The consequence for the patient of poor product quality can be therapeutic failure or toxicity. Some examples follow.
Low potency:
- A WHO press release in November 2003 stated inter alia:
- A recent WHO survey of the quality of antimalarials in seven African countries revealed that between 20% and 90% of the products failed quality testing. The antimalarials in question were chloroquine-based syrup and tablets, whose failure rate ranged from 23% to 38%; and sulphadoxine/pyrimethamine tablets, up to 90% of which were found to be below standard. The medicines were a mixture of locally produced and imported products 1
- Therapeutic failures in the Amazonian region have been attributed at least in part to poor and variable potency of antimalarial drugs2 as assessed by chemical assay.
- It has been suggested that suboptimal potencies observed in chloroquine and amoxicillin products purchased in Nigeria are likely to be a factor in the selection pressure for drug-resistant organisms3.
- Samples of chloroquine, amoxicillin, tetracycline, co-trimoxazole and ampicillin-cloxacillin taken in Nigeria and Thailand had lower than expected potencies, and six samples of chloroquine had no detectable potency4.
Method of manufacture:
- Variations in particle size, excipients or manufacturing process of the experimental preparations or capsules produced a marked change in bioavailability of rifampicin5.
- The order in which drugs were mixed during production had an alarming effect on bioavailability of rifampicin6.
- A change in the method of manufacture of carbamazepine tablets led to intoxication in some patients7.
Excipients:
- Formation of non-absorbable insoluble complexes between drugs and excipients is known for tetracyclines and dicalcium phosphate, amphetamine and sodium carboxymethylcellulose, and phenobarbitone and polyethylene glycol 40008.
- Change of excipients in a formulation led to an outbreak of phenytoin intoxication in an Australian city9.
- Use of an excipient without prior information on its toxicology led to an outbreak of toxicity in Haiti10.
Impurities:
- Fever, tachycardia, hypotension and rigors occurring with once daily dosing of gentamicin were attributed to impurities from a particular supplier of the drug11.
Stability:
- Decomposition was the cause of a number (but not all) of the observed low potencies of antimalarial and antibiotics in Nigeria and Thailand4.
- Fanconi syndrome has been known to result from consumption of degraded tetracycline12,13
- Allergic reactions to penicillin are enhanced by formulations that encourage polymerization and reactions with certain carbohydrates14.
Bioavailability
- Therapeutic failures due to poor bioavailability are well known, for example to rifampicin15.
- Higher bioavailabilities of artemether and benflumetol were associated with improved parasitic clearance time and 28 day cure rate respectively16
- Different brands of rifampicin have been shown to have different bioavailabilities at the same dose17.
- The bioavailability of rifampicin is sometimes reduced when formulated in an FDC, but the effect is inconsistent18,19,20,21,22
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