INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specification are incorporated herein by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

FIELD

The present disclosure relates to inspection systems, in particular to systems and methods for inspecting the contents of glass vials and identifying materials found therein.

BACKGROUND

Various products such as medicines are provided in glass vials. Medicines are often provided in a lyophilized form. Lyophilization is a freeze-drying process that removes water from a product after it is frozen and placed under a vacuum. Some of the typical pharmaceutical products that undergo lyophilization include bulk pharmaceutical/biopharmaceutical ingredients (chemical or biologics found in nature), protein, collagen, peptide, oligonucleotide, chemical API, enzymes, and monoclonal antibodies. If the bulk drug ingredients are not stable in liquid or frozen form, lyophilization is highly advantageous. This can be due to chemical reactions, degradation, aggregation, biological growth, heat sensitivity, etc. Lyophilization enables longer shelf life, often as long as two-five years and makes it much easier to transport the product. In addition, products can be stored at room temperature.

During the manufacture of pharmaceuticals, vial filling and/or lyophilization processes, contaminate particles may inadvertently be introduced into the vial. These particles need to be analyzed in order to determine their source and prevent similar particles from being introduced into later vials being processed. Typical analysis of the contaminate particles involves reconstitution and filtering of lyophilized product in order to isolate a particulate for analysis. This traditional process has the potential of introducing additional foreign particulate, can result in the loss of the particulate being analyzed, and can be time consuming.

What is needed and not provided by the prior art are improved systems and methods to inspect contaminants found in lyophilized medicines within glass vials.

SUMMARY OF THE DISCLOSURE

The present disclosure relates to systems and methods for inspecting/identifying the contents of a glass vial. The present disclosure provides new ways of accessing lyophilized cakes using the principals of glass fracture mechanics, and shows how Atomic Emissions Spectroscopy (AES)/Laser-induced breakdown spectroscopy (LIBS) can be used to identify a certain category of suspected particulate in a lyophilized protein cake.

According to aspects of the disclosure, a method of inspecting and performing material identification of a contaminant found in a vial containing a cake of lyophilized medicine is provided. In some embodiments, the method includes identifying the presence of a contaminant in the lyophilized medicine, detaching a base or other portion of the vial to create an enlarged opening in the vial, removing substantially an entire cake of lyophilized medicine through the enlarged opening, and analyzing the contaminant using an atomic emissions spectroscopy (AES) technique.

In some embodiments of the above method, the AES technique comprises laser-induced breakdown spectroscopy (LIBS). In some embodiments, the contaminant remains on the lyophilized cake while being analyzed by LIBS equipment. In some embodiments, the contaminant is a speck and may comprise stainless steel.

In some embodiments, the step of detaching the portion of the vial includes scoring a heel of the vial. A fixture may be used to position the vial relative to an awl. In some embodiments, the fixture allows the vial to be rotated relative to the awl. The vial has a central longitudinal axis and the fixture may hold the vial such that its axis is at a non-perpendicular angle relative to the awl. In some embodiments, the non-perpendicular angle is about 75 degrees. The step of detaching the portion of the vial may include applying a force to the base of the vial at a diameter that is smaller than a diameter of the base. In some embodiments, the force is applied to the base at a diameter that is about half of the diameter of the base. A force gauge may be used to measure the force being applied to the base. In some embodiments, the force gauge is mounted on a press configured to move the force gauge relative to the vial. The step of detaching the portion of the vial may include tapping a heel of the vial.

In some embodiments, the method further includes confirming the occurrence of the contaminant at least three times. The step of analyzing the contaminant may include comparing a signal associated with the contaminant with a signal associated with a sample taken from a component of pharmaceutical processing equipment. In some embodiments, the contaminant signal is compared to a library comprising at least ten samples taken from different components of pharmaceutical processing equipment.

