U.S. patent application number 10/472453 was filed with the patent office on 2004-05-06 for process and device for preparing radiopharmaceutical products for injection.
Invention is credited to le Freychet, Christ?egrave, Morelle, Jean-Luc, Philippart, Gauthier.
Application Number | 20040084340 10/472453 |
Document ID | / |
Family ID | 23086861 |
Filed Date | 2004-05-06 |
United States Patent
Application |
20040084340 |
Kind Code |
A1 |
Morelle, Jean-Luc ; et
al. |
May 6, 2004 |
Process and device for preparing radiopharmaceutical products for
injection
Abstract
Method for preparing, packaging and handling an individual dose
of a radiopharmaceutical compound, comprising the following steps:
filling a cartridge (1) with said dose of radiopharmaceutical
compound via a first end, the second end being closed by means of a
component serving as a piston (3); closing said cartridge (1) at
said first end by means of a closure device (2); placing said
cartridge (1) in a radiation shielding device (10), comprising an
inner part (4) and an outer part (5), said inner part serving as
radiation shielding for an operator and said outer part serving as
a transportation shielding container; closing said container by
means of an appropriate shielding lid (6); transporting said
container up to the place at which an injection of said
radiopharmaceutical compound will take place; removing the
shielding lid (6) of the container; fixing a plunger (7) to the
cartridge piston (3); extracting the cartridge and the inner part
(4) of the radiation shielding device (10) from the outer part (5)
serving as a container, and placing injection means (30) on the
cartridge end which has the setting closure device (2).
Inventors: |
Morelle, Jean-Luc; (Liege,
BE) ; Philippart, Gauthier; (Grand-Rechain, BE)
; Freychet, Christ?egrave;le; (Vise, BE) |
Correspondence
Address: |
MERCHANT & GOULD PC
P.O. BOX 2903
MINNEAPOLIS
MN
55402-0903
US
|
Family ID: |
23086861 |
Appl. No.: |
10/472453 |
Filed: |
September 18, 2003 |
PCT Filed: |
April 5, 2002 |
PCT NO: |
PCT/BE02/00050 |
Current U.S.
Class: |
206/365 ;
53/449 |
Current CPC
Class: |
A61M 5/24 20130101; G21F
5/018 20130101; A61M 5/1785 20130101 |
Class at
Publication: |
206/365 ;
053/449 |
International
Class: |
B65B 011/58 |
Foreign Application Data
Date |
Code |
Application Number |
Apr 13, 2001 |
US |
60283619 |
Claims
1. Device to be used in the automated preparation, packaging and
further handling of a radiopharmaceutical compound individual dose,
comprising the following set of elements a cartridge intended to
contain said individual dose, provided at a first end with a
closing element (2) and at a second end by means of a component
serving as a piston (3); a radiation-shielding container (10)
comprising an inner cylinder-like part (4) capable to enclose said
cartridge (1), and an outer cylinder-like part (5), serving as an
additional shielding for transportation, said outer part being
capable to enclose said inner part, said outer part being provided
with a shielding lid (6) a plunger (7) to be fitted to the
cartridge (1) at the time of an injection, while said cartridge is
still inside said inner cylinder-like part (4) of the radiation
shielding container (10), provided with a sliding rod (22) capable
to contact said piston (3) of the cartridge (1), with a push button
(23) and with support wings (25) for the fingers; an injection
means (30) to be fitted to the first end of the cartridge (1) at
the time of an injection, while said cartridge is still inside said
inner cylinder-like part (4) of the radiation shielding container
(4), wherein: the plunger is provided with fixing means (24) to
said inner cylinder-like part (4) of the radiation shielding
container (10); the closing element (2) is a septum, preferably an
elastomeric stopper and the injection means (30) is capable to
pierce the closing element (2) of the cartridge, (1) in a sterile
manner and to enter in contact with said radiopharmaceutical
compound.
2. Device according to claim 1, wherein the fixing means (24) of
the plunger comprise a rapid attachment device such as screwing or
clipping means.
3. Device according to claim 1, wherein said injection means (30)
comprises inwardly a spike (31) and outwardly a needle (33) or a
luer fitting (34) in connection to the spike (31), preferably of
the VACUTAINER.RTM. type.
4. Device according to claim 1, wherein said spike (31) is
protected in a sterile manner by an elastomeric sleeve (32) until
said closing element (2) of cartridge (1) has been pierced.
5. Device according to claim 3 or 4, wherein the injection means
elements (30) are covered by a protective cap (41,42) before
use.
6. Device according to claim 1, wherein the injection means (30)
are designed for rapid attachment to the cartridge such as screwing
or clipping.
7. Device according to claim 1, wherein said cartridge is a
standard cartridge of the type used for the packaging of
insulin.
8. Device according to claim 1, wherein it is suitable for using a
short-lived Positron Emission Tomography (PET) compound.
9. Device according to claim 1, wherein said inner cylinder-like
part (4) is made of high density metal such as tungsten or a
tungsten-based alloy.
10. Device according to claim 1, wherein said outer cylinder-like
part (5) and said shielding lid (6) are made of a high density
metal such as lead, tungsten, a high lead content alloy or a high
tungsten content alloy.
11. Device according to claim 1, wherein a see-through window (20)
is provided in the shielding (4).
12. Use of the device, according to anyone of claim 1 to 11, for
automatically preparing, packaging and handling an individual dose
of a radiopharmaceutical compound, comprising the following steps:
filling the cartridge (1) with said dose of radiopharmaceutical
compound via its first end, its second end remaining closed by
means of the piston (3); closing said cartridge (1) at said first
end by means of the closure device (2); placing said cartridge (1)
in the radiation shielding device (10), comprising an inner part
(4) and an outer part (5), said inner part serving as radiation
shielding for an operator and said outer part serving as a
transportation shielding container; closing said shielding
container (5) by means of the shielding lid (6); transporting said
container up to the place at which an injection of said
radiopharmaceutical compound will be carried out; removing the
shielding lid (6) of the container; fixing the plunger (7) to the
inner part (4) of the shielding device (10); extracting the inner
part (4) of the radiation shielding device (10), enclosing the
cartridge, from the outer part (5), and placing injection means
(30) on the cartridge end which is provided with the closing
element, (2), said cartridge (1) being still enclosed in the inner
part (4) of the shielding device (10).
Description
FIELD OF THE INVENTION
[0001] The present invention is related to practices in nuclear
medicine, and in particular to a process for preparing
radiopharmaceutical products for injection.
STATE OF THE ART
[0002] The development of nuclear medicine, in particular in the
field of diagnosis by positron emission tomography (PET), makes it
necessary to review the usual methods for producing, packaging and
handling radiopharmaceutical substances intended for administration
to patients.
[0003] Radiopharmaceutical substances are chemical compounds
labeled with radioactive isotopes, intended for medical use.
Problems of existing methods and equipment are mainly due to the
increase in the use of isotopes whose radiation energy is
relatively high, and by the fact that a higher level of automation
is required due to the short half-life of said isotopes.
[0004] Dose fractionation systems are available on the market. They
make it possible to dilute a base radiopharmaceutical product, to
prepare the dilute solution in vials and to place these vials in
radiation shielding for transportation. The vials are then
delivered to the nuclear medicine departments of hospitals. Such
devices are mainly used by radiopharmaceutical production
companies.
[0005] Vial di systems allow to provide radio-pharmaceutical in
vials according to the common practice in mos pean hospitals: the
vials may contain doses for several examinations or for several
patients. The injection is prepared by the hospital staff: the
doctor or a member of his specialist staff fills a syringe for each
patient or for each examination from a "multi-dose" vial, that is
to say a vial that may contain enough substance for several
examinations or for several patients. This handling exposes the
hospital staff on a repeated basis, giving rise to an appreciable
cumulative exposure. This dose is generally limited by performing
the operation behind lead protection such as a radiation-shielded
glove box. The syringe may be fitted into a syringe radiation
shielding.
[0006] The practice is different in the United States: hospitals
receive the syringes pre-filled with the individual "patient-dose".
The filling of these syringes is carried out in "radiopharmacies"
(this concept is not widespread in Europe). This operation remains
essentially manual: it is usually performed with handling tongs in
radiation-shielded cells. It is slow and labor-intensive. The
syringes are then placed, with their needle and cap, in a
radiation-shielded transportation container.
[0007] In the hospital, just before injection, the syringe is
removed from its transportation radiation shielding container and
generally fitted into a syringe radiation shielding. This operation
represents a certain level of exposure of the staff to the
radiation.
[0008] It should be noted that automation of the filling of
syringes is possible and that such devices exist, but they do not
solve all the production problems: the fixing of the needle or a
stopper is not automated, nor is the placing of the syringe in its
transportation container. For these reasons, they are not widely
used.
[0009] It should be noted that if the needle for the injection is
already in place, as is generally the case, the syringe is not
closed during transportation. The integrity of the product is not
ensured during the transportation. Alternatively, if the syringe is
closed by means of a stopper, this stopper will have to be removed
by the medical staff and replaced by the needle for the injection.
This manipulation represents an exposure to radiation and presents
a risk of radioactive contamination of the staff, and also a risk
of biological contamination of the substance.
[0010] A multi-dose radiopharmaceutical vial dispensing device is
of little interest to the American market since it does not allow
the automatic filling of individual patient-doses which may be used
directly in hospitals according to the common practice. In the
long-term, the practice of the individual patient-dose might spread
beyond the United States on account of the ease offered to the
hospital departments concerned.
[0011] The problem present in the state of the art that need to be
solved an be summarized as follows:
[0012] syringes are a form of packaging which does not lend itself
readily automation. The design of a system for the automated
filling of syringes, which would directly satisfy the need and
habits of the American market, would be complex;
[0013] the filling of a syringe as is currently performed in
American radiopharmacies, in particular for PET applications, is
essentially manual, slow and relatively inefficient;
[0014] Document U.S. Pat. No. 5,918,443 describes fluid leakproof
package for a single-dose radiopharmaceutical-filled medical
syringe. Said package is made of an inner container enclosing the
complete syringe and which is in turn enclosed within a
radiation-shielding outer container useful for shipment to a
medical treatment location. However the configuration of this
device implies that, before transportation, the syringe has to be
filled and the needle capped manually, thus exposing the operator.
Further, both above-mentioned containers have to be capped and
uncapped respectively. Only the outer container and its cap
comprise radiation-shielding material. Thus the medical staff
carrying out on-site injection is further exposed during uncapping
and during injection. the fixing of the needle or a stopper is not
automated, nor is the placing of the syringe in its transportation
container. For these reasons, they are not widely used.
[0015] It should be noted that if the needle for the injection is
already in place, as is generally the case, the syringe is not
closed during transportation. The integrity of the product is not
ensured during the transportation. Alternatively, if the syringe is
closed by means of a stopper, this stopper will have to be removed
by the medical staff and replaced by the needle for the injection.
This manipulation represents an exposure to radiation and presents
a risk of radioactive contamination of the staff, and also a risk
of biological contamination of the substance.
[0016] A multi-dose radiopharmaceutical vial dispensing device is
of little interest to the American market since it does not allow
the automatic filling of individual patient-doses which may be used
directly in hospitals according to the common practice. In the
long-term, the practice of the individual patient-dose might spread
beyond the United States on account of the ease offered to the
hospital departments concerned.
[0017] The problems present in the state of the art that need to be
solved can be summarized as follows:
[0018] syringes are a form of packaging which does not lend itself
readily to automation. The design of a system for the automated
filling of syringes, which would directly satisfy the need and
habits of the American market, would be complex;
[0019] the filling of a syringe as is currently performed in
American radiopharmacies, in particular for PET applications, is
essentially manual, slow and relatively inefficient;
[0020] Document JP-A-02 095380 proposes a device to safely and
surely transport and store a radioactive solution. This device
provides improvements intended to reduce medical staff and operator
exposure. For instance, for the needs of storage and
transportation, only a sealed syringe body is inserted into an
inner first radiation-shielding container itself enclosed in an
outer second radiation-shielding container, the latter being
provided with a radiation-shielding lid. The materials used for the
inner container are for example lead, tungsten alloy as well as
lead glass in the case where a see-through window is provided. The
outer container comprises lead.
[0021] The syringe body is maintained in the device by means of a
flange and a collar which are attached to the rear of the syringe
body inserted in the inner shielding container.
[0022] The advantage of this solution over the previous one is that
globally the shielding device is much more compact and thus less
heavy. At the injection location, a plunger rod, also made of
tungsten alloy to prevent radiation leakage to the rear, is screwed
into a sealing gasket located inside the syringe body. Thus the
syringe inserted in the inner shielding cylinder can be easily
retrieved from the second shielding container.
[0023] A first drawback of this device is the need to manually
remove a sealing rubber stopper at the front face of the syringe in
order to place the needle, which leads to personal exposure and
possible sterility loss or biological contamination. Moreover the
cantilevered gasket-plunger connection is weakened owing to the
weight of shielded parts. the fixing of the needle in a stopper is
not automated, nor is the placing of the syringe in its
transportation container. For these reasons, they are not widely
used.
[0024] It should be noted that if the needle for the injection is
already in place, as is generally the case, the syringe is not
closed during transportation. The integrity of the products is not
ensured during the transportation. Alternatively, the syringe is
closed by means of a stopper, this stopper will have to be removed
by the medical staff and replaced by the needle for the injection.
This manipulation represents an exposure to radiation and presents
a risk of radioactive contamination of the staff, and also a risk
of biological contamination of the substance.
[0025] A multi-dose radiopharmaceutical vial dispensing device is
of little interest to the American market since it does not allow
the automatic filling of individual patient-doses which may be used
directly in hospitals according to the common practice. In the
long-term, the practice of the individual patient-dose might spread
beyond the United States on account of the ease offered to the
hospital departments concerned.
[0026] The problems present in the state of the art that need to be
solved can be summarized as follows:
[0027] syringes are a form of packaging which does not lend itself
readily to automation. The design of a system for the automated
filling of syringes, which would directly satisfy the need and
habits of the American market, would be complex;
[0028] the filling of a syringe as is currently performed in
American radiopharmacies, in particular for PET applications, is
essentially manual, slow and relatively inefficient
[0029] Possible contamination or exposure of the radiopharmacies
staff is thus a risk inherent to manual handling of syringes.
Regarding this, automated filling is required. However usual
syringes constitute a form of packaging which does not lend itself
readily to automation. The design of a system for the automated
filling of syringes, which would directly satisfy the need and
habits of the American market, would be complex;
[0030] the use of individual syringes does not entirely avoid
manipulations at the hospital since they must be transferred from
their transportation radiation shielding container to the syringe
radiation shielding;
[0031] pre-filled individual syringes, possibly comprising needle,
syringe body and plunger, are very long and require large, and thus
heavy, transportation radiation shielding containers;
[0032] when the syringes are delivered with a needle, the container
(i.e. syringe) thus provided is open and the sterility of the
product is not ensured during transportation;
[0033] when the syringes are delivered with a stopper, an
additional manipulation is necessary, which exposes both the
product and the operator.
AIM OF THE INVENTION
[0034] The aim of the present invention is to offer a method and a
device for producing, packaging and handling injectable substances
of radiopharmaceutical compounds, preferably in the form of
individual patient-doses of radiopharmaceutical compounds, allowing
the exposure of the staff, the number of manipulations and the need
for accessory equipment to be reduced to the minimum, while
maintaining isolation and sterilization of said compounds from the
external environment.
SUMMARY OF THE INVENTION
[0035] The present invention relates to a method for preparing,
packaging and handling an individual patient-dose of a
radiopharmaceutical compound, in particular for use as a
short-lived compound in PET applications, comprising the following
steps:
[0036] filling a cartridge with said dose of radiopharmaceutical
compound via a first end, the second end being closed by means of a
component serving as a piston;
[0037] closing said cartridge at said first end by means of a
closure device;
[0038] placing said cartridge in a radiation shielding device,
comprising an inner part and an outer part, said inner part serving
as radiation shielding for an operator and said outer part serving
as a transportation container;
[0039] closing said container by means of an appropriate shielding
lid;
[0040] transporting said container up to the place at which an
injection of said radiopharmaceutical compound will take place;
[0041] removing the shielding lid of the container;
[0042] fixing a plunger to the cartridge piston;
[0043] extracting the cartridge and the inner part of the radiation
shielding device from the outer part serving as a container,
and
[0044] placing injection means on the cartridge end which has the
setting closure device.
[0045] The cartridge may be a standard cartridge, such as those
used for the packaging of insulin.
[0046] Further, according to the invention, a radiation shielding
device is provided, comprising an inner cylinder-like part being
able to comprise said cartridge, and an outer cylinder-like part,
serving as an additional shielding for transportation. The inner
part is capable to be placed inside the outer part. The outer part
is able to be closed by a shielding lid. The inner cylinder-like
part is preferably made of high density metal such as tungsten or a
tungsten-based alloy. The outer cylinder-like part and the
shielding lid are preferably made of a high density metal such as
lead, tungsten, a high lead content alloy or a high tungsten
content alloy.
[0047] Also, according to the invention, a plunger to be used in
the method is provided, said plunger comprising a sliding rod, a
push button, means for fixing said plunger to the inner part of the
radiation shielding device and support wings for the fingers.
[0048] Also according to the invention, an injection means to be
used in the method is provided, said injection means comprising a
needle or a luer fitting connected to a spike, said spike being
capable to pierce the set closure of the cartridge in a sterile
manner and to enter in contact with said radiopharmaceutical
compound, when said cartridge is inside the cartridge radiation
shielding. The spike is protected in a sterile manner by an
elastomeric sleeve until set closure of cartridge has been
pierced.
BRIEF DESCRIPTION OF THE DRAWINGS
[0049] FIGS. 1a and 1b represent an open cartridge with its setting
stopper and a closed cartridge respectively.
[0050] FIG. 2 represents, in a cutaway view, a radiation-shielding
device
[0051] FIGS. 3a, 3b and 3c represent a plunger, viewed separately,
viewed assembled on the cartridge radiation shielding and viewed
during extraction from the shielding device used for the
transportation respectively.
[0052] FIGS. 4a, 4b and 4c represent a first embodiment of
injection means comprising a spike and a needle, with and without
its sleeve and caps respectively.
[0053] FIGS. 5a, 5b and 5c represent a second embodiment of
injection means comprising a spike and a male luer-lock device,
with and without its cap and plug respectively.
[0054] FIG. 6 is a view of the ready-to-use injection device.
DETAILED DESCRIPTION OF SEVERAL PREFERRED EMBODIMENTS OF THE
PRESENT INVENTION
[0055] The present invention is related to a method and devices for
preparing, packaging and handling individual doses of an injectable
radiopharmaceutical compound. The method combines and incorporates
the functions of filling (production) and transportation
(packaging) and use while at the same time allowing the production
to be easily automated.
[0056] The method of the invention comprises the following
steps:
[0057] filling a "cartridge" 1 with an injectable substance of a
radiopharmaceutical compound (FIG. 1);
[0058] closing said cartridge 1 at one end by means of a setting
elastomeric (rubber) stopper 2 to be capable of being pierced, such
as a septum. The cartridge comprises a rubber piston 3 at the other
end. The filling and closing may be performed automatically using a
suitable dispensing device. A cartridge as is known to contain
insulin may be used for this purpose;
[0059] placing the cartridge in a radiation shielding device 10
consisting of two concentric parts (FIG. 2): a removable inner part
4, called a "cartridge radiation shielding", consisting of a tube
made of dense material which will also serve as protection for the
medical staff during the injection (thus fulfilling the function of
syringe radiation shielding), and an outer part 5 consisting of a
"radiation-shielding container" whose size and thickness are
suitable for transportation according to the nature of the
substance contained in the cartridge. The cartridge and its
shielding can be easily placed in this radiation shielding
container by means of an automated device;
[0060] fitting a shielding lid 6 on said container 5;
[0061] transporting said container 5 to the place where the
substance will be administered;
[0062] removing the lid 6 from the transportation container 5 and
attaching by clipping or screwing a plunger 7 to the cartridge
radiation shielding 4 (FIG. 3);
[0063] extracting the cartridge radiation shielding 4 from the
transportation container 5 by means of this plunger 7. At this
stage, the user has in his hands the equivalent of a filled
radiation-shielded syringe which lacks only the needle
[0064] placing a spike 31 by piercing the elastomeric stopper 2
opposite to the piston 3. The spike may be a double needle of
VACUTAINER.RTM. type (from Becton Dickinson) as used for taking
blood (FIG. 4) or the spike may be connected to a male luer fitting
(luer-lock or -slipper) adapted for any type of subsequent
connection of the device. This spike, which is protected from any
dust by an elastomeric (rubber) sleeve 32, is installed by piercing
the septum 2 of the cartridge 1;
[0065] removing the cap 42 from the intravenous (iv) needle or the
plug 45 of the luer fitting in order to carry out the injection
(FIGS. 4 and 5).
[0066] The main components used in the method of the invention are
described hereunder. Some of them are existing parts, used here for
the purpose of the invention. Others are specific to the
invention.
[0067] The cartridge (FIG. 1) is a type of tube 1 closed at one end
by means of a rubber piston 3 which can slide inside the tube, and
fitted at the other end with a system of closure by setting a
rubber stopper (not shown) used as a septum 2 with a crimped
aluminium ring.
[0068] The cartridge can be any standard commercially available
single-use component such as for example "1.5 ml Cartridge, flint
type I glass" from Forma Vitrum A.G. (Switzerland) or "1.8 ml
Cartridge, ref. No. 112" from Nuova Ompi (Italy).
[0069] The cartridge radiation shielding 4 (FIG. 2) is a
cylindrical component made of a dense radiation shielding alloy,
for example a tungsten-based alloy. It is hollow, with its inside
diameter adapted to the cartridge. The thickness of the wall is
adapted to the weight and radiation shielding constraints. The
cartridge radiation shielding is reusable and may be placed in the
transportation radiation shielding container 5. A window 20 may be
provided in the shielding 4 to allow the cartridge to be seen
through the lateral face. A conical inlet may be provided to
facilitate the automatic insertion of the cartridge 1. The
cartridge radiation shielding 4 is a purpose-designed and
purpose-made component, specifically for this invention.
[0070] The transportation container 5 is a cylinder made of dense
material, preferably lead, intended to protect the environment from
the radiation emitted by the contents of the cartridge during the
transportation and storage. The container is fitted with a
shielding lid 6. The internal dimensions are adapted to those of
the cartridge radiation shielding 4. The thickness of the walls is
adapted to the nature and intensity of the radioactive source.
[0071] The plunger 7 (FIG. 3) serves to push the cartridge piston 3
during the injection and to extract the cartridge radiation
shielding 4 from the transportation container 5. It is composed of
a sliding rod 22 fitted at one end with a push button 23 for the
thumb and at the other end with a back face 24 to enter into
contact with the cartridge piston 3. The fixed part comprises a
system for rapid attachment for example by screwing or clipping, to
the cartridge container described above and is fitted with two
support wings 25 for the fingers. This component is reusable. It is
a purpose-designed and purpose-made assembly, specifically intended
for this use.
[0072] According to a first preferred embodiment, as shown in FIGS.
4a, 4b and 4c, injection means 30 essentially consist in a device
presenting a needle 33, such as an iv needle, connected to a spike
31. The spike is designed to be able to pierce the set closure 2 of
the cartridge 1 when said cartridge is still inside the cartridge
radiation shielding 4.
[0073] Advantageously, said spike is protected by an elastomeric
sleeve 32 and both spike 31 and needle 33 are covered before use by
adequate protective caps 41 and 42.
[0074] According to another preferred embodiment, as shown in FIGS.
5a, 5b and 5c, the injection means 30 essentially consist in a
device comprising a spike 31 as described in the previous
embodiment and a luer-lock fitting 34 able to be closed by a plug
45.
[0075] Again, the spike 31 may advantageously be protected by an
elastomeric sleeve 32. The spike may also be covered before use by
a protective cap 41.
[0076] The injection means 30 is a device permitting rapid fixing
of a needle or luer lock using a screw pitch (threaded part) or a
clip (not shown). The fixing is made to the lower end of the
radiation-shielding 4. The spike 31 is designed to be able to
pierce the set closure 2 of the cartridge when the latter is inside
the cartridge radiation shielding 4. The opposite end of the
injection means is either an iv needle 33 (FIG. 4) or a male
luer-lock fitting 34 (FIG. 5). The direct use of a standard
single-use spike/needle of VACUTAINER.RTM. type as used for taking
blood is the most practical (Becton Dickinson, Vacutainer needle,
ref. 36-0213).
[0077] In FIG. 6 is described the manner in which the cartridge
radiation shielding 4 provided with its plunger 7 and internally
with a cartridge 1 is fitted with the injection means such as the
spike/needle 30 device described in FIG. 4a. Once the set closure 2
has been pierced by the spike 31, through a lower opening in said
shielding 4, the protective cap 42 only needs to be removed in
order to proceed with the injection.
* * * * *