1、Z264.1-02(reaffirmed 2011)Spacers and holding chambers for use with metered-dose inhalersBlank pageUpdate No. 2 CAN/CSA-Z264.1-02 January 2008 Note: General Instructions for CSA Standards are now called Updates. Please contact CSA Information Products Sales or visit www.ShopCSA.ca for information ab
2、out the CSA Standards Update Service. Title: Spacers and Holding Chambers for Use with Metered-Dose Inhalers originally published October 2002 Revisions issued: Update No. 1 October 2003 If you are missing any updates, please contact CSA Information Products Sales or visit www.ShopCSA.ca. The follow
3、ing revisions have been formally approved and are marked by the symbol delta () in the margin on the attached replacement pages: Revised Contents, Clauses 2, 3, and B1.5.1, Tables B3B6 and B9, and Figures B1 and B2 New Annex D Deleted None CAN/CSA-Z264.1-02 originally consisted of 57 pages (viii pre
4、liminary and 49 text), each dated October 2002. It now consists of the following pages: October 2002 vviii, 324, and 2738 October 2003 Cover, title page, and copyright page January 2008 iii, iv, 12A, 25, 26, and 3950 Update your copy by inserting these revised pages. Keep the pages you remove for re
5、ference. Blank page Canadian Standards Association Spacers and Holding Chambers for Use with Metered-Dose Inhalers January 2008 (Replaces p. iii, October 2002) iii Contents Technical Committee on Drug-Related Standards iv Subcommittee on Inhalant Aerosol Drug Delivery Systems vi Preface viii 0. Intr
6、oduction 1 1. Scope 1 2. Reference Publications 2 3. Definitions 2A 4. Construction Requirements 6 4.1 General 6 4.2 Components 7 4.2.1 General 7 4.2.2 Mouthpiece 7 4.2.3 Valves and Valve Components 7 4.2.4 Flow Indicators 7 4.2.5 Inlet/Outlet 7 4.3 Durability 7 4.3.1 Resistance to Shattering 7 4.3.
7、2 Environmental Conditions 7 4.3.3 Cleaning and Maintenance 8 5. Performance Characterization 8 5.1 In Vitro Performance 8 5.2 In Vivo Performance 8 6. Marking, Labelling, and Information to be Supplied 8 6.1 General 8 6.2 Device Package 9 6.2.1 General 9 6.2.2 Selection Information 9 6.3 Labelling
8、of the Device 9 6.4 Directions for Use 10 6.4.1 General 10 6.4.2 Selection Information 10 6.4.3 Usage Information 11 6.4.4 Maintenance Information 11 6.4.5 Reference Information 11 Annexes A (normative) Tests for Durability 13 B (normative) Performance Characterization of S-HCs 21 C (informative) Bi
9、bliography 49 D (informative) Spacers Used with Face Masks 50 Z264.1-02 Canadian Standards Association January 2008 iv (Replaces p. iv, October 2002) Technical Committee on Drug-Related Standards C.L. Bishop St. Vincents Hospitals, Heather Pavilion, Chair Providence Health Care, Vancouver, British C
10、olumbia M. Castle Whitby, Ontario Associate M. Cohen Institute for Safe Medication Practices, Associate Huntingdon Valley, Pennsylvania, USA M. Dolovich McMaster University, Hamilton, Ontario S. Dunington Michener Institute of Applied Health Sciences, Toronto, Ontario F. Gorenstein Sunnybrook and Wo
11、mens College Health Orthopaedic and Arthritic Campus, Toronto, Ontario H. Grad University of Toronto, Toronto, Ontario A. Lang-Berkowitz The Credit Valley Hospital, Associate Mississauga, Ontario J.P. Mitchell Trudell Medical International, London, Ontario P. Murphy AstraZeneca Canada Inc., Mississa
12、uga, Ontario S. Norrington Canadian Association of Emergency Physicians, Toronto, Ontario B. Orser Sunnybrook Health Sciences Centre, Toronto, Ontario G. Rachamin Ontario Ministry of Labour, Associate Toronto, Ontario D. Salois-Swallow York Central Hospital, Richmond Hill, Ontario J. Tam Canadian Dr
13、ug Manufacturers Association, Toronto, Ontario Canadian Standards Association Spacers and Holding Chambers for Use with Metered-Dose Inhalers January 2008 (Replaces p. 1, October 2002) 1Z264.1-02 Spacers and Holding Chambers for Use with Metered-Dose Inhalers 0. Introduction The purpose of this Stan
14、dard is to help ensure the safety, efficacy, and functionality of spacers and/or holding chambers (S-HCs) intended for use by spontaneously breathing patients without an artificial airway. A spacer is an add-on device for use with a pressurized metered-dose inhaler (pMDI). It consists of a reservoir
15、 into which the aerosol medication is dispensed and has no inhalation or exhalation valves to contain the medication after actuation of the inhaler. A holding chamber is an add-on device for use with a pMDI. It incorporates a reservoir but also utilizes an inhalation valve and possibly an exhalation
16、 valve, or is structurally designed, to retain the medication until inhalation by the user. The presence of an inhalation valve is the critical design feature; an exhalation valve is a design option. pMDIs are used with many different medications, on patients with a wide variety of physical capabili
17、ties and breathing patterns. Recognizing that no test can predict the performance of an S-HC with all medications and all patient populations, the tests outlined in this Standard are designed to provide a general indication of the effectiveness of the device. They are not intended to discern fine gr
18、adations of performance. S-HCs intended for use with a particular medication, or in a patient group with a specific medical profile, should also be tested under the conditions of intended use. The requirements of the Standard address the following critical factors: (a) Physical safety and durability
19、 of the device (shattering, loose parts, etc): this includes inspection for loose parts and small detachable parts, a test to demonstrate that the device is shatterproof, tests for performance after washing or disinfection, and tests of function after exposure to environmental challenges. (b) Effect
20、iveness of the device in delivering medication to the patient: this is based on in vitro testing, to ensure that the device delivers at least the same effective dose as the pMDI alone. (c) Labelling: this includes information supplied with the S-HC, to help users and health care professionals choose
21、 the right device and to help ensure the proper use and maintenance of the device. 1. Scope 1.1 This Standard sets out requirements for spacers and/or holding chambers (S-HCs) for use with pressurized metered-dose inhalers. It stipulates the material and components, the packaging and labelling, and
22、aerosol characterization as determined by in vitro testing. 1.2 This Standard does not address (a) pressurized metered-dose inhalers (pMDIs) and the medications that are delivered by these units; (b) S-HCs used with pMDIs in ventilator circuits or artificial airways; (c) S-HCs for use with dry powde
23、r inhalers or nebulizers; (d) tests of mask fit in S-HCs that are supplied with a mask; Z264.1-02 Canadian Standards Association January 2008 2 (Replaces p. 2, October 2002) (e) products that combine a pMDI and an integrated, usually non-detachable, S-HC in the same unit; and Note: These products ar
24、e covered by Canadian regulations governing pharmaceuticals. (f) the clinical effects and efficacy of medications when used in conjunction with S-HCs. Note: Clinical studies and professional literature should be consulted for information on the efficacy and long-term effects of the medications thems
25、elves. 1.3 This Standard does not address the interface between the S-HC and the pMDI canister on spacers and/or holding chambers with integral actuators. Note: It is expected that an S-HC with an integral actuator will meet the requirements of this Standard. 1.4 In CSA Standards, “shall” is used to
26、 express a requirement, i.e., a provision that the user is obliged to satisfy in order to comply with the standard; “should” is used to express a recommendation or that which is advised but not required; and “may” is used to express an option or that which is permissible within the limits of the sta
27、ndard. Notes accompanying clauses do not include requirements or alternative requirements; the purpose of a note accompanying a clause is to separate from the text explanatory or informative material. Notes to tables and figures are considered part of the table or figure and may be written as requir
28、ements. Legends to equations and figures are considered requirements. 2. Reference Publications This Standard refers to the following publications and where such reference is made it shall be to the edition listed below: Health Canada Canadian Medical Devices Regulations, SOR/DORS/98-282; Guidance f
29、or the Labelling of Medical Devices, Sections 21 to 23 of the Medical Devices Regulations, Therapeutic Products Directorate. UK Aerosol Society Nagel, M.W. et al (2003). Delay testing of valved holding chambers (VHCs) with a new apparatus. Drug Delivery to the Lungs XIV. London, UK: 7982; Nagel, M.W
30、. et al (2003). In vitro performance of a new non-electrostatic, transparent valved holding chamber (VHC). Drug Delivery to the Lungs XIV. London, UK: 7174. US Department of Defense MIL-STD-810E-1989, Environmental Test Methods and Engineering Guidelines. USP* Publication US Pharmacopeia (First Supp
31、lement to the Twenty-Fourth Edition), 2000. Chapter 601: Aerosols, Metered-Dose Inhalers, and Dry Powder Inhalers, 26742688. Other publication Rau, J.L. et al (2006). The importance of nonelectrostatic materials in holding chambers for delivery of hydrofluoralkane albuterol. Respir Care, 51(5): 5035
32、10. *US Pharmacopeial Convention. Canadian Standards Association Spacers and Holding Chambers for Use with Metered-Dose Inhalers January 2008 2A3. Definitions The following definitions apply in this Standard: Actuator the device normally supplied with the pMDI for enabling a metered dose of medicati
33、on to be released from the pressurized canister; usually integrated with a mouthpiece as a single unit. Breathing simulator a testing device that delivers predetermined inhalation-exhalation cycles to the spacer or holding chamber, simulating patient use. Cascade impactor a testing device that class
34、ifies and collects aerosol particles in specified ranges according to their aerodynamic particle size (aerodynamic diameter). Blank page Canadian Standards Association Spacers and Holding Chambers for Use with Metered-Dose Inhalers January 2008 (Replaces p. 25, October 2002) 25Note: It is not necess
35、ary to wash the surfaces of the stage jet-plates and inlet cone leading from the induction port to the impactor if total impactor internal losses are known to be less than 5% of the label claim dose from validation experiments. It is, however, good practice to periodically rinse the entire impactor
36、with a suitable solvent and always to rinse it before a change of formulation. The frequency of periodic cleaning will be determined by the user from experience with the formulations involved with these measurements. B1.4.18 If a filter is present, remove it carefully from its retainer below the fin
37、al stage and deposit it in a suitable container. Add an accurately known volume of solvent (typically 10 mL), and allow a suitable amount of time to elapse for any drug to desorb from the filter medium. Withdraw a sample from the container via a syringe and transfer the contents to a cuvette or vial
38、 via an in-line filter (0.2 m porosity) to remove any fibres or suspended material. B1.4.19 Using the method of analysis specified by the manufacturer of the formulation or by an appropriate, validated technique that meets the requirements for accuracy and precision, determine the mass of drug colle
39、cted on each of the disassembled components. B1.4.20 The total mass of drug collected on all components (material balance) divided by the total number of actuations (A in Table B1) shall be within 25% of the label claim dose (LCD). Note: If LCD is specified ex actuator, exclude the mass collecting i
40、n the actuator in this calculation (the mass collecting on the inhaler valve stem is not analyzed). If the total mass recovered is outside of this range, repeat the test. B1.4.21 A is the total mass recovered from the system, excluding the pMDI canister valve stem, and is used to determine if the ma
41、terial recovery is acceptable in cases where LCD is expressed ex metering valve of the pMDI (ie, metered dose). B defines the mass delivered by the S-HC to the induction port and impactor, equivalent to the emitted dose from the S-HC (EDS-HC), and is used to determine if the material recovery is acc
42、eptable in cases where LCD is expressed ex actuator mouthpiece of the pMDI. Either of these measures may therefore be used to determine if the drug recovery (mass balance) is acceptable, depending on the label claim of the formulation. Note: It is insufficient to determine only the mass recovered fr
43、om the impactor excluding the induction port. B1.5 Delay Testing B1.5.1 HCs are by design capable of delivering some of the medication even if the patient delays inhalation for a short time following actuation of the pMDI. These devices shall therefore be subjected to the following test, in which a
44、2 s delay is introduced between actuation and sampling by the impactor to represent the typical delay that may occur in their use. An apparatus has been designed and validated that can be incorporated into the testing set-up, enabling the delay time between pMDI actuation and aerosol sampling to be
45、varied. A description of the delay apparatus components and their use is given in several published papers J.L. Rau et al (2006); M.W. Nagel et al (2003). Note: Spacers, by definition, do not have an inhalation valve, and therefore cannot be effectively used with delay. If delay occurs, the medicati
46、on is likely to escape via the patient interface or be mixed with exhaled air before inhalation can take place. Because the purpose of this test is to evaluate the efficacy of add-on devices when used by a poorly coordinated patient, spacers need not be evaluated unless the manufacturer has made a c
47、laim that the device performance is not compromised by uncoordinated use. The fact that testing described in this Clause has not been performed should be recorded in the test report for the spacer to make it clear that its efficacy under these conditions has not been verified. B1.5.2 Actuation of th
48、e inhaler shall take place with the patient interface (mouthpiece or face mask adapter) of the HC disconnected from the induction port and at a defined distance of not less than 20 cm from its entry, preferably at right-angles above or below the plane of the induction port. Z264.1-02 Canadian Standa
49、rds Association January 2008 26 (Replaces p. 26, October 2002) Note: The purpose of locating the patient interface away from the induction port entry is to avoid capture of aerosol that may be released momentarily from the HC at the time of pMDI actuation (“blow-by” component). This aerosol is not available to the patient under these circumstances. B1.5.3 The patient interface of the HC shall be connected to the induction port at the expiry of the specified delay period with an airtig
