Stability of Essential Drugs in Tropical Climates: Zimbabwe - EDM Research Series No. 013: Annexes: Annex 1: Detailed results for each drug: 1.10 Ampicillin injection

Stability of Essential Drugs in Tropical Climates: Zimbabwe - EDM Research Series No. 013
(1994; 86 pages)

Table des matières

Abbreviations
1. Summary
2. Introduction
	2.1 Quality of pharmaceuticals in developing countries
	2.2 Background to the Zimbabwe stability study
	2.3 Research questions
	2.4 Acknowledgments
3. Study design and methods
	3.1 Outline of the study
	3.2 Sampling procedures
	3.3 Number and type of samples obtained
	3.4 Risk factors for poor drug quality
	3.5 Sample storage and laboratory tests
	3.6 Data processing and statistical analysis
4. Results
5. Discussion
	5.1 Drugs without failures
	5.2 Drugs with a low rate of failures
	5.3 Drugs with a high rate of failures
	5.4 Assumptions and limitations of data
	5.5 Pipeline times, expiry and shelf-life considerations
6. Conclusions and recommendations
	6.1 Initial quality of drugs
	6.2 Stability of drugs
	6.3 Factors influencing the quality of drugs
	6.4 Outcome of the study
	6.5 Practical recommendations for a quality assurance system
References
Annexes
	Annex 1: Detailed results for each drug
		1.1 Amoxycillin capsules
		1.2 Ampicillin capsules
		1.3 Acetylsalicylic acid tablets
		1.4 Doxycycline capsules
		1.5 Ferrous sulfate tablets
		1.6 Phenoxymethylpenicillin tablets
		1.7 Tetracycline capsules
		1.8 Retinol tablets
		1.9 Epinephrine injection
		1.10 Ampicillin injection
		1.11 Benzylpenicillin injection
		1.12 Ergometrine injection
		1.13 Procaine penicillin injection
	Annex 2: Validation of laboratory results

1.10 Ampicillin injection

SHELF LIFE	Manufacturer A: 2 years
ASSAY METHOD	Spectrophotometric method, BP 1988 p. 759, Contents of 10 vials mixed; measured three times; mean taken.
ASSAY LIMITS	95 - 105% (BP)
SAMPLES OBTAINED	Manufacturer A

*GMS samples*	no.	%
Total	10	100
Harare	5	50
Bulawayo	5	50
*Facility samples*	no.	%
Total	24	100
Age > 50% SLife	16	67
Facility type = PCH	0	0
Climate = hot	11	46
Transport = slow	19	79
*Longitudinal series*
Total	13	100

SUMMARY ASSAY RESULTS

**GMS samples**	Manufacturer A
Mean age (mths)		7.7
Mean assay		96.7%
95% CL	93.4 - 99.9%
No. and % fail	2	20%
No. and % low fail	2	20%
No. and % high fail	0	0%
*Facility samples*	Manufacturer A
Mean age (mths)		14.6
Mean assay		96.2%
95% CL	93.8 - 98.6%
No, and % fail	5	26%
No, and % low fail	5	26%
No. and % high fail	0	0%
*Longitudinal series*	at Manuf.		at GMS		at facility
Mean age (mths)		0		8.6		15.8
Mean assay		100.4%		98.6%		97.4%
95% CL	99.7-101.2%		96.4 - 100.8%		95.0 - 99.8%
No. and % fail	0	0 %	1	8%	2	15%

	Mean interval (mths)	7.2
	Mean loss (-) or gain (+)	-1.1%
	95% CL for loss/gain	-4.3 to +2.2%

Figure 1 - Results of GMS samples

Figure 2 - Results of facility samples

Findings:

a) Two of 26 facility samples (7%) were expired; these results were excluded when calculating averages.

b) Two of 10 GMS samples (20%) failed; both failures were below the lower limit (86.8, 90.9%),

c) Five of 24 facility samples (20%) failed: all failures were below the lower limit (82.7, 84.5, 84.5, 84.9, 93.3%).

d) 13 GMS/facility sample pairs showed a loss of potency (mean -1.1 %).

e) This potency loss for GMS/facility sample pairs was not significant (t-test: p>0.05).

f) The one batch 20 months past expiry and awaiting destruction at GMS had an assay of 103.6%.

g) The GMS and field sample groups show similar results (means 96.7 and 96.2% respectively), suggesting an initial quality problem rather than a loss of potency in the field.

h) No clear sign of instability even towards the end of shelf life and expired samples passed.