How to remove metal contaminants from glass syringes

Abstract

A method for removing metal-containing contaminants from the surface of a glass syringe includes contacting the surface of the glass syringe with an aqueous treatment medium containing fluoride ions, at least one acid, or both. The metal-containing contaminants are bound to the surface of the glass syringe and are present on the surface at a concentration of 50 ppb or greater prior to contact with the aqueous treatment medium, and contacting the surface with the aqueous treatment medium for a contact time reduces the concentration of the metal-containing contaminants on the surface of the glass syringe by 50% or greater. A method for making a glass syringe includes forming a glass syringe having at least a barrel and a syringe tip, and then removing the metal-containing contaminants from its surface by contacting it with an aqueous treatment medium.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority under 35 U.S.C. § 119 of U.S. Provisional Application No. 63 / 427,293, filed November 22, 2022, the contents of which are incorporated herein by reference in their entirety. [Background technology]

[0002] Technical Field FIELD OF THE INVENTION The present disclosure relates generally to glass syringes, and more particularly to a method for removing metal contaminants from the surface of a glass syringe.

[0003] Background technology Historically, glass has been used as a preferred material for packaging pharmaceuticals due to its hermeticity, optical transparency, and excellent chemical resistance compared to other materials. Specifically, glass used in pharmaceutical packaging must have adequate chemical resistance so as not to affect the stability of the pharmaceutical composition contained therein. Glasses with suitable chemical resistance include glass compositions within the ASTM standard "Type 1B" that have a proven history of chemical resistance. In addition, glass used in pharmaceutical packaging, such as glass syringes, must be substantially free of contaminants and chemical species that interact with the contents of the pharmaceutical packaging and reduce the effectiveness of the pharmaceutical composition contained therein. Summary of the Invention

[0004] According to a first aspect disclosed herein, a method for fabricating a glass syringe may include forming a glass syringe having at least a barrel and a syringe tip, where forming the syringe tip may include contacting at least one surface of the glass syringe with a forming tool, a forming pin, or both, where the contacting may cause migration of metal-containing contaminants to the at least one surface of the glass syringe. The method may further include contacting the at least one surface of the glass syringe with an aqueous treatment medium including fluoride ions, at least one acid, or both, where the contacting with the aqueous treatment medium may remove the metal-containing contaminants from the at least one surface of the glass syringe.

[0005] According to a second aspect disclosed herein, a method for removing metal-containing contaminants from at least one surface of a glass syringe may include contacting at least one surface of the glass syringe with an aqueous treatment medium comprising fluoride ions, at least one acid, or both, and the metal-containing contaminants may be bound to the at least one surface of the glass syringe, and the method may be performed in accordance with U.S.P. <797> The metal-containing contaminants may be present on the at least one surface at a concentration of 8.3 parts per billion by weight (ppbw) or greater prior to contact with the aqueous treatment medium, as determined according to the test method in U.S. Pat. No. 6,629,496. Contacting the aqueous treatment medium with the at least one surface for a contact time may reduce the concentration of metal-containing contaminants on the at least one surface of the glass syringe by 50% or greater.

[0006] A third aspect of the present disclosure may include any one of the first or second aspects, wherein the at least one surface of the glass syringe may be an inner surface of a syringe tip of the glass syringe.

[0007] A fourth aspect of the present disclosure may include any one of the first to third aspects, wherein the concentration of metal-containing contaminants on at least one surface of the syringe is in accordance with the United States Pharmacopoeia <797> When determined according to the test method of the present invention, the concentration may be 8.3 ppbw to 83 ppbw.

[0008] A fifth aspect of the present disclosure may include any one of the first to fourth aspects, wherein contacting at least one surface of the glass syringe with the aqueous treatment medium may remove 50% or more of the metal-containing contaminants from at least one surface of the syringe tip.

[0009] A sixth aspect of the present disclosure may include any one of the first to fifth aspects, wherein after contacting at least one surface of the glass syringe with the aqueous treatment medium, the at least one surface of the glass syringe is coated with a cellulose acetate solution according to the United States Pharmacopoeia <797> The present invention may have a concentration of metal-containing contaminants of less than 8.3 ppbw, 4 ppbw or less, 1 ppbw or less, 0.1 ppbw or less, 100 pptw or less, or 10 pptw or less, as determined in accordance with the test method of

[0010] A seventh aspect of the present disclosure may include any one of the first to sixth aspects, wherein the metal-containing contaminants may include one or more metals selected from the group consisting of tungsten, platinum, rhodium, tantalum, nickel, and combinations thereof.

[0011] An eighth aspect of the present disclosure may include any one of the first to seventh aspects, wherein the metal-containing contaminant may include tungsten or a derivative thereof.

[0012] A ninth aspect of the present disclosure may include any one of the first to eighth aspects, wherein the metal-containing contaminant may include tungsten oxide.

[0013] A tenth aspect of the present disclosure may include any one of the first to ninth aspects, wherein the aqueous treatment medium may include fluoride ions, and the concentration of fluoride ions in the aqueous treatment medium may be about 1000 ppm as calculated using Visual MINTEQ™ software with standard settings.

[0014] An eleventh aspect of the present disclosure may include any one of the first to tenth aspects, wherein the aqueous treatment medium may include fluoride ions, and a concentration of the fluoride ions in the aqueous treatment medium may be 0.001 wt % to 0.15 wt %, based on a total weight of the aqueous treatment medium.

[0015] A twelfth aspect of the present disclosure may include any one of the first through eleventh aspects, wherein the aqueous treatment medium may include a source of fluoride ions selected from the group consisting of hydrogen fluoride (HF), sodium fluoride (NaF), ammonium bifluoride (NHHF), and combinations thereof.

[0016] A thirteenth aspect of the present disclosure may include any one of the first to twelfth aspects, wherein the aqueous treatment medium may include at least one acid.

[0017] A fourteenth aspect of the present disclosure may include the thirteenth aspect, wherein the at least one acid may be an organic acid that is a chelating organic acid.

[0018] A fifteenth aspect of the present disclosure may include any one of the first to fourteenth aspects, wherein the at least one acid may be selected from the group consisting of HCl, HBr, HNO, HSO, HSO, HPO, HPO, acetic acid, citric acid, tartaric acid, ascorbic acid, EDTA, methanesulfonic acid, toluenesulfonic acid, and combinations thereof.

[0019] A sixteenth aspect of the present disclosure may include any one of the thirteenth to fifteenth aspects, wherein the at least one acid may be an organic acid selected from the group consisting of acetic acid, citric acid, tartaric acid, ascorbic acid, EDTA, methanesulfonic acid, toluenesulfonic acid, and combinations thereof.

[0020] A seventeenth aspect of the present disclosure may include any one of the thirteenth to sixteenth aspects, wherein the at least one acid may be citric acid.

[0021] An eighteenth aspect of the present disclosure may include any one of the first to seventeenth aspects, and includes contacting at least one surface of the glass syringe with an aqueous treatment medium comprising fluoride ions and at least one acid.

[0022] A nineteenth aspect of the present disclosure may include any one of the first through eighteenth aspects, wherein the aqueous treatment medium may include a source of fluoride ions selected from the group consisting of hydrogen fluoride (HF), sodium fluoride (NaF), ammonium bifluoride (NHHF), and combinations thereof, and the at least one acid may be selected from the group consisting of HCl, HBr, HNO, HSO, HSO, HPO, HPO, acetic acid, citric acid, tartaric acid, ascorbic acid, EDTA, methanesulfonic acid, toluenesulfonic acid, and combinations thereof.

[0023] A twentieth aspect of the present disclosure may include the nineteenth aspect, wherein the aqueous treatment medium may include citric acid and ammonium bifluoride.

[0024] A twenty-first aspect of the present disclosure may include the twentieth aspect, wherein the aqueous treatment medium may include 0.026 molar (M) to 0.26M ammonium bifluoride and 0.5M to 2M citric acid.

[0025] A twenty-second aspect of the present disclosure may include any one of the twentieth or twenty-first aspects, wherein the aqueous treatment medium may include a citric acid concentration of 1 M and an ammonium bifluoride concentration of 0.26 M.

[0026] A 23rd aspect of the present disclosure may include any one of the first to 22nd aspects, and includes contacting at least one surface of the glass syringe with the aqueous treatment medium at a contact temperature of 0°C to 105°C and a contact time of 10 seconds to 24 hours, such as 2.5 minutes to 30 minutes.

[0027] A twenty-fourth aspect of the present disclosure may include the twenty-third aspect, and includes contacting at least one surface of the glass syringe with the aqueous treatment medium for a contact time of 10 minutes or less, such as from 2.5 minutes to 10 minutes.

[0028] A 25th aspect of the present disclosure may include any one of the first to 24th aspects, and includes contacting at least one surface of the glass syringe with the aqueous treatment medium at a contact temperature equal to room temperature.

[0029] A 26th aspect of the present disclosure may include any one of the first to 25th aspects, wherein forming the glass syringe may include forming a syringe tip of the glass syringe and separating the glass syringe from the glass tube.

[0030] A twenty-seventh aspect of the present disclosure may include the twenty-sixth aspect, wherein forming the syringe tip may include heating a working end of the glass tubing, inserting a forming pin into an internal cavity of the glass tubing at the working end of the glass tubing, and contacting at least two opposing forming tools with an outer surface of the working end of the glass tubing. Contacting the at least two opposing forming tools with the outer surface of the working end of the glass tubing may reduce an outer diameter of the working end of the glass tubing to form the syringe tip, and the forming pin may maintain an opening extending axially through the syringe tip during contact with the at least two opposing forming tools.

[0031] A twenty-eighth aspect of the present disclosure may include the twenty-seventh aspect, further including releasing at least two opposing forming tools from contact with the outer surface of the working end of the glass tube and removing the forming pins from inside the glass tube, wherein removing the forming pins may cause friction between the forming pins and at least one surface of the glass tube, which transfers metal-containing contaminants from the forming pins to at least one surface of the glass tube.

[0032] Additional features and advantages of the glass syringes and methods disclosed herein will be set forth in the detailed description that follows, and in part will become readily apparent to those skilled in the art from that description, or may be learned by practicing the embodiments described herein, including the following detailed description, the claims, and the accompanying drawings.

[0033] It is to be understood that both the foregoing general description and the following detailed description are intended to describe various embodiments and provide an overview or framework for understanding the nature and characteristics of the claimed subject matter. The accompanying drawings are included to provide a further understanding of the various embodiments, and are incorporated into and constitute a part of this specification. The drawings illustrate various embodiments described herein and, together with the description, serve to explain the principles and operation of the claimed subject matter. [Brief explanation of the drawings]

[0034] [Figure 1] 1A and 1B schematically illustrate cross-sectional views of a glass syringe according to one or more embodiments shown and described herein. [Figure 2] 2A and 2B schematically illustrate cross-sectional views of glass tubing for making the glass syringe of FIG. 1 according to one or more embodiments shown and described herein. [Figure 3] 3A and 3B schematically illustrate a front view of a heating station for heating the working end of the glass tube of FIG. 2 according to one or more embodiments shown and described herein. [Figure 4] 2A and 2B schematically illustrate a front view of a forming station for forming a syringe tip of the glass syringe of FIG. 1 according to one or more embodiments shown and described herein. [Figure 5] 5 schematically illustrates a front view of the forming station of FIG. 4 at the result of forming a syringe tip of a glass syringe according to one or more embodiments shown and described herein. [Figure 6] 2A and 2B are schematic illustrations of cross-sectional views of the syringe tip of the glass syringe of FIG. 1 after forming the syringe tip according to one or more embodiments shown and described herein; [Figure 7] 7A and 7B are schematic illustrations of cross-sectional views of the syringe tip of FIG. 6 following treatment with an aqueous treatment medium according to one or more embodiments shown and described herein; [Figure 8] 1 graphically illustrates metal concentration (y-axis) on the surface of a glass syringe as a function of contact time with an aqueous treatment medium (x-axis) according to one or more embodiments shown and described herein. [Figure 9] 1 graphically illustrates the molar ratio of sodium to silicon (y-axis) as a function of contact time with an aqueous treatment medium (x-axis) according to one or more embodiments shown and described herein. [Figure 10] 1 graphically illustrates tungsten concentration (y-axis) on the surface of a glass syringe as a function of contact time (x-axis) for contact with an aqueous treatment medium and contact with phosphoric acid according to one or more embodiments shown and described herein. [Figure 11A] 1 is a scanning electron microscope (SEM) backscattered image of the surface of a glass syringe prior to contact with an aqueous treatment medium. [Figure 11B] 1 is a scanning electron microscope (SEM) backscattered image of the surface of a glass syringe prior to contact with an aqueous treatment medium. [Figure 12A] 1 is an SEM backscattered image of the surface of a glass syringe following contact with a citric acid solution at 80° C. for 7.5 minutes according to one or more embodiments shown and described herein. [Figure 12B] 1 is an SEM backscattered image of the surface of a glass syringe following contact with a citric acid solution at 80° C. for 7.5 minutes according to one or more embodiments shown and described herein. [Figure 13A] 1 is an SEM backscattered image of the surface of a glass syringe following contact with phosphoric acid at 80° C. for 7.5 minutes according to one or more embodiments shown and described herein. [Figure 13B] 1 is an SEM backscattered image of the surface of a glass syringe following contact with phosphoric acid at 80° C. for 7.5 minutes according to one or more embodiments shown and described herein. [Figure 14A]1 is an SEM backscattered image of the surface of a glass syringe following contact with an aqueous treatment medium at 20° C. according to one or more embodiments shown and described herein. [Figure 14B] 1 is an SEM backscattered image of the surface of a glass syringe following contact with an aqueous treatment medium at 20° C. according to one or more embodiments shown and described herein. DETAILED DESCRIPTION OF THE INVENTION

[0035] Reference will now be made in detail to various embodiments of glass syringes and methods for removing metal-containing contaminants from the surface of glass syringes, examples of which are illustrated schematically in the figures. Referring now to FIG. 1, one embodiment of a glass syringe 100 disclosed herein is illustrated generally. The glass syringe 100 has a barrel 102 and a syringe tip 110 at one end of the barrel 102. In embodiments, the syringe 100 may have a flange 120 at the other end of the barrel 102. The glass syringe 100 may be prepared from glass tubing by a conversion process, during which a working end of the glass tubing is heated and then acted upon by one or more forming tools to form the syringe tip 110, the flange 120, or other features of the glass syringe 100. A method of making the glass syringe 100 may include forming the glass syringe 100 having at least the barrel 102 and the syringe tip 110. Forming the syringe tip 110 may include contacting at least one surface of the glass syringe 100 with a forming tool, a forming pin, or both. The contact may transfer metal-containing contaminants to the at least one surface of the glass syringe 110. The method of making the glass syringe 100 may further include contacting at least one surface of the glass syringe 100 with an aqueous treatment medium including fluoride ions, at least one acid, or both, where the contacting with the aqueous treatment medium removes at least a portion or all of the metal-containing contaminants from the at least one surface of the glass syringe 100.

[0036] As indicated above, forming the glass syringe 100 from glass tubing can result in metal-containing contaminants migrating from the forming tool to one or more surfaces of the glass syringe 100. Aspects of the present disclosure can be directed to a method of removing metal-containing contaminants from the surface of the glass syringe 100, the method comprising contacting the surface of the glass syringe 100 with an aqueous treatment medium comprising fluoride ions, at least one acid, or both. Metal-containing contaminants can adhere to the surface of the glass syringe 100 and can be removed by a method according to USP <797> Prior to contact with the aqueous treatment medium, metal-containing contaminants may be present on the surface at a concentration of 8.3 parts per billion by weight (ppbw) or greater, as determined according to the test method in the U.S. Pat. Contacting the aqueous treatment medium with the surface of the glass syringe 100 for a contact time may reduce the concentration of metal-containing contaminants on the surface of the glass syringe 100 by 50% or more.

[0037] The methods disclosed herein can provide glass syringes that are substantially free of metal-containing contaminants, such as tungsten or its derivatives, on their surfaces, thereby enabling the use of the glass syringes for sensitive pharmaceutical products (e.g., protein-based pharmaceutical products that are sensitive to tungsten and / or other metal-containing contaminants). The aqueous treatment medium, among other things, has a low fluoride content (e.g., less than that of commercial toothpaste), is environmentally friendly, and is scalable for industrial production of glass syringes.

[0038] Unless otherwise expressly stated, it is in no way intended that any method set forth herein be construed as requiring its steps to be performed in a particular order, or that any apparatus require a particular orientation. Thus, where a method claim does not actually recite the order in which its steps are to be followed, or where any apparatus claim does not actually recite an order or orientation for individual components, or where the claim or the specification otherwise specifically states that the steps are to be limited to a particular order, or where no particular order or orientation for the apparatus components is recited, no order or orientation is intended to be inferred in any sense. This applies to all possible implicit bases for interpretation, including logical considerations regarding the arrangement of steps, workflow, component order, or component orientation, the plain meaning derived from grammatical organization or punctuation, and the number or type of embodiments described herein.

[0039] Directional terms used herein, e.g., up, down, right, left, front, back, top, bottom, are made with reference to the drawings only and are not intended to imply absolute orientations.

[0040] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a" element includes aspects having two or more such elements unless the context clearly dictates otherwise.

[0041] As used herein, terms such as "container" and "vessel" refer to any article adapted to hold a solid or fluid for storage.

[0042] As used herein, the "working end" of the glass tubing is the end of the glass tubing that is oriented toward the processing station of the glass tubing conversion machine and is heated and formed to produce one or more features of the glass syringe.

[0043] As used herein, the "unprocessed end" of the glass tube is the end of the glass tube that is oriented away from the processing station of the glass tube converter.

[0044] When used with respect to a forming tool in a forming station, the term "engaged" refers to the forming tool contacting the glass tube. When the forming tool is disengaged, the forming tool does not contact the glass tube.

[0045] As used herein, the term "circumference" of a glass tube refers to the set of points on the glass tube 130 at a certain radius r from the central axis D of the glass tube 130 up to 360 degrees from a particular Z position (i.e., a position on the + / -Z axis of the diagram). The circumference of the glass tube 130 may coincide, for example, with the outer surface 132 of the glass tube 130 at the particular Z position or the inner surface 134 of the glass tube 130 at the particular Z position.

[0046] Historically, glass has been used as a preferred material for packaging pharmaceutical materials due to its airtightness, optical transparency, and excellent chemical resistance compared to other materials. Specifically, glass used in pharmaceutical packaging must have adequate chemical resistance so as not to affect the stability of the pharmaceutical composition contained therein. Glasses with suitable chemical resistance include glass compositions within the ASTM standard "Type 1B," which have a proven history of chemical resistance. Glass can be formed into containers with a variety of shapes, including, but not limited to, vials, syringes, cartridges, ampoules, bottles, or other types of containers.

[0047] Referring again to FIG. 1 , one such outer shape is a glass syringe 100. The glass syringe 100 disclosed herein may include at least a barrel 102 and a syringe tip 110 formed at the outlet end 104 of the glass syringe 100. In embodiments, the glass syringe 100 may also include a flange 120 formed at the open end 106 of the glass syringe 100. The barrel 102 may include an inner surface 103 that defines an internal cavity 108 of the glass syringe 100. The internal cavity 108 of the glass syringe 100 may contain one or more medicinal materials when the glass syringe 100 is pre-filled. The syringe tip 110 may include an outer surface 112 and an inner surface 114. The outer surface 112 of the syringe tip 110 may have an outer diameter that is less than the outer diameter of the outer surface of the barrel 102. In embodiments, the outer surface 112 of the syringe tip 110 may taper from a larger outer diameter at the junction with the barrel 102 to a smaller outer diameter at the outlet end 104 of the glass syringe 100. The inner surface 114 of the syringe tip 110 may define a channel 116 that extends axially (e.g., in the + / Z direction of the coordinate axes of FIG. 1 ) through the syringe tip 110 from the interior cavity 108 of the glass syringe 100 to the outlet end 104. The channel 116 provides a flow path for pre-filling the glass syringe 100 and / or dispensing the contents of the glass syringe 100 from the interior cavity 108 out of the glass syringe 100 through the outlet end 104 of the glass syringe 100. In embodiments, the syringe tip 110 may be configured to receive one or more attachments, such as a needle assembly or other attachments, for filling the glass syringe 100 and / or dispensing the contents of the glass syringe 100.

[0048] The glass syringe 100 may be a container used to contain any composition, and in embodiments, may be used to contain a pharmaceutical composition. The glass syringe 100 may be constructed of glass suitable for holding sterile substances, such as, but not limited to, vaccines, biologicals, pharmaceutical compositions, foods, solutions, etc. Pharmaceutical compositions may include any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease. Examples of pharmaceutical compositions include, but are not limited to, drugs, medications, medicines, therapeutic agents, etc. Pharmaceutical compositions may be in the form of a liquid, solid, gel, suspension, powder, etc.

[0049] The glass syringe 100 disclosed herein can be formed from a variety of different glass compositions. The particular glass composition of the glass syringe 100 can be selected according to a particular application so that the glass has a desired set of physical properties. In embodiments, the glass of the glass syringe 100 can be a glass composition known to exhibit chemical durability and low thermal expansion, such as, but not limited to, alkali borosilicate glass. In embodiments, the glass composition of the glass article 102 can be silicate glass, aluminosilicate glass, alkali aluminosilicate glass, ion-exchanged aluminosilicate glass, ion-exchanged alkali aluminosilicate glass, borosilicate glass, ion-exchanged borosilicate glass, soda-lime glass, or a combination thereof. In embodiments, the glass syringe 100 can be a glass composition known to exhibit chemical durability and low thermal expansion, such as, but not limited to, alkali borosilicate glass, or a combination thereof, as defined in the United States Pharmacopeia (USP) <600> or a glass composition that meets the criteria for pharmaceutical glasses set forth in the European Pharmacopoeia 7. According to embodiments, the glass article 102 may be formed from Type I, Class B glass, as defined according to ASTM standard E438-92.

[0050] Glass syringe 100 is approximately 25 x 10 -7 / ℃~80×10 -7The glass syringe 100 may be formed from a glass composition having a thermal expansion coefficient in the range of 0.1 / °C. For example, in embodiments, the glass syringe 100 may be formed from an alkali aluminosilicate glass composition that can be easily strengthened through ion exchange. Such glass compositions may generally include a combination of SiO, AlO, at least one alkaline earth oxide, and one or more alkali oxides, such as NaO and / or KO. In embodiments, the glass composition may be free of boron and boron-containing compounds. In embodiments, the glass composition may further include small amounts of one or more additional oxides, such as SnO, ZrO, ZnO, TiO, and AsO. A small amount may include an amount of less than about 5 weight percent (mol%), less than about 2 mol%, or even less than about 1 mol% of the additional oxide, based on the total moles of glass. These additional oxide components may be added as fining agents during the glassmaking process to further improve the chemical durability of the glass composition or to impart other properties to the glass composition.

[0051] In one particularly exemplary embodiment, the glass syringe 100 may be formed from an ion-exchangeable glass composition as described in U.S. Patent No. 8,980,777, issued March 17, 2015, and entitled "Glass Compositions with Improved Chemical and Mechanical Durability," and owned by Corning, Incorporated. However, it should be understood that the glass syringe 100 described herein may be formed from other glass compositions, including, but not limited to, ion-exchangeable and non-ion-exchangeable glass compositions. For example, in embodiments, the glass syringe 100 may be formed from a borosilicate glass. In embodiments, the glass syringe 100 may be formed from a Type 1B glass composition, such as, for example, Schott Type 1B borosilicate glass. In embodiments, the glass syringe 100 may be formed from an ion-exchangeable borosilicate glass composition, such as that described in pending U.S. application Ser. No. 16 / 533,954, filed Aug. 7, 2019, and entitled "Ion Exchangeable Borosilicate Glass Compositions and Glass Articles Formed from the Same," owned by Corning Incorporated.

[0052] In the embodiments described herein, the glass syringe 100 may be formed from glass compositions that meet the standards for pharmaceutical glasses set forth by regulatory agencies such as USP (United States Pharmacopoeia), EP (European Pharmacopoeia), and / or JP (Japanese Pharmacopoeia) based on their resistance to hydrolysis. <660> According to the EP7 and EP100, borosilicate glass meets Type I criteria and is routinely used for parenteral packaging. Examples of borosilicate glass include, but are not limited to, Corning® Pyrex® 7740, 7800, and Wheaton® 180, 200, and 400, Schott Duran, Schott Fiolax, KIMAX® N-51A, Gerrescheimer GX®-51, Flint, and others. Soda-lime glass meets Type III criteria and is acceptable for packaging dry powders that are subsequently dissolved to create solutions or buffers. Type III glass is also suitable for packaging liquid formulations that have proven alkali-insensitive. Examples of Type III soda-lime glass include Wheaton 800 and 900. Dealkalized soda-lime glass has high levels of sodium hydroxide and calcium oxide and meets Type II criteria. These glasses are less resistant to leaching than Type I glasses, but more resistant than Type III glasses. Type II glasses may be used for products whose shelf life remains below pH 7. Examples include ammonium sulfate-treated soda-lime glasses. These pharmaceutical glasses have a variety of chemical compositions and range from 20 to 85 x 10 -7 / °C.

[0053] The glass syringe 100 can be produced from a glass tube. Referring now to FIG. 2 , the glass tube 130 can be a long, hollow, cylindrical tube made of glass. The glass tube 130 can have a circular cross-sectional shape and can have an outer surface 132, an inner surface 134, and a thickness t. The thickness t of the glass tube 130 can be the distance between the outer surface 132 and the inner surface 134 and in the radial direction of the glass tube 130. The glass tube 130 can have a length L in the + / - Z direction of the coordinate axes of FIG. 2 . The glass tube 130 can have an outer diameter OD, as shown in FIG. 2 . As discussed above, the glass tube 130 can be rotated about a central axis B of the glass tube 130 through the conversion process. The glass tube 130 can have a worked end 136 and an unworked end 138. The working end 136 of the glass tube 130 is the end of the glass tube 130 oriented toward a processing station of the converter, and the end of the glass tube 130 is heated and flame worked to produce various features of the glass syringe 100. The non-working end of the glass tube 130 is the end opposite the working end 150 (i.e., the end of the glass tube 130 in the +Z direction of the coordinate axis of FIG. 2).

[0054] The glass tubing 130 can be converted into glass syringes 100, or other glass containers, for use in pharmaceutical applications, including, but not limited to, vials, syringes, ampoules, cartridges, and other glass articles, using a converting process that may be performed using a “converting machine.” Converting machines have been in use for over 75 years and are currently made by a variety of commercial and internal equipment suppliers. Throughout this disclosure, the terms “converting machine” and “converter” mean the same thing and may be used interchangeably. The glass tubing 130 can be converted into glass syringes 100 using a converting machine that includes multiple processing stations. The processing stations may include heating stations, forming stations, separation stations, cooling stations, or other types of processing stations. Converting machines typically reshape long lengths of glass tubing into multiple glass articles using steps that include, but are not limited to, flame processing, turning and stationary tool forming, separation (e.g., thermal separation or score and shock cutoff steps), cooling, measuring, polishing, or other processing steps. Therefore, the glass articles produced through the converting process carried out on the converting machine are subjected to a series of flame burners, other heating elements and forming tools to form the glass tube into a particular shape and size and to separate the formed glass article from the glass tube.

[0055] The converter may be an indexing converter or a continuous converter. In embodiments, the converter may be an indexing converter, which may be operable to continuously index the glass tube 130 through each of a plurality of processing stations. In an indexing converter, each of the processing stations may be stationary at a specific location within the converter's circuit. The glass tube 130 may remain at each of a plurality of processing stations for a fixed residence time and then be indexed to the next processing station in the circuit during the converter's indexing time. In embodiments, the converter may be a continuous converter, which may be operable to continuously move the glass tube 130 through a plurality of processing stations. In embodiments, heating elements, burners, forming tools, measurement devices, and other elements of the conversion process may move with the glass tube 130 as it passes through the processing stations. For both indexing converters and continuous converters, the "active time" of a processing station is the duration that the glass tube 130 is maintained engaged with at least one heating element, at least one forming tool, at least one cooling nozzle, or other device while within the processing station.

[0056] Examples of converting machines for converting glass tubing 130 into glass articles include the Vial Forming Machine Model RP16 or RP18 with automatic tube feeder manufactured by AMBEG Dr. J. Dichter GmbH. Other examples include the Vial Forming Machine Model RP32 manufactured by AMBEG Dr. J. Dichter GmbH and the Zeta 098 Vial Forming Machine manufactured by Euromatic SRL. Another example may include the Zeta 103 Cartridge Forming Machine manufactured by Euromatic SRL, which is a converting machine for converting glass tubing into glass cartridges. Cartridge converting machines have similar characteristics to the vial converting machines described above, but are utilized to produce glass articles with a cartridge outer shape rather than a vial. Examples of converting machines for converting glass tubing into glass syringes may include, but are not limited to, the Model GS24 / 16 and Model GS36 / 15-2 syringe converting machines manufactured by Stevanato Group. Other makes and models of syringe conversion machines can also be used to convert glass tubing to glass syringes.

[0057] As discussed above, a converter for producing glass syringes 100 may include multiple processing stations. The shape of the glass syringe 100 to be made from the glass tubing 130 may affect the total number of processing stations in the converter. The processing stations may include, by way of example and without limitation, one or more heating stations, forming stations, frame polishing stations, cooling stations, separation stations, measuring stations, feeding stations, draining stations, other processing stations, or combinations thereof, to produce the glass syringe 100 from the glass tubing 130. The type and / or shape of the glass syringe 100 may affect the type of processing stations 106 and / or the order of the processing stations 106 in the converter 100.

[0058] The converter may have a main circuit of processing stations for forming one or more features on the working end of the glass tubing and separating the partially finished glass syringe from the glass tubing. The converter may further include a secondary circuit having multiple processing stations for forming one or more features on the open end 106 of the glass syringe 100, such as a flange 120 or other structure. The main circuit may include a processing station configured to form a syringe tip 110 on the outlet end 104 of the glass syringe 100. The main circuit of the converter may include one or more heating stations, one or more forming stations, a separation station, one or more cooling stations, a measuring station, a tube length drop station, a tube loading station, or other types of processing stations. The secondary processing stations of the secondary circuit may include one or more heating stations, forming stations, flame polishing stations, cooling stations, measuring stations, ejection stations, or other stations, or a combination of secondary processing stations.

[0059] Referring now to FIG. 3 , the converter may include multiple holders 140 configured to removably secure each glass tube 130 and sequentially translate each glass tube 130 through each of the converter's processing stations. The holders 140 may be clamps, chucks, or other holding devices, or a combination of holding devices. The holders 140 may orient each glass tube 130 so that the working end 136 of the glass tube 130 is positioned at each of the processing stations as the holders 140 index or sequentially pass the glass tube 130 through the multiple processing stations. The converter may be oriented vertically or horizontally. When oriented vertically, the holders 140 may hold the glass tube 130 so that the central axis B of the glass tube 130 is parallel to the vertical direction. When oriented horizontally, the holders 140 may hold the glass tube 130 so that the central axis B of the glass tube 130 is horizontal (e.g., perpendicular to the vertical direction). Holder 140 is shown in Figure 2 as holding glass tube 130 such that central axis B is parallel to the + / -Z direction of Figure 2. It should be understood that the + / -Z direction can be vertical, horizontal, or any other direction.

[0060] Each holder 140 may be individually pivotable relative to the processing station to pivot the glass tube 130 about its central axis B. Pivoting the holders 140 allows for pivoting of the glass tube 130 about its central axis B relative to a stationary burner, forming tool, cooling nozzle, or other feature of the processing station. A heating element or forming tool within the processing station may be maintained in a fixed position relative to the glass tube 130, and pivoting of the glass tube 130 about its central axis B may allow for the entire circumference of the glass tube 130 to be exposed to the heating element or forming tool.

[0061] In a typical converter, a forming station in the main circuit may be positioned downstream of a heating station in the direction of translation of the glass tube 130 through the main circuit of processing stations. The forming station may repeatedly shape the glass tube 130 to form one or more features, such as the syringe tip 110 of the glass syringe 100. As described above, one or more heating stations may be positioned before each forming station to preheat a target area of ​​the glass tube 130 to a temperature at which the glass tube 130 can be shaped and formed into the desired feature. The forming station in the main circuit may shape the working end 136 of the glass tube 130 to form a feature at the outlet end 104 of the glass syringe 100, and a forming station in a secondary turret may shape the open end of the glass syringe 100 after the partially formed glass syringe is separated from the glass tube 130.

[0062] As discussed above, with respect to the translational direction of the glass tube 130 through each of the processing stations, the converter may include one or more heating stations upstream of the forming stations to preheat a target region of the glass tube 130 prior to forming in the forming station. Referring again to FIG. 3 , one embodiment of a heating station 150 for heating a target region 151 of the glass tube 130 is shown schematically. Each of the heating stations 150 may include one or more heating elements 152. As shown in FIG. 3 , in an embodiment, the heating elements 152 may include one or more burners 154 used to heat the target region 151 of the glass tube 130 prior to the forming operation performed in the forming station 170 ( FIG. 4 ). While FIG. 3 shows a single burner 154, it should be understood that multiple burners 154 may be employed within a single heating station 150. A fuel gas 156, an oxygen-containing gas 158, and, optionally, air 160 may be passed to the burners 154. Examples of fuel gas 156 for the burner 154 may include, but are not limited to, hydrogen, hydrocarbon fuel gases such as methane, propane, and butane, other fuel gases, or combinations thereof. The burner 154 combusts the fuel gas 156 in the presence of oxygen from an oxygen-containing gas 158 and / or air 160 to generate a flame that heats at least a target region 151 of the glass tube 130. While the converter's heating station 150 is described herein as using the burner 154 to heat the glass tube 130, it should be understood that the heating element 152 may comprise other types of heating devices, such as, but not limited to, a laser, e.g., a CO laser, an induction heater, other heating devices, or combinations thereof. The heating station 150 may further include a heating element positioner 162 coupled to the heating element 152. The heating element positioning device 162 may be operable to position the heating element 152 in one or more directions relative to the position of the working end 136 of the glass tube 130 within the heating station 150 .

[0063] 4 and 5, one embodiment of a forming station 170 for forming the syringe tip 110 of the glass syringe 100 is shown schematically. The forming station 170 for forming the syringe tip 110 may include a plurality of forming tools 172 and forming pins 180. The forming tools 172 may form wheels that are pivotable about a tool axis C. The forming tools 172 may be driven or freely pivotable such that the forming wheels pivot through contact with the pivoting glass tube 130 in the forming station 170. The forming tools 172 may have forming surfaces 174 that may contact the outer surface 132 of the glass tube 130 when the forming tools 172 engage the glass tube 130 in the forming station 170.

[0064] Each of the forming tools 172 may include a forming tool actuator 176 that may be operable to move each forming tool 172 into and out of engagement with the glass tube 130, as indicated by arrows 178. Moving the forming tools 172 into and out of engagement with the glass tube 130 may control the timing of contact between the forming tools 172 and the glass tube 130. Contact timing refers to the timing of engagement and disengagement of each of the forming tools 172 with the glass tube 130 within the forming station 170. Adjusting the contact timing of the forming tools 324 may adjust the total contact time of each of the forming tools 324 in contact with the glass tube 102, the contact sequence of the forming tools 324 with the glass tube 102, or both. Additionally, the forming tool actuators 176 may be operable to incrementally move the forming tools 172 toward each other (i.e., in the + / -X directions of the coordinate axes of FIG. 4) to form the working end 136 of the glass tube 130 into the shape of the syringe tip 110 (FIG. 5). In embodiments, each forming tool actuator 176 may include one or more servo motors operable to automatically and / or incrementally adjust the position of the forming tool 172 in one or more directions of the coordinate axes of FIGS. 4 and 5. Any other type of positioning device that is commercially available or to be commercially available may be used as at least a portion of the forming tool actuators 176.

[0065] Referring again to FIG. 4 , the forming station 170 further includes a forming pin 180. The forming pin 180 may be a thin rod inserted into the opening in the working end 136 of the glass tube 130 during the formation of the syringe tip 110. The forming pin 180 forms an opening or channel extending axially through the syringe tip 110 after forming the syringe tip 110. In embodiments, the forming pin 180 may be constructed of a material that does not oxidize under glass-forming conditions. Suitable materials for the forming pin 180 in the forming station 170 may include, but are not limited to, the following: metals or alloys containing tungsten or its derivatives; metals or alloys containing tantalum or its derivatives; metals or alloys containing platinum, platinum-based metals, or their derivatives; metals or alloys containing nickel or its derivatives; ceramics; silicides; and combinations thereof. In embodiments, the forming pin 180 may be formed from tungsten or its derivatives. Other semi-precious hard metals may be used. The forming station 170 may further include a pin actuator 182 operable to translate the forming pin 180 axially (i.e., in the + / -Z direction of the coordinate axes in FIG. 4) into and out of the opening in the working end 136 of the glass tube 130, as indicated by arrow 184 in FIG. 4.

[0066] Referring again to FIG. 4 , in operation of the forming station 170, the glass tube 130, heated at its working end 136 in one or more upstream heating stations 150, is translated to the forming station 170. In the forming station 170, the pin actuator 182 may actuate the forming pin 180 axially (i.e., in the +Z direction of the coordinate axes of FIG. 4 ) into an opening in the working end 136 of the glass tube 130. As the glass tube 130 is pivoted about axis B by the holder 140, the forming tool actuator 176 may be actuated to move the forming tool 172 radially (i.e., in the + / −X direction of the coordinate axes of FIG. 4 ) to bring the forming surface 174 of the forming tool 172 into contact with the outer surface 132 of the glass tube 130. The forming tool actuator 176 may continue to incrementally move the forming tools 172 toward each other to form the working end 136 of the glass tube 130 into the shape of the syringe tip 110.

[0067] 5 , the forming pin 180 provides a barrier to prevent the inner surface 134 of the glass tube 130 from contacting or collapsing, thereby maintaining a channel axially through the syringe tip 110 after forming. Contact between the forming pin 180 and the inner surface 134 of the glass tube 130 at the working end 136 forms a channel through the syringe tip 110. When the syringe tip 110 is formed at the end of the contact time, the forming tool actuator 176 can be actuated to move the forming tool 172 out of engagement with the outer surface 132 of the glass tube 130. When pressure on the outer surface 132 of the glass tube 130 from the forming tool 172 is released, the pin actuator 182 can be actuated to withdraw the forming pin 180 from the working end 136 of the glass tube 130. Removal of the forming pin 180 from the working end 136 leaves a channel extending axially (i.e., in the + / −Z direction) through the syringe tip 110 formed at the working end 136.

[0068] Pre-filled glass syringes are an important pharmaceutical packaging solution due to their convenience when administering pharmaceutical products. While these glass syringes offer usage advantages over other types of containers, such as pharmaceutical vials, pre-filled glass syringes may expose pharmaceutical products to different contaminants than vials. Referring again to FIG. 5, as discussed above, during the conversion process to form the glass syringe 100, the syringe tip 110 may contact a forming pin 180 containing a metal—such as, but not limited to, tungsten (W), tantalum, or other metals or derivatives thereof—to create an opening through which the pharmaceutical composition enters and exits the syringe barrel 102 (FIG. 1). Referring to FIG. 5, due to frictional contact between the forming pin 180 and the inner surface 114 of the syringe tip 110, the forming pin 180 may peel off materials, such as metal-containing contaminants, onto the inner surface 114 of the syringe tip 110. During removal of the forming pin, frictional contact between the forming pin 180 and the inner surface 114 of the syringe tip 110 leads to wear and consumption of the forming pin 180. Furthermore, in embodiments, the glass-forming temperatures during conversion may be high enough to volatilize metal atoms or molecules from the surface of the forming pin 180, and the volatilized metal components may condense on the surface of the glass syringe 100. In some cases, the forming pin 180 may include a metal pin coated with a ceramic coating. If the mechanical integrity of the ceramic coating is maintained, the ceramic coating can effectively inhibit metal deposition during formation. However, if the coating is compromised, at glass-forming temperatures, volatility of the underlying metal may create a path for metal deposition from the ceramic-coated metal forming pin onto the surface of the glass syringe 100.

[0069] Metal-containing contaminants detached from the forming pin 180 may accumulate on the inner surface 114 of the syringe tip 110. In continuous operation, the forming pin 180 is changed at an hourly rate. As a result, glass syringes manufactured via this conversion method may be contaminated at trace levels with metal-containing contaminants, such as, but not limited to, tungsten, derivatives of tungsten, or other metals or their derivatives. Metal contaminants may be detected by inductively coupled plasma mass spectrometry (ICP-MS) based on USP <797> They may be present at concentrations of about 8.3 parts per billion by weight (ppbw) to about 83 ppbw per 100 glass syringes, as determined according to the test method of 2000. Interactions between metal-containing contaminants and sensitive biopharmaceuticals (e.g., protein therapeutics) can lead to aggregation of the active ingredient of the biopharmaceutical, which impairs the efficacy of the drug.

[0070] Metal-containing contaminants, such as tungsten, other metals, or their derivatives, can be removed from the interior of glass syringes in a research environment by washing with a low-concentration inorganic acid. However, washing with a low-concentration inorganic acid may not provide a practically scalable solution for removing the metal-containing contaminants. Inorganic acids generally require a reduction in the treatment solution following removal of the metal-containing contaminants. For example, if the metal-containing contaminants include tungsten or its derivatives, a mixture of phosphoric acid and another inorganic acid may be used. However, treatment with phosphoric acid can lead to the formation of acid-soluble tungsten species, making the phosphate treatment solution or other inorganic acid treatment solution difficult to dispose of and therefore difficult to employ in an industrial environment. In addition, treatment with a low-concentration inorganic acid has a slow reaction rate, which requires heating the low-concentration inorganic acid solution to a high temperature to increase the reaction rate to a rate fast enough for industrial manufacturing processes. Furthermore, due to the increased chemical resistance of tungsten-containing particles and other metal-containing contaminants relative to other components of the glass or contaminants on the glass surface (e.g., Sn particles), non-uniform dissolution can occur when cleaning with low concentrations of inorganic acids.

[0071] The present disclosure is directed to a method for removing metal-containing contaminants from the interior surface of a glass syringe using an aqueous treatment medium comprising fluoride ions, at least one acid, or both. The aqueous treatment medium and method for treating a glass syringe with the aqueous treatment medium can effectively reduce the concentration of metal-containing contaminants on the surface of the syringe tip to a concentration below the detection limit of inductively coupled plasma mass spectrometry (ICP-MS) after contacting the syringe tip at room temperature for a contact period of less than 10 minutes. The method for removing metal-containing contaminants from the surface of a glass syringe can include contacting the surface of the glass syringe with an aqueous treatment medium comprising fluoride ions, at least one acid, or both, wherein the metal-containing contaminants adhere to the surface of the glass syringe and are removed by inductively coupled plasma mass spectrometry (ICP-MS). <797> is present on the surface prior to contact with the aqueous treatment medium at a concentration of 8.3 ppbw or greater, as determined in accordance with the test method of 2000. Contacting the aqueous treatment medium with the surface for a contact time reduces the concentration of metal-containing contaminants on the surface of the glass syringe by 50% or greater.

[0072] The methods disclosed herein can provide glass syringes that are substantially free of metal-containing contaminants, such as tungsten or its derivatives, on their surfaces, thereby enabling the use of the glass syringes for sensitive pharmaceutical products (e.g., protein-based pharmaceutical products). The aqueous treatment medium has a low fluoride content (less than that of commercial toothpaste), is environmentally friendly, and is scalable for industrial production of glass syringes. The methods disclosed herein are generally shown to be scalable, unlike the use of inorganic acids, which require extensive mitigation. The methods disclosed herein use scalable and relatively environmentally friendly solutions to remove undesirable metal-containing contaminants, such as, but not limited to, tungsten or its derivatives. In addition, the aqueous treatment medium can include ingestible components, which, among other things, can reduce the barrier to using the aqueous treatment medium on an industrial manufacturing scale.

[0073] 6 , as previously discussed, forming glass syringes 100 by converting glass tubing into multiple glass syringes 100 may produce glass syringes 100 having metal-containing contaminants deposited on one or more surfaces of the glass syringes 100. In embodiments, the metal-containing contaminants may be present on the surface of the glass syringe 100 as metal-containing particles 190 bonded to the surface of the glass syringe 100. The metal-containing contaminants may be deposited on any of the surfaces of the glass syringe 100. In embodiments, the metal-containing contaminants may be present on both the outer surface 112, the inner surface 114, or the syringe tip 110 of the glass syringe 100. In embodiments, the metal-containing contaminants may be present on at least the inner surface of the syringe tip 110. As discussed above, metal-containing contaminants may deposit on the inner surface 114 of the syringe tip 110 during formation of the syringe tip 110 at the forming station 170 (FIG. 5) through frictional contact between the outer surface of the forming pin 180 (FIG. 5) and the inner surface 114 of the syringe tip 110.

[0074] The metal-containing contaminants may include one or more metals or their derivatives. The metal of the metal-containing contaminants may be a hard, precious metal. In embodiments, the metal of the metal-containing contaminants may include, but is not limited to, tungsten, platinum, rhodium, tantalum, nickel, derivatives or alloys of these metals, oxides of these metals, or combinations thereof. In embodiments, the metal-containing contaminants may include one or more metals selected from the group consisting of tungsten, platinum, rhodium, tantalum, nickel, derivatives or alloys of these metals, or combinations thereof. In embodiments, the metal-containing contaminants may include tungsten or a derivative thereof. Derivatives of the metals in the metal-containing contaminants may include, but are not limited to, metal oxides or other metal-containing compounds.

[0075] Following conversion of the glass tubing 130 to produce the glass syringe 100, the glass syringe 100 is compliant with the United States Pharmacopeia (USP) <797> or may have a concentration of metal-containing contaminants of 8.3 parts per billion by weight (ppbw) or greater, such as 8.3 ppbw to 83 ppbw, as determined according to the test method ISO 3749:2022.

[0076] The method disclosed herein for removing metal-containing contaminants from one or more surfaces of a glass syringe may include contacting one or more surfaces of the glass syringe with an aqueous treatment medium comprising fluoride ions, at least one acid, or both, where the contacting with the aqueous treatment medium removes the metal-containing contaminants from at least one surface of the glass syringe. The aqueous treatment medium may be an aqueous composition capable of dissolving the metal-containing contaminants from the surface of the glass syringe. The aqueous treatment medium comprises fluoride ions, one or more acids, or a combination thereof. In embodiments, the aqueous treatment medium comprises fluoride ions. When the aqueous treatment medium comprises fluoride ions, a source of the fluoride ions may be selected from one or more of HF, NaF, NH4HF2, and the like. In embodiments, the source of the fluoride ions may be selected from the group consisting of HF, NaF, NH4HF2, and combinations thereof. In fluoride-containing embodiments, the aqueous treatment medium can include 0.001% to 0.15% by weight of fluoride ions, such as 0.001% to 0.12% by weight of fluoride ions, 0.001% to 0.10% by weight of fluoride ions, based on the total weight of the aqueous treatment medium. In embodiments, the aqueous treatment medium can include fluoride ions, and the concentration of fluoride ions in the aqueous treatment medium can be 1500 ppm or less, 1200 ppm or less, or even 1000 ppm or less, as calculated using Visual MINTEQ™ software, a tool for estimating the dissociation of molecules and their mixtures in aqueous solutions.

[0077] In embodiments, the aqueous treatment medium may include an acid, such that the aqueous treatment medium is an acidic aqueous treatment medium. A variety of acidic compounds may be used, alone or in combination, to formulate an acidic aqueous treatment medium suitable for treating the surface of a glass syringe to remove metal-containing contaminants. The aqueous treatment medium may include an inorganic acid, an organic acid, or a combination thereof. In embodiments, the aqueous treatment medium may include an organic acid that is a chelating organic acid. In embodiments, the aqueous treatment medium may include an aqueous solution of an inorganic acid, an organic acid, or both. Suitable acids for the aqueous treatment medium may include, but are not limited to, one or more of HCl, HBr, HNO3, H2SO4, H2SO3, H3PO4, H3PO2, HOAc, citric acid, tartaric acid, ascorbic acid, EDTA, methanesulfonic acid, toluenesulfonic acid, mixtures thereof, and combinations comprising at least one of the foregoing. In embodiments, the aqueous treatment medium may include at least one acid selected from the group consisting of HCl, HBr, HNO3, H2SO4, H2SO3, H3PO4, H3PO2, acetic acid (HOAc), citric acid, tartaric acid, ascorbic acid, EDTA, methanesulfonic acid, toluenesulfonic acid, and combinations thereof. In embodiments, the aqueous treatment medium may include at least one organic acid selected from the group consisting of acetic acid (HOAc), citric acid, tartaric acid, ascorbic acid, EDTA, methanesulfonic acid, toluenesulfonic acid, and combinations thereof. In embodiments, the aqueous treatment medium includes at least one acid, and the acid may include citric acid.

[0078] In embodiments, the aqueous treatment medium includes fluoride ions and an acid. The components of the aqueous treatment medium can be selected from materials found in commodity consumer goods and can meet two performance requirements: etching glass articles at a slower rate than existing formulations and reducing precipitation of dissolved species by complexing metal ions in solution. Citric acid is a naturally occurring organic acid found in citrus fruits. It is a common complexing or chelating agent. Ammonium bifluoride provides a source of fluoride ions for etching glass. In embodiments, the aqueous treatment medium includes an aqueous solution of ammonium bifluoride and citric acid. In embodiments, the aqueous treatment medium can include 0.026 molar (M) to 0.26 M ammonium bifluoride, or about 0.26 M ammonium bifluoride. In embodiments, the aqueous treatment medium can include 0.5 M to 2 M citric acid, or about 1.0 M citric acid.

[0079] In embodiments, the aqueous treatment medium may have a pH of 3 or less, such as 2.5 or less, 1 or less, or even 0.5 or less. In some embodiments, the aqueous treatment medium may not be acidic or may be mildly acidic. For example, in embodiments, the aqueous treatment medium may have a pH of 4 to 12, such as a pH of 6 to 12, 6 to 10, or even 8 to 10.

[0080] In embodiments, the composition of the aqueous treatment medium is generally considered to be substantially fluoride-free. As used herein, the phrase "substantially fluoride-free" means that the aqueous treatment medium may contain 0.15% by weight or less (i.e., 1500 parts per million by weight (ppmw)) of fluoride ions based on the total weight of the aqueous treatment medium. In embodiments, the aqueous treatment medium may contain 0.12% by weight or less (i.e., 1200 ppmw), such as 0.10% by weight or less (i.e., 1000 ppmw), 0.095% by weight or less (i.e., 950 ppmw), or about 0.09% by weight or less (i.e., 900 ppmw), of fluoride ions based on the total weight of the aqueous treatment medium. For comparison, the fluoride ion content found in toothpaste is approximately 1500 ppmw. In some embodiments, the aqueous treatment medium may have no fluoride ions. A variety of compounds can be used alone or in combination to formulate a substantially fluoride-free aqueous treatment medium suitable for removing metal-containing contaminants from the surface of a glass syringe. In embodiments, the aqueous treatment medium can be an aqueous solution containing water and fluoride ions. In embodiments, the substantially fluoride-free aqueous treatment medium can be an aqueous solution containing a basic component such as NH3, or an alkali hydroxide (e.g., NaOH, KOH, LiOH, etc.), or an alkaline earth metal hydroxide (e.g., Ca(OH)2 or Ba(OH)2, etc.).

[0081] A method for removing metal-containing contaminants from a surface of a glass syringe may include contacting the surface of the glass syringe with an aqueous treatment medium. The step of contacting the surface of the glass syringe with the aqueous treatment medium can be implemented by a variety of techniques, including, but not limited to, spraying the aqueous treatment medium onto the surface of the glass syringe, partially or completely immersing the glass syringe in a vessel containing the aqueous treatment medium, or other similar techniques for applying a liquid to a solid surface.

[0082] It should be understood that in the embodiments described herein, the treatment conditions can affect the removal rate of metal-containing contaminants from the surface of the glass in the aqueous treatment medium (e.g., the etching rate or the rate of dissolution of components from the glass) and can be adjusted to control the rate of dissolution of one or more components from the glass. For example, the temperature of the aqueous treatment medium and / or the glass syringe can be increased to increase the rate of dissolution of metal-containing contaminants in the aqueous treatment medium, thereby reducing treatment time. Alternatively, the concentration of active components (e.g., acid, fluoride ions, etc.) in the aqueous treatment medium can be increased to increase the rate of dissolution of metal-containing contaminants in the aqueous treatment medium, thereby reducing treatment time.

[0083] The surface of the glass syringe can be contacted with the aqueous treatment medium at a contact temperature and for a contact time sufficient to remove metal-containing contaminants from the surface of the glass syringe to a concentration that is less than 50% of the starting concentration before contact with the aqueous treatment medium. The contact temperature can be sufficient to remove the metal-containing contaminants at an acceptable etching rate. In embodiments, a method for removing metal-containing contaminants can include contacting the surface of the glass syringe with the aqueous treatment medium for a contact temperature between 0°C (zero°C) and 105°C, such as between 0°C and 100°C, between 0°C and 80°C, between 0°C and 50°C, between 10°C and 105°C, between 10°C and 100°C, between 10°C and 80°C, between 10°C and 50°C, between 20°C and 105°C, between 20°C and 100°C, between 20°C and 80°C, or between 20°C and 50°C. In embodiments, the aqueous treatment medium may include components capable of removing metal-containing contaminants from the surface of the glass syringe at room temperature (about 20° C.) without the need to increase the temperature to achieve an acceptable etching or removal rate. In embodiments, the method for removing metal-containing contaminants may include contacting the surface of the glass syringe with the aqueous treatment medium at a contact temperature equal to room temperature. In embodiments, the aqueous treatment medium may include ammonium bifluoride and citric acid, and the method for removing metal-containing contaminants may include contacting the surface of the glass syringe with the aqueous treatment medium at room temperature.

[0084] The method may include contacting at least one surface of the glass syringe with the aqueous treatment medium for a contact time sufficient to remove at least 50% of the metal-containing contaminants. In embodiments, the method may include contacting the surface of the glass syringe with the aqueous treatment medium for a contact time of 10 seconds to 24 hours, such as 10 seconds to 30 minutes, 10 seconds to 10 minutes, 1 minute to 24 hours, 1 minute to 30 minutes, 1 minute to 10 minutes, 2 minutes to 24 hours, 2 minutes to 30 minutes, 2 minutes to 10 minutes, 2.5 minutes to 24 hours, 2.5 minutes to 30 minutes, 2.5 minutes to 10 minutes, 10 minutes to 24 hours, 10 minutes to 30 minutes, or 30 minutes to 24 hours.

[0085] Following contacting the surface of the glass syringe with the aqueous treatment medium, the surface of the glass syringe can be removed from contact with the aqueous treatment medium. Removing the surface of the glass syringe from contact with the aqueous treatment medium can include removing any residual aqueous treatment medium from the surface of the glass syringe, such as by rinsing the surface of the glass syringe with water. Following the water rinse, the surface of the glass syringe can be dried.

[0086] Contacting the surface of the glass syringe with the aqueous treatment medium at a contact temperature for a contact time removes at least a portion or all of the metal-containing contaminants from the surface of the glass syringe. Referring now to Figure 7, in an embodiment, the inner surface 114 of the syringe tip 110 may be contacted with the aqueous treatment medium, and contacting the inner surface 114 of the syringe tip 110 with the aqueous treatment medium at a contact temperature for a contact time removes at least a portion or all of the metal-containing contaminants from the inner surface 114 of the syringe tip 110.

[0087] In embodiments, contacting at least one surface of the glass syringe 100, such as, but not limited to, the inner surface 114 of the syringe tip 110, with an aqueous treatment medium may remove 50% or more of the metal-containing contaminants from at least one surface of the glass syringe 100. In embodiments, contacting at least one surface of the glass syringe 100, such as, but not limited to, the inner surface 114 of the syringe tip 110, with an aqueous treatment medium may remove 60% or more, 70% or more, 80% or more, 90% or more, 95% or more, 98% or more, or even 99% or more of the metal-containing contaminants from the surface of the glass syringe 100. In embodiments, after contacting the surface of the glass syringe 100 with an aqueous treatment medium, the at least one surface of the glass syringe 100 may be soluble in at least 10% of the metal-containing contaminants as defined in the United States Pharmacopeia (USP) 10 ... <797> The present invention may have a concentration of metal-containing contaminants of less than 10 parts per billion by weight (ppbw), 8.3 ppbw or less, 8 ppbw or less, 5 ppbw or less, 4 ppbw or less, 2 ppbw or less, 1 ppbw or less, 0.1 ppbw or less, 100 parts per trillion by weight (pptw) or less, or even 10 pptw or less, as determined in accordance with the test method of

[0088] While contacting the surface of the glass syringe 100 with the aqueous treatment medium, the aqueous treatment medium may also etch away glass components from the surface of the glass syringe 100. Referring to FIG. 7 , etching away glass components from the surface of the glass syringe 100, such as from the inner surface 114 of the syringe tip 110, may cause very little change in glass thickness, such that the thickness t2 of the syringe tip 110 after contact with the aqueous treatment medium may be less than the thickness t1 of the syringe tip 110 before contact with the aqueous treatment medium. The features of FIGS. 6 and 7 are exaggerated for illustrative purposes. The contact temperature, contact time, and composition of the aqueous treatment medium may affect the amount of glass removed from the inner surface 114 of the syringe tip 110. The contact temperature, contact time, and composition of the aqueous treatment medium may be selected to remove a desired amount of metal-containing contaminants while avoiding excessive removal of glass components from the surface of the glass syringe 100. In embodiments, the change in thickness (i.e., t1 to t2) after contact with the aqueous treatment medium may be less than 1 micrometer. In embodiments, the dimensions of the glass syringe 100, such as, but not limited to, the dimensions of the syringe tip 110, may be within specifications for the glass syringe 100 after contact with the aqueous treatment medium.

[0089] Referring again to FIG. 1 , in embodiments, a method of making a glass syringe 100 of the present disclosure may include forming a glass syringe 100 having a barrel 102 and a syringe tip 110, where forming the glass syringe 100 includes contacting at least one surface of the glass syringe with a forming tool, a forming pin, or both, where the contacting transfers metal-containing contaminants to the surface of the glass syringe 100. The method may further include contacting the surface of the glass syringe 100 with an aqueous treatment medium including fluoride ions, at least one acid, or both, where the contacting with the aqueous treatment medium removes at least a portion of the metal-containing contaminants from the surface of the glass syringe 100. The glass syringe 100 may be formed from glass tubing using a converting machine as discussed previously herein. The aqueous treatment medium may have any of the compositions or properties discussed previously herein for aqueous treatment media.

[0090] In embodiments, forming the glass syringe 100 may include forming a syringe tip 110 of the glass syringe 100 at a working end of the glass tube and separating the glass syringe 100 from the glass tube. In embodiments, a method for forming the syringe tip 110 may include heating the working end 136 of the glass tube 130 (FIG. 3), inserting a metal forming pin 180 into an interior cavity of the glass tube 130 at the working end 136 of the glass tube 130 (FIG. 4), and contacting at least two opposing forming tools 172 with an exterior surface of the working end 136 of the glass tube 130 (FIG. 4). 5 , contacting the two opposing forming tools 172 with the outer surface 132 of the glass tubing 130 reduces the outer diameter of the working end 136 of the glass tubing 130 to form the syringe tip 110, and the metal forming pin 180 maintains an axially extending channel through the syringe tip 110 while in contact with the forming tools 172. The method of making the glass syringe 100 may further include releasing the two opposing forming tools 172 from contact with the outer surface 132 of the working end 136 of the glass tubing 130 and removing the metal forming pin 180 from the interior of the glass tubing 130. Removing the metal forming pin 180 may cause friction between the metal forming pin 180 and a surface of the glass syringe, such as the inner surface 114 of the syringe tip 110, which may transfer metal-containing contaminants from the metal forming pin 180 to the surface of the glass syringe. Following formation of the glass syringe 100, a surface of the glass syringe 100, such as, but not limited to, the inner surface 114 of the syringe tip 110, may be contacted with an aqueous treatment medium at a contact temperature and for a contact time sufficient to remove some or all of the metal-containing contaminants from the surface of the glass syringe 100. [Example]

[0091] The various embodiments of the glass syringes and methods for removing metal-containing contaminants from the surfaces of the glass syringes disclosed herein are further clarified by the following examples, which are illustrative in nature and should not be construed as limiting the subject matter of the present disclosure.

[0092] Example 1 In Example 1, metal-containing contaminants were removed from the inner surface of the syringe tip of a glass syringe by contacting the syringe tip with an aqueous treatment medium according to the methods disclosed herein. The contact time for removing metal-containing contaminants from the inner surface of the syringe tip was investigated. For Example 1, the glass syringe was produced from glass tubing using the conversion process described herein. Referring to FIGS. 4 and 5, the forming station 170 for producing the syringe tip 110 of the glass syringe 100 included a forming pin 180 constructed of a tungsten-containing metal. The conversion resulted in metal-containing contaminants, including tungsten oxide, being deposited on the inner surface 114 of the syringe tip 110. Following the conversion, the inner surface 114 of the syringe tip 110 had an average concentration of tungsten oxide, as determined by normalizing the ICP-MS data. For the glass syringe exposed to 2.5 minute contact time increments, the initial concentration of tungsten oxide on the inner surface 114 of the syringe tip 110 was approximately 0.04 μg / g, as determined by normalization of the ICP-MS data. For the glass syringe 100 treated with 10 minute contact time increments, the initial concentration of tungsten oxide was measured to be approximately 1.4 μg / g, which was an order of magnitude greater than the other syringes tested at 2.5 minute contact time intervals. This demonstrates the variability in the concentration of tungsten species deposited on the surface from glass syringe to glass syringe.

[0093] To remove metal-containing contaminants from the inner surfaces of the syringe tips, the glass syringes were grouped into bundles of 8 units and then exposed to a volume of aqueous treatment medium sufficient to immerse the syringe tips of the glass syringes. The aqueous treatment medium contained 1 molar (M) citric acid and 0.26 M ammonium bifluoride in water. The syringe tips of the glass syringes were contacted with the aqueous treatment medium in time increments of 2.5 minutes and 10 minutes at a contact temperature equal to room temperature. Between each contact step, the glass syringe bundles were rinsed in a 1 M citric acid wash solution. Following each repetition of contact with the aqueous treatment medium and after washing with the citric acid wash solution, the aqueous treatment medium and the citric acid wash solution were chemically analyzed to determine the concentrations of tungsten or other metal species in the aqueous treatment medium and the citric acid wash solution. This time-sequence approach, with a rinse step between each step of stepwise contacting with the aqueous treatment medium, allowed for the determination of the time required to remove metal-containing contaminants from the surface of the glass syringe. The stepwise contacting method of Example 1 also allowed for the determination of whether the tungsten oxide was loosely bound to the surface, as indicated by the presence of tungsten in the citric acid wash solution, or whether the tungsten oxide was tightly bound to the glass surface, as indicated by the presence of tungsten in the citric acid wash solution. Contacting with the aqueous treatment medium also removed tin from the surface of the glass syringe, which was found to be another surface contaminant found on the surface of the glass syringe.

[0094] Referring now to Figure 8, a graph shows the concentrations of tungsten and tin in the aqueous treatment medium recovered from each contact step conducted at 2.5 minute or 10 minute time increments. For the 2.5 minute contact time increments, the total contact time with the aqueous treatment medium was 7.5 minutes, and for the 10 minute contact time increments, the total contact time with the aqueous treatment medium was 30 minutes. Reference numbers for Figure 8 are provided in Table 2. [Table 1]

[0095] As shown in Figure 8, the tungsten concentration decayed monotonically with each contact step for the 2.5 and 10 minute contact intervals. The tungsten concentration was reduced to <0.02 μg / g, below the detection limit, after the first contact interval for both the 2.5 minute and 10 minute intervals, despite a two-order of magnitude difference in the initial concentration of tungsten in the aqueous treatment medium.

[0096] Furthermore, no tungsten was found in the citric acid cleaning solution recovered from the rinsing step, indicating that the tungsten species were well attached to the surface of the glass syringe. Therefore, the glass cleaning procedure removed the tungsten species by an etching mechanism, rather than by leaching them out.

[0097] Interestingly, tin (Sn), another known surface contaminant, was more "sticky" and took significantly longer to remove from the glass syringes with the aqueous treatment medium. For short time increments (i.e., 2.5 min), the tin concentration increased with each step. For longer time increments (i.e., 10 min), the tin concentration decayed with each contact step, albeit at a slower rate compared to tungsten removal. To ensure valid time series between experiments, a first-order mass balance calculation was performed assuming Sn was homogeneously distributed among the syringes. We found that Sn was accounted for between time series, and the variation in tungsten was likely due to syringe-to-syringe variation. This syringe-to-syringe variation may be reasonable because the tungsten pins wear rapidly during the syringe formation process, resulting in variations in the starting concentration of tungsten species on the glass syringe surface.

[0098] Referring now to FIG. 9 , the molar ratio of sodium to silicon in the aqueous treatment medium as a function of time is graphically shown for Example 1. Series 902 refers to experiments conducted at 2.5 minute contact time intervals, and series 904 refers to experiments conducted at 10 minute contact time intervals. FIG. 9 depicts that the glass surface was mildly etched by the aqueous treatment medium, as indicated by the Na / Si molar ratio normalized to the bulk glass Na / Si molar ratio value after 10 minutes. Because Na is a volatile element and is lost from glass during flame exposure, and Si is relatively refractory, flame-processed surfaces are known to have a low Na / Si molar ratio relative to the bulk glass. Therefore, FIG. 9 shows that the surface of the glass is mildly etched by the aqueous treatment medium to the bulk composition of the glass, without substantially preferentially removing either Na or Si species from the glass.

[0099] Example 2: After one 7.5 minute wash In Example 2, a glass syringe was contacted with the aqueous treatment medium for a single 7.5-minute contact time interval. The glass syringe was manufactured according to the method disclosed herein using a forming pin comprising tungsten, as described in Example 1. The aqueous treatment medium contained 1 molar (M) citric acid and 0.26 M ammonium bifluoride in water. The syringe tip of the glass syringe was contacted with the aqueous treatment medium for a contact time of 7.5 minutes at a contact temperature equal to room temperature.

[0100] 11A and 11B, SEM backscattered images of the surface of a glass syringe prior to contact with an aqueous treatment medium are shown. FIG. 11B is taken at a higher resolution compared to FIG. 11A. The bright spots in FIG. 11B indicate the presence of tungsten oxide deposits on the surface of the untreated glass syringe.

[0101] 14A and 14B, SEM backscattered images of the surface of a glass syringe after contact with an aqueous treatment solution at room temperature for 7.5 minutes are shown, taken at two different resolutions. As shown in FIGS. 14A and 14B, the surface of the glass syringe appears to be completely free of light regions indicative of tungsten oxide deposits.

[0102] Comparative Example 3: Treatment with citric acid solution For Comparative Example 3, a glass syringe having tungsten oxide deposits on its surface was treated with a citric acid solution at a contact temperature of 80°C for a contact time of 7.5 minutes. The glass syringe was prepared as described in Example 1. The citric acid solution used for Comparative Example 3 comprised a 1 M citric acid solution in water. Referring to FIGS. 12A and 12B, SEM backscattered images of the surface of the glass syringe of Comparative Example 3 at two different resolutions are shown. As shown in FIGS. 12A and 12B, treatment of the glass with a citric acid solution without fluoride ions, even at an elevated temperature of 80°C instead of room temperature, was not sufficient to remove the tungsten oxide deposits from the glass.

[0103] Comparative Example 4: Treatment with Phosphoric Acid Solution For Comparative Example 4, a glass syringe having tungsten oxide deposits on its surface was treated with a phosphoric acid solution at a contact temperature of 80°C for a contact time of 7.5 minutes. The glass syringe was prepared as described in Example 1. The phosphoric acid solution used for Comparative Example 4 comprised a 1 M phosphoric acid solution in water. Referring to FIGS. 13A and 13B, SEM backscattered images of the surface of the glass syringe of Comparative Example 4 at two different resolutions are shown. As shown in FIG. 13B, treatment of the glass with the phosphoric acid solution for a contact time of 7.5 minutes did not remove all of the tungsten oxide deposits, as indicated by the bright spots in FIG. 13B, despite being treated at a high temperature of 80°C instead of room temperature.

[0104] Referring now to FIG. 10, the concentration of tungsten in the aqueous treatment medium of Example 2 (reference numeral 1002) and the concentration of tungsten in the phosphoric acid solution of Comparative Example 4 (reference numeral 1004) are graphically shown as a function of time. As shown in FIG. 10, the aqueous treatment medium of Example 2 resulted in faster removal of tungsten oxide deposits from the surface of the glass syringe compared to the phosphoric acid solution of Comparative Example 4. At 10 seconds, the concentration in the aqueous treatment medium of Example 2 (reference numeral 1002) had already risen to 0.04, indicating nearly instantaneous removal of tungsten oxide by the aqueous treatment medium. In contrast, the phosphoric acid solution of Comparative Example 4 (reference numeral 1004) exhibited a much lower tungsten concentration at 10 seconds, indicating a slower removal rate. The concentration of tungsten in the phosphoric acid solution did not reach 0.04 μg / g until 2.5 minutes into the contact period. Furthermore, the aqueous treatment medium of Example 2 (Reference No. 1002) had a tungsten species concentration of zero by about 5 minutes, indicating nearly complete removal of tungsten oxide within 5 minutes. After 5 minutes, the phosphoric acid solution of Comparative Example 4 (Reference No. 1004) still had a tungsten species concentration of greater than 0.02 μg / g, indicating that the phosphoric acid solution was still removing tungsten species from the glass surface. The tungsten concentration in the phosphoric acid solution of Comparative Example 4 did not reach zero until 7.5 minutes. Therefore, the aqueous treatment medium of Example 2 removed tungsten oxide species at least 2.5 minutes faster than the phosphoric acid solution of Comparative Example 4.

[0105] It will be apparent to those skilled in the art that various modifications and variations can be made in the embodiments described herein without departing from the spirit or scope of the claimed subject matter. Thus, it is intended that the present specification cover modifications and variations of the various embodiments described herein, provided that such modifications and variations come within the scope of the appended claims and their equivalents.

Claims

1. 1. A method of making a glass syringe, said method comprising: forming the glass syringe having at least a barrel and a syringe tip, wherein forming the syringe tip includes contacting at least one surface of the glass syringe with a forming tool, a forming pin, or both, wherein the contacting causes migration of metal-containing contaminants to the at least one surface of the glass syringe; contacting the at least one surface of the glass syringe with an aqueous treatment medium comprising fluoride ions, at least one acid, or both, wherein the contacting with the aqueous treatment medium removes the metal-containing contaminants from the at least one surface of the glass syringe.

2. 10. The method of claim 1, wherein the concentration of the metal-containing contaminant on the at least one surface of the syringe is between 8.3 parts per billion and 83 parts per billion by weight as determined according to the test method of U.S. Pharmacopeia <797>.

3. 10. The method of claim 1, wherein said contacting said at least one surface of said glass syringe with said aqueous treatment medium removes 50% or more of said metal-containing contaminants from said at least one surface of said syringe tip.

4. 10. The method of claim 1, wherein after contacting the at least one surface of the glass syringe with the aqueous treatment medium, the at least one surface of the glass syringe has a concentration of metal-containing contaminants of less than 8.3 ppbw as determined according to the test method in U.S. Pharmacopeia <797>.

5. 10. The method of claim 1, wherein the metal-containing contaminants comprise one or more metals selected from the group consisting of tungsten, platinum, rhodium, tantalum, nickel, and combinations thereof.

6. The method of claim 1 , wherein the metal-containing contaminants comprise tungsten or a derivative thereof.

7. 2. The method of claim 1, wherein the aqueous treatment medium comprises the fluoride ions, and wherein the concentration of the fluoride ions in the aqueous treatment medium is about 1000 ppm as calculated using Visual MINTEQ™ software with standard settings.

8. The aqueous treatment medium may be hydrogen fluoride (HF), sodium fluoride (NaF), ammonium bifluoride (NH ４ HF ２ 2. The method of claim 1, comprising a source of said fluoride ions selected from the group consisting of:

9. The aqueous treatment medium is HCl, HBr, HNO ３ , H ２ SO ４ , H ２ SO ３ , H ３ P.O. ４ , H ３ P.O. ２ 2. The method of claim 1, wherein the at least one acid is selected from the group consisting of acetic acid, citric acid, tartaric acid, ascorbic acid, EDTA, methanesulfonic acid, toluenesulfonic acid, and combinations thereof.

10. 10. The method of claim 1, comprising contacting the at least one surface of the glass syringe with the aqueous treatment medium comprising fluoride ions and at least one acid.

11. The aqueous treatment medium may be hydrogen fluoride (HF), sodium fluoride (NaF), ammonium bifluoride (NH ４ HF ２ ), and combinations thereof; The at least one acid is HCl, HBr, HNO ３ , H ２ SO ４ , H ２ SO ３ , H ３ P.O. ４ , H ３ P.O. ２ acetic acid, citric acid, tartaric acid, ascorbic acid, EDTA, methanesulfonic acid, toluenesulfonic acid, and combinations thereof.

12. 10. The method of claim 1, wherein the aqueous treatment medium comprises 0.026 molar (M) to 0.26M ammonium bifluoride and 0.5M to 2M citric acid.

13. 10. The method of claim 1, comprising contacting the at least one surface of the glass syringe with the aqueous treatment medium at a contact temperature of from 0° C. to 105° C. and a contact time of from 10 seconds to 24 hours.

14. 1. A method for removing metal-containing contaminants from a surface of a glass syringe, comprising contacting the surface of the glass syringe with an aqueous treatment medium comprising fluoride ions, at least one acid, or both; the metal-containing contaminants are bound to the surface of the glass syringe and are present on the surface at a concentration of 8.3 ppbw or greater prior to contact with the aqueous treatment medium as determined according to the test method in U.S.P. <797>; The method, wherein contacting the aqueous treatment medium with the surface for a contact time reduces the concentration of the metal-containing contaminants on the surface of the glass syringe by 50% or more.

15. 15. The method of claim 14, wherein the concentration of the metal-containing contaminants on the surface of the glass syringe is between 8.3 ppb and 83 ppb as determined by the test method in USP <797>.

16. The method of claim 14 , wherein the surface of the glass syringe is the interior surface of a syringe tip of the glass syringe.

17. 15. The method of claim 14, wherein after contacting the surface of the glass syringe with the aqueous treatment medium, the surface of the glass syringe has a concentration of metal-containing contaminants of less than 8.3 ppbw as determined according to the test method in USP <797>.

18. 15. The method of claim 14, wherein the metal-containing contaminants comprise one or more metals selected from the group consisting of tungsten, platinum, rhodium, tantalum, nickel, and combinations thereof.

19. 15. The method of claim 14, wherein the metal-containing contaminants comprise tungsten or a derivative thereof.

20. The aqueous treatment medium may be hydrogen fluoride (HF), sodium fluoride (NaF), ammonium bifluoride (NH ４ HF ２ ), and combinations thereof; The at least one acid is HCl, HBr, HNO ３ , H ２ SO ４ , H ２ SO ３ , H ３ P.O. ４ , H ３ P.O. ２ 15. The method of claim 14, wherein the acid is selected from the group consisting of acetic acid, citric acid, tartaric acid, ascorbic acid, EDTA, methanesulfonic acid, toluenesulfonic acid, and combinations thereof.

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