Endotoxin Limit and MVD Calculator for Your Product List
K/M, the MVD and the test plan for every product, by gel-clot or a standard curve.
Try before you buy.
- Free preview: the method, the limits that apply and the verdict for your input; computed figures stay hidden until the pass.
- Locked until you unlock it: download and print.
- Unlock: Ultimate pass, ₹1,199 for 30 days or ₹449 for 1 week, a one-time payment unless you choose automatic renewal. Unlock: Ultimate pass, $24.99 for 30 days or $9.99 for 1 week, a one-time payment unless you choose automatic renewal.
Ways to unlock shows how to get the full result.
Printing this result is locked in the free preview.
Limits and test plan
Locked in the free preview. Opens the ways to unlock this result.
Locked in the free preview. Batch runs unlock with a pass.
Locked in the free preview. Query results unlock with a pass.
About the Endotoxin Limit and MVD Calculator for Your Product List
Sets the endotoxin limit of each product on your list from its dose and route — K/M, with K the threshold pyrogenic dose (5.0 EU/kg for any route other than intrathecal, 0.2 EU/kg intrathecally) and M the largest dose per kg of body mass in a single hour — and its maximum valid dilution for your method’s sensitivity: MVD = endotoxin limit × concentration of the sample solution / λ. These are the formulas of the harmonised bacterial endotoxins test (Japanese Pharmacopoeia 4.01, harmonised with Ph. Eur. 2.6.14 and USP <85>, which ICH Q4B makes interchangeable).
For each product the plan gives the largest two-fold dilution within the MVD, checks your own test dilution against it, and sets the positive product control: 2λ for a gel-clot limit test, or endotoxin at the middle of the standard curve for a photometric or recombinant-reagent test, with the solutions, replicates and validity criteria of the harmonised tables. A limit your monograph or specification gives is used instead of K/M. The free preview shows the K that applies, the test plan’s structure and every product’s verdict; the limits, the MVDs, the dilutions and the spikes stay hidden, and the PDF, Excel and Print record opens with an Ultimate pass.
How to use it
- Choose gel-clot or a method with a standard curve, and enter λ: the labelled lysate sensitivity, or the lowest standard of the curve (and its highest standard, for the spike).
- Add the products, one per line: product; route; the largest dose in one hour with its unit; the body mass in kg (empty for a dose per kg); the concentration of the sample solution. A monograph’s limit and your test dilution are optional.
- Read each product’s verdict — whether its limit can be tested at this λ, and whether your dilution is within the MVD — and the test plan.
- Without a pass the report stays a free preview with its computed figures hidden; the PDF, Excel and Print record unlocks with an Ultimate pass.
Examples
Intravenous, 10 mL/kg in one hour, the product as it is (1 mL/mL), λ = 0.125 EU/mL
Limit 5.0 / 10 = 0.5 EU/mL; MVD = 0.5 × 1 / 0.125 = 4
Intravenous, 2 g in one hour for 70 kg, sample solution 100 mg/mL, λ = 0.125 EU/mL
M = 28.57 mg/kg; limit 0.175 EU/mg; 17.5 EU/mL at 100 mg/mL; MVD 140; largest two-fold dilution 1:128
12 mg in one hour for 70 kg, 2.5 mg/mL, tested at 1:32
K = 0.2 EU/kg: limit 1.17 EU/mg, MVD 23.3, so 1:32 is beyond the MVD
Common uses
- Setting the endotoxin limit and MVD of each new product, strength and route.
- Planning the dilutions and spikes of the test for interfering factors before validating the method on a product.
- Checking that the test dilutions in an SOP stay within each product’s MVD after a dose change.
- Seeing which products need a more sensitive lysate or reagent.
The formulas
- Endotoxin limit = K/M. K is 5.0 EU/kg for any route of administration other than intrathecal and 0.2 EU/kg for intrathecal use; M is the maximum dose per kg of body mass, and when the product is injected at frequent intervals or infused continuously, the maximum total dose in a single hour period.
- MVD = endotoxin limit × concentration of the sample solution / λ, the concentration in mg/mL for a limit per mg, Units/mL per Unit, mEq/mL per mEq or mL/mL per mL.
- λ is the labelled lysate sensitivity of a gel-clot test, or the lowest concentration of the standard curve of a turbidimetric or chromogenic test.
The test plan
- Gel-clot limit test: A, the sample solution at a dilution not beyond the MVD; B, the same with 2λ added (positive product control); C, water for BET with 2λ; D, water for BET; two replicates each. Valid when both B and C replicates are positive and both D negative.
- Interfering factors (gel-clot): the sample solution spiked with 2λ and diluted two-fold to 0.25λ, in 4 replicates, against the same series in water; the geometric mean endpoint of the spiked sample must be from 0.5λ to 2.0λ.
- Photometric: A, the sample solution; B, the same with endotoxin at or near the middle of the standard curve; C, at least 3 standards; D, water for BET; the curve’s |r| not less than 0.980 and the spike recovery from 50 % to 200 %.
Sources
- The Japanese Pharmacopoeia, English version — 4.01 Bacterial Endotoxins Test, harmonised with the European Pharmacopoeia and the U.S. Pharmacopeia: the MVD, K/M and Tables 4.01-1 to 4.01-4
- FDA Inspection Technical Guide: Bacterial Endotoxins/Pyrogens — K of 5.0 EU/kg, 0.2 EU/kg for intrathecal use, and K/M
- ICH Quality guidelines — Q4B: the harmonised bacterial endotoxins test texts are interchangeable
Limitations
- Products dosed per person need the body mass your method uses; products for children or dosed by body surface area need the dose per kg your specification states.
- K is 0.2 EU/kg for intrathecal use and 5.0 EU/kg for any other route. An epidural product asks for its K: write K = 0.2 or K = 5.0 in the route column, as your justification gives.
- Medical devices, radiopharmaceuticals and products whose monograph sets a limit: enter that limit in the “limit given” column.
- The plan does not run the test or read its results; the interfering factors test and the validation of the method on each product are yours.
- Up to 500 products at a time, worked out on your device in a moment.
- MySmartCoPilot is not affiliated with or endorsed by the pharmacopoeias, FDA or ICH. This plan applies the method you choose; your QA approves the limits and the test plan.
Privacy
On this device: nothing is sent
Your products and doses stay in this browser and are never sent anywhere. The PDF and Excel files are made on your device.
Frequently asked questions
What do I get without a pass?
Without a pass, Endotoxin Limit and MVD Calculator for Your Product List shows the method, the limits that apply and the verdict for your input; computed figures stay hidden until the pass. Until you unlock it, the result can’t be downloaded or printed. An Ultimate pass, a one-time payment unless you choose automatic renewal, unlocks the full result. The pricing page lists the passes and their prices.
What does the Ultimate pass add here?
This tool in full, and every other Pro, Premium and Ultimate tool, for 7 days, 30 days or a year (a pass bought with PayPal leaves out email-address extractors). The pass is a one-time payment unless you choose automatic renewal.
How is the endotoxin limit of an injection calculated?
As K/M: K is 5.0 EU/kg for any route other than intrathecal (0.2 EU/kg intrathecally), and M is the largest dose per kg of body mass given in a single hour. A product given at 10 mL/kg in an hour has a limit of 5.0 / 10 = 0.5 EU/mL.
What is the maximum valid dilution?
The largest dilution of the sample solution at which the endotoxin limit can still be detected: the limit × the concentration of the sample solution / λ. Below an MVD of 1 the limit cannot be shown with that sensitivity.
What is λ for a kinetic chromogenic or recombinant factor C test?
The lowest concentration of the standard curve you run, in EU/mL. For a gel-clot test it is the labelled sensitivity of the lysate.
Where does the positive product control go?
In a gel-clot limit test, 2λ is added to the sample solution at the dilution tested. In a photometric test the spike is at or near the middle of the standard curve, and its recovery must be from 50 % to 200 %.
Can I test at a dilution beyond the MVD?
No: a sample diluted beyond the MVD could hide endotoxin above the limit. The tool flags any test dilution of yours that is beyond its product’s MVD.