114
FREEZE—DRYING
for short periods and then only when the residual moisture content of the material being
dried has reached a level, determined experimentally, at which inactivation by heat is
minimized.
'
For our recent studies predicting the stabilities of liquid suspensions of measles virus
in Medium 199 plus additive stored at + 4 °C, we used preparations of virus superior to
those available for our earlier investigations. The predicted changes and actual changes
*
in titers for three lots of suspensions of virus were as follows :
Predicted
EXÊÎËed Actual titer
-
\
Virus
time
Original
at end
at end
Lot
for 1 log
titer
of period
Of perro_d
loss of t1ter
(PFU/ml)
f
diction
of pred1ct10n
__
(days)
0
pre
(PFU/ml)
(PFU/ml)
;.
A—
100
105-2
,
-
104-2
104-3
jÿ:ï
_
B
140
105'8
10.4°8
10‘*'5
‘
Ï f
ci
'
.
110
105-4
104.4
104-3
The excellent correlation between the expected changes in titers and the actual changes
in titers at the end of the calculated peri0d of time required for liquid suspensions of viruses
stored at + 4 °C to lose 1 log of titer,
the direct applicability of the accelerated
'
storage test for predictinglosses in the activities of nonfrozen, nondried, cooled suspensions.
Although the several lots of virus tested were prepared in a similar manner from the same
seed virus, the test as developed can be used successfully for distinguishing between “storage
labile” and “storage stable” suspensions of virus.
_
'
THERMODYNAMIÇ ANALYSIS OF VIRUS INACTIVATION
(In collaboration With our colleague, Dr. V. Damjanoviè, Senior Research Fellow, Department of Pathology, Marquette University School of Medicine and Chief of Section for Freeze-drying, Institute for Sera
and Vaccines, Beograd, Yugoslavia.)
-
:
_
_
Consciously or unconsciously,two
have been imposedon kinetic investigations.
-
First, the actual velocity of a reaction, to render it measurable,
been conned to rela—
tively…narrow
if relevant data were tobe obtained easily, the reacting
systems were restricted Α?° those Which undergo a comparatively small number of simulta—
neous reactions.— In studies of biologicalrreacüons, because a—‘highdegree of complexity is
frequently‘present, it-Çi‘s:gdifcult to simplify :thes‘e‘ processes in a manner such that the
simpliedïtreatment used ‘nh&S a direct relationship to the: unsimplied. natural process.
For—the,
the… data of many velOcity studies have not… beent‘-fu3ablefor kinetic
studies; br for kinetic - interpretation—_, ThuS,
inuence of Various experimental: factors
ong‘the'rat‘es of
the rates of permeation
’Qfëundesirable foreign matter through protective coatings
speCideects:oçpreserv'
of value merely as;
data,—, In
FREEZE—DRYING
for short periods and then only when the residual moisture content of the material being
dried has reached a level, determined experimentally, at which inactivation by heat is
minimized.
'
For our recent studies predicting the stabilities of liquid suspensions of measles virus
in Medium 199 plus additive stored at + 4 °C, we used preparations of virus superior to
those available for our earlier investigations. The predicted changes and actual changes
*
in titers for three lots of suspensions of virus were as follows :
Predicted
EXÊÎËed Actual titer
-
\
Virus
time
Original
at end
at end
Lot
for 1 log
titer
of period
Of perro_d
loss of t1ter
(PFU/ml)
f
diction
of pred1ct10n
__
(days)
0
pre
(PFU/ml)
(PFU/ml)
;.
A—
100
105-2
,
-
104-2
104-3
jÿ:ï
_
B
140
105'8
10.4°8
10‘*'5
‘
Ï f
ci
'
.
110
105-4
104.4
104-3
The excellent correlation between the expected changes in titers and the actual changes
in titers at the end of the calculated peri0d of time required for liquid suspensions of viruses
stored at + 4 °C to lose 1 log of titer,
the direct applicability of the accelerated
'
storage test for predictinglosses in the activities of nonfrozen, nondried, cooled suspensions.
Although the several lots of virus tested were prepared in a similar manner from the same
seed virus, the test as developed can be used successfully for distinguishing between “storage
labile” and “storage stable” suspensions of virus.
_
'
THERMODYNAMIÇ ANALYSIS OF VIRUS INACTIVATION
(In collaboration With our colleague, Dr. V. Damjanoviè, Senior Research Fellow, Department of Pathology, Marquette University School of Medicine and Chief of Section for Freeze-drying, Institute for Sera
and Vaccines, Beograd, Yugoslavia.)
-
:
_
_
Consciously or unconsciously,two
have been imposedon kinetic investigations.
-
First, the actual velocity of a reaction, to render it measurable,
been conned to rela—
tively…narrow
if relevant data were tobe obtained easily, the reacting
systems were restricted Α?° those Which undergo a comparatively small number of simulta—
neous reactions.— In studies of biologicalrreacüons, because a—‘highdegree of complexity is
frequently‘present, it-Çi‘s:gdifcult to simplify :thes‘e‘ processes in a manner such that the
simpliedïtreatment used ‘nh&S a direct relationship to the: unsimplied. natural process.
For—the,
the… data of many velOcity studies have not… beent‘-fu3ablefor kinetic
studies; br for kinetic - interpretation—_, ThuS,
inuence of Various experimental: factors
ong‘the'rat‘es of
the rates of permeation
’Qfëundesirable foreign matter through protective coatings
speCideects:oçpreserv'
of value merely as;
data,—, In