The effects of freeze-drying on the potency and stability of live varicella virus vaccine.
Investigations into methods for improving the potency and stability of live varicella-zoster virus (Oka strain) vaccines have included the use of different lyophilization procedures which yielded products with different moisture levels. Three procedures were used: an 8-hour controlled-vacuum (0.47 mBars) procedure, a 14-hour controlled-vacuum (0.14 mBars) procedure, and a 48-hour high-vacuum (less than 0.07 mBars) procedure. Samples were stored for 24 months at -24 degrees C, -15 degrees C (in a frost-free freezer), and 4 degrees C. Potency was determined by a plaque assay in MRC-5 cells; moisture content was measured by the Karl Fisher method. Moisture content was 6 to 8 percent for the product made using the 8-hour procedure, 2 to 7 percent for the 14-hour procedure, and 0.5 to 1.5 percent for the 48-hour procedure. In addition to higher moisture, the 8-hour procedure resulted in a higher initial potency, indicating a lower loss during lyophilization, and better stability than did the 14- and 48-hour procedures. Although the initial potency from the 14-hour procedure was not statistically different from that for the 48-hour procedure, the product made with the 14-hour procedure did have better stability characteristics than that made with the 48-hour procedure.
Bennett
P S
PS
Merck Pharmaceutical Manufacturing Division, Division of Merck & Co., Inc., West Point, PA 19486.
Maigetter
R Z
RZ
Olson
M G
MG
Provost
P J
PJ
Scattergood
E M
EM
Schofield
T L
TL
D019433:Chickenpox Vaccine; D004355:Drug Stability; D005612:Freeze Drying / Q000379:methods*; D014645:Herpesvirus 3, Human / Q000276:immunology*; D011312:Pressure; D013696:Temperature; D013997:Time Factors; D014765:Viral Vaccines / Q000302:isolation & purification*; D014867:Water / Q000032:analysis
D019433:Chickenpox Vaccine; D014765:Viral Vaccines; D014867:Water