Vaccine nebulizers

Abstract

The invention provides a method of selecting or optimising a nebuliser device to be used to deliver a vaccine comprising selecting a nebuliser capable of producing a plurality of vaccine particles having the following particle droplet size distribution: (i) D v10 : 2.0 + /−0.2 μm (ii) D v50 : 5.0 + /−0.5 μm (iii) D v90 : 10.0 + /−1.0 μm (iv) a mean mass aerodynamic diameter (MMAD) of 4.5 to 8.0 μm This allows the selection of, for example, commercially available nebulisers, previously used for drug delivery, for vaccine delivery. This considerably reduces the work required to identify suitable nebulisers. The additional preferred features are disclosed for the selection of nebulisers for use in mass vaccination programs. Nebulisers identified by the methods of the invention are also claimed.

1 . A method of selecting or optimising a nebuliser device to be used to deliver a vaccine comprising selecting a nebuliser device capable of producing a plurality of vaccine particles having the following particle droplet size distribution:
 (i) D v10 : 2.0 + /−0.2 μm   (ii) D v50 : 5.0 + /−0.5 μm   (iii) D v90 : 10.0 + /−1.0 μm   (iv) a mean mass aerodynamic diameter (MMAD) of 4.5 to 8.0 μm   
   
   
       2 . A method according to  claim 1 , wherein the mean mass aerodynamic diameter (MMAD) is 6.5 μm with a Geometric Standard Deviation (GSD) of 1.7. 
   
   
       3 . A method according to any preceding claim, wherein in use the nebuliser device allows at least 75% potency retention for reconstituted vaccine delivered by the nebuliser device to a patient after 40 doses have been delivered by the device, preferably using Edmonston-Zagreb vaccine. 
   
   
       4 . A method according to any preceding claim wherein the nebuliser device is provided with a receptacle for receiving two or more doses of vaccine. 
   
   
       5 . A method according to any preceding claim, wherein the nebuliser device is selected to produce a substantially consistent dose delivery between uses. 
   
   
       6 . A method according to any preceding claim wherein at least 95% of the particles are greater than 0.5 μm in diameter (MMAD). 
   
   
       7 . A method according to  claim 3 , wherein the potency retention is achieved without the use of cooling of the reconstituted vaccine. 
   
   
       8 . A method according to any preceding claim, wherein the nebuliser device is selected so that it provides an immunizing dose of vaccine to an infant or child within 40 to 20 seconds. 
   
   
       9 . A method according to any one of  claims 4  to  8 , wherein the receptacle for receiving the two or more doses of vaccine, optionally together with a nebulising element, is detachable to allow the receptacle, with vaccine in place to be stored between vaccinations, substantially without contaminating the vaccine within the receptacle 
   
   
       10 . A method according to any preceding claim, wherein the nebuliser device comprises a piezoelectric nebulising element. 
   
   
       11 . A method according to any preceding claim, the nebuliser device comprising a compressor or other air delivery means. 
   
   
       12 . A method according to  claim 11  wherein the compressor or other air delivery means comprises an air intake filter means capable of filtering airborne microorganisms. 
   
   
       13 . A method according to any preceding claim wherein the nebuliser device comprises a face mask, or other suitable interface, adapted to fit substantially to the contours of a patient's face when in use. 
   
   
       14 . A method according to any preceding claim, wherein a nebuliser element is attached to a face mask, mouthpiece or nasal prongs via a spacer. 
   
   
       15 . A method according to any preceding claim wherein the nebuliser device comprises one or more air hoses between two or more of the components defined in any preceding claim. 
   
   
       16 . A method according to any preceding claim, wherein one or more of the receptacle, nebuliser element, face mask, mouthpiece, nasal prong, filter or air hose are disposable. 
   
   
       17 . A method according to any preceding claim, wherein the nebuliser device comprises a one-way valve between the patient, a nebuliser element and/or compressor when used. 
   
   
       18 . A method according to any preceding claim wherein the nebuliser device weighs less than 3 kg. 
   
   
       19 . A method according to any preceding claim wherein an energy source for the nebuliser comprises a rechargeable battery. 
   
   
       20 . A method according to any preceding claim wherein the nebuliser device is provided with a needle-free vaccine loading device. 
   
   
       21 . In combination, a nebuliser device having two or more of the characteristics identified by the methods of  claims 1  to  21 , in combination with a vaccine in a receptacle. 
   
   
       22 . A nebuliser device comprising two or more of the following properties:
 (a) in use, the nebuliser device is capable of producing vaccine particles having the following particle droplet size distribution:
 (i) D v10 : 2.0 + /−0.2 μm 
 (ii) D v50 : 5.0 + /−0.5 μm 
 (iii) D v90 : 10.0 + /−1.0 μm. 
 (iv) a mean mass aerodynamic diameter (MMAD) of 4.5 to 8.0 μm 
   (b) a piezoelectric nebulising means;   (c) a compressor having an air intake filter capable of filtering airborne microorganisms;   (d) a face mask adapted to fit substantially to the contours of the face of a patient;   (e) a nebuliser element attached to a face mask, or other suitable interface, adapted to fit substantially to the contours of a patient's face when in use;   (g) a rechargeable receptacle;   (h) one or more of a receptacle for receiving a supply of vaccine, a nebuliser means, a mouthpiece, a nasal prong, a filter and/or an air hose are disposable and/or   (i) a receptacle for receiving the two or more doses of vaccine, optionally together with a nebuliser element is detachable to allow the receptacle, with vaccine in place to be stored between vaccinations, substantially without contaminating the vaccine within the receptacle   
   
   
       23 ) A nebuliser device according to  claim 22  comprising:
 (a) in use, the nebuliser device is capable of producing vaccine particles having the following particle droplet size distribution:
 (i) D v10 : 2.0 + /−0.2 μm 
 (ii) D v50 : 5.0 + /−0.5 μm 
 (iii) D v90 : 10.0 + /−1.0 μm. 
 (iv) a mean mass aerodynamic diameter (MMAD) of 4.5 to 8.0 μm 
   (e) a nebuliser element attached to a face mask, or other suitable interface, adapted to fit substantially to the contours of a patient's face when in use;   (g) a rechargeable receptacle; and   (i) a receptacle for receiving the two or more doses of vaccine, optionally together with a nebuliser element is detachable to allow the receptacle, with vaccine in place to be stored between vaccinations, substantially without contaminating the vaccine within the receptacle   
   
   
       24 . A nebuliser device according to  claim 22  or  claim 23 , in combination with a vaccine. 
   
   
       25 . A method of administering a vaccine comprising providing the vaccine as an aerosol via a nebuliser device as defined in  claim 21 ,  claim 22 ,  claim 23  or  claim 24 . 
   
   
       26 . Use of a nebuliser device according to any one of claims  claim 21  to  24 , to administer a vaccine to a patient. 
   
   
       27 . A vaccine kit comprising a nebuliser device according to any one of  claims 21  to  24  and a vaccine. 
   
   
       28 . A kit according to  claim 27  additionally comprising a rechargeable battery as a source of energy for the nebuliser device. 
   
   
       29 . A kit according to  claim 27  or  claim 28  in a lockable, watertight carrying case.