Patent Description:
Various products such as medicines are provided in glass vials. Medicines are often provided in a liquid or lyophilized form. Small cracks or fissures may develop in the glass vials, either before or during the vial filling process. These defects often occur in the heel of the vial (i.e. its outer, bottom edge) or just beneath the neck where the cap attaches to the top of the vial. These defects can be difficult to detect and can compromise the integrity of the vial and/or its contents. For example, medicine may leak from the vial through the crack. Air, moisture or other contaminants may enter the vial through the crack and contaminate the medicine. A fissure may propagate into a larger crack and cause the vial to break open. When this occurs at the base of the vial it is referred to as "lensing.

What is needed and not provided by the prior art are improved systems and methods to detect lensed vials.

The present invention relates to an inspection system according to claim <NUM> and inspection methods according to claim <NUM> and claim <NUM>.

In some embodiments, the light source is a flashlight and the stand is configured to receive the flashlight in a central bore therein. The stand may be configured to hold the light source in a vertical orientation and configured to hold the vial above the light source. In some embodiments, the stand further comprises a base having a generally square shape. According to the invention a top portion of the stand is provided with at least two castellations. A top portion of the stand is configured to hold a first type of vial, and the top portion is configured to releasably receive a vial adapter for holding a second type of vial that is different from the first type of vial. The adapter includes a plurality of recesses around its circumference, wherein the recesses are configured to mate with castellations extending from the stand. The recesses and castellations cooperate to prevent the adapter from rotating with respect to the stand. The system may further comprise multiple vial adapters, each configured to receive a different type of vial.

In some embodiments, the system further comprises a vial adapter configured to hold a vial at a non-vertical angle. The vial adapter may be configured to hold a vial at an angle that is about <NUM> degrees from vertical. In some embodiments, the system may further comprise a bottom lid configured to releasably retain the light source within the internal cavity of the stand.

According to other aspects of the disclosure, methods of inspecting a glass vial are provided. The method includes providing an illumination and inspection system as described above, inserting a glass vial into the recess of the stand, and inspecting the vial for defects. The method further includes spinning the vial within the recess while.

inspecting the vial for defects. In some embodiments of the method, the vial is spun at least two revolutions.

Before the present invention is further described, it is to be understood that this disclosure is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present disclosure will be limited only by the appended claims.

The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, and are also encompassed within the invention, subject to any specifically excluded limit in the stated range.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, the preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited.

It must be noted that as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "the component" includes reference to one or more components, and so forth.

The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present disclosure is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed.

Referring to <FIG>, an exemplary glass medicine vial <NUM> is shown. Medicine vials are manufactured in various shapes and sizes, but typically have a main portion <NUM> of constant diameter, a neck <NUM> having a reduced diameter, and a lip <NUM> or flange located around the vial opening (not shown) at the top of the neck <NUM>. Flange <NUM> may have a diameter greater than that of neck <NUM> to provide an undercut portion or collar <NUM>. After vial <NUM> is filled with medicine, the top may be sealed with a septum material or crown <NUM> held in place by a metal band, crimp, seal or finish <NUM> that covers a portion of crown <NUM>, flange <NUM> and collar <NUM>. Crown <NUM> may be pierced with a hypodermic needle to withdrawn medicine from the vial into a syringe. The curved edge located at the bottom of main portion <NUM> as the sidewalls <NUM> transition into the bottom surface or base <NUM> of the vial may be referred to as the heel <NUM> of the vial.

Lensing (which is identifiable by the base of the vial detached from the body) may occur in the glass vial. A vial lensing event is preceded by a defect in the heel <NUM> of the vial <NUM> that can be difficult to detect due to refraction of light in the curvature of the vial heel. A defect in the neck of the vial can also occur during crimping of the seal. Though this neck defect is not considered lensing, it can also be difficult to detect due to the seal partially obscuring it.

The above-described defects can compromise the integrity of the vial and/or its contents. For example, in some cases medicine might leak from the vial through the crack. Air, moisture or other contaminants might enter the vial through the crack and contaminate the medicine. A fissure might propagate into a larger crack and cause the vial to break open. Therefore, detecting a defect in a vial before any of the above adverse consequences occurs is desirable. Detecting defects as early as possible allows a vial to be removed from distribution early, thereby increasing public safety and reducing costs. According to aspects of the present disclosure, vials may be inspected for cracks or fissures immediately before and/or after filling and sealing.

Referring to <FIG>, a first exemplary embodiment of a vial illumination and inspection system <NUM> constructed according to aspects of the present disclosure will be described. In this exemplary embodiment, inspection system <NUM> is configured to hold one vial <NUM> at a time for inspection, with each vial <NUM> being a <NUM> cc clear glass vial, but system <NUM> may be modified to inspect other sizes and types of vials, as will be subsequently described. System <NUM> includes a vial stand bottom <NUM> and a vial stand top <NUM>. Vial stand bottom <NUM> may be provided with a base <NUM> that has a generally square shape as shown to increase stability and allow system to be more easily indexed in a desired orientation. Vial stand bottom <NUM> has an internal cavity (not shown) configured to receive a light source <NUM>. Light source <NUM> shines light in an upward direction toward vial <NUM>. In this exemplary embodiment, light source <NUM> is a standard LED flashlight with a maximum diameter of <NUM> inch, but other types of light sources may also be used, such as a remotely located light source optically coupled to vial stand bottom <NUM> with a fiber optic bundle. An upper cylindrical portion of stand bottom <NUM> may be provided with an external groove <NUM> sized to partially receive an O-ring <NUM>. In some embodiments, vial stand bottom <NUM> and vial stand top <NUM> may be fabricated from a thermoplastic, such as a polylactic acid (PLA. ) These components may be produced using <NUM>-D printing, injection molding or other fabrication techniques.

Referring to <FIG>, vial stand top <NUM> may be provided with an internal bore <NUM> sized to receive the upper cylindrical portion of stand bottom <NUM>. Internal bore <NUM> may be provided with an internal groove <NUM> sized to partially receive O-ring <NUM>. With this arrangement, vial stand top <NUM> may be slid on to vial stand bottom <NUM> and releasably locked in place by O-ring <NUM>.

Vial stand top <NUM> may be configured to hold one <NUM> cc clear glass vial in an inverted position such that its heel may be inspected for defects. As shown in <FIG>, stand top <NUM> may be provided with an internal cavity <NUM> for receiving vial <NUM>. Cavity <NUM> may have a stepped down portion <NUM> sized to abut against the shoulder of vial <NUM> so that the vial is maintained at a predetermined height. In this exemplary embodiment, the bottom surface of vial <NUM> is recessed below the top edge <NUM> of stand top <NUM> when fully inserted therein so that stand top <NUM> provides a uniform background for viewing the bottom surface or 'base' of the vial. This white uniform background enhances an inspector's ability to identify dark/opaque defects that may be present on the base of lower sidewall regions of the vial. In other embodiments, the bottom surface of vial <NUM> may be flush with or stand proud of top edge <NUM>. Stand top <NUM> may be made from or coated with a white material to aid in inspecting vial <NUM>. Stand top <NUM> may be provided with a cutout portion <NUM> extending circumferentially <NUM> degrees as shown for exposing a portion of the side of vial <NUM>. With this arrangement, an inspector can rotate vial <NUM> while it is inserted in stand top <NUM>, such as by using his or her thumb on the side of the vial.

As shown in <FIG>, system <NUM> may be provided with a diffusion plate <NUM> in stand bottom <NUM> between light source <NUM> and vial <NUM> to optimize the lighting conditions for locating defects in vial <NUM>. In some embodiments, diffusion plate <NUM> is <NUM> thick. In some embodiments, multiple diffusion plates of various thicknesses are provided and are configured to be interchangeable depending on the type of defects being inspected. A bottom lid or spacer ring <NUM> may be located inside the bottom of vial stand bottom <NUM> to retain light source <NUM> therein. Bottom lid <NUM> may be provided with an outside diameter that is larger than the inside diameter of stand bottom <NUM>, and its circumference may be provided with a longitudinal gap. With this arrangement, bottom lid <NUM> may be flexed inward (narrowing the longitudinal gap) when inserting or removing it from stand bottom <NUM>. When inside the stand bottom <NUM>, bottom lid <NUM> exerts an outward force that retains itself and light source <NUM> within stand bottom <NUM>. This allows for easy removal and access to an on/off switch of light source <NUM>.

In operation, an inspector removes bottom lid <NUM> and/or light source <NUM> to turn on the light source, and replaces both in vial stand bottom <NUM>. In some embodiments (not shown), light source <NUM> may be inserted from the top of vial stand bottom <NUM> with or without first removing vial stand top <NUM>. The inspector then places a vial <NUM> in the top recess of vial stand top <NUM> in an inverted orientation. The lighting, viewing and background conditions provided by inspection system <NUM> allow defects in the heel of vial <NUM> to be more easily detected. The inspector may rotate vial <NUM>, vial stand top <NUM> and/or vial stand bottom <NUM> at least <NUM> degrees to view it from every angle. In some implementations, vial <NUM> may then be removed and replaced in stand top <NUM> in an upright orientation to inspect other portions of vial <NUM>, such as the neck region just below the seal. Vial <NUM> may then be removed from system <NUM> and replaced with the next vial to be inspected. If the inspector desires to inspect a different vial type and/or inspect for a different defect type, vial stand top <NUM> may be removed from vial stand bottom <NUM> and replaced with a different vial stand top customized for the different vial type and/or defect type. Diffuser <NUM> may also be replaced with a different diffuser at this time.

Referring to <FIG>, a second exemplary embodiment of a vial illumination and inspection system <NUM> constructed according to aspects of the present disclosure will be described. Inspection system <NUM> is constructed and operated in a similar manner to system <NUM>. In this exemplary embodiment, inspection system <NUM> includes a vial defect illumination stand <NUM> that is configured to receive light source <NUM> within a central cavity from below. A light source pedestal <NUM> may be provided within illumination stand <NUM> to retain light source <NUM> and raise it as close as possible to vial <NUM>. Light from source <NUM> travels upward through the central cavity of stand <NUM> to illuminate vial <NUM>, which is received directly in the top of stand <NUM> in an inverted orientation. In some embodiments, stand <NUM> is configured to receive a <NUM> cc glass vial.

The top of illumination stand <NUM> may be provided with two, three or more castellations <NUM>. In this exemplary embodiment, castellations <NUM> serve several functions. First, they are configured to hold vial <NUM> securely while allowing more complete viewing of the illuminated vial. A reduced diameter shoulder <NUM> at the base of castellations <NUM> allows the inverted neck of vial <NUM> to extend into stand <NUM> but prevents the main body of the vial from descending below castellations <NUM>. Therefore, the bottom heel and entire main body of vial <NUM> may be viewed as it is rotated within castellations <NUM>. Additionally, castellations <NUM> serve to releasably interlock with mating recesses on vial adapters, as will be subsequently described, to prevent rotation of the adapters relative to stand <NUM>, and to prevent light from escaping from between the adapters and stand <NUM>.

Referring to <FIG>, vial inspection system <NUM> is shown with a vial adapter <NUM>. Adapter <NUM> fits into the top of illumination stand <NUM> (where a <NUM> cc vial fits as previously described) and allows a <NUM> cc vial to be illuminated and inspected for defects. In this exemplary embodiment, adapter <NUM> has three recesses <NUM> arranged around its lower periphery and configured to receive the three castellations <NUM> extending from the top of stand <NUM>. Adapter <NUM> has a central bore configured to receive a <NUM> cc vial in an upright orientation. In some embodiments, adapter <NUM> has a cutout portion <NUM> as shown that allows part of the main body and/or bottom heel of vial <NUM> to be inspected. As previously described, the entire main body and/or heel may be inspected by rotating vial <NUM> within adapter <NUM>. Adapter <NUM> has an upper portion that may be inclined relative to a lower portion of the adapter. In some embodiments, the angle of inclination is <NUM> degrees from vertical, as shown in <FIG>. Applicants have found this angle to provide exceptional illumination of defects in vial <NUM>. In other embodiments, the angle of inclination is between about <NUM> and about <NUM> degrees from vertical. Adapter <NUM> may be made from or coated with a dark colored or opaque material to reduce light bleed through the adapter.

Referring to <FIG>, various dimensioned views of vial adapter <NUM> as described above are provided.

Referring to <FIG>, vial inspection system <NUM> is shown with a vial adapter <NUM>. Adapter <NUM> fits into the top of illumination stand <NUM> (where a <NUM> cc vial fits as previously described) and allows a <NUM> cc vial to be illuminated and inspected for defects. In this exemplary embodiment, adapter <NUM> has three recesses <NUM> arranged around its lower periphery and configured to receive the three castellations <NUM> extending from the top of stand <NUM>. Adapter <NUM> has a central bore configured to receive a <NUM> cc vial in an inverted orientation. In some embodiments, adapter <NUM> has a cutout portion <NUM> as shown that allows light from light source <NUM> to ideally illuminate portions of vial <NUM> prone to defects while limiting the amount of light that is directed toward the inspector. A label or inscribed printing <NUM>, such as "FACE THIS SIDE", may be provided on adapter <NUM> opposite cutout portion <NUM> to indicate which side of adapter <NUM> should face the inspector.

The inspection systems disclosed herein may be used to perform spot checking on a lot of vials or may be used to inspect <NUM>% of the vials in a lot. According to aspects of the present disclosure, in some implementations inspection personnel must first be qualified/certified on the use of the fixtures. Once inspectors are qualified on the proper use of the fixtures, a Good Manufacturing Practice (GMP) inspection and release of a vial lot can occur. In some qualification protocols, a kit may be provided with a vial lot containing defects and acceptable vials numbered and randomly assembled. In some cases, there is a mixing of not less than four acceptable vials to one defect vial. The kit may also include a master defect list that describes the defect categories, types and defect location for each vial contained within the kit. Manual inspectors are considered qualified under some protocols when a <NUM>% detection rate of the defects is achieved.

In some embodiments, the following definitions may be used to categorize defects:.

Claim 1:
A glass vial illumination and inspection system comprising:
a light source (<NUM>);
a stand (<NUM>) having an internal cavity configured to receive at least a portion of the light source (<NUM>);
a recess located in the stand (<NUM>) and configured to receive at least a portion of the glass vial (<NUM>); and
a vial adapter (<NUM>);
wherein the stand (<NUM>) is configured to aim light output from the light source (<NUM>) toward the glass vial (<NUM>) to illuminate the vial (<NUM>), and wherein the stand (<NUM>) is configured to position the vial (<NUM>) such that an inspector can manually inspect the illuminated vial (<NUM>) for defects,
wherein a top portion of the stand (<NUM>) is configured to hold a first type of vial (<NUM>), and the top portion is configured to releasably receive the vial adapter (<NUM>) for holding a second type of vial (<NUM>) that is different from the first type of vial (<NUM>),
wherein the top portion of the stand (<NUM>) is provided with at least two castellations (<NUM>),
wherein the adapter (<NUM>) includes a plurality of recesses (<NUM>) around its circumference,
wherein the recesses (<NUM>) are configured to mate with castellations (<NUM>) extending from the stand (<NUM>), and
wherein the recesses (<NUM>) and castellations (<NUM>) cooperate to prevent the adapter (<NUM>) from rotating with respect to the stand (<NUM>), but allow the illuminated vial (<NUM>) to be rotated relative to the adapter (<NUM>) and the stand (<NUM>).