Strength Conversion in Drug Listing
A drug strength or concentration of its active ingredient(s)/active moiety can be expressed in many ways. The United States Pharmacopeia (USP) General Chapter <7> Labeling has issued standards for expressing the strength for drug and biological products1. The standards align with FDA guidance, and are used throughout the FDA-approved labeling, including the container labels, carton labeling, and prescribing information. In order to align with USP standards and FDA guidance and standardize the expression of active ingredients in drug listing Structured Product Labeling (SPL) submitted to FDA, the Agency has adopted a series of automated validation rules to allow for certain expressions.
For example, the strength of active ingredient is not allowed to be included as a percentage value but can be a concentration of an amount of solute in an amount of solution:
- As w/w - mass (grams) of solute in mass (100 g) of solution, like topical creams and ointments
- As w/v - mass (grams) of solute in a volume (100 mL) of solution, like oral liquids
- As v/v - volume (milliliters) of solute in a volume (100 mL) of solution, like alcohol
The strength data element in a listing SPL is designed to accept submissions mostly in concentrations of w/w or w/v format, when the strength of an active ingredient is expressed as a percentage. Percentages must be converted into ratios of w/w or w/v with a value in the numerator and in the denominator including the correct units of measure in order to pass the SPL validation rules. Exceptions to this rule are alcohol, medical gases and water. Strength of active ingredients in these products can be included in the SPL as v/v and should not be converted into w/w or w/v. In cases like alcohol, the value of density can fluctuate depending on the temperature. Converting the strength into w/w or w/v may lead to an incorrect strength. It is therefore recommended that the strength of active ingredient for these products be included as v/v in the listing SPL.
In most cases, the listed active ingredient strength in SPL should align with the labeling where the Numerator Unit reflects the weight of the active ingredient, and the Denominator Unit reflects the volume or each container2,3. An example of “weight” is milligram, an example of “volume” is milliliter, an example of “time” is hour, and an example of “each” is tablet.
Similar to the labeling, listed active ingredient strengths should avoid the use of error-prone abbreviations (e.g., use “Unit” instead of “IU” or “U”; use “mcg” instead of “μg”; and use a leading zero before a decimal point when the dose is less than one measurement unit (use “0.125 mg” instead of “.125 mg”)4.
Note for injectable products that are solids intended to be constituted/reconstituted, the active ingredient strength in SPL should be listed as the amount per vial. For injectable products that are liquids (e.g., solutions, suspensions, and emulsions), the active ingredient strength in SPL should be listed as the total amount per total volume. Examples:
Table 1: Example of Strength Conversion for Injectable Products
| Product and strength | SPL Numerator Value | SPL Numerator Unit | SPL Denominator Value | SPL Denominator Unit |
|---|---|---|---|---|
|
Drug A Each vial contains Drug A lyophilized powder 100 mg |
100 | mg | 1 | Each |
|
Drug B Each vial contains Drug B 100 mg |
100 | mg | 20 | mL |
Table 2: Product Type and Associated Strength Listing
|
Dosage Form* Type |
SPL Numerator Unit |
SPL Denominator Unit |
|---|---|---|
|
Alcohol, Medical Gases, Water |
Volume |
Volume |
|
Oral Solid (e.g., tablet, capsule, oral film) |
Weight |
Each |
|
Oral Liquid |
Weight |
Volume |
|
Oral powder for reconstitution with a known volume |
Weight |
Volume |
|
Oral powder for reconstitution with a variable volume |
Weight |
Each |
|
Suppository |
Weight |
Each |
|
Injectable, liquid (e.g., solution, suspension, emulsion) |
Weight |
Volume |
|
Injectable, solid intended for constitution/reconstitution |
Weight |
Each |
|
Inhalation powder (e.g., dry powder inhaler) |
Weight |
Each |
|
Inhalation liquid, non-metered (e.g., inhalation solution in an ampule/vial) |
Weight |
Volume |
|
Inhalation liquid, metered (e.g., metered dose inhaler, metered spray) |
Weight |
Each |
|
Ophthalmic solution, suspension |
Weight |
Volume |
|
Topical cream or ointment |
Weight |
Weight |
|
Topical gel |
Weight |
Weight |
|
Topical lotion or solution |
Weight |
Volume |
|
Transdermal systems** |
Weight |
Time |
|
Topical system** |
Weight |
Weight |
|
Swab, Cloth, Sponge (Alcohol) |
Volume |
Volume |
|
Swab, Cloth, Sponge (non-Alcohol) |
Weight |
Volume |
|
Vaginal systems*** |
Weight |
Time |
*See Dosage Forms: SPL Acceptable Terms.
**Transdermal and topical system is the current dosage form term for products previously known as transdermal and topical patch.
***Vaginal system is the current dosage form term for products previously known as vaginal rings.
Mathematical errors have been detected in many cases with strength conversions in the listing SPLs. One example is the incorrect placement of decimal points when the strength expression is converted from percentage (%) into w/v, w/w or v/v. In some submissions, the units of measurement (for example, grams and milligrams) are used incorrectly, are interchanged, are missing or the calculation itself is done incorrectly. Another error associated with strength conversion can be a data entry error which does not correlate with the actual strength included on the product’s label.
In many of these submissions, no automated validation errors are generated, as there are no reference points which can be made to the labeling information. These errors are later detected through our surveillance projects. If not corrected by the firms, an error in the listing data submitted to the FDA can result in the removal of the incorrect data by FDA from public listing sites as well as possible further actions, such as untitled letters or warning letters.
1 USP General Chapters numbered below 1000 are requirements only if referenced in an USP/NF monograph or made applicable through USP General Notices for products with USP/NF monographs. Otherwise, they are general recommendations.
2 See USP General Chapter <7> Labeling for drug products that have exceptions to the strength expression standards.
3 For products with the strength of the active ingredient/active moiety expressed in potency, the Numerator Unit will be expressed in units (e.g., International Units).
4 The Institute for Safe Medication Practices publishes a list of error-prone abbreviations that should be avoided.