Challenge Sets and Methods of Making and Using the Same

Abstract

A surrogate challenge set including a plurality of containers containing a fluid, wherein at least one of the containers contains particulate matter; and reference probability-of-detection (POD) data for the at least one container containing the particulate matter is described. The fluid may be water containing at least about 0.5 wt % of a preservative, such as benzyl alcohol. The containers may be pharmaceutically acceptable containers such as vials, bottles, syringes, ampules and intravenous bags. The particulate matter may consist of a single particle having a particle size of at least about 50 μm. A method of making the challenge set may include: disposing particulate matter in at least one of a plurality of containers comprising a fluid; generating probability-of-detection (POD) data for the plurality of containers; and including the probability-of-detection (POD) data in the challenge set. Methods of using the surrogate challenges sets are also provided.

What is claimed is: 
     
         1 . A challenge set comprising:
 a plurality of containers containing a fluid, wherein at least one of the containers contains particulate matter; and   reference probability-of-detection (POD) data for the at least one container containing the particulate matter.   
     
     
         2 . The challenge set of  claim 1 , wherein the fluid is water containing at least about 0.5 wt % of a preservative. 
     
     
         3 . The challenge set of  claim 1 , wherein the containers are pharmaceutically acceptable containers selected from the group consisting of vials, bottles, syringes, ampules and intravenous bags; and the containers are made of glass or plastic. 
     
     
         4 . The challenge set of  claim 2 , wherein the preservative is benzyl alcohol or EDTA. 
     
     
         5 . The challenge set of  claim 1 , wherein the particulate matter consists of a single particle. 
     
     
         6 . The challenge set of  claim 1 , wherein the particulate matter has a particle size of at least about 50 μm. 
     
     
         7 . The challenge set of  claim 1 , wherein about 10% to about 20% of the plurality of containers contain particulate matter. 
     
     
         8 . The challenge set of  claim 1 , having a usable shelf-life of at least about 3 years. 
     
     
         9 . The challenge set of  claim 1 , wherein the particulate matter is glass, rubber, metal, fibers or combinations thereof. 
     
     
         10 . The challenge set of  claim 1 , wherein the reference probability-of-detection (POD) data for the at least one container containing particulate matter is obtained at a pre-defined light intensity. 
     
     
         11 . A method of making a challenge set comprising:
 disposing particulate matter in at least one of a plurality of containers comprising a fluid; and   including reference probability-of-detection (POD) data for the at least one container containing the particulate matter in the challenge set.   
     
     
         12 . The method of  claim 11 , further comprising generating the probability-of-detection (POD) data for the at least one container containing the particulate matter. 
     
     
         13 . The method of  claim 12 , wherein generating the reference probability-of-detection (POD) data for the at least one container containing the particulate matter comprises:
 inspecting, multiple times, each of the plurality of containers containing the particulate matter;   recording, for each inspection, whether or not the particulate matter was detected; and   developing a statistical likelihood of detecting the particulate matter.   
     
     
         14 . The method of  claim 12 , wherein generating the probability-of-detection (POD) data for the at least one container containing particulate matter is carried out at a pre-defined light intensity. 
     
     
         15 . The method of  claim 11 , wherein the fluid is water containing at least about 0.5 wt % of a preservative. 
     
     
         16 . The method of  claim 11 , wherein the containers are pharmaceutically acceptable containers selected from the group consisting of vials, bottles, syringes, ampules and intravenous bags; and the containers are made of glass or plastic. 
     
     
         17 . The method of  claim 11 , wherein the particulate matter has a particle size of at least about 50 μm. 
     
     
         18 . The method of  claim 11 , wherein the particulate matter is glass, rubber, metal, fibers or combinations thereof. 
     
     
         19 . The method of  claim 15 , wherein the preservative is benzyl alcohol or EDTA. 
     
     
         20 . The method of  claim 11 , wherein the particulate matter consists of a single particle. 
     
     
         21 . The method of  claim 11 , wherein about 10% to about 20% of the plurality of containers contain particulate matter. 
     
     
         22 . A method of using a challenge set, the challenge set comprising: a plurality of containers containing a fluid, wherein at least one of the containers contains particulate matter; and reference probability-of-detection (POD) data for the at least one container containing the particulate matter; the method comprising:
 generating comparative probability-of-detection (POD) data for the at least one container containing the particulate matter; and   comparing the comparative probability-of-detection (POD) data for the at least one container containing the particulate matter against the reference probability-of-detection (POD) data for the at least one container containing the particulate matter.   
     
     
         23 . The method of  claim 22 , wherein generating the comparative probability-of-detection (POD) data for the at least one container containing the particulate matter comprises:
 inspecting, multiple times, each of the plurality of containers containing the particulate matter;   recording, for each inspection, whether or not the particulate matter was detected; and   developing a statistical likelihood of detecting the particulate matter.   
     
     
         24 . The method of  claim 22 , wherein generating the comparative probability-of-detection (POD) data for the at least one container containing the particulate matter is carried out at a same pre-defined light intensity as the reference probability-of-detection (POD) data for the at least one container containing the particulate matter. 
     
     
         25 . The method of  claim 22 , wherein the fluid is water containing at least about 0.5 wt % of a preservative. 
     
     
         26 . The method of  claim 22 , wherein the containers are pharmaceutically acceptable containers selected from the group consisting of vials, bottles, syringes, ampules and intravenous bags; and the containers are made of glass or plastic. 
     
     
         27 . The method of  claim 22 , wherein the particulate matter has a particle size of at least about 50 μm. 
     
     
         28 . The method of  claim 22 , wherein the particulate matter is glass, rubber, metal, fibers or combinations thereof. 
     
     
         29 . The method of  claim 25 , wherein the preservative is benzyl alcohol or EDTA. 
     
     
         30 . The method of  claim 22 , wherein the particulate matter consists of a single particle. 
     
     
         31 . The method of  claim 22 , wherein about 10% to about 20% of the plurality of containers contain particulate matter. 
     
     
         32 . The challenge set of  claim 1 , wherein the fluid is aqueous based, drug product based or placebo based. 
     
     
         33 . The method of  claim 11 , wherein the fluid is aqueous based, drug product based or placebo based. 
     
     
         34 . The method of  claim 22 , wherein the fluid is aqueous based, drug product based or placebo based.