Validation of the shake test for detecting freeze damage to adsorbed vaccines

• Published in: Bulletin of the World Health Organization 2010-08, Vol.88 (8), p.624-631
• Main Authors: KARTOGLU, Umit, ÖZGÜLER, Nejat Kenan, WOLFSON, Lara J, KURZATKOWSKI, Wiesław
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cross-Over Studies; Crossovers; Damage; Design; Diphtheria; Double-Blind Method; Drug Stability; Evaluation Studies as Topic; Freezing - adverse effects; General aspects; Health; Hepatitis B; Medical sciences; Microscopes; Microscopy; Miscellaneous; Organizations; Phase contrast; Precipitates; Predictive Value of Tests; Prevention and actions; Public health. Hygiene; Public health. Hygiene-occupational medicine; Sample size; Sedimentation & deposition; Sensitivity and Specificity; Temperature; Tetanus; Vaccines; Vaccines - chemistry; Vaccines - standards; Vials; Whooping cough
• ISSN: 0042-9686; 1564-0604
• DOI: 10.2471/BLT.08.056879

To determine the validity of the shake test for detecting freeze damage in aluminium-based, adsorbed, freeze-sensitive vaccines. A double-blind crossover design was used to compare the performance of the shake test conducted by trained health-care workers (HCWs) with that of phase contrast microscopy as a "gold standard". A total of 475 vials of 8 different types of World Health Organization prequalified freeze-sensitive vaccines from 10 different manufacturers were used. Vaccines were kept at 5 degrees C. Selected numbers of vials from each type were then exposed to -25 degrees C and -2 degrees C for 24-hour periods. There was complete concordance between HCWs and phase-contrast microscopy in identifying freeze-damaged vials and non-frozen samples. Non-frozen samples showed a fine-grain structure under phase contrast microscopy, but freeze-damaged samples showed large conglomerates of massed precipitates with amorphous, crystalline, solid and needle-like structures. Particles in the non-frozen samples measured from 1 microm (vaccines against diphtheria-tetanus-pertussis; Haemophilus influenzae type b; hepatitis B; diphtheria-tetanus-pertussis-hepatitis B) to 20 microm (diphtheria and tetanus vaccines, alone or in combination). By contrast, aggregates in the freeze-damaged samples measured up to 700 microm (diphtheria-tetanus-pertussis) and 350 microm on average. The shake test had 100% sensitivity, 100% specificity and 100% positive predictive value in this study, which confirms its validity for detecting freeze damage to aluminium-based freeze-sensitive vaccines.