1. Storage and Handling: Science to Policy
Howard Backer, MD, MPH
Chief, Immunization Branch
Sandra Jo Hammer, RN, PHN
Nurse Consultant
Steve Vantine, LVN
Senior Field Representative Bay Area
California Department of Public Health

2. Hypothesis Objectives
Storage and handling is an important, underappreciated problem. Policies and recommendations could be better aligned with available science.
Objectives
Evaluate inconsistencies between current storage and handling recommendations and science
Apply industry technology to storage unit recommendations
Propose policy options for storage recommendations and provider accountability

3. "This is a substantial problem that needs to be addressed through prevention…”
Lance Rodewald
44% (95% CI: 35.79, 51.23) of offices had at least 1 documented storage problem
Bell KN, et al. Pediatrics, 2001
In January 2008, McKesson logged 117 instances of non-viable vaccine due to the cold chain process or temperature monitor.
2007 New Mexico loss of $4 Million
St. Cloud, MN, revaccination 8,600 patients

4. Refrigeration Problems Extrapolation to state
Documented Losses By Category 2006 San Francisco Bay Area 10 County Region
Category
# of Incidences
Loss
(dollars)
Refrigeration Problems 16
$42,958.00
Shipping/
Receiving 4
$34,772.00
Improper
Storage 6
$187,133.00
Expired
Vaccines 51
$127,289.00
Total
Losses 77
$392,717.00
Extrapolation to state
$2,352,426.00
Which are storage and handling?

5. Vaccine Inventory Removed from Clinic X med size due to Refrigeration Problem 10/26/06
DOSES
PRICE/DOSE
TOTAL COST
IPV
810
$11.06
$8,958.60
DTAP
680
$13.25
$9,010.00 TD
$17.38
$11,818.40
TDAP
420
$30.75
$12,915.00
HIB
600
$8.12
$4,872.00
HPV (Gardisil)
150
$96.75
$14,512.50
MMR
640
$17.60
$11,264.00
HEP B (GSK)
800
$9.10
$7,280.00
HEP B (MERCK)
770
$9.50
$7,315.00
HEP A
460
$12.25
$5,635.00
PCV
310
$62.14
$19,263.40
DTAP/HEP B/IPV
$47.25
$19,845.00
MCV 4
185
$73.09
$13,521.65
TOTAL
6925
$146,210.55

6. "We just didn't notice it" (Clinic administrator)
The refrigerator at the clinic repeatedly dropped below freezing over a 17-month period in 2005 and 2006
"We just didn't notice it" (Clinic administrator)
Both of these providers documented similar out of range temperatures for at least 6 months

7. Freeze Sensitivity of Vaccines
Freezing may cause a significant reduction of potency due to dissociation of aluminum adjuvant
The HBsAg antigen must remain bonded to the alum adjuvant to confer protection against hepatitis B.
“…Hepatitis B vaccine loses its immunological potency upon freezing or freeze-drying.”
Freezing point is -0.5C
Diminsky D, et al. Vaccine18 (2000)

8. General Recommendations on Immunization, 2006
A combination refrigerator/freezer unit sold for home use is acceptable for storage of limited quantities of vaccines if the refrigerator and freezer compartments each have a separate external door.
vaccines should not be stored on the top shelf near the cold air outlet from the freezer to the refrigerator
What is limited quantities?
Separate doors do not assure separate cooling systems.
Not all cold air outlets are on or near top shelf
Cold air falls, pooling in the boottom.

9. Limitations of Domestic Refrigerators
Domestic fridges have different temperature zones.
Compressor blows cold air from the freezer to the fresh food sections
Vaccine storage space is very limited in modified domestic refrigerators
Need space from walls, cold plate, for air circulation
Proceedings of the National Vaccine Storage Workshop, Brisbane 2004

10. 38.5 41.7 37.4 31.2 Air vent 29F 803 doses $32,000 of vaccine
Usable space is approximately 30% of volume
Do not use top or bottom shelves
Leave 3” on each side and back wall

11. Provider trying to organize but not getting correct information

12. Inventory, Value, and Volume
Practice size
Value of vaccine inventory
Cu ft of refrigerator
Optimal frig size
cu ft
Small
$19,945 12 16
Small-medium
$45,738
(1,114 doses) 18 26
Medium
$131,086 24 34
Large
$1,073,464 80 63

13. VFC Provider Operations Manual Q&A, Feb 2008
Dormitory-style refrigerators should only be used to store a clinic's single-day supply of refrigerated vaccines…. 
Dormitory-style refrigerators are not adequate for long-term or permanent storage of biological products because they do not maintain appropriate temperatures.

14. “Dorm” Style Frig

15. General Recommendations on Immunization, 2006
Refrigerators without freezers and stand-alone freezers usually perform best
single-purpose units sold for home use are less expensive alternatives to medical specialty equipment

16. MidMark under counter medical unit sold by McKesson: unusable because vaccine froze in the back and dripping condensation

17. General Recommendations on Immunization, 2006
“After the vaccine has been moved, determine if the vaccine is still useable by contacting the manufacturer or state/local health department.” Do we call freeze sensitive vaccines damaged at 32º or only when below 32º? New Mexico $4 Million loss—the vaccine was found to be at 32°F. No attempt was made to evaluate vaccine viability.

19. Stability of common vaccines
Freezing
Tetanus, diphtheria toxoids
> 3yrs
Months
Weeks;
53C--days
Unstable
Hepatitis B
> 4 yrs
Weeks
45C--days
MMR
2 yrs
> 1 month
> 1 week
Pertussis
18-24 months
2 weeks
1 week
≥10% loss of potency/day
IPV
1-4 years
Little data
Conjugate vaccines
> 2 years
No data
Possibly unstable
Unstable, if aluminum adjuvant
Polysacc-haride
2 years
Weeks to months
Add reference

20. WHO Recommendations Short term
Ensure that frozen icepacks are conditioned
You can hear water when shaken (15 to 45 minutes, depending on room temperature)
Medium term (currently being adopted by WHO):
Create a “two temperature” cold chain
Freeze-sensitive vaccines transported with chilled water packs and/or at ambient temperature (without ice or icepacks)
Heat-sensitive vaccines (Measles, OPV, BCG) transported with frozen icepacks (No need to condition them!)

21. Freezing irreversibly reduces vaccine potency
Tetanus vaccine (in DPT, DT, TT, Td)
Pertussis vaccine (in DTP)

22. Recommendations
Develop science-based recommendations for storage and handling and management of vaccine and patients
NIP, AIM, NVAC, IOM, ACIP, to participate in consensus conference
Obtain or require stability data from vaccine manufacturers, especially for freeze threshold
Fund or encourage vaccine thermal research
Develop rational revaccination guidelines
Standards for purpose built equipment

23. Proceedings of the Brisbane 28 – 30 June 2004
National Vaccine Storage Workshop
Andrew Langley Sandi Grant (editors)
Brisbane
28 – 30 June 2004

24. Recommendations (2)
Set rational, effective, uniform storage guidelines and policy that account for volume and value of vaccine
Collect uniform data on vaccine loss
Exert market influence on vaccines and packaging
Require vaccine vial monitors for improved monitoring during shipment and storage

25. Purpose-built fridges
Superior temperature uniformity: Designed to keep the temperature at a set point between 2°C and 8°C
Glass doors Digital control
Food industry far ahead of vaccine/biologics
All usable space

26. CDPH Storage and Handling Quality Improvement Activities
New VFC policies for provider responsibility to replace vaccines and inadequate storage units
Develop specifications and identify specific options/recommendations for storage units
On-line training in vaccine management and administration
VFC quality improvement tools

27. Solid bins promoted by pharma co (sanofi) retain cold, esp if out of packaging.

28. CA VFC Storage and Handling Policy
Prioritize changes by provider volume, vaccine inventory, and vaccine loss
High volume (2000 doses/year)
Frig and freezer only units required
Medium volume ( doses/year)
Allow existing combination units if meet specifications
Low volume (less than 500 doses/year)
All combination units that meet specifications AND purpose built under counter units without exposed coils

29. We must collaborate and use the best scientific evidence to develop correct, uniform and effective policies and recommendations for storage and handling of vaccines.
41-43F
If the food and beverage industry can do it, so can our national vaccine program!