A discussion of freeze/thaw physics, consideration for why appropriate levels of thermal processing is critical to desired results http://pharmequipment.com/products/#BLAST_AND_CONTROLLED

1. Farrar Scientific Corp
Information sharing on freeze/thaw
physics: ISPE Jan 2018
Jan 25, 2018

2. Presentation Goals
 Compared to Storage Freezers and ULT
freezers, how do ‘Rate’ chambers differ
 1st pass physics- key on the physics we can
manipulate for a desired result
 Example: product load and location
independence applied to a specified/target
solid phase freeze rate
 Q/A

3. Storage vs. Rate Freezer
 Storage freezer
Tamb
Q'product
Tcntl
insulation
Product
Q' wall = (Tamb - Tpcm)/ Rwall
(ideal package)
Refrig system
1st Law Applied to control volume of the storage chamber enclosure
Energy In to product - Energy Out of package = Energy Stored
E'in - E'out = E'stored
Q'wall - Q'refr = E'stored
Q'wall = Q'refr (with a little margin for door openings)

4. Storage vs. Rate Freezer
 Storage Performance Interests
 Control temperature
 Temperature uniformity
 Recovery from a door opening or reserve
capacity

5. Storage vs. Rate Freezer
 Storage Performance non-interests
 Changing the temperature of the product
(especially not a phase change)
 Dynamics of how energy exchanges
between product and ambient
 Thawing rates i.e. increasing the
temperature of the product

6. Storage vs. Rate Freezer
 Rate Chamber
Q'blower
Q'wall
This area is for
the machine section
Apply 1st law to the enclosure
Energy in - Energy out = Energy Stored
(Q'wall + Q'blower) - Q'refr = (- Q'product )
Q' refr = Q'product + Q'wall + Q'blower
BI wheel
motor
door
Refrigeration machine
section
Q'refr
Product
Q'product

7. Storage vs Rate Freezer
 Rate interests
 Product temperature
 Rate of product temperature change in both
cooling and warming

8. Storage vs Rate Freezer
 Rate Application interests :
 Temp and uniformity as previous
 Add:
 Product temperature, Tproduct, and dTprod/dt
as affected by
 Energy exchange at product/medium interface i.e. the
heat transfer at the product
 Thermal conductivity between the medium (air, water,
or refrigerant)
 ΔT = Tmedium – T product
 Thermal resistance between medium and product

9. Summary ‘Storage’ vs ‘Rate’
 Ambient or ‘storage space’ temp vs ‘Product Temperature’
 Storage applications typically address static conditions of the ambient
surrounding the product. Rate applications address rate of change of the
product temp (dynamic by nature)
 Product energy is typically the dominant load in a Rate application.
 A storage chamber application using air as the medium (walk-in or ULT
freezer) will have an air flow rate typically measured in 0.5 to 1.5
exchanges per minute. A ‘Rate’ chamber exchange air at 1 exchange per
second.
 Interior volume of a storage chamber will be large compared to the
volume of the conditioning equipment. A rate application will have
conditioning equipment approximately the same size as the interior
volume.

10. Product ‘Package’
dx
Tair (t)
(Tair -Tprod)
Q'prod = U*A* (Tair - Tprod) = -----------------
Rtotal
Tprod (t)

11. Product ‘Package’ : Model of typical ‘product’ or ‘package’
V, Tair
dx
External shell
container
product container
product @ solid
phase
product @
liquid phase

12. Product Package: Focused look at section ‘dx’
dx Tair
Tair, Vair temp
resis= O(1 or 2) convection
conduction
Contact gap or resistance cond/conv?
resis= O(1 or 2)
conduction
conduction
O(0)
conduction
O(0)
shell resis=O(1)
container resis=O(0)
solid phase
resis= O(0)
liquid phase
resis= O(0)
Tcore
Q' (energy flow
rate)

13. Package evaluation: Analytical
perimeter path for energy
Ambient temperature= Tamb
Tp (product temp)
Face path for energy
bag 1
bag/shell 2 Air 1
Air 2

14. Package Evaluation : Analytical
Tamb
convective resistance @ outer surface
conduction resistance of bag 2
conductive resistance of air 2
conductive resistance of bag1
conductive resistance of air1
conductive resistance of product dish
Tamb
Tproduct
Face path
Perimeterpath

15. Package Evaluation : Analytical
Perimeter path
Tamb
Tproduct
face path
conductive
resistanceof
product
conductiveresistance
ofair1
conductiveresistance
ofbag1
conductiveresistance
ofaIr2
conductiveresistance
ofbag2
convectiveresistance
atexterior

16. Package Evaluation : Analytical
Series/Parrallel resistors simplify to:
Tproduct Tamb
Rtotal

17. Package Evaluation: Analytical

18. Package Evaluation: Experimental
 Unique feature of the time constant
approach … reaches 63% final result
in one time constant.
 Example: Product originally at a uniform
temperature of 60oC enters a controlled
space at 10oC. At t= 1.0 Ƭ, the product
temperature will have changed 31.5oC
(0.63 x 50oC).

19. Package Evaluation: Experimental
 A couple of cautions regarding the use of the time
constant approach
 Lumped heat capacitance model
 Can’t span a phase change
 Does not provide detail of the dominant resistance, only the
overall thermal resistance
 Positive aspects of using the time constant approach
 Good for package-to-package comparison
 Works particularly on single use bags

20. Application: Example
 Targets
 30L bag with 16L fill
 From -5oC to -35oC  0.13 to 0.94oC/min
 Goals:
 Determine simple profile to achieve target
 Evaluate location and load variance

21. Application: Example
 Single bag orientation in unit

22. Application: Example

23. Application: Example: Test 1
 Single bag: 1st
 Input and output profile
 Cooling Rate (table)

24. Application: Example: Test 2
 Single bag: 2nd
 Input and output profile
 Cooling rate (table)

25. Application: Example: Test 3
 (8) bag orientation

26. Application: Example : Test 3
 8 bag test
 Input and output profile
 Cooling rate (table)

27. Application: Example: Test 4
 8 bag test (increase rate)
 Input and output profile
 Cooling rate (table)

28. Application: Example: take-away
 This example showed load
independence using only step changes
in freeze mode only
 The Bio-Process paper goes on to show
location independence and similar
approach for the thawing process. Link
on web site.

29. Q&A
Margaret Stava mstava@pharmequipment.com mobile 909-784-8993
Sylvain Riendeau sriendeau@farrarscientific.com mobile 740-350-8269
Scott Farrar sfarrar@farrarscientific.com mobile 740-706-1252

30. Backup Material
Insert any detail information after
this slide

31. Ideal binary Tx phase diagram
Ta,frz
liquid
Termperature
liquid/solid
solid
Tb,frz
xa=1 composition xa=0
xb=0 xb=1
outer layer, rich a inner layer, rich b

32. Equipment photos

34. Other related graphs

35. ULT Chamber performance: freeze profile
130723 23cuft -86°C ULT Freezer
4 ASI 16L Bags in Plastic Compression Rack Freeze Profile
Product Temperatures
-100.00
-80.00
-60.00
-40.00
-20.00
0.00
20.00
40.00
0 500 1000 1500 2000 2500
Time "Minutes"
Temperature"°C"
Cabinet Air"°C"
Top Bag"°C"
Top Mid Bag "°C"
Bot Mid Bag "°C"
Bot Bag"°C"

36. Rate Chamber performance: freeze profile
130729 Rate Chamber
4 ASI 16L Bags in Plastic Compression Rack Freeze Profile
Product Temperatures
-50
-40
-30
-20
-10
0
10
20
30
40
0 500 1000 1500 2000 2500
Time "Minutes"
Temperature"°C"
Cabinet Air"°C"
Top Bag"°C"
Top Mid Bag"°C"
Bot Mid Bag"°C"
Bot Bag"°C"

37. Chamber Rate performance: thaw profile
130802 Rate Chamber
4 ASI 16L Bags in Plastic Compression Rack Thaw Profile
Product Temps
-50.00
-40.00
-30.00
-20.00
-10.00
0.00
10.00
20.00
30.00
40.00
0 500 1000 1500 2000 2500
Time "Minutes"
Temperature"°C"
Cabinet Air
Top Bag
Top Mid Bag
Bot Mid Bag
Bot Bag

38. Rate Chamber performance: freeze profile
130722 Rate Chamber
7 ASI 16L Bags in Plastic Compression Rack Freeze Profile
Product Temperatures
-40.00
-30.00
-20.00
-10.00
0.00
10.00
20.00
30.00
0 500 1000 1500 2000 2500
Time "Minutes"
Temperature"°C"
203 <Bag 1 Temp> (C)
204 <Bag 2 Temp> (C)
205 <Bag 3 Temp> (C)
206 <Bag 4 Temp> (C)
207 <Bag 5 Temp> (C)
208 <Bag 6 Temp> (C)
209 <Bag 7 Temp> (C)

39. Rate Chamber performance: thaw profile
130723 Rate Chamber
7 ASI 16L Bags in Plastic Compression Rack Thaw Profile
Product Temperatures
-40.00
-35.00
-30.00
-25.00
-20.00
-15.00
-10.00
-5.00
0.00
5.00
10.00
15.00
20.00
25.00
30.00
35.00
0 500 1000 1500 2000 2500
Time "Minutes"
Temperature"°C"
110 <Cab Air> (C)
203 <Bag 1 Temp> (C)
204 <Bag 2 Temp> (C)
205 <Bag 3 Temp> (C)
206 <Bag 4 Temp> (C)
207 <Bag 5 Temp> (C)
208 <Bag 6 Temp> (C)
209 <Bag 7 Temp> (C)

40. Rate Chamber performance: freeze profile
130724 Rate Chamber
9 ASI 16L Bags in Plastic Compression Rack Freeze Profile
Product Temperatures
-40.00
-35.00
-30.00
-25.00
-20.00
-15.00
-10.00
-5.00
0.00
5.00
10.00
15.00
20.00
25.00
30.00
0 500 1000 1500 2000 2500
Time "Minutes"
Temp"°C"
203 <Bag 1 Temp> (C)
204 <Bag 2 Temp> (C)
205 <Bag 3 Temp> (C)
206 <Bag 4 Temp> (C)
207 <Bag 5 Temp> (C)
208 <Bag 6 Temp> (C)
209 <Bag 7 Temp> (C)
210 <Bag 8 Temp> (C)
211 <Bag 9 Temp> (C)

41. Rate Chamber performance: thaw profile
130725 Rate Chamber
9 ASI 16L Bags in Plastic Compression Rack Thaw Profile
Product Temperatures
-40
-35
-30
-25
-20
-15
-10
-5
0
5
10
15
20
25
30
0 500 1000 1500 2000 2500
Time "Minutes"
Temperature"°C"
203 <Bag 1 Temp> (C)
204 <Bag 2 Temp> (C)
205 <Bag 3 Temp> (C)
206 <Bag 4 Temp> (C)
207 <Bag 5 Temp> (C)
208 <Bag 6 Temp> (C)
209 <Bag 7 Temp> (C)
210 <Bag 8 Temp> (C)
211 <Bag 9 Temp> (C)

42. Rate Chamber w/ augmented compression rack
130801 Rate Chamber
4 ASI 16L Bags in Aluminum Compression Rack Freeze Profile
Product Temperatures
-40.00
-35.00
-30.00
-25.00
-20.00
-15.00
-10.00
-5.00
0.00
5.00
10.00
15.00
20.00
25.00
30.00
0 500 1000 1500 2000 2500
Time "Minutes"
Temperature"°C"
110 <Cab Air> (C)
203 <Top Bag> (C)
204 <Top Mid Bag> (C)
205 <Bot Mid Bag> (C)
206 <Bot Bag> (C)

43. ULT Chamber performance: thaw profile
130724 ASI
16L ASI Bag in Plastic Compression Rack Lab Ambient Thaw Profile
Product Temperature
-50
-40
-30
-20
-10
0
10
20
30
40
0 500 1000 1500 2000 2500
Time "Minutes"
Temperature"C"
Ambient
Bag Temp

44. Chamber Rate performance: thaw profile
130801 Rate Chamber
4 ASI 16L Bags in Aluminum Compression Rack Thaw Profile
Product Temperatures
-40.00
-35.00
-30.00
-25.00
-20.00
-15.00
-10.00
-5.00
0.00
5.00
10.00
15.00
20.00
25.00
30.00
35.00
0 500 1000 1500 2000 2500
Time "Minutes"
Temperature"°C"
110 <Cab Air> (C)
203 <Top Bag> (C)
204 <Top Mid Bag> (C)
205 <Bot Mid Bag> (C)
206 <Bot Bag> (C)

45. Chamber Rate performance: freeze profile
130730 Rate Chamber
7 ASI 16L in Aluminum Compression Rack Freeze Profile
Product Temperatures
-40.00
-35.00
-30.00
-25.00
-20.00
-15.00
-10.00
-5.00
0.00
5.00
10.00
15.00
20.00
25.00
30.00
0 500 1000 1500 2000 2500
Time "Minutes"
Temperature"°C"
110 <Cab Air> (C)
203 <Bag 1 Temp> (C)
204 <Bag 2 Temp> (C)
205 <Bag 3 Temp> (C)
206 <Bag 4 Temp> (C)
207 <Bag 5 Temp> (C)
208 <Bag 6 Temp> (C)
209 <Bag 7 Temp> (C)

46. Chamber Rate performance: thaw profile
130731 Rate Chamber
7 ASI 16L in Aluminum Compression Rack Thaw Profile
Product Temperatures
-40.00
-35.00
-30.00
-25.00
-20.00
-15.00
-10.00
-5.00
0.00
5.00
10.00
15.00
20.00
25.00
30.00
0 500 1000 1500 2000 2500
Time "Minutes"
Temperature"°C"
110 <Cab Air> (C)
203 <Bag 1 Temp> (C)
204 <Bag 2 Temp> (C)
205 <Bag 3 Temp> (C)
206 <Bag 4 Temp> (C)
207 <Bag 5 Temp> (C)
208 <Bag 6 Temp> (C)
209 <Bag 7 Temp> (C)

47. Summary: Freeze/Thaw Profiles ULT vs Rate Chamber
Freeze and Thaw Rate comparison- ULT vs. Rate Chamber w/ Plastic container
No. Bags ULT Freezer Rate Chamber
Frz time Thaw time Frz time Thaw time
1 940 1300 625 545
4 1414 793 614
7 851 741
9 890 709
Test conditions notes:
1. ASI 30 l. tufted bag with 16l fill of water
2. Frz time = 25o
C to core temp of -30o
C (minutes)
3. Thaw time = -40o
C to core temp of 5o
C (minutes)
4. ULT thaw in open ambient- static

48. Summary: Freeze/Thaw Profiles ULT vs Rate Chamber
Freeze and Thaw Rate comparison- ULT vs. Rate Chamber w/Enhanced container
No. Bags ULT Freezer Rate Chamber
Frz time Thaw time Frz time Thaw time
1 560 568 253 267
4 1226 350 265
7 468 413
Test conditions notes:
1. ASI 30 l. tufted bag with 16l fill of water
2. Frz time = 25o
C to core temp of -30o
C (minutes)
3. Thaw time = -40o
C to core temp of 5o
C (minutes)
4. ULT thaw in open ambient- static

49.  Fundamental differences between
storage freezers and rate chambers
 Flow rate
 Product vs ambient temperature
 Dynamic vs static (often looking for a 1st
derivative response)
 …..