TABLE 1.

Characteristics of substandard and counterfeit antimicrobials

Group and characteristic	Comments (references)
Substandard antimicrobials
Reduced concn of AIa	Quantification of the AI content of an antimicrobial agent shows that the concn of the AI is lower than the claimed content declared on the packaging
	Poor manufacturing or transportation, decomposition, and poor storage conditions (2, 34, 35) and dilution of drugs with other chemicals (25, 26, 27) may lead to low concn of the AI
	In a recent report of published prevalence studies regarding substandard/counterfeit antimicrobials, 14/15 (93%) studies reported this problem (59)
Reduced stability (dissolution failure) and bioavailability	Solubility or release of AI is not within the specified time range due to reduced stability of the drug, and this leads to reduced bioavailability of the antibiotic (59)
	Most of the limited no. of studies that have assessed the stability of antimicrobials had suboptimal design (29–33, 35, 36)
	Antibiotics such as ampicillin (34), but not others such as penicillins and tetracyclines (7, 35), may degrade with high temperatures and humidity (30)
	Reduced bioavailability may lead to suboptimal activity of antimicrobials (36); examples include antibacterials such as co-trimoxazole (38), tetracyclines (37), and metronidazole (38) and antiparasitic agents such as chloroquine (39), mefloquine (40), and pyrimethamine (41–43)
	In a recent report of published prevalence studies regarding substandard/counterfeit antimicrobials, 5/15 (33%) studies reported this problem (59)
Impurities/unknown ingredient	Substandard wt of a tablet or capsule (59)
	Altered odor due to diluted AI or harmful additives
	Inactive or harmful ingredients, impurities, or contamination such as mold
	In a recent report of published prevalence studies regarding substandard/counterfeit antimicrobials, 2/15 (13%) studies reported this problem (59)
Counterfeit antimicrobials
Absence of pharmaceutical AI	Quantification of the AI content of an antimicrobial agent shows that the AI as declared on the packaging is absent (59)
	Antibiotics may contain no AI (9, 44, 48, 49)
	The AI is replaced by cheap substances, such as flour in oral presentations and water in drinkable or injectable presentations (15, 17)
	In a recent report of published prevalence studies regarding substandard/counterfeit antimicrobials, 7/15 (47%) studies reported this problem (59)
Reduced amt of AI	The antimicrobial may be considered counterfeit when the substandard amt of the AI is included deliberately in the drug (59)
Increased amt of AI	The concn of the AI may be higher than the amt reported in the packaging (59)
	In a recent report of published prevalence studies regarding substandard/counterfeit antimicrobials, 6/15 (40%) studies reported this problem (59)
Altered chemical content/wrong ingredient	Detection of AI in the drug that is not declared on the packaging (59)
	Examples of wrong ingredients include erythromycin (45), flour, starch, or powder (26, 45–47), and tap water (9, 44, 48, 49)
	These products may contain toxic chemical impurities (15, 17)
	In a recent report of published prevalence studies regarding substandard/counterfeit antimicrobials, 4/15 (27%) studies reported this problem (59)
Impurities/unknown ingredient	Extraneous contaminants that should not be present in a drug (if done deliberately and not the result of poor manufacturing) (59)
	In a recent report of published prevalence studies regarding substandard/counterfeit antimicrobials, 2/15 (13%) studies reported this problem (59)
Inappropriate packaging	Packaging has incorrect labeling information about a drug origin or authenticity, and the color, size of pills, and bar codes are often similar to those for the original drug (25)
	False representation of identity is commonly used, by copying the packaging of another marketed product; the brand name may be modified to try to escape laws on infringing intellectual property
	They are generally undisguisable in their outward packaging
	In developing countries, many of the purchased drugs without packaging were counterfeit (57)
	Antimicrobials with false packaging and labeling include penicillins (24), co-trimoxazole (50), tetracyclines (1, 51–54), chloramphenicol (1), quinolones (51), aminoglycosides (55, 56), and antimalarials (40, 57, 60).
	Very few studies performed packaging analysis of the samples collected (40, 58, 59)
Mass uniformity test failure	The wt of a tablet or capsule is not within the avg range specified (if done deliberately and not the result of poor manufacturing) (59)

^aAI, active ingredient.