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EP2007340B1 - Systeme de production, de qualite et de securite pharmaceutique integre - Google Patents

Systeme de production, de qualite et de securite pharmaceutique integre Download PDF

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Publication number
EP2007340B1
EP2007340B1 EP06724017A EP06724017A EP2007340B1 EP 2007340 B1 EP2007340 B1 EP 2007340B1 EP 06724017 A EP06724017 A EP 06724017A EP 06724017 A EP06724017 A EP 06724017A EP 2007340 B1 EP2007340 B1 EP 2007340B1
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EP
European Patent Office
Prior art keywords
module
substance
therapy
per
therapy module
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Not-in-force
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EP06724017A
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German (de)
English (en)
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EP2007340A1 (fr
Inventor
Oliver Buck
Christoph Ehlers
Tuomo Nikula
Michael Schilp
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Isotopen Technologien Muenchen AG
Original Assignee
Isotopen Technologien Muenchen AG
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Priority to PL06724017T priority Critical patent/PL2007340T3/pl
Publication of EP2007340A1 publication Critical patent/EP2007340A1/fr
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Publication of EP2007340B1 publication Critical patent/EP2007340B1/fr
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
    • A61J1/14—Details; Accessories therefor
    • A61J1/20—Arrangements for transferring or mixing fluids, e.g. from vial to syringe

Definitions

  • the present invention relates to a system and components for providing a diagnostic or therapeutic substance compound, and more particularly to providing a diagnostic or therapeutic substance compound containing a short-lived substance and a corresponding method.
  • diagnostic or therapeutic compound compounds are used that contain short-lived substances such as short-lived chemicals, living cells, proteins, or radioactive substances.
  • the process steps involve the preparation of a medicament by combining several substances needed and developed for the treatment, quality control of the medicament produced, transfer of the medicament into a dosage form and administration of the medicament drug.
  • Patient diagnosis will include data on the patient's constitution, clinical picture, specific expression of specific targets, the applicability of specific targeted treatments, the type and strategy of treatment, the frequency and frequency of treatment and treatment generated the single doses of drugs or diagnostic substances to be administered as well as the necessary control and aftercare.
  • the next step is the preparation of the starting materials or substances for the drug, which may comprise, for example, chemically and / or biologically short-lived or radioactive starting materials, but also other temporally substantially stable biological or chemical substances.
  • radioactive isotopes are usually produced by different manufacturers and often in research institutes, with high demands on the chemical and radiochemical unit for medical applications and production due to legal regulations taking place under environments according to cGMP standards or using comparable methods, and the Production must be monitored and documented qualitatively.
  • Isotopes with half-lives in the range of several days or weeks are supplied directly in containers, while isotopes with shorter half-lives can only be obtained on site with the aid of an accelerator, reactor or generators containing a radioactive isotope and the disintegrated, desired daughter isotopes by physicochemical means provide.
  • the resulting radiation dose as well as due to the resulting balance between parent and daughter isotopes available from the generator systems amounts of radioactive isotopes are usually limited. Due to the temporal variability of these substances as well as other materials used for the production of medicaments, time-varying substances, an exact planning of the treatments in terms of an optimal utilization of the available radiation dose is necessary.
  • the necessary for the production of the drug combination of the starting materials and the binding or the incorporation of isotopes or other temporally unstable substances in the drug usually takes place by means of biochemical and physical methods in the laboratory of a clinic.
  • the biochemical processes for the preparation of the drug are usually performed manually by the clinic staff. This requires a high degree of concentration, practice and speed and thus a total of training in order to achieve the highest possible yield of a radioactive isotope or other temporally unstable substance with the necessary quality and safety.
  • the data generated in the patient diagnosis which include all the necessary diagnostic and therapeutic measures, including the type and extent of treatment with all the drugs needed, the radiation dose and mode of administration are so far only recorded manually and stored in patient records.
  • a connection or feedback between the diagnosis and the manufacture of the drug is either not at all or only in the context of individually tailored and tailored to individual clinics systems.
  • US 5,415,843 discloses a device for the production of radiopharmaceuticals comprising a lead chamber and a loading device on which a chemical system in the form of a disposable kit is mounted.
  • US 2004/0028573 A1 discloses an apparatus for synthesizing radiopharmaceutical products based on bottled chemical reagents, the apparatus having a plurality of reaction chambers, transfer means between the bottles and the reaction chambers, and mechanical means acting on the transfer means to allow monitoring and control of the transfer of chemical reagents ,
  • a therapy module for providing a diagnostic or therapeutic substance compound comprising at least two containers which can be connected to each other for receiving at least one substance and means or part of a means for supplying a quantity of the at least one substance from one of the containers to another container of the therapy module.
  • the therapy module according to the invention is suitable for storage, delivery and provision of one or more temporally substantially immutable substances and further includes a container in which substances immediately before administration to a patient and in particular in a clinic with one or more, in particular also temporally unstable and possibly externally supplied substances brought together or can be united. It is conceivable to make the therapy module at least partly reusable or as a disposable product.
  • the means for supplying substances from one of the containers to another container of the therapy module has the function of transporting the substances between the containers, but can also be used for metering the substances and for controlling the amount of an optionally supplied from the outside further substance ,
  • the chemical / physical structure of the therapy module including reservoirs, pumps, other components or parts thereof may be manufactured as a block by means of suitable manufacturing methods or constructed from standard components. Furthermore, suitable coatings can be used on the insides of the components used to influence the dosage, quality assurance and the reactions that may occur.
  • the therapy module according to the invention thus forms a cost-producible, usable for a variety of substance compounds, empty, partially or completely filled deliverable device for producing a diagnostic or therapeutic substance compound immediately at the place of administration to a patient, wherein temporally variable, physically; chemically or biologically unstable or radioactive substances may be added immediately prior to administration, so that production controlled in relation to the state of the time-varying substance or radiation dose can be effected in a substantially automated manner and contamination of persons, e.g. Clinical staff or people working in the lab largely avoided.
  • the therapy module has a plurality of containers, of which at least one container is connected directly to at least two further containers of the therapy module. Furthermore, at least one of the containers can have at least one access, in particular for a sensor means, in particular for carrying out quality-assurance measures, or a mechanical interface to the outside of the therapy module exhibit.
  • a substantially unified form is used by all manufacturers of basic substances and therapy modules, in which certain requirements, such as the dimensions and location of the access to the therapy module are met and other features of the structure, such as the number of containers contained in the therapy module and their arrangement and the number and type of provided in the therapy module technical components are variable.
  • the therapy module can comprise one or more pumping means associated with at least one container, dosing means as a means for supplying a quantity of the at least one substance from one of the containers to another container of the therapy module and / or sensor means or parts thereof. If only parts of the dosing agent, sensor means and / or a pumping means are provided in the therapy module, and other, essential parts of these means outside and in a reusable with a variety of therapy modules form, the manufacturing cost of the therapy module can be reduced, is for the therapy module only one smaller space and need the individual therapy modules only a smaller probability of failure.
  • the therapy module comprises a housing in which the containers are received, and lines, by means of which the containers are connectable to each other.
  • the therapy module is externally controllable and has means for receiving control and / or power supply signals for the means for supplying a quantity of the at least one substance from one of the containers to another container of the therapy module and / or for a sensor means ,
  • expensive control devices and the power supply can be provided externally and used several times.
  • a base module for providing a diagnostic or therapeutic compound which comprises a receptacle for a therapy module and means for controlling one or more of the therapy module Means for supplying a quantity of a substance from one of the containers to another container of the therapy module and / or one or more sensor means, in particular for carrying out quality assurance measures.
  • the basic module is used primarily for the preferably automatic control of the production of a substance compound in a therapy module, wherein in principle it can be reused as often as desired and can be coupled to a plurality of therapy modules, possibly provided by different drug manufacturers and suppliers, possibly with one or more basic substances ,
  • a largely automatic, non-contact and controlled parameters production of substance compounds is possible, in particular temporally unstable substances at the site of the base module, which is preferably chosen close to the site of administration, directly in the production the substance compound and before the administration of the drug can be added in a controlled manner.
  • the base module may comprise means for detecting at least one parameter from the group comprising the type, amount, temperature, radiation dose, radiation spectrum, residual life, in particular a short-lived substance, the residence time, concentration and the pH of at least one in the therapy module comprising substance.
  • This can be a controlled production and quality assurance of the substance compound or drug produced in the therapy module.
  • Such means may additionally or alternatively also be provided on other modules.
  • the base module has, according to a further embodiment, a data processing unit for process control and a data storage means.
  • This can be a management and storage of the detected data with the base module, in particular with respect to the parameters of the substances used to produce the drug or substance compound at the time of manufacture, as well as externally supplied data, such as patient data and the entire therapy and capacity planning done in the base module.
  • the basic module can also be supplied with external "quality data" from central databases in order to comply with quality requirements for the substance compounds to be produced.
  • the base module comprises means for controlling the delivery of a substance into the therapy module from outside, such as one or more pumping or dosing means.
  • the base module may comprise means for controlling one or more accesses or interfaces of the therapy module.
  • the base module comprises at least part of at least one pumping means, dosing means, sensor means and / or evaluation electronics of the sensor means provided in the therapy module.
  • the base module comprises at least part of at least one pumping means, dosing means, sensor means and / or evaluation electronics of the sensor means provided in the therapy module.
  • a prerequisite for such a division of the components is the use of standardized therapy modules that are standardized to a certain degree, so that all therapy modules, if any, supplied by different manufacturers can be used on a base module.
  • the base module can be coupled to a computer or computer network. Via a corresponding network connection, quality data, patient and therapy data as well as data for process planning can be communicated and remote maintenance can be realized. Detected or provided by the base and / or therapy module Quality, manufacturing, identification and monitoring data may also be communicated over this network port or provided via suitable data storage such as a memory card or a writable RFID chip for external use.
  • the base module may further serve for powering and / or controlling electrical components provided in the therapy module and / or other modules and further optionally includes an operator interface, such as a keyboard and / or a touch-sensitive screen, via which input and display of data can be done. Furthermore, in addition to a docking option, such as, for example, a mechanical interface for the therapy module, the base module can have further interfaces for other modules.
  • the base unit according to the invention is that it is preferably designed so that it is never contaminated with substances and the chemical / physical processes take place exclusively in the therapy module and / or other modules.
  • a prevention of contamination of the base module by substances can be achieved, on the one hand, by one or more modules containing at least one substance being connected directly to the therapy module.
  • the interface of the modules with the base module can be used, for example, for powering the modules or for establishing control connections for controlling the connected modules by the base module.
  • a system comprising a therapy module and a base unit is furthermore provided.
  • the system may further comprise an active agent module or isotope module for storing and / or producing physically, biologically or chemically short-lived substances, such as radioactive isotopes.
  • the modular structure of the system according to the invention has various advantages.
  • the preparation of the substance compound takes place at the place of installation of the base module, ie preferably in the clinic, and preferably under the quality control by the base module.
  • the drugs to be administered to a patient can be prepared individually and patient-appropriate immediately before the administration, whereby even short-lived substances can be added effectively and without the necessity of taking into account already existing decomposition processes.
  • the preparation is carried out without substances come into contact with persons, essentially automatically under the control of the base module, but depending on the individual treatment planning and the substances contained in the therapy module or added from the outside completely different substance compounds can be produced under qualitative and quantitative control ,
  • the system can be used to comprehensively monitor and if necessary control the production and / or therapy process, including quality monitoring and feedback to the suppliers of the modules and substances.
  • the inventive system enables the effective and flexible handling of a variety of time-varying substances and in particular radioactive isotopes in a variety of pharmaceutical applications and prevents bottlenecks in the supply of or in the provision of temporally variable substances and in particular of isotopes, at the same time Quality control in manufacturing and safety aspects in the manufacture and administration of compound compounds can be improved.
  • the reusable valuable or expensive technical means such as quality assurance facilities, means for dosing substances, means for determining parameters of the substances, drive means, power supply devices and / or computer, processor and data storage means at least partially in the reusable base module can be arranged while the storage of particular temporally substantially invariable, ie storable substances and for the production of individual substance compounds serving therapy module, preferably as a disposable article or at least partially recyclable can be performed.
  • the base module may also be used to manage therapy data, such as patient data and treatment history, as well as quality data production, identification, and monitoring data.
  • An interface of the base unit may be occupied in the longer term by the active agent module, which is the production or storage of short-lived, i. biologically or chemically unstable and radioactive substances used and can be temporarily filled by a manufacturer, so that the agent module must be coupled in the clinic only to the device.
  • the active agent module can be made exchangeable or recyclable, preferably again a part of the technical components, such as. for removing substances from the active agent module or for measuring parameters of the substances contained therein in the base module can be provided.
  • the system comprises a transfer module for storing and transporting one or more substances or substance compounds, wherein the transfer module may comprise means for metering an amount of the substance or substance compound depending on the already disintegrating substance portions of a substance or substance compound.
  • the transfer module is used i.a. the transport of the prepared compound substance from the therapy module to the patient for administration and may be adapted to a particular application form, such as the shape of a syringe, a catheter or a needle.
  • the transfer module has means for performing a patient authentication to ensure a clear association with a patient and to avoid confusion.
  • the therapy module, the active agent module, the base module and / or the transfer module can be connected to one another by means of mechanical, in particular sterile interfaces.
  • the system may comprise means for transporting substances from the active agent module into the therapy module and / or from the therapy module into the transfer module without the base module being contaminated.
  • Some or all of the interfaces may further be made connectable or separable from each other without leaks and dead volumes.
  • An easy way to implement them is to use a septum (rubber disc) which is pierced with a needle.
  • An alternative, but technically more complex solution is a self-closing coupling.
  • suitable identification solutions can be provided, based on which a module clearly can be identified. This can be done optically by means of a bar code, by radio technology by means of an RFID chip or by tactile contact by means of integrated memory elements or by a shape identification or the like. respectively.
  • the above-mentioned modules arranged to receive one or more substances can either be connected directly to one another or can also be coupled to the base module.
  • some or all of the modules arranged to contain one or more substances are preferably designed to be directly connectable to another such module for the transport of substances without contaminating the base module to which they can be connected.
  • the modules may be e.g. have a finger or tube-like section.
  • the base module is preferably provided at the intended for connection with these modules interfaces with a passage and may optionally serve for power supply and / or control of the modules connected thereto.
  • the therapy module, the active agent module, the base module and / or the transfer module can have a shielding against radioactive radiation and / or a structure that prevents substances from escaping.
  • contamination of the hospital staff can be avoided and the number of administered individual doses and the number of patients treated can be increased.
  • the active agent module is prepared in a standardized form that can be used by a variety of drug and isotope manufacturers and suppliers.
  • a nationwide and geographically unlimited standardized supply of active substances can be achieved.
  • the invention further provides a method for providing a diagnostic or therapeutic substance compound. It comprises the steps of providing a therapy module with at least one first and one connectable second container and at least one substance received in the first container, arranging the therapy module on a base unit, feeding a quantity of the at least one substance from the first container into the second Container of the therapy module under Controlled by the base module and feeding a quantity of another substance into the second container.
  • the method according to the invention also has the advantages of a largely automated production of a substance compound under the control of the parameters of the substances used under the control of a central unit.
  • the method may comprise that the further substance is supplied by a third container enclosed by the therapy module and connectable to the second container.
  • the further substance is supplied by a third container enclosed by the therapy module and connectable to the second container.
  • the therapy module may contain several substances, the storage of which is unproblematic and which are not subjected to changes in the short term.
  • a further substance can also be supplied from outside to the therapy module.
  • This is particularly advantageous in the case of short-lived chemically and / or biologically unstable substances or radioactive substances, since these can be supplied immediately before the administration of the drug, whereby previous changes in the substances and decays need not be taken into account, since the state of the short-lived substance is immediate can be determined in the feed to the substance compound.
  • the required quality assurance can be performed immediately at the time of manufacture of the drug on-site at the clinic.
  • the method may comprise combining a plurality of different substances contained in a plurality of containers of the therapy module into a container of the therapy module directly connected to the plurality of containers.
  • the method may include the step of introducing into the therapy module a substance that temporally changes with respect to at least one of its properties and detecting at least one parameter from the group comprising the type, amount, temperature, radiation dose, radiation spectrum, remaining life, Residence time, concentration, and the pH of the substance delivered to the transfer module include.
  • parameters of the substances contained in the substance compound can be determined before or after their combination. These data are preferably stored in a data storage unit preferably contained in the base module and can be taken into account in an automated process control.
  • the method comprises the step of introducing into the therapy module a short-lived, in particular chemically or biologically unstable or radioactive substance.
  • the method may include the step of delivering at least one substance from the therapy module into a transfer module.
  • the transfer module is used to transport a prepared substance-compound compound to the patient and may comprise means for metering the correct amount depending on disintegrating substances contained in the substance compound. Further, it may be adapted to the form of application, such as a syringe, a catheter, a needle. Furthermore, the transfer module can be provided with a means for identifying a patient in order to ensure correct allocation and to avoid confusion.
  • the method may comprise supplying the substances from and into the individual modules under the control of the base module.
  • the modular structure of the system wherein important control tasks are performed by the base module, is used to control the process flows and acquisition of the data, so that a largely complete automation can be achieved and changes to process flows can be made easily.
  • the invention provides a computer program comprising a program code which, when installed on a computer, causes it to carry out the method according to the invention. Furthermore, a computer-readable medium is provided on which this computer program is implemented. A computer may also be provided which is set up to carry out the method according to the invention.
  • inventive method as well as the therapy module, the base module and the system can be used for a variety of therapeutic and diagnostic purposes Particularly preferred are applications in which a preparation of a therapeutic or a diagnostic substance compound close to the administration site, such as in a clinic, is advantageous.
  • Exemplary applications include the administration of radioactive nuclide (radioisotope) -compound compounds, for example, for the treatment and diagnosis of cancer, in pain therapy, and in wound treatment.
  • radioactive nuclide radioactive nuclide
  • isotopes with suitable half-lives and dose rates and the shortest possible ranges are used.
  • isotopes enable the visualization of metabolic processes and the localization of cell types.
  • the isotopes are incorporated into molecules that participate in the metabolism, or coupled to antibodies and similar proteins, which in turn are bound to specific receptors.
  • small dose rates and a very short half-life of a few hours or minutes are sought.
  • radioactive substances for PET tomography, X-ray or CT examination or fluorescent substances can be used.
  • All substance compounds prepared by means of the system and method according to the invention must meet the requirements of the drug and health. This means that in particular chemically or biologically unstable starting substances after their connection with other substances after the manufacturing process must result in a stable, safe and logistically manageable substance compound.
  • the figure shows schematically the integrated radiopharmaceutical product quality assurance and safety system (IQS) according to one embodiment of the invention.
  • IQS integrated radiopharmaceutical product quality assurance and safety system
  • the system shown in the figure comprises a therapy module 1 with at least two containers (not shown) connectable to each other for receiving at least one substance and one or more agents, in particular pumps or dosing, for supplying at least one substance from one of the containers to another container Therapy module 1 or at least parts of these agents.
  • the therapy module includes interfaces 7, 9 to individual containers or modules and may also include one or more external accesses (not shown) for delivery of substances or introduction of sensor means.
  • a plurality of containers provided for receiving basic substances and at least one further container can be provided, which is directly connected to at least two other containers and is used to produce a substance compound in the therapy module 1.
  • the internal structure of the therapy module, the number of containers contained therein and their connections, the number of pumping means and / or sensor means may vary with different therapy modules.
  • the dimensions of the therapy module are in principle variable, although a size corresponding approximately to a video cassette is preferred.
  • the therapy module preferably has the shape of a cuboid with a side length of preferably less than 20 cm, more preferably less than 5 cm, a width of preferably less than 10 cm, particularly preferably less than 2.5 cm and a height of preferably less than 5 cm and more preferably less than 1 cm.
  • the therapeutic module 1 or the chemical / physical structure contained therein, if appropriate, including reservoirs and pumps, can be produced by means of suitable production methods as a single mono-block or constructed with standard components.
  • suitable materials for the production of the base module and in particular of the containers and of lines to their connection include plastics, metals, in particular oxidation-free metals and glass or combinations thereof.
  • suitable coatings can be used on the insides of the components used to influence the dosage, quality assurance and ongoing reactions.
  • the system comprises a base module 2 with a receptacle 3 into which the therapy module 1 can be inserted.
  • the base module 3 comprises a control panel 6, entered via the parameters for controlling processes and optionally detected data or Processes can be displayed.
  • the base module 2 further preferably comprises at least a portion of drive, power and sensor means, notably for quality assurance, for the therapy module 1, such as one or more pump motors for pump heads optionally provided in the therapy module and a drive - And evaluation for possibly arranged in the therapy module piezo pumps or sensor heads.
  • the sensor means can also be completely provided on the base module 2.
  • the sensor means may comprise means for detecting parameters of the substances contained in the therapy module 1 as well as prepared substance compounds, such as the type, the amount, the temperature, the radiation dose, the radiation spectrum, the remaining life, the residence time, the concentration and the PH value.
  • prepared substance compounds such as the type, the amount, the temperature, the radiation dose, the radiation spectrum, the remaining life, the residence time, the concentration and the PH value.
  • non-contact sensor means are used, e.g. Radiation detectors, means for measuring the refraction of light u.a. for determining the presence and type of a liquid, light barriers for determining the presence of solids, means for measuring color changes, in particular for detecting and detecting the course of chemical reactions.
  • Radiation detectors means for measuring the refraction of light u.a. for determining the presence and type of a liquid, light barriers for determining the presence of solids, means for measuring color changes, in particular for detecting and detecting the course of chemical reactions.
  • sensors include gamma, beta sensors, borehole scintillation counters, HPLC columns, CCD and video cameras, etc.
  • the base module 2 may be used in a variety of therapy modules 1, which may differ in structure.
  • the base module 2 comes at no time in contact with the substances or substance compounds and find the running processes exclusively in the therapy module 1, if necessary with the involvement of other modules. Also persons involved in the preparation and administration of the compound of substance do not come in contact with the substances.
  • the basic module 2 further preferably includes an information system, preferably comprising a processor, for storing data, for linking data, for example for therapy and capacity planning, and / or for displaying the technical status of individual modules. Furthermore, the base module 2 further preferably provides access 8 to a local or global network, such as the Internet, so that data from other involved components, such as the drug manufacturers, can be included in the process control and data collected by the base module 2 to drug manufacturers or other users.
  • an information system preferably comprising a processor, for storing data, for linking data, for example for therapy and capacity planning, and / or for displaying the technical status of individual modules.
  • the base module 2 further preferably provides access 8 to a local or global network, such as the Internet, so that data from other involved components, such as the drug manufacturers, can be included in the process control and data collected by the base module 2 to drug manufacturers or other users.
  • the base module 2 shown in the figure is merely exemplary and could also have a modified structure or another shape.
  • the receptacle 3 for the therapy module 1 could be designed so that therapy modules 1 different size or multiple therapy modules 1 can be connected simultaneously.
  • the system further comprises an active agent module 4, which can preferably be coupled by means of a further interface to the base module 2 or directly to the therapy module 1.
  • the active agent module 4 can be coupled to the base module 2. So that the base module 2 is protected against contamination by substances, the active agent module 4 on the provided for connection to the base module 2 side a finger-like portion (not shown), which in a provided on the base module 2 and the therapy module 2 leading (not shown) opening and implementation can be introduced and directly connected to the therapy module 2, so that substances without being able to come into contact with the base module 2 can be transferred.
  • the active agent module 4 is used for storage or production of chemical or physically unstable or radioactive substances.
  • the active agent module 4 is preferably secured against leakage of toxic substances or provided with a radiation shield.
  • the short-lived substances taken from the active agent module 4 are immediately and under the control of the base module 2 in an intended for the preparation of the substance compound Container of the therapy module 1 supplied. Since the use of the base module 2 or its location is preferably in the clinic, the ephemeral substances can be used essentially without a time delay shortly before administration of the substance compound to a patient for the production.
  • Exemplary time-unstable substances include radioactive isotopes, such as the beta emitters yttrium, iodine, holmium, fluorine, rhenium, lutetium and alpha emitters, and also other chemically or biologically unstable substances that can be used, for example, for chemotherapy.
  • Half-lives of therapeutically or diagnostically used chemically or biologically unstable or radioactive substances are, according to one embodiment, less than 2 weeks, preferably less than 100 hours, and more preferably less than 50 minutes.
  • a transfer module 5 can be connected to the base module 2 with the aid of a further interface 7. So that the base module 2 is protected against contamination by substances, also the transfer module 5 on the provided for the connection to the base module 2 side a finger-like portion (not shown), which provided in a provided on the base module 2 and the interface for the Therapy module 2 connected (not shown) opening can be inserted. Thus, the transfer module 5 is directly connected to the therapy module 1 and it can be exchanged substances between the modules without contamination of the base module 2 takes place. In the portion of the transfer module passed through the base module 2, e.g. the quality control of substances or substance compounds transferred into the transfer module 5 takes place.
  • the transfer module 5 is used to receive a substance compound prepared in the therapy module 1 and the transport for administration to a patient.
  • the transfer module 5 is adapted to a particular application form, such as a syringe, a catheter, a needle and has a corresponding connection interface 10. It may further comprise means for metering the correct amount, optionally in dependence on the contained since the filling disintegrated substances. Depending on the application, it may include a shield for toxic and / or radioactive substances to the persons in contact, such as the clinic staff or doctors.
  • the transfer module 5 may further include means (not shown) for identifying and associating with a particular patient so that the contained substances are released only after unambiguous identification and assurance of compliance with temporal quality parameters. Furthermore, it can be an information interface 9 as well a corresponding (not shown) data storage for the acquisition of data, such as patient data, identification data, therapy and diagnostic data, product and quality data include.
  • the illustrated transfer module 5 is merely exemplary and may be designed differently. In particular, it is conceivable to provide functions or features of the transfer module 5 in the therapy module 1, so that, if necessary, the transfer module 5 can be dispensed with.
  • modules that can be connected to the base module 2 can also be provided and designed to be connectable to the therapy module 1 or the transfer module 5 in the manner described above. Alternatively, however, it is also conceivable to carry out some or all of the modules directly coupled to the therapy module 1.
  • the physician determines the necessary diagnosis or therapy when examining a patient.
  • the resulting data is entered into the IQS information system and possibly via the detour of the information system of a clinic.
  • a therapy or diagnostic plan is subsequently created based on an available amount of a radioactive isotope or a chemically unstable substance with the help of possibly specially trained personnel.
  • a therapy plan where appropriate, besides the drug and patient aspects, e.g. the type, amount, time of administration, etc. of the drug also takes into account the equipment, laboratory capacity, personal availability and treatment capacities of the clinic.
  • the therapy plan may be adapted and approved by a responsible person, such as the head of a nuclear medicine laboratory or the head of the oncology department.
  • the active agent module On the day of treatment, in the active agent module, the necessary amount of a substance which is unstable in time, or e.g. of the isotope for that day and booked for each treatment.
  • the active agent module is connected to the IQS base module 2.
  • the therapy module 1 is inserted into the base module 2, the corresponding patient data are retrieved and the corresponding transfer module 5, such as a syringe applicator, is connected.
  • the connected modules are identified, their identity and the stored quality data are checked, the desired amount for the therapy / diagnosis is determined or retrieved, alarm messages are issued in the event of errors or the manufacturing process is started. All generated data is saved and added to the patient data and production data in the base module 2.
  • the required amount of an isotope solution is pumped from the active agent module 4 into the therapy module 1.
  • the therapy module 1 There it is, for example, mixed with labeled monoclonal antibodies (MAB), which are already present in the therapy module 1.
  • MAB monoclonal antibodies
  • the process is optimized and correct chemical values are set.
  • suitable environmental conditions such as a predetermined pressure and a predetermined temperature are ensured for an optimal process.
  • the substance compound is separated from unbound isotopes, for example, and the quality of the product can be measured by determining the ratio of bound and unbound isotopes via a chromatography step. All acquired data is stored via the IQS base module 2.
  • the product or the substance compound is transferred into the transfer module 5.
  • the used therapy module 5 is optionally automatically recycled by the IQS base module 2.
  • the transfer module 5 is separated from the IQS base module 2 and transported to the patient.
  • Administration of the substance compound contained therein can be accomplished by introducing the antibody-bound substance compound into the body, i. into the bloodstream or into body cavities created by surgery, by injecting into natural joints or artificially e.g. surgery-induced body orifices for irritating or destroying tissue, inserting a catheter into a blood vessel to locally affect tissue, binding a substance compound to peptides (proteins), sugars or other metabolically implicated substances for imaging or cancer therapy.
  • the change i. the disintegration of the product can be checked by means of the transfer module 5 and it can be ensured that a defined expiration time is not exceeded by an excessively long transfer to the patient.
  • a patient for example with the aid of biometric methods, a card or a bar code, etc.
  • the application itself which can be done for example by an intravenous injection, can be controlled by the transfer module by means of a blocking device provided on this or a suitable interface.
  • the relevant parameters are the quantity, the applied pressure and the injection rate. Due to the special automatic transfer module 5, the doctor is relieved of a time-consuming slow injection.
  • the transfer module 5 is recycled and possibly sent the isotope module for refilling to a supplier.
  • patient data on the success of the treatment as well as, if necessary, the administered radiation dose are stored in the IQS base module 2 or transmitted to a patient file provided at another location, with which processes can be continuously improved or even study data can be collected.

Landscapes

  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Radiation-Therapy Devices (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Claims (23)

  1. Module de thérapie pour préparer un composé de substance de diagnostic ou de thérapie radioactive, caractérisé par
    - un boîtier,
    - au moins deux conteneurs placés dans le boîtier, reliés l'un à l'autre au moyen de conduites, pour recevoir au moins une substance, dans lequel
    - le module de thérapie peut être couplé à un module de base (2),
    - une partie comprenant des moyens de pompage pouvant être commandés par le module de base pour transférer une quantité de la au moins une substance à partir de l'un des conteneurs dans un autre conteneur du module de thérapie (1), et
    - une interface mécanique pouvant être commandée par le module de base, comportant un autre module (4, 5) pouvant être directement connecté au module de thérapie pour transporter une substance entre les modules sous la commande du module de base.
  2. Module de thérapie selon la revendication 1, caractérisé en ce qu'il comporte plusieurs conteneurs dont au moins un conteneur est directement relié à au moins deux autres conteneurs du module de thérapie (1).
  3. Module de thérapie selon la revendication 1 ou 2, caractérisé en ce qu'au moins un des conteneurs comporte au moins un accès, en particulier pour un détecteur.
  4. Module de thérapie selon l'une quelconque des revendications précédentes, caractérisé en ce qu'il comporte un ou plusieurs éléments parmi au moins des moyens de pompage, des moyens de dosage et/ou des moyens de détection, ou des parties de ceux-ci, associés à un conteneur.
  5. Module de thérapie selon l'une quelconque des revendications précédentes, caractérisé en ce qu'il peut être commandé extérieurement et en ce qu'il comporte des moyens pour recevoir des signaux de commande ou d'alimentation en courant pour des moyens destinés à transférer une quantité de la au moins une substance depuis l'un des conteneurs dans un autre conteneur du module de thérapie (1), ou pour des moyens de détection ou une combinaison de ces moyens.
  6. Module de base pour préparer un composé de substance de diagnostic ou de thérapie radioactive, caractérisé par
    - un récepteur (3) pour un module de thérapie (1) selon l'une quelconque des revendications précédentes, pouvant être couplé au module de base,
    - des moyens pour commander des moyens de pompage du module de thérapie afin de transférer une quantité d'une substance depuis l'un des conteneurs dans un autre conteneur du module de thérapie et
    - des moyens pour commander une interface mécanique du module de thérapie (1) et des moyens pour commander le transfert d'une substance depuis un autre module (4, 5) pouvant être relié au module de base dans le module de thérapie.
  7. Module de base selon la revendication 6, caractérisé en ce qu'il inclut des moyens pour détecter au moins un paramètre choisi dans le groupe comportant le type, la quantité, la température, la dose de rayonnement, le spectre de rayonnement, la durée de vie restante, la durée de séjour, la concentration et le pH d'au moins une substance contenue dans le module de thérapie (1).
  8. Module de base selon la revendication 6 ou 7, caractérisé en ce qu'il comporte une unité de traitement de données pour la commande de processus, et des moyens de mémorisation de données.
  9. Module de base selon l'une quelconque des revendications 6 à 8, caractérisé en ce qu'il comporte des moyens pour commander des moyens de détection.
  10. Module de base selon l'une quelconque des revendications 6 à 9, caractérisé en ce qu'il comporte au moins une partie d'au moins des moyens de dosage prévus dans le module de thérapie, des moyens de détection et/ou une électronique d'évaluation des moyens de détection.
  11. Module de base selon l'une quelconque des revendications 6 à 10, caractérisé en ce qu'il peut être couplé à des moyens informatiques ou à un réseau informatique.
  12. Système comportant un module de thérapie (1) selon l'une des revendications 1 à 5, et un module de base (3) selon l'une des revendications 7 à 11.
  13. Système selon la revendication 12, caractérisé en ce qu'il comporte un module d'ingrédient actif (4) pour le stockage et/ou la préparation de substances à courte durée de vie, en particulier des substances chimiquement et/ou biologiquement instables et/ou des isotopes radioactifs.
  14. Système selon la revendication 12 ou 13, caractérisé en ce qu'il comporte un module de transfert (5) pour le stockage et le transport d'une ou plusieurs substances ou composés de substances, dans lequel le module de transfert (5) comporte des moyens pour doser une quantité de la substance ou du composé de substance en fonction des proportions de substances déjà décomposées de la substance ou du composé de substance.
  15. Système selon l'une quelconque des revendications 12 à 14, caractérisé en ce que le module de thérapie (1), le module d'ingrédient actif (4), le module de base (2) et/ou le module de transfert (5) sont reliés les uns aux autres au moyen d'interfaces, et en ce qu'il comporte des moyens pour le transport de substances à partir du module d'ingrédient actif (4) dans le module de thérapie (1) et/ou à partir du module de thérapie (1) dans le module de transfert (5).
  16. Système selon l'une quelconque des revendications 12 à 15, caractérisé en ce que le module de thérapie (1), le module d'ingrédient actif (4), le module de base (2) et/ou le module de transfert (5) comportent un écran contre le rayonnement radioactif et/ou une structure empêchant la sortie de substances.
  17. Procédé de préparation d'un composé de substance de diagnostic ou de thérapie radioactive, comportant les étapes consistant à :
    - fournir un module de thérapie (1) selon l'une quelconque des revendications 1 à 5 comportant au moins un premier conteneur et un deuxième conteneur relié à celui-ci, et au moins une substance contenue dans le premier conteneur,
    - agencer le module de thérapie (1) sur un module de base (2) selon l'une quelconque des revendications 6 à 11,
    - transférer une quantité de la au moins une substance à partir du premier conteneur dans le deuxième conteneur du module de thérapie (1) sous la commande du module de base (2),
    - raccorder un autre module au module de base (2) et raccorder directement le module de thérapie (1) au module (4, 5),
    - transférer une quantité d'une autre substance dans le deuxième conteneur à partir du module (4, 5) sous la commande du module de base.
  18. Procédé selon la revendication 17, caractérisé en ce que l'autre substance est transférée à partir d'un troisième conteneur pouvant être relié au deuxième conteneur et inclus dans le module de thérapie (1).
  19. Procédé selon l'une quelconque des revendications 17 ou 18, caractérisé en ce qu'il comporte l'étape consistant à transférer conjointement plusieurs substances différentes contenues dans plusieurs conteneurs du module de thérapie (1), dans un conteneur du module de thérapie (1) directement relié à la pluralité de conteneurs.
  20. Procédé selon l'une quelconque des revendications 17 à 19, caractérisé en ce qu'il comporte les étapes consistant à transférer dans le module de thérapie (1) une substance dont au moins une des propriétés varie dans le temps, et détecter au moins un paramètre choisi dans le groupe comportant le type, la quantité, la température, la dose de rayonnement, le spectre de rayonnement, la durée de vie restante, la durée de séjour, la concentration et le pH de la substance transférée dans le module de transfert (5).
  21. Procédé selon l'une quelconque des revendications 17 à 20, caractérisé en ce qu'il comporte l'étape consistant à transférer dans le module de thérapie une substance à courte durée de vie, en particulier une substance chimiquement ou biologiquement instable ou radioactive.
  22. Procédé selon l'une quelconque des revendications 17 à 21, caractérisé en ce qu'il comporte l'étape consistant à transférer au moins une substance à partir du module de thérapie (1) dans un module de transfert (5).
  23. Support lisible par ordinateur, sur lequel sont mises en oeuvre des commandes qui, lorsqu'elles sont exécutées sur un ordinateur, entraînent la mise en oeuvre d'un procédé selon l'une quelconque des revendications 17 à 22.
EP06724017A 2005-04-06 2006-04-04 Systeme de production, de qualite et de securite pharmaceutique integre Not-in-force EP2007340B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PL06724017T PL2007340T3 (pl) 2005-04-06 2006-04-04 System zintegrowanej produkcji farmaceutycznej, zapewnienia jakosci i bezpieczeństwa (IQS)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102005015843A DE102005015843A1 (de) 2005-04-06 2005-04-06 Integriertes pharmazeutisches Produktions-, Qualitätssicherungs- und Sicherheitssystem (IQS)
PCT/EP2006/003062 WO2006105936A1 (fr) 2005-04-06 2006-04-04 Systeme de production, de qualite et de securite pharmaceutique integre

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EP2007340A1 EP2007340A1 (fr) 2008-12-31
EP2007340B1 true EP2007340B1 (fr) 2011-02-09

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US (1) US8403906B2 (fr)
EP (1) EP2007340B1 (fr)
AT (1) ATE497752T1 (fr)
AU (1) AU2006232818B2 (fr)
CA (1) CA2590665C (fr)
DE (2) DE102005015843A1 (fr)
PL (1) PL2007340T3 (fr)
WO (1) WO2006105936A1 (fr)

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US8435454B2 (en) 2009-07-09 2013-05-07 Siemens Medical Solutions Usa, Inc. Modular system for radiosynthesis with multi-run capabilities and reduced risk of radiation exposure
EP2606334B1 (fr) * 2010-08-20 2018-04-25 GE Healthcare Limited Cassette de contrôle de la qualité et procédé pour produits pharmaco-radioactifs
WO2012109032A1 (fr) * 2011-01-28 2012-08-16 Aquavit Pharmaceuticals, Inc. Système et procédé de traitement par injection personnalisé
US10106278B2 (en) 2011-01-28 2018-10-23 Aquavit Pharmaceuticals, Inc. System and method for personalized injection treatment
US9475025B2 (en) * 2011-12-29 2016-10-25 General Electric Company Microfluidic handling system
US10980865B2 (en) 2012-08-10 2021-04-20 Aquavit Pharmaceuticals, Inc. Direct application system and method for the delivery of bioactive compositions and formulations
US20140170758A1 (en) * 2012-12-18 2014-06-19 General Electric Company System and method for controlling a microfluidic handling device
DE102015117407A1 (de) 2015-10-13 2017-04-13 Wietmarscher Ambulanz- Und Sonderfahrzeug Gmbh Frachtkontrollsystem für Transportmaschinen
US20180209921A1 (en) * 2017-01-20 2018-07-26 Mallinckrodt Nuclear Medicine Llc Systems and methods for assaying an eluate of a radionuclide generator
US11202753B1 (en) 2020-03-06 2021-12-21 Aquavit Pharmaceuticals, Inc. Systems and methods for generating immune responses in subjects using microchannel delivery devices

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US5312592A (en) 1990-06-13 1994-05-17 Scanditronix Ab Disposable kit for preparation
US5415483A (en) * 1993-08-20 1995-05-16 Tooling Research, Inc. Sealed linear positioning apparatus
DE19817328B9 (de) * 1998-04-18 2006-11-16 Eberhard-Karls-Universität Tübingen Universitätsklinikum Verfahren zur Herstellung eines Thrombozytenpräparates
DE19824057C1 (de) * 1998-05-29 1999-07-22 Fresenius Medical Care De Gmbh Verfahren und Vorrichtung zur Versorgung einer Dialysevorrichtung mit Dialysierflüssigkeit oder Dialysierflüssigkeitskonzentrat
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US6975924B2 (en) * 1999-12-03 2005-12-13 Baxter International Inc. Method and apparatus for controlling the strategy of compounding pharmaceutical admixtures
EP1216715A1 (fr) * 2000-12-22 2002-06-26 Ion Beam Applications S.A. Dispositif de synthèse de produits radiopharmaceutiques

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Publication number Publication date
AU2006232818A1 (en) 2006-10-12
US20080140046A1 (en) 2008-06-12
AU2006232818B2 (en) 2009-04-23
CA2590665A1 (fr) 2006-10-12
ATE497752T1 (de) 2011-02-15
WO2006105936A1 (fr) 2006-10-12
CA2590665C (fr) 2011-12-13
PL2007340T3 (pl) 2011-07-29
US8403906B2 (en) 2013-03-26
DE102005015843A1 (de) 2006-10-12
EP2007340A1 (fr) 2008-12-31
DE502006008897D1 (de) 2011-03-24

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