GXP

Medication Safety: Industry Considerations Part 1 - Problem Overview

INTRODUCTION

This is the first of a series of discussions on medication safety and presents an overview of those situations and factors that can lead to errors, examples of some mistakes and what the pharmaceutical industry can do to preclude and reduce the incidence rate of errors.  Subsequent articles in this series will include, for example, in-depth discussions on high alert medications, look-alike/sound-alike drugs, and additional approaches the pharmaceutical industry can apply to help to reduce medication errors.

From the understandings behind medical errors, the pharmaceutical industry can subsequently apply concepts to design dosage forms to reduce the conditions that lay the foundation for mistakes to take place.  This applied awareness approach can result in reduced mistakes, enhanced patient care and improved risk management for all parties.  The pharmaceutical industry also plays a role in and has a responsibility for the public health and safety.

Topics to be discussed in this article include:

  • The problem scope and current state of medication errors in various healthcare practices
  • The causes and understandings of errors
  • What the industry can do to reduce the conditions for errors to take place

DEFINITIONS

Medication errors are unintended acts of either omission or commission that do not achieve its intended outcome involving an error of execution, an error in planning, or a deviation from the care process that may cause patient harm. (1)  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 healthcare professional, patient, or consumer,” according to the National Coordinating Council for Medication Error Reporting and Prevention.(2)  Medication errors are a serious problem in medical/pharmaceutical practice.

Patient harm from medical error can occur at the patient and/or system level.  Medication errors entail several concurrent impacting situations many necessitating a deeper level of investigation.  Human error is inevitable.  However, we can understand and strive to reduce the frequency of human error through proactive approaches to ultimately reduce the potential for the occurrence of these errors.  Medication errors are preventable.

PROBLEM SCOPE and SIZE

Total medical errors currently represent a serious problem and has been reported and extrapolated to be the third leading cause of death in US. (1)

From a total of 13,416,020 hospital admissions in the US in 2013, an extrapolation of hospital based of total medical errors (fatal and non-fatal) was conducted on the 2013 US admissions to be about 252,000. (1)

  • The Institute of Medicine (IOM) stated that from 44,000 to 98,000 deaths occur yearly due to fatal medical errors making medical errors the eighth leading cause of death in the United States.  The report identified medication errors as the most common type of error in health care.  Seven thousand (7,000) deaths annually were attributed to medication errors. (3) (4)
  • In another study, 20% of 2,500 surveyed patients had experienced medical errors on a firsthand basis. (5)
  • Reported community pharmacy mistake rates range from 0.12% - 1.72%, where 1.5% to 4% of those errors have the potential to cause patient harm. (6) (7) (8)
    • About 3 billion Rx’s were recently dispensed in US. (8)
  • Therefore, for example, if the error rate is as low as 0.1%, then that would equate to 51.5 million prescription errors per year. (9)
  • The FDA has received 30,000 reports of medication errors. (2)
  • The IOM published a report titled “Preventing Medication Errors” which cited labeling and packaging issues as the cause of 33% of all medication errors and 30% of the fatalities from medication errors. (10)
  • The patient impacts from medical errors include the following:
    • Adverse patient/drug reactions and therapeutic outcomes are not realized.
      • The adverse impacts from errors are especially more pronounced in neonates, pediatrics and the elderly as they are less physiologically able to tolerate mistakes.
    • Patients who experience a longer hospital stay and/or disability as a result of errors and consequently pay with physical and psychological discomfort.
      • The financial costs of medication errors are significant.
    • The dollar value impact of preventable errors is roughly $21 billion. (9)
    • Inpatient preventable medication errors cost approximately $16.4 billion annually.
    • Outpatient preventable medication errors cost approximately $4.2 billion annually.
    • The IOM reports that medication errors have been estimated to result in total costs (including the expense of additional care necessitated by the errors, lost income and household productivity, and disability) of between $17 billion and $29 billion per year in hospitals nationwide. (4)

HIGH-ALERT MEDICATIONS

The industry needs to be cognizant of and pay special attention to high-alert medications.  High-alert drugs are compounds that have a heightened risk of causing significant patient harm when they are erroneously used.  High-alert medications are an important consideration when addressing the problem of medication safety.  Medication errors may not occur more often with high-alert medications, but the consequences of an error can be devastating. (11)(12)

Some examples of high-alert medications include the following: (12)

  • Narcotics/Opioids
  • Insulins
  • General anesthetics
  • Neuromuscular blocking agents
  • Adrenergic agonist and antagonist injectables
  • Antithrombotic agents
  • Chemotherapeutic agents
  • Epidurals and intrathecals
  • Concentrated potassium chloride Injection
  • Concentrated sodium chloride injections (> 0.9%)
  • Concentrated dextrose injections (> 20%)
  • Potassium and sodium phosphate injections
  • Nitroprusside injection
  • EPINEPHrine subcutaneous injection
  • Radiocontrast IV agents

The Institute for Safe Medication Practices (ISMP) is an international independent organization dedicated to the prevention of medication errors.  The top drug therapeutic classes for medication errors as reported by the ISMP are listed below. (13)  Notice that the preponderance of involved of medication errors entail high-alert drugs.

  • Narcotics/opioids (high-alert medications)
  • Antimicrobial agents
  • Antihypertensive agents
  • Antithrombotic agents (high-alert medication)
  • Insulin and antidiabetic agents (high-alert medications)
  • Anticonvulsants
  • Anesthetic agents (high-alert medications)
  • Epinephrine (high-alert medication)

Insulin is a high-alert medication that is especially prone to errors.  Some examples include: (14)(15)

  • Confusion with higher concentration insulins
    • Prescribing in syringe units rather than by dose
    • Dose conversion errors (calculations)
    • U-100 syringes used for U-500 insulin
    • U-500 HumaLIN-R vial mistaken for U-100 HumaLIN-R
    • Mix-ups with U-200, U-300, U-500 insulin pens
  • Confusion among glucagon-like peptide-1 (GLP-1) agonist containing products (78)
    • Insulin degludec and liraglutide (Xultophy 100/3.6)
    • Insulin glargine and lixisenatide (Soliqua (100/33)
  • One patient died because 20 units of insulin was abbreviated as "20 U," but the "U" was mistaken for a "zero." As a result, a dose of 200 units of insulin was accidentally injected

High-alert medications will be discussed in greater detail in a subsequent article.

HUMAN ERRORS

Specific areas to be cognizant of and considered by the pharmaceutical industry in this discussion include the following:

  • Understanding human factors
  • How the inherent functioning of our brains can lead to errors.
  • Look-Alike/Sound-Alike (LA/SA) errors
    • LA/SA errors entail confusion and mix-ups involving visual, verbal and transcription mistakes.
      • Look-alike packaging, graphics and labeling
      • Look-alike and sound-alike drug names
  • Zero’s and decimal points
    • How the use of zero’s and decimal points can lead to errors.
  • Abbreviations and symbols
    • A review of abbreviations and symbols that should not be used.
  • Calculations
  • Drug shortage impact
    • How the current shortages increase errors
  • Work environment
  • The criminalization of errors

Human Factors

Humans make mistakes.  Human factors, that is the way our minds operate, also inherently contribute to creating the conditions for mistakes to take place.  Human factors affect how users will interact with the drug product within various work environments within the medication use system.

How and why do these errors, such as mix-ups, happen?  The paragraph below, for example, is full of errors but yet it can be read: (16)

“Aoccdrnig to rscheearch at Cmabridge Uinervtisy, it deosn’t mttaer waht oredr the ltteers in a wrod are, the olny iprmtoent tihng is that the frist and lsat lteer be at the rhgit pclae.  The rset can be a taotl mses and you can sitll raed it wouthit a porbelm.  This is bcuseae the huamn mnid deos not raed ervy lteter by istlef, but the word as a wlohe.”

See Figure 7 below.  What do you see?  Is this a rabbit or a duck? (17)

 

FIGURE 1

Rabbit or Duck?

Answer: It’s either one, but not both at the same time.  Note that we have to switch between the two images in order to see a rabbit or a duck. This is known as aspect-switching. (17)

What is going on in the above examples?  How are our brains working, or not correctly working?  How does this contribute to medication safety and mistakes?

  • The mind accepts errors.
    • The human brain uses previous experience to fill in the gaps. (16) This explains how we are able to read the paragraph from Cambridge University that is full of errors.
    • Human cognitive processes, while adaptive in most contexts, can also promote – or fail to detect – errors. (16)
  • Confirmation bias is also taking place. (18)
    • Confirmation bias is a type of selective thinking in which people select out information that is familiar or what they expect to see, rather than what is actually there.
    • Confirmation bias increases the chances for mistakes. Many errors occur when practitioners, because of their familiarity with a certain product, see the product they believe it is rather than what the product actually is.
  • In summary, it’s not what we see but how we think about what we are seeing.

Look-Alike/Sound-Alike (LA/SA) Drugs

LA/SA drug mix-ups are a frequent and significant cause of mistakes which can and do result in serious patient harm. (14)  For example, the Institute of Medicine reported that labeling and packaging issues (i.e., LA/SA) comprised 33% of all medication errors and 30% of the patient deaths from medication errors. (3)  Examples of LA/SA medication errors include confusion with drug names, visual errors, verbal errors, compounding errors and transcription errors.

LA/SA – Drug Names A common area of LA/SA mistakes involve drug names.  Table 1 includes only a few examples of drug names that have been reported to cause LA/SA errors. (19)(20) Tall man lettering, with bolding, is utilized in the table and through-out this discussion which is an FDA approved methodology to avoid mix-ups.

Look-Alike/Sound-Alike drug names will be discussed in greater detail in a subsequent article.

 

Drug Name

Confused Drug Name

CeleBREX®

CeleXA®, Cerebyx®

cycloSERINE

cycloSPORINE

Enjuvia®

Januvia®

GlycoTrol®

Glucotrol®

glyBURIDE

glypiZIDE

HumaLOG®

HumaLIN®

Lantus®

Lente®

Neulasta®

Nuedexta®

niCARdipine

NIFEdipine

predniSONE

prednisoLONE

Tobradex®

Tobrex®

zolpidem

Zyloprim®

Table 1

Examples of Confused LA/SA Drug Names

A LA/SA example that occurred in the past was the mix-ups with the first brand name of the proton pump inhibitor drug omeprazole (Losec®) and the brand name of the diuretic drug furosemide (Lasix®).  Following the report of the death of a patient due to this confusion, the brand name Losec was changed to PriLOSEC® in the United States. Unfortunately, the name change introduced another unanticipated problem: mix-ups between PriLOSEC® and the antidepressant drug PROzac® (FLUoxetine).  Similarities in how these drug names look and sound as well as their overlapping dosage strengths (i.e., 10, 20, and 40 mg) further contributed to these mix-ups. (21)

LA/SA – Packaging, Labeling and Graphics Packaging and labeling are involved in about 1/3 of all medication errors. (10)  Visual errors causing mix-ups can also occur with look-alike packaging and labels of drug products.  Such look-alike packaging, labels and graphics can take place within a pharmaceutical company’s product line or with different products between unrelated companies.

Figure 2 below illustrates an example of two different products, both for coughs and colds, in similar sized and shaped bottles, caps, label graphics and naming, but with very different respective drug contents which can provide the conditions for mix-ups.

FIGURE 2

Different Drugs in Similar Primary Packaging, Labels, Naming and Graphics from Same Company

Figure 3 illustrates the same electrolyte, but with different concentrations from two different unrelated companies, but in identical vials, closures, label fonts/graphics and colors. (22)  Note that the concentration of one company’s product is twice that of the other company’s product.  As can be envisioned, such similarities can lay the foundation for mix-ups.

FIGURE 3

Same Drug, but Double Strength in Similar Primary Packaging, Labels and Graphics from Different Companies (22)

LA/SA – High-Alert Drugs Figure 4 below is an example of packaging and graphics that are very similar for two completely different high-alert drugs. (22)  That is, the Novolog® is for the treatment of diabetes while the Nimbex® is a neuromuscular blocking agent used in anesthesia.  The results of such a mix-up could most likely be fatal if the Nimbex® is accidentally administered instead of the Novolog®.  Please note that this is not a staged photograph and is a real-life situation in a pharmacy.

FIGURE 4

Neuromuscular Blocking Agent (Nimbex®) Stored with Diabetes Drug (Novolog®) (22)

Figure 5 is another example of a look-alike situation of drug products where identical vials, caps, label graphics/colors/fonts are used within a company’s product line, but the differences between the drugs are very significant.  For example, the enalaprilat is a cardiovascular drug while the pancuronium is a powerful neuromuscular blocking anesthetic agent that could result in serious outcomes if the pancuronium is incorrectly administered. (22)

FIGURE 5

Similar Packaging and Labels Between a Cardiovascular (enalaprilat) and a Neuromuscular Blocking Agent (pancuronium) (22)

LA/SA – Prescription Compounding Figure 6 illustrates another example situation of two different bulk drugs, but with both look-alike packaging and labels and also with sound alike names - tetracaine hydrochloride and tetracycline hydrochloride.

 

FIGURE 6

Products Within a Company Product Line in Look-Alike Identical Packaging and Graphics but Different Sound-Alike Drug Names

Figure 7 is another example of two liquids that have similar appearances - clear and colorless liquids, with similar packaging and labeling.  One is propylene glycol while the other is polyethylene glycol 400, both of which are used in extemporaneous prescription compounding.

Figure 7

Different Products Within a Company Product Line with Identical Physical Appearances, Packaging and Labeling

As an example of a LA/SA mix-up during the compounding of a prescription, a pharmacy received a verbal order for 2 L of a polyethylene glycol (PEG) solution for a colonoscopy preparation.  Instead of using Polyethylene Glycol 3350, the pharmacy incorrectly used 2 L of propylene glycol (PG).  The patient was hospitalized within hours after ingesting the first 500 mL with severe metabolic acidosis requiring hemodialysis. (23)

In another example case, an Emergency Department nurse administered the neuromuscular blocking agent pancuronium instead of influenza vaccine to several patients.  This was because the vials were of the same size with labels that were quite similar.  These look-alike vials were being stored next to each in the refrigerator.  The patients suffered difficult breathing and respiratory depression, but fortunately in this case sustained no permanent injuries. (24)

LA/SA - Transcription Errors Transcription errors occur when drug names are mistakenly mixed-up upon receiving a verbal prescription order, confusing it with a different drug of a similar sounding name and dosing regimen, and then writing a transcription of the verbal order.  For example, a telephone prescription was taken that was verbally prescribed for the diuretic drug metolazone 2.5 mg tablets; take 1 tablet daily.  The Rx was incorrectly transcribed as the cancer drug methotrexate 2.5 mg tablets; take 1 tablet daily.  The patient died one month later from the methotrexate.  The pharmacy was sued for negligence and the patient’s family was awarded $2 million. (25)(26)

Other example sound-alike transcription errors include: (27)

  • “Sixteen” misheard as “sixty”
  • “1 to 5 mg” misheard as “125 mg”

Abbreviations and Symbols

The use of abbreviations and symbols can also lead to mistakes.  This list in Table 2 represents a combination of only a few of the abbreviations and symbols from The Joint Commission and the ISMP that should not be used.  (28)(29)

 

Do Not Use

Potential Problem

Instead Use

“U”, “u”

Mistaken for “0” (zero), or the number “4”

Use “unit”

“IU”

Mistaken for IV

Use “international units”

“hs”

Mistaken for “half strength”

Use “bedtime”

“Q.D.”, “QD”, “q.d.”, “qd”

Mistaken with QOD (every other day)

Use “daily”

“Q.O.D.”, “QOD”

Mistaken with QD (daily)

Use “every other day”

“MS”, “MSO4” and “MgSO4

Confused with “morphine sulfate” or “magnesium sulfate” or one another

Use “morphine sulfate” or “magnesium sulfate”

“µ” and “µg”

Mistaken for “mg”

Use “mcg”

“&”

Mistaken for “2”

Use “and”

AD, AS, AU

Mistaken for “OD, “OS”, “OU”

Use “right ear”, “left ear”, “both ears”

OD, OS, OU

Mistaken for “AD”, “AS”, “AU”

Use “right eye”, “left eye”, “both eyes”

Table 2

List of Do Not Use Abbreviations and Symbols (28)(29)

Zero’s and Decimal Points

Leading zeros should always be used when writing a number. (11)

  • For example, 0.45 contains a leading zero, while .45 does not.  The decimal point can be missed without a leading zero.
  • In other words, if .45 is written, then the number can be misread as 45 which would be a 100-fold error

On the other hand, a trailing zero after the decimal point should never be used. (11)

  • For example, the number 345.0 should be written as 345, and 34.50 should be written as 34.5
  • The use of a trailing zero in the number increases the chances that the decimal point will be overlooked.

As an example, there have been several reported cases of 10-fold overdoses with the chemotherapeutic agent topotecan. (30)

  • The decimal point was overlooked.
    • 2.5 mg dose misread as 25 mg
  • There was lack of a leading zero.
    • .7 mg dose misread as 7 mg
  • A trailing zero was used.
    • 4.0 mg misread as 40 mg

Calculations (31)

Calculation errors pose one of the significant risks of causing harm.  Calculation errors are often made by misplacing a decimal point, or using the wrong conversions

Here are only a few examples of calculations errors.  Many calculation errors entail pediatric patients as custom doses are needed.

  • 17 babies at one hospital received heparin 100x overdoses; 2 infants died (32)
  • 4-month-old baby; pharmacist to make flecainide oral suspension; used 6,000 mg instead of 600 mg; each dose was 100 mg/mL instead of 10 mg/mL; a 10X overdose; a resultant cardiac emergency (33)
  • 6-year-old patient had a routine tonsillectomy; the prescription was for dextrose 5% IV; the wrong infusion rate was calculated and administered too fast; child died (34)
  • 8-month infant was to receive 140 mg of calcium chloride IV; instead 1,400 mg was administered; the baby died and the distraught nurse who did the erroneous calculations and drug administration then committed suicide (35)
  • Bone marrow transplant patient was to receive 2,400 mg of foscarnet; instead 24,000 mg was administered; a 10X overdose causing renal failure; patient died; pharmacy was ruled to be negligent; jury awarded $3.3 million to the family (36)

Drug Shortages

There is an on-going nationwide shortage of various drug products, such as electrolytes, diluents, anesthetics, antimicrobials, anti-neoplastics, CNS, hormonals, et.al.  This situation presents issues with pharmacists who in turn have to scramble to obtain what is needed and then adjust the dosing to match that of the shorted product.  This situation with shortages then subsequently exacerbates the conditions for errors to take place.  Most of the dosing errors pertain to calculation mistakes when switching between different products and working with unfamiliar drug concentrations (e.g., heparin injections).

Drug shortages can also lead to LA/SA mix-ups, errors in volumes, concentrations and dosing which can lead to adverse patient outcomes.  For example: (37)

  • An Associated Press article on September 24, 2011 reported 15 deaths in 15 months that were directly linked to drug shortages.
  • In early April 2011, a survey conducted by the American Society of Anesthesiologists (ASA) and reported by ABC news revealed that 7 anesthesiologists had drug shortages that led to death in their patients.

In a 2011 survey by the ISMP, 96 hospitals responded “yes” when asked if they had a serious adverse drug event that occurred in their hospital as direct result of a drug shortage.  Those medications in short supply most commonly involved in the reported adverse events of patient harm include chemotherapy (27%), opioids (17%), electrolytes (7%) and antibiotics (5%).  Some examples of the patient harm in relation to the drug shortage can be seen in Table 3. The types of harm include progression of disease, transient or permanent injuries and death.  In many cases, patients suffered from more than one type of harm from the drug shortage. (37)

Examples of Reported Patient Harm

Progression of disease and hospitalization

Medication overdoses

Respiratory depression and excessive sedation

Treatment with rescue agents

Debilitating and life-threatening side effects from alternative drug (e.g., ileus, GI toxicity, mucositis, malabsorption, seizures)

Severe hypotension or hypertension

Severe electrolyte and acid/base imbalances

Untreated pain

Death

Table 3

Examples of Incurred Patient Harm in Relation to Drug Shortages (37)

The ongoing drug shortage crisis extracts a notable toll on patient safety.  For example, Table 4 lists drugs that were in short supply during that were most commonly involved reported adverse effects in March 2011-March 2012. (37)

Adverse Events of Drugs in Short Supply

% Adverse Events

Chemotherapy, particularly DOXOrubicin liposomal injection

27%

Opioid analgesics, mostly fentaNYL and morphine

17%

Electrolytes

7%

Antibiotics

5%

Phentolamine

4%

Phytonadione

4%

Table 4

Reported Adverse Events of Drugs in Short Supply; n ≈ 100 (37)

As per the ISMP, the problems associated with a drug shortage that resulted in harm primarily fell into four categories: (37)

  1. Alternative medication provided, but it was not the drug of choice, which led to inadequate treatment (35%).
  2. An error with an alternative drug or form/strength of a drug used as a substitution for the drug in short supply (27%).
  3. An omission of vital medication leading to non-treatment of the patient (27%).
  4. An error when a hospital pharmacy attempted to compound a product or drug strength no longer available (6%).

Table 5 are the results of an additional ISMP survey, primarily of pharmacists, who reported mistakes with drug products that were in short supply. (38)  The types of errors in this example primarily entail dose conversions when switching between differing unavailable and available products.  As can be seen, the depth and breadth of the mistakes can be significant.  

Drug Product/Ingredient

% Yes

Trace Elements

28

Sodium Phosphate

27

Potassium Phosphate

25

Multi-Vitamins (adult)

23

Calcium Gluconate

19

IV Fat Emulsions

19

Zinc Injection

16

Magnesium Sulfate

13

Amino Acids

13

Selenium

12

Sodium Chlorides

10

Multi-Vitamins (pediatric)

10

Table 5

Percent Respondents to ISMP Survey Reporting Drug Shortage Related Errors 2012-2014; n=1,800 (38)

E-Prescribing: Computerized Physician Order Entry (CPOE) (39)(40)(41)

Computerized prescription ordering is increasing common in an attempt to reduce errors.  However, such systems have not yet been completely implemented; currently as high as 77% implementation.  Errors are still taking place, but the types of errors or now different. The causes of errors are due to the human element.  Such errors for example, can include:

  • Order entry input errors: wrong product selection, typed in wrong number, entered into wrong field
  • LA/SA - Similar product descriptions
  • Mnemonics - order entry auto fill
  • "Ox” could mean Oxcarbazepine (an anticonvulsant) or oxaprozin (a nonsteroidal anti-inflammatory drug)
  • "Ve” could mean Versed (a mild sedative) or vecuronium (a neuromuscular blocking agent)
  • A patient died when vecuronium was accidentally given instead of Versed (42)
  • Inaccurate patient information in the records
  • Pharmacy transcription errors
  • Alarms set too low
  • Alert fatigue
  • Boilerplate warnings ignored when thought to be not applicable
  • Copying and pasting of orders
  • Improper patient selection from electronic lists
  • Incorrect or difficult product selection

The texting of prescription orders is a growing concern – mobile phones are being used to send and receive orders. 45% of responding surveyed pharmacists reported receiving texted orders on regular basis, of which 7% were aware of errors and close calls.  The autocorrection function on mobile phones has led to the dispensing of wrong drugs and incorrect abbreviations. (43)

Other texting issues, in addition to autocorrection are included below.  As can be seen, the texting of prescriptions lacks control. (43)

  • Cannot authentic the sender and/or receiver
  • Lack of a hard copy to document the order
  • Lack of order retention
  • Lack of completeness
  • Lack of security and encryption
  • Controlled substances handling issues
  • Complex order sets not amenable to texting

Work Environment

There are a variety of factors that contribute to the nation’s epidemic of medical errors.  Medication errors are usually due to confluence of multiple simultaneous factors.  Among these factors in drug dispensing and administration settings are the work environment and conditions – busy personnel, being rushed, no breaks/fatigue, interruptions, incorrect prescriptions, changes in the work place and/or procedures, inability to concentrate, bad hand writing, work flow process patterns, distractions, short cuts, too many telephone calls, missing prescription information, facility layouts, multi-tasking, inadequate staffing and excessive workloads.  This all results in high-pressure/high-stress working conditions which lays the foundation for errors to take place. (44)

Criminalization of Errors

A shift is underway where healthcare practioneers are now being criminally charged with negligence for medication errors.  What used to be considered to be regulatory (civil) violations are now being viewed in stark criminal terms, including murder. (48)

In the case of the New England Compounding Center, injectables were prepared that were contaminated.  For example: (45-51)

  • 64 patients killed in 9 states in fall of 2012; 3,500 total victims
  • 753 people in 20 states with 384 cases of fungal meningitis; 360 spinal infections, 7 strokes
  • 131 count indictment issued; 14 people arrested
  • 25 acts of second-degree murder filed in 7 states
  • Pharmacy director and lead pharmacist sentenced to prison for 9 years and 8 years respectively

Another error resulted in the creation of “Emily’s Law” in Ohio where pharmacy technicians must first pass a competency test. (52)

  • Pharmacy technician prepared etoposide with 23.4% instead of 0.9% sodium chloride injection; pharmacist missed the error.
  • Baby died two days later due to cerebral edema.
  • Pharmacist was charged with involuntary manslaughter and pleaded no contest.
  • Pharmacist penalties included 6 months in prison, 6 months home confinement, loss of license, 400 hours of community service, a $5,000 fine and court costs

    PHARMACEUTICAL INDUSTRY CONSIDERATIONS

    The pharmaceutical industry can indeed play a significant role in reducing the potential for mistakes by instituting approaches and practices that address the potential for medication errors.  By understanding and considering the how our brains work (i.e., human factors, LA/SA), combined with the working environment and conditions of healthcare professionals, this thinking can be subsequently utilized in the development of drug dosage forms to help to reduce the propensity for errors.  Reducing medication errors should be a unified goal for all pharmaceutical companies.

    Below is a brief overview of what the pharmaceutical industry can do to preclude errors.  A more in-depth discussion on approaches that could be utilized by the pharmaceutical industry will be in a subsequent article in this series

    Safety by Design

    The FDA has recognized medical errors as a serious problem and as such has issued guidance documents to the industry to address these situations.  Medication errors can be avoided at the design stage by drawing on lessons learned from past medication errors and by conducting risk assessments before marketing. (3)

    Safety by design should be considered at all steps in the development process, especially when making decisions on what the finished dosage form of the drug will be, what physical characteristics it will have, and what type of container closure will be used for marketing.  This approach should be initiated early in the product development process. (3)

    The FDA expects manufacturers to consider the use of analytical methodologies and risk assessments when developing drug products to build safety into the drug product throughout the product’s development and its lifecycle to identify those safety characteristics of the product that may considered to be critical.

    Look-Alike/Sound-Alike Drugs (LA/SA?

    • Do not use proprietary names that are similar in spelling or pronunciation to other proprietary names, established names, or ingredients of other products. Accurate interpretation of the drug name by the end user is essential.  (53)
  • The FDA may consider a proposed proprietary name to be misleading if it can be confused with the proprietary name or the established name of a different drug or ingredient because of similar spelling or pronunciation. (53)
    • Conduct a preliminary screening to eliminate names with obvious similarities to the names of existing products.  Perform a full assessment of the safety concerns later in the development process to identify less obvious but still confusing similarities. (53)

    Product Appearance

    Some suggestions on how to approach the product appearance can include, for example:

    • Use size, shape and color to differentiate and minimize medication errors. (54)
    • Consider using the product name along with a numeric code or product strength to help distinguish different products with similar imprint codes. (4)
    • Make the strengths of extended or delayed release products different from those of immediate-release products. The risk for medication error can be increased when strengths overlap or the strength of the extended release products is achievable from the marketed immediate-release product strength. (4)

    Labeling and Graphics

    The labeling and graphics used for drug products can be very significant in helping to preclude medical errors in the field, especially in the case of LA/SA drugs.  Clear, easy to read labels, while avoiding LA/SA situations, probably has the biggest impact to improving medication safety.  More specifically, for example:

    • Keep the labeling clear and simple for both the container label and the carton.  Simple is best. Design the container labels to help the healthcare providers and/or consumers select the right drug product. (2) (10)
    • Use TALL man lettering. TALL man letters help to draw attention to the dissimilarities in look-alike drug names. The use of TALL man lettering has been endorsed by the ISMP, The Joint Commission and the FDA (as part of the FDA’s Name Differentiation Project), the WHO and the International Medication Safety Network (IMSN).  The ISMP also suggests that TALL man lettering be bolded for enhanced readability. (19)
  • Refer to Table 1 for examples of the use of TALL man lettering in look-alike/sound-alike names.
    • If a drug is made in multiple strengths – e.g., 5 mg, 10 mg, and 25 mg, – then the labels of those three containers should be easy to differentiate. The label design may use different colors or identify the strength in large bold numbers and letters. (2)
    • Always use the metric system for weights and measures.  Do not use the apothecary system (e.g., drams, grains, etc.), household measures (teaspoon, tablespoon) nor ratios (1:000). (10)
    • Avoid abbreviations, symbols and characters.  Do not use any error-prone abbreviations. (10)
    • Avoid look-alike labels, cartons and corporate dress. (10)

    Packaging

    • Use different bottles and container closures to differentiate between products.
    • Do not use container closures that look confusingly similar to those of other products within the same product line or a different product line. Distinguish container closures by size, shape, color or tactile features.  Drug products packaged in container closures that have a similar appearance have led to product selection errors in which the wrong drug or wrong strength have been dispensed and administered. (3)
    • Commercial containers should not provide an amount of drug that is incongruent with the recommended doses. This has led to overdose with products designed with excessive fill volume, such as single-dose injection vials. (3)
    • The dosing device should deliver an oral solution in a volumetric unit of measure consistent with recommended dosing. Medication dosing errors have been reported when an oral dosing device is labeled in milligrams but the dose is prescribed in milliliters, leading to patients being unable to measure a specific volume of oral solution. (3)

    FUTURE DISCUSSIONS

    Additional in-depth discussions on the industry-related topics briefly described above are planned for future issues of this journal.  Comments and examples related to medication errors or successful practices to reduce errors from readers are most welcome.

    ACKNOWLEDGEMENTS

    Contributions by Darryl Rich, PharmD, MBA, FASHP, Medication Safety Specialist, Institute for Safe Medication Practices (ISMP) (ret.), and Administration Coordinator, Medication Safety Officer Society (MSOS) (ret.), and Paul Pluta, PhD, UIC College of Pharmacy, Associate Professor Pharmaceutics (ret.) and also the Institute for Safe Medication Practices (ISMP) are greatly appreciated.

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