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26 Pharmaceutical Technology ® Trends in Manufacturing eBook May 2024 PharmTech.com Compounding FIGURES COURTESY OF THE AUTHORS quires personal discipline, time, serious thought, and common sense; some may argue this to be a waste of time—until they make a mistake. Forcing proactive thought is the objective of estimation. Equation design with units of measure. Equa- tions are then set up; equations must include units of measure for all values. Calculations must be clear and simple. As complexity increases, risk of error increases. Setting up the equation must ultimately yield the calculations objective with unit of measure. Always use multiple equations or dimensional analy- sis with written units of measure. If the units of mea- sure are not included, one can get "lost" within the equations, and extra time will be needed to repeat the equations. Never do the calculations in your head; put pen to paper, and always write equations with units of measure. Designed equations must consider minimum and maximum amounts in measurement devices; accuracy and risk of contamination are pri- mary considerations (22,23). Equations must not be copied from previous compounding; just because they have been approved and previously used, they are not always correct. Time will be saved by doing the equations right first time. The importance of sim- ple and clear equation design and associated docu- mentation cannot be underestimated (Figure 1). Documentation–Calculations Record. The Cal- culations Record contains calculations and related information to be used in compounding. Each site must have a standard operating procedure (SOP) that describes calculations activities at the site. A Calcula- tions Record template (Figure 2) should be provided in the site SOP. Each dosage form to be compounded requires a Calculation Record. The Calculations Re- cord is used throughout and after the calculations process. Final verification by an independent qual- ified person reviews the Calculations Record. Post compounding, the Calculations Record is used in in- vestigations and training. The Calculations Record may be filed with Rx files, patient records, or man- ufacturing batch records. A site may have several calculation record templates for different types of compounded dosage forms. Stage 1 accountability. Signature/date of person- nel responsible for Stage 1 activities is recorded in the Calculations Record. Stage 2. Numeric operations Stage 2, numeric operations, comprise execution of Stage 1 designed equations in the Calculations Record followed by critical evaluation of calculated values. Compounding personnel must understand numeric and measurement system principles and execute cal- culations on a secured calculation device. Consider the following: • Mathematics. Ever yone learns f undamental math in schooling; however, proficiency without ongoing practice may diminish over time. Prin- ciples involving significant figures, fractions, decimals, rounding, and ratio/proportion may be forgotten; ratio strength, ppm, mEq, milli- moles, and mOsmol/L may be intimidating. Par- enteral nutrition, radioactivity, and veterinary dosages are specializations requiring additional education; interpolating tabular data or graphs may be unfamiliar. • Measurement systems. Measurement systems familiarity is also required for pharmaceutical calculations. Calculations primarily involves metric units, but also include British and US standard systems. Apothecary system units (e.g., grains) may be used by prescribers. Units of mea- sure are easily confused (does 1 kg = 2.2 lbs, or 1 lb = 2.2 kg?). Calculations personnel must be aware of common problematic units of measure. • Calculators. Calculators and other devices used for ca lculations should be restricted to com- pounding use. Correct calculator performance must be assured. If not dedicated, calculators may be programmed for specific use (and not de-programmed af ter use) causing erroneous results; worn or unresponsive keys may affect number entry. Calculators with hardcopy print- outs are recommended to confirm data entr y; hardcopy printouts must use ink that does not FIGURE 1. Example medication order equations and estimate. Medication Order John Doe, 135 lbs. Drug A 10 mg/kg in 1000 mL saline every 8 hours Calculations Objective Determine mL of Drug A to be added to 1000 mL Normal Saline. Use Drug A, 50 mg/mL, 30 mL vials for compounding. Equations Patient weight: 135 lbs x kg/2.2 lb = kg patient weight Drug A amount needed: kg x 10 mg/kg = mg Drug A needed Drug A volume: mg Drug A x mL/50 mg = mL Drug A needed Estimate Patient weight ~150 lbs x kg/2 lb = ~75 kg patient weight ~75 kg patient weight x 10 mg/kg dosage = ~750 mg Drug A needed ~75 mg Drug A needed x mL/50 mg = ~15 mL Drug A needed Since patient weight is less than 150 lb, drug amount will be less than 15 mL