USP General Chapter <7> Labeling

USP General Chapter <7> provides definitions and standards for labeling of official articles. Labeling standards for an article recognized in USP–NF are expressed in the article's monograph and applicable general chapters. It is intended that all articles in USP or NF will be subject to the labeling requirements specified in this chapter by means of a provision in General Notices, 10 Preservation, Packaging, Storage, and Labeling, unless different requirements are provided in a specific monograph. As with compendial standards for naming, identity, strength, quality, and purity, compendial requirements for labeling have a role in the adulteration and misbranding provisions of federal law [see the Federal Food, Drug, and Cosmetic Act (FDCA) sections 501(b), 502(e)(3)(b), 502(g), and 502(h)]. Exceptions or additional requirements specific to animal drug products and compounded preparations are provided in separate sections. Vaccine labeling is not included in this general chapter.

Important Updates

 

Elimination of Ratio Expression For Single Entity Drug Labels

DROP the RATIO Go METRIC

The USP General Chapter <7> Labeling became official on May 1, 2016. The standard calls for the elimination of ratio expression of single-entity injectable products and moves to the metric system as the acceptable method for expressing strength.

Note the label changes!

Table 1: Conversion Table

Medication

Ratio

Metric

Epinephrine    
  1:1000 1 mg/mL
  1:10,000 0.1 mg/mL
Isoprotenerol    
  1:5000  0.2 mg/mL
  1:50,000  0.02 mg/mL
Neostigmine    
  1:2,000  0.5 mg/mL
  1:1,000  1 mg/mL
  1:400    2.5 mg/mL

At this time, the USP-NF standard does not apply to the multi-ingredient local anesthetic with epinephrine products, such as bupivacaine with epinephrine 1:200,000. The concentration of epinephrine in those products may still be expressed as a ratio.[1]

 

Ratio Expression & Medication Error

USP has changed the labeling standard in an effort to improve patient safety by eliminating a source of medication error which has been associated with the use of these products. A medication error is defined as "any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient, or consumer."[2]

Medication errors injure approximately 1.3 million people annually in the United States[3] and can be caused by ambiguities in product names, labeling, and dosing.  

Studies show that labeling drugs through ratio expressions is inadequate and error-prone.[4],[5],[6]  One case report points to the death of a teenager who inadvertently received 4 mL of epinephrine 1:1,000 (= 4 mg) by intracavernous injection to treat priapism.[7]

USP General Chapter <7> sets standards to eliminate ratio expression for single-entity injectable products

Recognizing the potential medication error related to incurred dosing of products with ratio expression, labeling, the United States Pharmacopeial Convention revised USP-NF General Chapter <7>, Labeling in 2015. One of the elements of the General Chapter covers the elimination of ratios as an acceptable method for expressing the strength of single-entity injectable for products, such as epinephrine, isoproterenol, and neostigmine.

The standard became official May 1, 2016. After this date, the strength on the labels for all single entity products must be expressed only as the strength per milliliter (e.g., mg/mL). The official date was delayed to provide manufacturers time to adjust to the standard requirements.

These USP standards do not affect multi-ingredient local anesthetic with epinephrine products. The concentration of epinephrine in those products may still be expressed as a ratio. At this time, the ratio expression for local anesthetics such as lidocaine 1% and epinephrine 1:100,000 injection, and bupivacaine 0.25% and epinephrine 1:200,000 injection, will retain ratio expressions for the epinephrine component because a decimal notation for such a low strength could easily be misread.

Be Prepared, Note the label changes!

 

checklist

* This list may not be fully inclusive for your specific area of practice. There may be action items and preparation steps needed beyond those listed here.

**ISMP Canada Safety Bulletin:  Changes in Expression of Ratios On Single Entity Injectable Products -  Volume 16, Issue #2, March 20, 2016 https://www.ismp.org/errorReporting/reportErrortoISMP.aspx

For questions please contact: HealthcareQuality@usp.org


[1] United States Pharmacopeia, 39th edition, and National Formulary, 34th edition (USP39-NF34). Rockville (MD): U.S. Pharmacopeial Convention

[2] National Coordinating Council on Medication error reporting and Prevention retrieved from: http://www.nccmerp.org/about-medication-errors

[3] https://www.fda.gov/drugs/drug-safety-and-availability/medication-guides

[4] Rolfe S, Harper NJ. Ability of hospital doctors to calculate drug doses. BMJ 1995; 310:1173-4.

[5] Jones SJ, Cohen AM. Confusing drug concentrations. Anaesthesia 2001;56:195-6.

[6] Nelson LS, Gordon PE, Simmons MD, et al. The benefit of houseofficer education on proper medication dose calculation and ordering. Academic Emergency Medicine 2000; 1311-16.

[7] Just say no to ratio! ISMP Med Saf Alert. 2004 [cited 2016 Feb 13]:9(15):2. Available from https://www.ismp.org/resources/just-say-no-ratio