Haemonetics Anticoagulant Citrate Phosphate Double Dextrose Solution (CP2D)

Haemonetics Corporation

Haemonetics Anticoagulant Citrate Phosphate Double Dextrose Solution (CP2D)

FULL PRESCRIBING INFORMATION: CONTENTS*

• Instructions for Use
• I. Indications for Use
• Dosage Form
• Dosage and Administration:
• III. Clinical Data
• IV. Warnings and Cautions
• Side Effects:
• Drug Abuse / Dependence:
• Overdosage:
• How Supplied:
• Storage and Handling:
• Package Label
• Product Label - Package

FULL PRESCRIBING INFORMATION

Instructions for Use

For use with Haemonetics Apheresis Devices
Rx Only

Products: Anticoagulant Citrate Phosphate Double Dextrose (CP2D)
and Additive Solution Formula 3 (AS-3)

Company:
Haemonetics Corporation
400 Wood Road
Braintree, MA 02184

I. Indications for Use

The Haemonetics 250mL Anticoagulant Citrate Phosphate Double Dextrose (CP2D)
and 250mL Additive Solution Formula 3 (AS-3) nutrient solution are intended to be
used only with automated apheresis devices for collecting human blood and blood
components. The anticoagulant solution is metered by the apheresis machine into
the collected whole blood. It is not to be infused directly into the donor. After the
anticoagulant is used, the bag in which it was contained is discarded. When
collecting plasma in the RBCP protocol, the plasma is collected into an empty plasma
collection bag. One hundred milliliters (100ml) of AS-3 is transferred into one RBC
collection bag when using the RBCP protocol or 2 separate bags when using the
2RBC protocol. AS-3 solution provides nutrients to keep the red blood cells viable for
42 days when refrigerated.

CP2D is also indicated for the collection of FFP and PF24 plasma, collected and
stored plasma collected using the 822, 822-2P and 822F-2P disposable sets may be
frozen within 8 hours (FFP) or within 24 hours which includes 8 hours room
temperature storage and 16 hours refrigeration storage (PF24).

The 300mL AS-3 is used in conjunction with automated red blood cell washing
devices. AS-3 serves as the nutrient solution for storage of the red blood cell product
after deglycerolization. The red blood cells are washed using the Model 215 System.
AS-3 is used for priming the disposable and for the last wash of the red blood cells.
The washed cells are then re-suspended in 100mL of the AS-3 before transfer into a
product collection bag or storage bag. Additive Solution Formula 3 (AS-3) provides
nutrients to keep the washed red blood cells viable for up to 14 days after washing
when refrigerated.

Neither the CP2D nor the AS-3 container is used for the storage of blood or blood
components.

Dosage Form

The container for all CP2D and AS-3 solutions is a flexible polyvinyl chloride (PVC)
bag sized for holding the appropriate amount of solution. The bag has a single port
that is used for bag filling. The port is sealed after filling with a male luer assembly
(CP2D) or female luer assembly (AS-3). Both the male and female luers are gamma
irradiated prior to use. The plastic bag is contained in an overwrap which is added
prior to sterilization.

The formulations for these products are as follows:

Citrate Phosphate Double Dextrose Solution (CP2D)
Each 100 mL contains:
Citric Acid (Monohydrate), USP 0.327 g
Sodium Citrate (Dihydrate), USP 2.630 g
Monobasic Sodium Phosphate (Monohydrate), USP 0.222 g
Dextrose (Anhydrous), USP 4.640 g

Additive Solution 3 (AS-3)
Each 100mL contains:
Citric Acid (Monohydrate), USP 0.042 g
Monobasic Sodium Phosphate (Monohydrate), USP 0.276 g
Sodium Chloride, USP 0.410 g
Adenine, USP 0.030 g
Dextrose (Anhydrous), USP 1.000 g
Sodium Citrate (Dihydrate), USP 0.588 g
containing 15 mEq of Sodium.

Dosage and Administration:

CP2D Anticoagulant Solution and AS-3 Solution may be used with Haemonetics
apheresis devices. See the Haemonetics Operation Manual for full operating
instructions.

Prior to use of the solutions, check the solutions for leaks by squeezing each of the
bags firmly. If leaks are found, discard the solution.

III. Clinical Data

Studies of the effectiveness of 250mL CP2D and 250mL AS-3 made by Haemonetics
Corporation Union, South Carolina facility included in vivo survival data in healthy
subjects at one test site and in vitro characterization of stored red blood cells at
three test sites.

Haemonetics Clinical Evaluation #95012, involved autologous in vivo recovery and
survival studies, and in vitro red blood cell characterization conducted at a single
site. RBC results collected with Haemonetics CP2DjAS-3 were compared to crossover
controls of manually collected RBCs from the same donors using CP2D/AS-3 made by
Medsep Corporation (crossover manual controls). In addition, results were
compared to data from other RBC apheresis donors using CP2D/AS-3 solutions
manufactured by MedSep (unmatched apheresis controls). Test parameters included
hematocrit, hemoglobin, RBC and WBC counts, ATP levels, pH, supernatant
potassium, free hemoglobin, supernatant glucose levels, and product weight. The
RBC quality of test units after 42-day storage was equivalent or slightly superior to
those of the control units. RBCs collected by the two different collection protocols
(Red Blood Cells with or without Plasma) showed no significant differences in terms
of RBC quality and red blood cells from all groups met FDA and AABB guidelines for
24-hour recovering at 42 days storage.

Study #98001 was performed using 250mL CP2D and 250mL AS-3 to confirm, in
vitro, the results of Clinical Evaluation #95012. Three test sites each performed three
RBCP and three 2RBC apheresis procedures using the MCS+ LN8150 and associated
collection sets. In addition, each site collected six manual whole blood units as
concurrent (unmatched) controls using Medsep sets and prepared RBCs according to
standard procedures.

In vitro tests of red blood cell functional and physical integrity were conducted at
Days 0 and 42 of storage. All plasma units from the RBCP and manual procedures
were evaluated on Day 0 for in vitro product characteristics. Group t-tests (two
tailed) were performed to examine any statistically significant differences between
the properties of apheresis and manual RBCs. Statistically significant differences
(plactate levels, hematocrit, pH, and supernatant potassium were not considered
clinically relevant because these parameters have not been found to correlate
significantly with the in vivo 24 hour percent recovery.

The results from this study confirmed the observations from Clinical Evaluation
#95012. The quality of stored RBC products collected by apheresis is similar to RBC
products collected manually. A difference in ATP and hemolysis levels, both after
processing and on day 42 of storage, for the apheresis units were not statistically
significant when compared to ATP and hemolysis levels from manually collected
RBCs and were similar to historicai reference values.

AS-3 300ml was used in conjunction with an automated closed system, the
Haemonetics Model 215 (now called the ACP) in Clinical Evaluation #97002. Five test
sites were used in this study. 100 samples were tested in vitro and 30 in vivo. Red
blood cells derived from CPDA-1 whole blood units were used. AS-1 red blood cells
were used as a control. A total of 140 red blood cell units were glycerolized and
deglycerolized. The in vitro RBC quality and in vivo RBC viability data obtained on
these units demonstrate that red cell units glycerolized and deglycerolized using the
Model 215 System and resuspended in 300ml AS-3 solution manufactured by
Haemonetics, Union, South Carolina are processed in a closed system and can be
stored for 15 days at 4°C.

Clinical report TR-CLN-100229-A was conducted to support the use of CP2D for the
collection of FFP and PF24 {plasma collected and stored Plasma collected using the
822, 822-2P and 822F-2P disposable sets may be frozen within 8 hours (FFP) or
within 24 hours which includes 8 hours room temperature storage and 16 hours
refrigeration storage (PF24). The following tables provide a summary of the results
of this evaluation.

Note: Table 1, Table 2, and Table 3 below demonstrate the results of a clinical
study conducted for various coagulation factors on plasma that was frozen within
8 hours (FPP) versus plasma frozen within 24 hours, which includes 8 hours
room temperature storage and 16 hours refrigeration storage (PF24).

As noted in Table 1 below, Significant differences were observed between PF24 and
FFP for assays Prothrombine Time, Partial Thromboplastin Time, FVlla, and
FVIII.

Table 2 provides the results for Plasma Sample A, which was an outlier and
subsequently excluded from the analysis.

Table 3 provides a summary of how many samples tested in each group differed by
>20% when FFP and PF24 were compared.

*Sample size = 58. The outlier pair was excluded from the analysis based on the statistical criteria or laboratory errors.

One sample (Plasma Sample A) showed significantly increased levels for Factor Vlla, F1.2, and
TAT (Table 2). This data was excluded from Table 1 since the values for Factor Vlla and F1.2
were more than 4 SD from the mean. The TAT was not more than 4 SD from the mean but
was significantly higher in PF24 as compared to FFP. While other parameters in this sample
did not show significant differences when compared to the control FFP the FDA could not
exclude the possibility that the activation found in the PF24 sample was related to the
preparation procedure. The rate of such event occurrence was unknown and, based on
review of published values for PF24 products, is most likely very rare. The clinical
significance of the elevated markers of clotting activation for transfusion recipients is
undetermined.

IV. Warnings and Cautions

Contraindications:
None known

Precautions for use:
• Solutions are NOT INTENDED FOR DIRECT INFUSION.
• Do not use if particulate matter is present or if the solution is cloudy
Note: Some opacity of the plastic container due to moisture absorbance by
the PVC during the sterilization process may be observed. This is normal and
does not affect the quality or the safety of the product. This white, hazy
appearance will diminish gradually over time. This advice only applies to the
plastic container. Do not use if the solution itself is cloudy or contains
particulate matter.
•Do not use if the container is damaged, leaking or if there is any visible sign
of deterioration.
Note: The over wrap serves as a moisture barrier. Upon removing the
solution bag, small droplets of condensation may be present in the
packaging. This is considered normal. After removing the over wrap gently
squeeze the inner bag which protects the sterility of the solution. Discard if
any leaks are observed or if an excessive amount of solution is noted within
the over wrap.
• Do not reuse solution. Discard any unused or partially used solutions.
• Protect from sharp objects.
• Verify that solutions have been appropriately connected to avoid leaks.
• Do not remove the unit from the overwrap until immediately before use.
• Carry out the apheresis procedure in accordance with the detailed
instructions of the manufacturer of the apheresis device.

Side Effects:

Donors being reinfused with citrated blood or blood components may experience
side effects due to the presence of citrate. Patients being transfused with the blood
components could also experience a reaction to the citrated blood components.
The major symptom experienced by donors is paraesthesia. Should this occur the
reinfusion should be stopped or the reinfusion rate decreased. In the event of
inadvertent bolus of the product administer calcium gluconate.

Drug Abuse / Dependence:

Both solutions are intended to be used only with automated apheresis devices for
collecting human blood and blood components. CP2D is used as an anticoagulant
solution and AS-3 is intended for use a nutrient solution. Neither solution is
intended for direct infusion; neither solution produces a pharmacological effect.

Overdosage:

Both solutions are intended to be used only with automated apheresis devices for
collecting human blood and blood components. CP2D is used as an anticoagulant
solution and AS-3 is intended for use a nutrient solution. Neither solution is
intended for direct infusion.

How Supplied:

250mL CP2D Anticoagulant Solution is supplied in flexible PVC containers with a
sterile, non-pyrogenic fluid path.
250mL and 300mL AS-3 Nutrient Solution is supplied in flexible PVC containers with
a sterile, non-pyrogenic fluid path.

Storage and Handling:

Room temperature (25°C/77°F). Avoid excessive heat. Protect from freezing.

113692-00
RevAA

Package Label

HAEMONETICS®
ANTICOAGULANT CITRATE PHOSPHATE
DOUBLE DEXTROSE SOLUTION
(CP2D)

Intended for use only with automated red cell apheresis devices to collect
red blood cells and plasma (FFP and PF24). See the appropriate Operator’s
manual for additional information and complete usage instructions.

Each 100 mL contains:
Citric Acid (Monohydrate), USP                                      0.327 g
Sodium Citrate (Dihydrate), USP                                   2.630 g
Monobasic Sodium Phosphate (Monohydrate), USP      0.222 g
Dextrose (Anhydrous), USP                                           4.640 g

CAUTION: Not for direct intravenous infusion.
The pouch is a moisture barrier.
Do not use unless solution is clear and no leaks detected.
Single use container. Discard unused portion.
Sterile, nonpyrogenic fluid path.
Rx Only

RECOMENDED STORAGE: Room Temperature (25°C / 77°F)
Avoid excessive heat. Protect from freezing.

L065 DA                                      Product code 455A
Haemonetics Corporation           Lot No.
Braintree, MA 02184 USA            Exp Date

Product Label - Package