The quality and stability of essential drugs in rural Zimbabwe: controlled longitudinal study

In 1988 an alarming WHO report of substandard ergometrine injection in three developing countries¹ led to field studies on the stability of essential drugs during international transport to the tropics and to specific stability studies on oxytocic drugs.² We performed a controlled longitudinal study to measure the quality of essential drugs within rural Zimbabwe and to determine whether any failure was due to poor initial quality or to instability of the drugs during inland distribution and storage.

Subjects, methods, and results

During a two year period (January 1991 to December 1992), samples of drugs arriving at central medical stores in Harare and Bulawayo were retained as controls, and samples of the same batches were later retrieved from hospitals and health centres in five remote, hot, rural districts. We studied 789 samples of 26 brands of 13 essential drugs (selected for relevance to public health and suspected stability problems); 176 samples were taken from central stores and 613 from rural facilities. Of the latter, 261 samples were matched with central samples of the same batch to make longitudinal pairs. Drug quality was measured by level of active ingredient as percentage of stated content and by compliance (pass/fail) with assay standards of the British Pharmacopoeia. Drug stability was measured by comparing mean assay values at central and rural level and by paired analysis of central and rural samples of the same batch.

Drug quality in rural facilities was satisfactory for injectable benzylpenicillin and oral forms of acetylsalicylic acid, amoxicillin, ampicillin, doxycycline, ferrous sulfate, phenylmethoxypenicillin, and tetracycline; it was indeterminate for epinephrine injection. Poor initial quality accounted for problems in injectable ampicillin (2/10 central samples failed, with 87% and 91% content) and retinol tablets (5/5 failed; mean assay 73%, 95% confidence interval 63% to 83%), with similar results at rural facilities. An aqueous formulation of injectable procaine benzylpenicillin showed moderate instability with 4% (1% to 6%) loss after 4.3 months but the assay remained within pharmacopoeial limits. Poor initial quality of all three brands of ergometrine injection (17/26 failed; mean assay 82%, 78% to 87%) was compounded by serious instability, with a mean loss of 17% (13% to 22%) after 4.8 months in paired samples. The figure shows the results of the paired analysis. Full data are available on request.³

Comment

Serious instability occurred only with ergometrine injection. This result is in line with two earlier longitudinal studies during transport to and within tropical countries, in which only ergometrine injection, methylergometrine injection, and retinol capsules showed a loss of active ingredient; 12 other essential drugs were stable.⁴,⁵ As all three studies focused on essential drugs suspected of being unstable we conclude that, even under the most adverse tropical conditions, clinically relevant instability of essential drugs is rare. Poor initial quality (as with ampicillin, retinol, and ergometrine in our study) poses a much more serious problem as it could, in principle, occur with any drug.

The practical implication of this conclusion is that careful selection of suppliers and quality control at the entry point of the distribution chain are essential to ensure drug quality. Even in tropical climates subsequent quality checks at the district level are not necessary.

Figure.

Stability of essential drugs in Zimbabwe. Matched pairs from same batch of retinol (gain) and ergometrine (loss) were unstable; acetylsalicylic acid, amoxicillin, ampicillin, benzylpenicillin, doxycycline, epinephrine, ferrous sulfate, phenoxymethylpenicillin, procaine benzylpenicillin, and tetracycline were stable