quality and performance. These changes typically:

Involve minor quantitative adjustments within narrow ranges
Use comparable equipment or materials
Maintain the same manufacturing principles

Regulatory pathway: Most Level 1 changes require only annual report (AR) submission with stability data commitments.

Examples of Level 1 changes:

Minor changes in excipients (±5% w/w for excipients ≥10% in formula, ±3% w/w for excipients <10%)
Deletion or partial deletion of an ingredient intended to affect color or flavor
Up to 10-fold increase in batch size using equipment of similar design and operating principles

Pro Tip

Level 1 changes are the fastest regulatory pathway-you can implement immediately while submitting your annual report, provided you commit to ongoing stability monitoring. This is ideal for minor supplier changes or small batch size increases where you have strong chemistry data supporting equivalence. Document your chemistry rationale early-it strengthens your classification if FDA questions it.

Level 2 Changes: Moderate Risk

Level 2 changes could have a significant impact on formulation quality and performance. These changes require:

Dissolution testing on representative batches
Stability data on primary batches
Sometimes in vivo bioequivalence studies

Regulatory pathway: Most Level 2 changes require changes being effected in 30 days (CBE-30) submission, giving FDA 30 days to review before implementation.

Examples of Level 2 changes:

Moderate changes in excipients exceeding Level 1 ranges but within ±10% w/w for ≥10% excipients or ±5% w/w for <10% excipients
Change in drug release mechanism or coating material
Batch size increase beyond 10-fold
Addition or replacement of equipment of different design and operating principles

Pro Tip

For CBE-30 submissions, submit at least 45 days before your planned implementation date. This accounts for eCTD validation delays and potential FDA questions. If FDA issues an information request, you'll have time to respond without delaying your manufacturing change.

Level 3 Changes: Highest Risk

Level 3 changes are likely to have a significant impact on formulation quality and performance. These changes:

Require comprehensive in vitro and in vivo data
Must demonstrate bioequivalence to approved formulation
Need prior FDA approval before implementation

Regulatory pathway: All Level 3 changes require prior approval supplement (PAS) submission.

Examples of Level 3 changes:

Major changes in excipients exceeding Level 2 quantitative ranges
Changes in excipient qualitative characteristics (e.g., different grades, sources, or vendors)
Change in release mechanism
Change to different manufacturing site
Change in batch size greater than factor of 10 with different equipment

Change Level	Risk to Product	Typical Filing	Review Time	Implementation
Level 1	Minimal impact	Annual Report	N/A (post-change)	Immediate with stability commitment
Level 2	Moderate impact	CBE-30	30 days	After 30-day waiting period
Level 3	Significant impact	Prior Approval Supplement	4-6 months	After FDA approval only

SUPAC IR Change Categories and Requirements

The guidance addresses seven major categories of post-approval changes. Each category has specific criteria defining Level 1, 2, and 3 classifications.

Components and Composition Changes

Changes to drug substance, excipients, or compositional ratios require different levels of scrutiny based on magnitude and functional impact.

Level 1 (Annual Report):

Minor changes in excipients within ±5% w/w for excipients ≥10% or ±3% w/w for <10%
Deletion or partial deletion of ingredients intended to affect only color or flavor

Level 2 (CBE-30):

Moderate changes exceeding Level 1 but within ±10% w/w for ≥10% excipients or ±5% w/w for <10%
Any other change in excipients not covered by Level 1 or 3

Level 3 (Prior Approval):

Changes exceeding Level 2 quantitative ranges
Qualitative change in excipient characteristics (different grade, vendor, source)
Change that affects drug release mechanism

Required documentation:

All levels: Dissolution data on three production batches
Level 2/3: Stability data on primary stability batches
Level 3: In vivo bioequivalence study for certain changes

Site of Manufacture Changes

Moving manufacturing operations to a different facility is consistently classified as a Level 3 change requiring prior approval.

Level 3 (Prior Approval) - ALL site changes:

Manufacturing site change for drug substance
Manufacturing site change for drug product (finished dosage form)
Manufacturing site change for any intermediate used in drug product

Required documentation:

Complete manufacturing description at new site
Equipment list and specifications
In-process controls and test methods
Batch records from validation batches
Stability data (3-month accelerated, commitment for long-term)
Comparative dissolution profiles (new vs. approved site)
In vivo bioequivalence study (may be waived based on BCS classification and dissolution similarity)

“
Critical note: Site changes cannot be implemented until FDA approves the supplement. Manufacturing at an unapproved site is a significant GMP violation.

Batch Size Changes

Batch size increases are evaluated based on scale-up factor and equipment similarity.

Scale-Up Factor	Equipment	Level	Filing Type	Required Studies
Up to 10×	Same design/principles	Level 1	Annual Report	Dissolution (3 batches), Stability commitment
Beyond 10×	Same design/principles	Level 2	CBE-30	Dissolution (3 batches), Stability data
Beyond 10×	Different design	Level 3	Prior Approval	Dissolution, Stability, Possible BE study

Key consideration: "Same design and operating principles" means equipment scaled proportionally with equivalent process parameters (e.g., mixing time, compression force, drying temperature).

Pro Tip

When scaling up batch size, document equipment design similarity thoroughly. Get detailed equipment specifications from your vendor showing equivalent operating principles (surface area ratios, residence times, mixing mechanisms). This documentation can support a Level 1 or 2 classification rather than Level 3, saving months of regulatory review time.

Manufacturing Process Changes

Process changes range from minor parameter adjustments to fundamental changes in manufacturing method.

Level 1 (Annual Report):

Deletion or modification of a non-significant process step (e.g., deletion of an overage, modification of sifting procedure)
Minor process changes (e.g., changes in mixing times, operating speeds within approved ranges)

Level 2 (CBE-30):

Change in type of process used to granulate (e.g., wet granulation to dry granulation)
Change in the equipment but not the type of process used for granulation or coating
Introduction of new process step

Level 3 (Prior Approval):

Changes from non-continuous to continuous manufacturing
Major changes in equipment or process that fundamentally alter manufacturing approach
Changes that could significantly affect drug product quality or performance

Required documentation:

Documentation Type	Level 1	Level 2	Level 3
Process flow diagram	✓	✓	✓
Batch records (validation batches)	-	✓	✓
Dissolution data (3 batches)	✓	✓	✓
Stability data	Commitment	3 months accelerated	3 months accelerated + long-term commitment
In vivo BE study	-	Rarely	Case-dependent

Equipment Changes

Equipment changes are evaluated based on design similarity and potential impact on critical quality attributes.

Level 1 (Annual Report):

Replacement with same or closely similar design and operating principles (e.g., replacing one fluid bed dryer with another of similar design)

Level 2 (CBE-30):

Alternative equipment of different design but same or improved operating principles (e.g., replacing tray dryer with fluid bed dryer)
Automation of manual operation using equivalent operating principles

Level 3 (Prior Approval):

Change to fundamentally different equipment that could affect drug product characteristics
Change in equipment coupled with other significant changes (e.g., batch size increase >10× with different equipment)

Container Closure System Changes

Changes to packaging components are evaluated based on their potential to affect product stability and drug quality.

Level 1 (Annual Report):

Change in container closure size or shape with same materials of construction and no change in headspace or other critical parameters
Change in secondary packaging

Level 2 (CBE-30):

Change in container closure configuration (e.g., different closure liner, addition of desiccant)
Change that could affect moisture permeation

Level 3 (Prior Approval):

Any change in container closure material (e.g., glass to plastic, HDPE to PET)
Any change expected to affect product stability

Required stability testing:

All levels require comparative stability data demonstrating equivalence to approved container closure
Level 3 requires accelerated stability data (3 months) and long-term commitment (typically 12-24 months)

Dissolution Test Method Changes

Changes to dissolution testing methods require validation that the new method provides equivalent quality control.

Level 1 (Annual Report):

Changes in test conditions (e.g., stirring speed, temperature) within USP ranges
Change in sample handling or analytical procedure that doesn't alter test sensitivity

Level 2 (CBE-30):

Change in dissolution medium within pH range expected in GI tract (pH 1.2 to 6.8)
Change in paddle speed or basket rotation speed outside USP recommendations
Change in dissolution apparatus (e.g., Apparatus 1 to Apparatus 2)

Level 3 (Prior Approval):

Change in dissolution specification
Change in dissolution method that requires correlation with in vivo data

Regulatory Filing Pathways for SUPAC IR Changes

Understanding which filing pathway applies to your change is critical for regulatory compliance and product availability timelines.

Prior Approval Supplement (PAS)

When required: All Level 3 changes

FDA review timeline:

Standard review: 6 months from submission
May be extended if FDA issues information requests

Implementation timeline: Cannot implement until FDA approval letter received

Required contents:

CMC section documenting the change
Comparative data (dissolution, stability)
In vivo bioequivalence study (when required)
Validation protocols and reports
Proposed labeling changes (if applicable)

Strategy tip: Submit PAS well in advance of planned implementation. Include comprehensive data to minimize information requests.

Pro Tip

For PAS submissions, include a detailed justification section explaining your SUPAC classification decision. Cite specific guidance sections that support Level 3 determination. FDA reviewers appreciate clear rationale-it reduces information requests and accelerates approval timelines. Avoid generic change descriptions; be specific about quantitative changes, equipment models, and process parameters.

Changes Being Effected in 30 Days (CBE-30)

When required: Most Level 2 changes

FDA review timeline: 30 days before implementation permitted

Implementation timeline: Can implement 30 days after FDA receipt (confirmed by eCTD acknowledgment)

Required contents:

Description of change with justification
Dissolution data on three batches
Stability data (3 months accelerated, commitment for long-term)
Validation summary
Assessment of change impact on bioavailability

Strategy tip: Submit CBE-30 at least 45 days before planned implementation to account for eCTD validation time and potential submission issues.

Changes Being Effected (CBE-0)

When required: Specified Level 2 changes (less common in SUPAC IR)

Implementation timeline: Can implement immediately upon FDA receipt

Note: Most SUPAC IR Level 2 changes require CBE-30, not CBE-0.

Annual Report (AR)

When required: Level 1 changes and certain Level 2 changes specified in guidance

FDA review timeline: Reviewed during annual report cycle

Implementation timeline: Can implement immediately with stability commitment

Required contents:

List of all changes implemented in previous year
Cross-reference to supporting data location
Stability commitment statement
Brief description of each change

Strategy tip: Maintain detailed documentation for all AR changes. FDA may request full data packages during facility inspections.

Filing Type	Implementation	FDA Review	When Required	Risk Level
PAS	After approval only	4-6 months	All Level 3 changes	High
CBE-30	30 days after receipt	30-day review period	Most Level 2 changes	Moderate
CBE-0	Immediately	Post-change	Certain specified Level 2	Moderate
Annual Report	Immediately	Annual cycle	Level 1 changes	Low

Stability Testing Requirements Under SUPAC IR

Stability testing is the cornerstone of demonstrating that post-approval changes don't adversely affect drug product quality over shelf life.

Stability Protocol Design

Primary stability batches:

Minimum 3 production-scale batches manufactured with the change
Batch sizes: pilot scale acceptable for PAS submissions, production scale required for commercial distribution
Container closure: Test in proposed commercial container closure system

Accelerated stability conditions:

Temperature: 40°C ± 2°C
Humidity: 75% RH ± 5%
Duration: Minimum 3 months for regulatory submission
Testing intervals: 0, 1, 2, 3 months

Long-term stability conditions:

Temperature: 25°C ± 2°C (or 30°C ± 2°C for regions with hot climates)
Humidity: 60% RH ± 5% (or 65% RH ± 5%)
Duration: Up to approved shelf life
Testing intervals: 0, 3, 6, 9, 12, 18, 24, 36 months (as applicable)

Intermediate stability conditions (if applicable):

Temperature: 30°C ± 2°C
Humidity: 65% RH ± 5%
Used when significant change observed at accelerated conditions

Pro Tip

Start stability testing immediately after batches are manufactured, even before you draft your regulatory submission. This ensures your three-month accelerated data is ready for inclusion. If you discover out-of-specification results, you have time to investigate before submission rather than facing FDA questions or needing to restart studies post-approval.

Stability Test Parameters

Test	Frequency	Specification Impact
Appearance	All time points	Must remain consistent
Assay	All time points	Must remain within ±5% of label claim
Degradation products	All time points	Must not exceed qualified levels
Dissolution	All time points	Must meet acceptance criteria
Water content	As appropriate	For hygroscopic products
Hardness/Friability	As appropriate	For tablets

Stability Commitments

When submitting CBE-30 or annual report with only accelerated data:

Required commitment language:

“
"The applicant commits to conduct long-term stability studies on production batches manufactured with the change and to report results in the annual report. If stability results do not support the approved shelf life, the applicant will notify FDA and take appropriate action."

FDA expectations:

Place first three production batches on long-term stability
Test according to approved stability protocol
Report results in annual reports
Notify FDA immediately if out-of-specification results occur

When Stability Studies Can Be Waived

SUPAC IR allows stability data reduction or waiver for certain low-risk changes:

Acceptable scenarios:

Level 1 changes with stability commitment (full protocol not required initially)
Changes that decrease moisture permeation (e.g., more protective packaging)
Changes involving deletion of inactive ingredients (no addition)

Not acceptable for waiver:

Any change to container closure material
Any change affecting drug substance stability
Changes to moisture-sensitive products
Site changes or major process changes

Dissolution Testing Strategy for Post-Approval Changes

Dissolution testing provides critical quality control data demonstrating manufacturing consistency and predicting in vivo performance.

Comparative Dissolution Profile Requirements

Test batches:

Minimum 3 batches manufactured with proposed change
Minimum 3 batches of approved formulation (for comparison)
Production-scale or pilot-scale batches representative of commercial manufacturing

Test conditions:

Apparatus: Same as approved dissolution method (typically USP Apparatus 1 or 2)
Medium: Test in multiple pH conditions (1.2, 4.5, 6.8) for immediate release products
Sampling time points: Sufficient to characterize dissolution profile (e.g., 10, 15, 20, 30, 45, 60 minutes)

Acceptance criteria:

Profiles considered similar if f2 (similarity factor) ≥ 50
Alternatively, profiles similar if dissolution ≥85% in 15 minutes in all three media

Pro Tip

If your pre-approval dissolution data shows ≥85% dissolution at 15 minutes across all pH conditions, you can build a compelling case for BCS-based biowaiver. Test multiple pH conditions upfront (1.2, 4.5, 6.8) rather than just your approved medium. This expands your regulatory flexibility and may eliminate the need for costly and time-consuming in vivo bioequivalence studies.

When In Vivo Bioequivalence Studies Are Required

SUPAC IR specifies when dissolution data alone is insufficient and in vivo BE studies are necessary.

Always required for:

Level 3 composition changes affecting drug release
Site changes (unless waived based on BCS Class 1 with rapid dissolution)
Changes to narrow therapeutic index drugs
Changes to products with poor aqueous solubility or permeability

May be waived if:

Drug substance is BCS Class 1 (high solubility, high permeability)
Dissolution profiles are similar (f2 ≥ 50 or ≥85% in 15 minutes)
Change is Level 1 or Level 2 with demonstrated dissolution equivalence

BCS-Based Biowaivers

The Biopharmaceutics Classification System enables science-based decisions to waive in vivo studies:

BCS Class	Solubility	Permeability	Biowaiver Eligibility
Class 1	High	High	Yes (with rapid dissolution)
Class 2	Low	High	Limited (certain conditions)
Class 3	High	Low	Case-by-case
Class 4	Low	Low	No

Requirements for BCS-based biowaiver:

Drug substance meets BCS Class 1 criteria
Dissolution ≥85% in 30 minutes across pH 1.2, 4.5, 6.8
Excipients are same or qualitatively/quantitatively similar
No excipients affecting GI transit time or permeability

Common SUPAC IR Scenarios and Classifications

Understanding real-world applications helps regulatory teams classify changes correctly.

Scenario 1: Scaling Up from Pilot to Commercial Batch Size

Change: Increase batch size from 100 kg (pilot) to 500 kg (commercial), 5× scale-up

Equipment: Same tablet press model, larger fluid bed dryer (same design principles)

SUPAC classification: Level 1 (scale-up factor <10×, equipment of same design)

Filing pathway: Annual Report

Required data:

Dissolution testing on first 3 commercial batches
Stability commitment for long-term studies
Brief description in next annual report

Scenario 2: Changing Excipient Supplier

Change: New supplier for microcrystalline cellulose (MCC), functionally equivalent grade

Composition: No change to formula or amounts

SUPAC classification: Level 3 (qualitative change in excipient source)

Filing pathway: Prior Approval Supplement

Required data:

Comparative excipient characterization (particle size, moisture, compressibility)
Dissolution profiles (new vs. approved batches)
3-month accelerated stability data
Long-term stability commitment
Possible in vivo BE study (case-dependent)

Scenario 3: Moving Manufacturing to Contract Manufacturer

Change: Transfer all tablet manufacturing from in-house site to contract manufacturing organization (CMO)

Process: Same manufacturing process, same equipment types

SUPAC classification: Level 3 (all site changes are Level 3)

Filing pathway: Prior Approval Supplement

Required data:

Complete CMC section describing manufacturing at CMO
Process validation report (minimum 3 batches)
Comparative dissolution data
3-month accelerated stability data
In vivo bioequivalence study (may be waived if BCS Class 1 with comparable dissolution)

Scenario 4: Increasing Batch Size with New Equipment

Change: Increase from 200 kg to 5,000 kg batches (25× scale-up) using larger tablet press with different compression technology

SUPAC classification: Level 3 (scale-up >10× with different equipment design)

Filing pathway: Prior Approval Supplement

Required data:

Process validation at new scale
Tablet characterization (hardness, friability, thickness, dissolution)
Stability data
Compression force studies
Content uniformity data
Possible in vivo BE study

Scenario 5: Changing from Wet to Dry Granulation

Change: Eliminate wet granulation step, implement roller compaction for dry granulation

Formulation: No change to approved composition

SUPAC classification: Level 2 (change in type of process)

Filing pathway: CBE-30

Required data:

Process description and validation
Dissolution profiles on 3 batches
3-month accelerated stability
Long-term stability commitment
Particle size distribution data
Blend uniformity data

Documentation Best Practices for SUPAC Submissions

High-quality documentation accelerates FDA review and minimizes information requests.

Change Assessment Documentation

Before implementing any change, document:

Change description: What specifically is changing (be precise with amounts, parameters, equipment models)
Change justification: Why the change is necessary (business reasons, quality improvement, supply chain)
SUPAC classification: Level determination with specific citation to guidance
Impact assessment: Potential effects on product quality, performance, stability, bioavailability
Regulatory pathway: Which filing type based on classification

Use this template:

CMC Section Preparation

Section 3.2.P.2 (Pharmaceutical Development):

Describe rationale for change
Explain how change maintains or improves product quality
Reference any development studies supporting change

Section 3.2.P.3 (Manufacture):

Updated batch formula
Updated manufacturing process description
Updated process flow diagram
Equipment list with specifications
Critical process parameters and ranges

Section 3.2.P.5 (Control of Drug Product):

Updated specifications (if changed)
Validation of analytical methods (if changed)
Batch analysis data for batches manufactured with change

Section 3.2.P.8 (Stability):

Stability protocol
Stability data (accelerated minimum, long-term as available)
Stability commitment
Photostability data (if relevant)

Common Documentation Deficiencies

Deficiency	Impact	Solution
Insufficient batch data	Information request delay	Include data from ≥3 representative batches
Incomplete dissolution profiles	Cannot assess similarity	Test at multiple pH values, adequate time points
Missing equipment specifications	Cannot assess equivalence	Provide detailed specs, operating principles
Vague change description	Unclear classification	Use precise quantities, parameters, model numbers
No stability commitment language	Regulatory hold	Include explicit commitment statement

Key Takeaways

SUPAC IR guidance is FDA's framework for managing post-approval changes to immediate release solid oral dosage forms. Published in November 1995, it categorizes changes into three risk-based levels (1, 2, 3) and specifies required testing and regulatory filing pathways. The guidance applies to tablets and capsules approved under NDA, ANDA, or AADA applications.

Key Takeaways

SUPAC IR guidance categorizes changes into three levels: Level 1 (minimal risk, annual report), Level 2 (moderate risk, CBE-30), and Level 3 (significant risk, prior approval required).
All site changes are Level 3: Moving manufacturing to a different facility always requires prior approval supplement, regardless of process similarity.
Scale-up factor and equipment design determine batch size classification: Up to 10× with similar equipment is Level 1; beyond 10× or different equipment is Level 2 or 3.
Stability testing is required for all changes: Level 1 requires commitment only, Level 2/3 require 3-month accelerated data at submission with long-term commitment.
Bioequivalence studies may be waived for BCS Class 1 drugs: If dissolution is rapid and similar across pH conditions, in vivo studies are often unnecessary.
Documentation quality determines review speed: Comprehensive, well-organized submissions minimize information requests and approval delays.
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Next Steps

Post-approval change management is complex, requiring coordination across quality, regulatory, and manufacturing functions. Misclassifying changes or incomplete documentation can delay product availability and trigger regulatory findings.

Need help managing SUPAC IR changes? Assyro's AI-powered platform validates CMC documentation automatically, flags classification inconsistencies, and ensures your post-approval supplements meet FDA expectations before submission. See how pharmaceutical companies are accelerating change control timelines while maintaining compliance.

Sources

Last updated: January 25, 2026