Immunotherapy Safety for the Primary Care ... - U.S. Coast Guard

J ALLERGY CLIN IMMUNOL
VOLUME 120, NUMBER 3
Cox et al S53
Phoenix in the summer and Alaska in the winter. The
results of these studies are on file under each manufacturer’s
product licenses. Each study is specific to each
manufacturer because the packaging (eg, use of insulation)
varies from company to company. It is the responsibility
of each supplier or manufacturer to ship allergen
extracts under validated conditions that have been shown
not to adversely affect the product’s potency or safety.
Storing dilute extracts. Summary Statement 34a: More
dilute concentrations of allergy immunotherapy extracts
(diluted greater than 1:10 vol/vol) are more sensitive to the
effects of temperature and lose potency more rapidly than
do more concentrated allergen immunotherapy extracts.
The expiration date for more dilute concentrations should
reflect this shorter shelf life. B
Summary Statement 34b: In determining the allergy
vaccine expiration date, consideration must be given to the
fact that the rate of potency loss over time is influenced by
a number of factors separately and collectively, including
(1) storage temperature, (2) presence of stabilizers and
bactericidal agents, (3) concentration, (4) presence of
proteolytic enzymes, and (5) volume of the storage vial. D
The potency of concentrated allergen immunotherapy
extracts (1:1 vol/vol up to 1:10 vol/vol) when kept at 48Cis
relatively constant and allows the allergen immunotherapy
extract to be used until the expiration date that is present on
the label. Less concentrated allergen immunotherapy
extracts are more sensitive to the effects of temperature
and might not maintain their potency until the listed
expiration date. 249,250
The mixing of other allergens might decrease the loss of
potency with time because the additional allergens might
prevent adherence of proteins to the vial’s glass wall. Thus
highly concentrated extracts are more stable than diluted
ones. Extracts are prepared as aqueous, glycerinated, freezedried,
and alum formulations. Aqueous and glycerin diluents
are compatible for mixing standardized with nonstandardized
products. Lyophilization is used to maintain the
strength of the dry powder, but once the allergen immunotherapy
extract is reconstituted, stabilizing agents, such
as human serum albumin (0.03%) or 50% glycerin, are
needed to maintain potency. 250 Phenol is a preservative
added to extracts to prevent growth of microorganisms.
Phenol can denature proteins in allergen extracts. 251,252
Human serum albumin might protect against the deleterious
effect of phenol on allergen extracts. 251 Human serum
albumin might also prevent the loss of potency within storage
vials by preventing absorption of allergen on the inner
surface of the glass vial. Glycerin is also a preservative. At
a concentration of 50%, glycerin appears to prevent loss of
allergenic potency, 250,253 possibly through inhibition of
the activity of proteolytic and glycosidic enzymes that
are present in certain extracts. However, it is irritating
when injected and should be diluted before beginning immunotherapy.
Recommendations for extract stability are
found in the manufacturers’ product insert sheets. The extract
manufacturers’ package insert advises care when administering
a volume greater than 0.2 mL of an extract in
50% glycerin because of the potential discomfort and pain
TABLE IX. Potency of selected manufacturer’s extracts
currently available
Extract
Potency
Cat hair and pelt 5000 and 10,000 BAU/mL
Dust mite
3000, 5000, 10,000, and 30,000 AU/mL
Bermuda grass 10,000 AU/mL
Short ragweed 1:10-1:20 wt/vol or 100,000 AU/mL
Other grasses* 10,000 and 100,000 BAU/mL
Other pollen
1:10 to 1:40 (wt/vol) or 10,000 PNU/mL
Molds 1:10 to 1:40 (wt/vol) or 20,000
to 100,000 PNU/mL
AU, Allergy unit; BAU, bioequivalent allergy unit; PNU, protein nitrogen unit.
*Perennial rye, Kentucky blue/June, timothy, sweet vernal, redtop, orchard,
and meadow.
it might cause. The pain associated with glycerin increases
in proportion to the glycerin concentration and injection
volume, and the pain is proportional to the total injected
dose of glycerin. 254 However, individual pain perception
can vary substantially. Total glycerin doses of less than
0.05 mL rarely produce clinically important pain.
There have been few studies that have investigated the
potency of dilutions of allergen extract mixture over time.
Expiration dates for allergen extract dilutions are somewhat
empiric and not strongly evidence based. A study
undertaken by the AAAAI Immunotherapy and Allergy
Diagnostic committee designed to study the stability of a
mixture of standardized extracts in 4 conditions of storage
(with and without intermittent room temperature exposure
and diluted in normal saline or human serum albumin)
found that short ragweed at 1:10 vol/vol dilution, as
measured by means of radial immunodiffusion, was stable
in all conditions of storage over 12 months. Dust mite and
cat at 1:10 and 1:100 vol/vol dilution were also stable in all
conditions of storage over 12 months, as measured by an
ELISA assay using an mAb for Der p 1, Der f 1, and Fel d 1.
The expiration date of any dilution should not exceed
the expiration date of the earliest expiring constituent that
is added to the mixture.
IMMUNOTHERAPY SCHEDULES AND DOSES
Summary Statement 35: A customized individual
allergen immunotherapy extract should be prepared from
a manufacturer’s extract or extracts in accordance to the
patient’s clinical history and allergy test results and can be
based on single or multiple allergens. D
An allergen extract is a solution of elutable materials
derived from allergen source materials, such as pollens or
molds. They consist of complex mixtures of proteins and
glycoproteins to which antibodies can bind. Animal
dander contains between 10 and 20 antigens, 255 house
dust mites between 20 and 40 antigens, 256 and pollens between
30 and 50 antigens, 257,258 and fungal extract can
contain as many as 80 antigens. 259
Extracts obtained from extract manufacturing companies
should be called the manufacturer’s extract. Vials of
manufacturer’s extract contain individual or limited