MACO Calculator

Maximum Allowable Carryover Calculation Tool

APIC Cleaning Validation Guide 2021

📦 Product Database & Worst Case Analysis

Add products, configure equipment settings, and calculate all combinations

Add New Product
Enter product details
📋
Product List
0 products added
# Product Name MBS (kg) TDD Min (mg) TDD Max (mg) ADE (µg) LD50 (mg/kg) TTC (µg) Route Actions
No products added yet. Add products above to begin.
⚙️
Equipment & Sampling Settings
Common parameters for all calculations
Enter the MACO value to calculate swab and rinse limits. Leave empty to use worst case MACO from above.

🧮 Manual MACO Calculator

Calculate MACO for a specific product pair

📦
Next Product Information
Mandatory parameters
Smallest production batch of the next product
Highest daily therapeutic dose of next product
🧬
Health-Based Approach (ADE/PDE)
Preferred method per APIC 2021
Acceptable Daily Exposure or Permitted Daily Exposure
💊
Dose-Based Approach (1/1000th Rule)
Using therapeutic daily dose
Minimum therapeutic daily dose of previous product
Typically 1000 for oral, 100 for topical
⚠️
Toxicological Approach (LD50)
When limited data available
Oral LD50 in rodents (usually rats)
🔬
TTC-Based Approach
Threshold of Toxicological Concern
Select based on toxicity classification
📊
General Limits
Fixed ppm and visual criteria
10 mg/kg = 10 ppm general limit
🧪
Sampling Parameters
For swab and rinse limit calculations
Validated swab recovery percentage
Choose how recovery correction is applied

📊 Calculation Results

MACO values based on different calculation methods

Method Formula Applied MACO Value Status
Final Proposed MACO (Lowest Value)
mg
Basis:
🧫
Swab Limit (per dm²)
µg/dm²
🧪
Swab Acceptance Limit
µg/swab
💧
Rinse Limit
mg/L
📏
Concentration in Next Batch
ppm

📐 APIC 2021 Formulas Reference

All calculation formulas used in this tool

MACO Calculation Methods

Health-Based (ADE/PDE)
MACO = (ADE × MBS) / (TDD_next × SF)
Preferred method using toxicological data
Dose-Based (1/1000th Rule)
MACO = (TDD_prev × MBS) / (SF × TDD_next)
SF typically 1000 for oral products
LD50-Based
MACO = (LD50 × BW × MBS) / (SF × TDD_next)
SF typically 2000, BW = 70 kg
TTC-Based
MACO = (TTC × MBS) / TDD_next
Based on Threshold of Toxicological Concern
10 ppm Limit
MACO = 10 mg/kg × MBS (kg)
General conservative limit
0.1% Dose Rule
MACO = 0.001 × TDD_prev × MBS / TDD_next
Visual inspection criteria

Sampling Limits

Swab Limit
Limit = MACO (µg) / Surface Area (dm²)
Theoretical limit per unit area
Rinse Limit
Limit = MACO (mg) / Rinse Volume (L)
Concentration in final rinse
Method 1: Apply Recovery to Limit
Acceptance = Limit × (Recovery/100)
Adjusted limit, compare result directly
Method 2: Apply Recovery to Result
Corrected = Measured × (100/Recovery)
Correct result before comparing to limit

Abbreviations

MACO - Maximum Allowable Carryover
ADE - Acceptable Daily Exposure
PDE - Permitted Daily Exposure
TDD - Therapeutic Daily Dose
MBS - Minimum Batch Size
TTC - Threshold of Toxicological Concern
LD50 - Lethal Dose 50%
SF - Safety Factor
BW - Body Weight

📚 Help & How to Use MACO Calculator

🎯 Overview

This calculator helps you determine Maximum Allowable Carryover (MACO) values for pharmaceutical cleaning validation based on the APIC Cleaning Validation Guide 2021. MACO represents the maximum amount of residue from a previous product that can remain in equipment without affecting the safety or quality of the next product.

📦 Tab 1: Products & Combinations

1. Product Database

Adding Products:
  • Fill in the single-row form with product details:
    • Product Name: Name of the pharmaceutical product
    • MBS (kg): Minimum Batch Size in kilograms
    • TDD Min/Max (mg/day): Therapeutic Daily Dose range
    • ADE/PDE (µg/day): Acceptable/Permitted Daily Exposure
    • LD50 (mg/kg): Lethal Dose 50% (for toxicological assessment)
    • TTC (µg/day): Threshold of Toxicological Concern
    • Route: Administration route (oral, parenteral, etc.)
  • Click "➕ Add Product" to add to the database
  • Use Excel-like navigation: Arrow keys, Tab, Enter to move between cells
  • Press F2 or click to edit cells in the product table
Managing Products:
  • Edit: Click the edit icon or press F2 on any cell
  • Delete: Click the delete (🗑️) icon for a product
  • Export: Click "📥 Export Products" to save as Excel (.xlsx) or JSON (.json)
  • Import: Click "📤 Import Products" to load from Excel or JSON file
    • Supports .xlsx, .xls, .csv, and .json formats
    • Choose to replace or append existing products
  • Clear All: Remove all products from database

2. MACO Calculation

Calculate All Combinations:
  • Click "⚡ Calculate MACO Values" button
  • The system calculates MACO for all product combinations using multiple methods:
    • ADE/PDE Method: Based on Acceptable Daily Exposure
    • TDD Method: Based on Therapeutic Daily Dose
    • LD50 Method: Based on Lethal Dose 50%
    • TTC Method: Threshold of Toxicological Concern
    • 10 ppm Method: Visual inspection limit
    • 0.1% Visual Rule: Percentage-based limit
  • Results show:
    • Worst Case MACO: The most stringent limit across all combinations
    • Combinations Matrix: All product-to-product MACO values
    • Ranked List: All combinations sorted by MACO value
  • Export results to PDF with detailed calculations

3. Equipment & Sampling Settings

Configure Equipment Parameters:
  • Equipment Surface Area (cm²): Total cleanable surface area
  • Swab Area (cm²): Area covered by each swab sample
  • Rinse Volume (mL): Volume used for rinse sampling
  • Swab Recovery Factor (%): Percentage of residue recovered by swabbing
  • Recovery Method: Choose how recovery factor is applied:
    • To calculation results (swab results)
    • To specification limit
Calculate Swab & Rinse Limits:
  • Enter the MACO Value (from worst case or manual entry)
  • Click "Calculate Swab & Rinse Limits"
  • Results show:
    • Swab Limit: Maximum residue per swab (µg/swab)
    • Swab Acceptance Limit: Adjusted for recovery factor (µg/swab)
    • Rinse Limit: Maximum residue in rinse (µg/mL)
  • Detailed calculation steps are displayed for each limit
  • Export limits to PDF with full calculation details

🧮 Tab 2: Manual Calculator

Single Product MACO Calculation:
  • Enter values for one product at a time
  • Fill in all required fields (marked with red asterisk *)
  • Click "Calculate MACO" to get results
  • Results show MACO values for all applicable methods
  • Useful for quick calculations without managing a product database

📐 Tab 3: Formulas Reference

Calculation Methods Explained:
  • ADE/PDE Method: MACO = (ADE × MBS_next) / TDD_previous
  • TDD Method: MACO = (TDD_min × MBS_next) / (TDD_max × SF)
  • LD50 Method: MACO = (LD50 × MBS_next × BW) / (SF × TDD_max)
  • TTC Method: MACO = (TTC × MBS_next) / TDD_previous
  • 10 ppm Method: MACO = MBS_next × 10 ppm
  • 0.1% Visual Rule: MACO = MBS_next × 0.001
Swab & Rinse Limit Formulas:
  • Swab Limit: MACO / (Equipment Area / Swab Area)
  • Swab Acceptance: Swab Limit × (Recovery Factor / 100)
  • Rinse Limit: MACO / Rinse Volume

📊 Workflow Diagram

1️⃣ Add Products
2️⃣ Calculate MACO
3️⃣ Configure Equipment
4️⃣ Calculate Limits
5️⃣ Export Results

💡 Tips & Best Practices

  • Data Entry: Use Excel import for bulk product entry - it's faster and less error-prone
  • Worst Case Selection: Always use the worst case (lowest) MACO value for cleaning validation
  • Recovery Factor: Ensure recovery factor is validated for your specific swabbing method
  • Documentation: Export PDF reports for regulatory documentation - they include all calculation details
  • Verification: Always verify calculations with qualified personnel before use in validation
  • Excel Navigation: Use keyboard shortcuts (Arrow keys, Tab, Enter, F2) for efficient data entry

❓ Frequently Asked Questions

Q: Which MACO method should I use?
A: Use the most stringent (lowest) value from all applicable methods. The calculator automatically identifies the worst case.

Q: Can I edit products after adding them?
A: Yes! Click the edit icon or press F2 on any cell in the product table to edit inline.

Q: How do I import products from Excel?
A: Export a template first, fill it in Excel, then use "Import Products" button. The system recognizes column headers automatically.

Q: What's the difference between Swab Limit and Swab Acceptance Limit?
A: Swab Limit is the theoretical limit. Swab Acceptance Limit accounts for recovery factor - this is what you use for acceptance criteria.

Q: Can I export calculation details?
A: Yes! Use the PDF export buttons to generate comprehensive reports with all calculation steps and formulas.

🔗 Keyboard Shortcuts

Navigate between cells
Tab Move to next cell
Enter Move to cell below
F2 Edit selected cell
Esc Cancel editing