PROTECTIVE SHEATH FOR VIALS

INTRODUCTION

Aspects of the present invention relate to protective sheaths for vials, methods for housing vials inside protective sheaths, and methods of using protective sheaths to prevent contact and environmental contamination with hazardous drugs.

While hazardous drugs are widely used in healthcare facilities, this use has significant consequences, as many active agents have a carcinogenic, teratogenic, or mutagenic potential and may be toxic to various organs or reproduction. Over the past two decades, a number of studies have documented the presence of hazardous drugs in the urine of pharmacy personnel and healthcare workers engaged in direct patient care, particularly in the hematology-oncology sector (Ensslin et al., Occupational and Environmental Medicine (1994) 51:229-33; Sessink era/., Mutat Res (1994) 309:193-9; Minoia et al., Rapid Commun Mass Spectrom (1998) 12:1485-93; Pethran et al., Int Arch Occup Environ Health (2003) 76:5-10; Turci et al. Chromatogr B Analyt Technol Biomed Life Sci (2003) 789:169-209). Several studies have revealed the presence of contaminated hazardous drugs on work surfaces used for preparing and storing pharmaceutical products (Vandenbrouke and Robays, J Oncol Pharm Practice (2001) 6(4): 146-52; Schmaus et al., Am J Health Syst Pharm (2002) 59:956-61; Hedmer era/., J Environ Monit (2004) 6:979-84; Acampora et al., Ann Occup Hyg (2005) 49:611-8; Connor et al., Am J Health Syst Pharm (2005) 62:475-84; Crauste-Manciet et al., Ann Occup Hyg (2005) 49:619-28). The publication of these findings has prompted regulatory bodies, health agencies and occupational health and safety boards, as well as professional associations, to draft guidelines, policies and procedures to control the use of hazardous drugs and reduce the risk of occupational exposure (Am J Hosp Pharm (1990) 47:1033-49; USP 27th revision chapter 797 (2003); NIOSH in health care settings (2004); Am J Health Syst Pharm (2006) 63:1172-93).

Some of the intravenous drugs are ready-to-use solutions, and some are lyophilized products. For lyophilized products, a diluent is required for reconstitution. When the diluent is injected into a vial through a needle by the operation of the diluent containing syringe, there is sufficient volume of solution within the vial to displace the gas therein into a smaller volume and hence to increase its pressure.

It is generally well known that this increase in pressure may cause an aerosol release when the needle is removed. This aerosol release may involve the passage outwardly through the elastomeric stopper assembly of portions of the hazardous drug in the form of droplets. This aerosolizing action presents a highly dangerous situation to the medical or paramedical staff who is involved in reconstitution of the medicament vial with a diluent.
There are many situations where this most favorable method of operation cannot be utilized. For example, in many hospital situations, the reconstituting of the drug must be performed in the pharmacy, remote from and at a time prior to the actual use of the reconstituted drug in the ward or patient's room.

The presence of varying concentrations of hazardous drugs has led healthcare professionals to speculate about the potential sources of environmental contamination. Contamination may occur during various stages of the drug circuit, from purchasing and receiving products to storing, preparing and verifying container content and administering and disposing of waste. Whereas many studies have documented the presence of contamination during the preparation and administration stages of the hazardous drug, there have been little data on contamination that occurs prior to drug preparation in hospital pharmacies. It must also be pointed out that contamination present from vials at the time of unpackaging is as significant as that present in the rest of the subsequent process, including that found on pharmacy work surfaces.

It is therefore important that surface contamination of vials be recognized and prevented. Good manufacturing practices are similar in most markets and there are relatively few manufacturing plants around the world for a given drug. Moreover, no regulatory requirements have been made regarding a maximum permissible level of contamination on the external surfaces of vials or the application of transparent protective films by the manufacturer at the end of the manufacturing process.

Several sources of contamination exist in the handling of hazardous drugs in healthcare facilities. One is contamination on the external surfaces of vials that come directly from manufacturers that supply hospital centers with hazardous drugs. Studies have demonstrated the presence of contamination on the external surfaces of hazardous drug vials (Sessink et a/., Int Arch Occup Environ Health (1992) 64:105-12; Ros et a/., Ziekenhuisfarmacie (1997) 13:168-71; Hepp and Gentshew,

Krankenhauspharmazie (1998) 19:22-7; Paul etal., Krankenhauspharmazie (1998) 4:181-6; Delporte etal., Eur Hosp Pharm (1999) 5:119-21; Nygren etal., Ann Occup Hyg (2002) 46:555-7; Favier etal., J Oncol Pharm Pract (2003) 9:15-20; Mason et ai, Ann Occup Hyg (2003) 47:681-5; Funck and Shierl, Dtsch Apoth Ztg (2004) 10:1089-94; Connor etal., Am J Health Syst Pharm (2005) 62:475-84; Hedmer etal., Ann Occup Hyg (2005) 49:629-37; Iglesias, Farm Hosp (2006) 30:300-3). With respect to cyclophosphamide, Sessink et ai, Sessink et ai, Int Arch Occup Environ Health (1992) 64:105-12) reported an initial measurement of 0.06 ug of external vial surface contamination.

Furthermore, studies have documented contamination of work surfaces in pharmacy areas by cyclophosphamide (Minoia etal., Rapid Commun Mass Spectrom (1998) 12:1485-93; Connor etal., Am J Health Syst Pharm (1999) 56:1427-32; Vandenbrouke and Robays, J Oncol Pharm Practice (2001) 6(4):146-52; Schmaus et ai, Am J Health Syst Pharm (2002) 59:956-61; Acampora et ai, Ann Occup Hyg (2005) 49:611-8; Crauste-Manciet et ai, Ann Occup Hyg (2005) 49:619-28; Harrison et ai, Am J Health Syst Pharm (2006) 63:1736-44; Hedmer et ai, Int Arch Occup Environ Health (2008) 81:899-911). The ASSTSAS guide recommends to wholesalers that a cytotoxic or hazardous drug label, for example, be clearly marked on the outside of the drug transport container in order to indicate to receiving staff that the boxes require the use of personal protection equipment (such as wearing a gown and gloves) during handling (Gallant er ai, Guide (2008) Montreal, QC: ASSTSAS. p. 158). Furthermore, the guide specifies the optimal layout of an unpacking/reception area as well as the precautions to be taken to avoid accidental exposure in case of breakage or in view of regular shipments. It also suggests the cleaning of vials when stock is received.

Numerous authors have expressed interest in evaluating the efficacy of various agents used to decontaminate and breakdown hazardous drugs (Monteith et ai, Environ Mol Mutagen (1987) 10:341-56; Lunn etai, J Pharm Sci (1989) 78:652-9; Benvenuto etai, J Pharm Sci (1993) 82:988-91; Castegnaro etai, Int Arch Occup Environ Health (1997) 70:378-84; Barek etai, Ann Occup Hyg (1998) 42:259-66; Allwood etai, The cytotoxics handbook (2002) 4th. Oxford: Radcliffe Medical Press). This growing interest has led to the publication of a number of studies aimed at evaluating the decontamination power of various detergents or oxidizing agents such as sodium hypochlorite, hydrogen peroxide, and Fenton's reagent. Some of these publications contend that NaOCI is a very effective agent for the elimination of hazardous drug contamination without, however, leading to the production of mutagenic residues (Hansel et al., Int Arch Occup Environ Health (1997) 69:109-14).

Another study completed by Roberts et al. J Oncol Pharm Pract (2006) 12:95-104) revealed that the use of a towel wipe soaked in sterile water or an alcohol solution also eliminates the presence of contamination on work surfaces contaminated with fluouracil, cyclophosphamide and doxorubicin.

Although this measure may reduce contamination, cleaning may nevertheless lead in certain cases to an increase in the risk of breaking vials or damaging the manufacturer's labeling. The addition of another step to the receiving process that would involve washing vials in the hospital pharmacy may, however, be difficult to apply, given the layout and resources available.

The United States Pharmacopeia (USP), Pharmaceutical compounding— sterile preparations, 27th revision, and the national formulary, in General information, chapter 797 (2003) 22nd, United States Pharmacopeail Convention, Inc., Rockville, MD give recommendations regarding hazardous drugs, it is recommended to separately store hazardous products away from other inventory, in a manner to prevent contamination and personnel exposure. As many hazardous drugs have sufficient vapor pressures that allow volatilization at room temperature, they should be stored preferably within a containment area such as a negative pressure room with sufficient general exhaust ventilation (e.g., at least 12 air changes per hour) and they should be handled with caution at all times using appropriate chemotherapy gloves during receiving, distribution, stocking, inventorying, preparation for administration and disposal. The National Institute for Occupational Safety and Health Alert and USP 797 reinforce the importance of prevention at all stages to reduce the risk of professional exposure to hazardous drugs (2008).

Recent studies have shown that the effects of exposure to anti-neoplastic drugs, including cytotoxic agents, can be quite severe. Particularly, this is true when the exposure is on a day-to-day basis over an extended period. A definite cause and effect relationship between exposure and fetal loss has been observed in a study reported in "A Study of Occupational Exposure to Antineoplastic Drugs and Fetal

Loss in Nurses," New England Journal of Medicine, Vol. 311, No. 19, pages 1173-1178, Nov. 7, 1985. See also the editorial in the same edition, pages 1220-1221.

Presently, some of the procedures are available for allowing a user to accomplish both the reconstituting and air expelling operations, without exposing the cytotoxic drugs to the immediate atmospheric environment. These method involves the use of a glove box, where the user inserts his hands into gloves so that the user can manipulate the syringe or syringes and the vial with the gloves within an enclosed space. This procedure is bothersome and somewhat cumbersome to perform. Some manufacturers do proceed with the addition of a protective film at the end of the process for some hazardous drugs.

A second presently available procedure for preventing aerosolization is using a dispensing pin of the type disclosed in U.S. Patent No. 4,211,588, wherein the elastomeric stopper of the vial is never pierced by a needle but rather only by a pin having two parallel passages extending there through. One of the passages functions to maintain the interior pressure within the vial substantially at atmospheric pressure by venting the one passage to atmosphere through a filter. The other passage functions as a conduit for conducting diluent into the vial and hazardous material solution out of the vial. This procedure is cumbersome and inherently fraught with the hazard of environmental and/or accidental exposure to the user.

U.S. Patent No. 3,882,909 discloses an apparatus similar to that disclosed in U.S. Patent No. 4,211,588 noted above, except that the dual passage pin is straight and the upper ends of the pin and passages are surrounded by a chamber having a septum in the upper end thereof and a parallel vent with a filter therein. U.S. Patent No. 4,588,403 discloses a functionally similar apparatus with a different structural arrangement.

U.S. Patent Nos. 4,619,651 and 4,582,207 disclose an exterior chamber vented to atmosphere through a filter. U.S. Patent Nos. 4,552,277 and 4,576,211 disclose a telescoping closed chamber with special needle.

U.S. Patent Nos. 4,982,769 and 4,768,568 disclose a device in the form of a controlled assembly for use with a vial having a hazardous material, but these devices are complex and cumbersome.

The above devices can be effective in minimizing the possibility of hazardous material entering the immediate environment. However, the devices are quite

complex, thereby posing manufacturing problems, and also do not provide any protection against contamination of the environment in the event that the vial container itself should be accidentally fractured so as to release its contents to the environment.

Current safe-handling procedures for vials containing chemotherapy products are apparently insufficient. Recent U.S. and European tests have determined that product residues adhering to the outside of chemotherapy vials are a pharmacy hazard.

Nevertheless, it is very difficult to gather information from suppliers regarding the nature of specific cleaning and decontamination procedures for hazardous drug vials. The presence of contamination on the external surfaces of vials needs to be taken into consideration in pharmaceutical practice and the importance of environmental monitoring combined with a cleaning procedure is highly desirable.

The present invention provides a protective sheath which is aesthetically pleasing, unbreakable, tamper evident, and eliminates surface contact by medical staff to avoid contact of any possible spillage of product on the surface of the vial during filling, packing, sample preparation and withdrawal.

SUMMARY

An aspect of the present invention relates to a protective sheath for vials, and other aspects relate to methods in which a protective sheath houses a vial and methods of using protective sheaths to prevent contamination with a hazardous drug.

The present invention provides protective sheaths which are aesthetic, unbreakable, tamper evident, and which eliminate surface contact by medical staff to avoid spillage of product on the surface of the vial during packaging.

An aspect of the present invention provides protective sheaths for vials, comprising a hollow interior chamber wherein the vial is disposed within the hollow interior chamber and remains there as though sealed. In embodiments, a protective sheath includes an open end neck or skirt at its upper end extending to the exterior, wherein the skirt has a tamper evident member which is linked to an removable cap which is sealed onto the vial. By stripping off or moving aside the tamper evident member, which otherwise would reflect any tampering, the removable cap can be peeled off, making the vial closure available for penetration by a needle.

In embodiments, the invention includes protective sheaths comprising an interior chamber, wherein a vial is disposed within the interior chamber and the protective sheath has an open end neck or skirt extending to the exterior, which prevents a user from coming into contact with any drug on the surface of the vial.

In embodiments, an interior dimension of the peripheral wall of the hollow interior chamber is greater than the exterior dimension of the medicament vial.

In further embodiments, a protective sheath is transparent, thereby reducing any need for further labeling of the vial and/or allowing it to be molded in a light filtering color, if the nature of the medicament is light sensitive.

Another aspect of the present invention provides protective sheaths that are simple in construction, aesthetic, effective in operation and economical to manufacture.

Further aspects include methods of disposing or arranging a vial inside a protective sheath.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 is a side elevational view of a protective sheath according to the present invention.

Figure 2 is a side elevational view of a medicament vial to be positioned in the protective sheath of Figure 1.

Figure 3 is a perspective view of a protective sheath with the medicament vial therein and the tamper evident member in a position to prevent removal of a removable cap.

Figure 4 is a perspective view of a protective sheath with the medicament vial therein and the tamper evident member peeled away to a position to permit removal of a removable cap.

Figure 5 is a perspective view of a protective sheath with the medicament vial therein and the tamper evident member peeled away and the removable cap partially removed.

Figure 6 is a perspective view of a protective sheath with the medicament vial therein and the tamper evident member peeled away and the removable cap fully removed.

Figure 7 is vertical cross sectional view of a protective sheath with 'L' shaped lower protrusions at the bottom of the sheath and 'triangle' shaped upper protrusions at shoulder of the sheath.

Figure 8 is horizontal cross sectional view of a protective sheath showing two 'L' shaped lower protrusions facing each other and two 'straight line' lower protrusions facing each other at the bottom of the sheath.

Figure 9 is front view of protective sheath showing tamper evident member with root like joint connecting tamper evident member with hollow interior chamber of sheath and two thread like joints connecting tamper evident member with the ends of the skirt of the sheath.

Figure 10 shows how the protective sheath prevents the contact with the hazardous drug while handling and sample preparation and withdrawal, wherein:

a) represents a method of injecting diluent into medicament vial;

b) represents a method of mixing the solution through repeated inversions of the vial until powder is completely dissolved; and

c) represents a method of withdrawal of sample from the medicament vial and

d) transfer of the sample into an intravenous fluid bag for administration.

DETAILED DESCRIPTION

The present invention relates to protective sheaths for vials, and also relates to methods in which a protective sheath houses a vial, and methods of using a protective sheath to prevent contact and environmental contamination with a hazardous drugs.

Hazardous drugs such as antineoplastic drugs are widely used for cancer treatment. Intravenous administrations of antineoplastic drugs are usually prepared individually for each patient in centralized facilities within hospitals. Although strict health and safety rules have been established and applied, the potential health hazard to persons manipulating these drugs is still a concern for hospital staff members. Studies have found traces of these drugs in the urine of hospital personnel directly and indirectly involved in drug preparation and administration.

An aspect of the present invention provides protective sheaths for vials, comprising a hollow interior chamber wherein a vial is disposed within the hollow interior chamber and stays there as though sealed. The protective sheath has an open end neck or skirt extending to the exterior, wherein the skirt has a tamper evident member which is linked to a removable cap that is sealed onto the vial. By stripping off or moving away the tamper evident member, which otherwise would reflect any tampering, the removable cap can be peeled off, making the vial available for withdrawing and injecting the contents.
Referring to the drawings, a protective sheath 10 for a medicament vial 12 includes a main body 14 having a hollow interior chamber in which medicament vial 12 is disposed in a sealed manner. Medicament vial 12 includes a removable cap 16 which seals the upper end thereof. An open end neck or skirt 18 is provided at the upper end of main body 14 which is subtended on the hollow interior chamber of main body 14 and extends to the exterior of main body 14. Skirt 18 includes a tamper evident member 20 which is linked to a removable cap 16 that is sealed onto medicament vial 12. Specifically, tamper evident member 20 is attached to skirt 18 through root like or hinged projections 20a at the bottom of tamper evident member thereof and by thread-like or perforated projections 20b on either side, in such a way that in order to obtain access to medicament vial 12, which is housed in the hollow interior chamber of main body 14, so as to permit use for an injection, the user needs to tear or peel away tamper evident member 20. In this regard, projections 20b are broken and tamper evident member 20 can be pivoted down about hinged projections 20a. Additionally there is flip like projection 20c on tamper evident member to hold while tearing off. By stripping off or moving tamper evident member 20, which otherwise reflects any tampering, removable cap 16 can then be peeled away from medicament vial 12, thereby making vial 12 available for injection.

Medicament vial 12 is of a conventional construction, and typically includes a glass vial container 22 having an exteriorly beaded open neck 24 at the upper end thereof, which is sealed by an elastomeric stopper assembly 26 mounted to the opening of neck 24.
Protective sheath 10 has an open end 28 leading to a hollow interior chamber which extends down to a circular bottom wall 30 thereof. Circular bottom wall 30 can be flat, concave or convex, and main body 14 can be formed by a cylindrical peripheral wall 32, providing a housing for mounting medicament vial 12 therein. Bottom wall 30 can have a concavo-convex configuration which bulges inwardly so that the central portion of bottom wall 30 engages the central bottom of the medicament vial 12 which is usually flat or of a concavo-convex configuration and bulges inwardly.

Circular bottom wall 30 and cylindrical peripheral wall 32 can include lower connected protrusions 14a and 14b integrally formed on inner surfaces thereof at the intersection of peripheral wall 32 with bottom wall 30, and upper protrusions 14c integrally formed on the inner surface of peripheral wall 32, both of which function as a cushion for medicament vial 12, as well as centering medicament vial 12 within protective sheath 10 and retaining such centered relationship. The protrusions at upper and lower end may be of any shape suitable such as 'L' shaped, 'triangle' shaped, 'rectangle' shapes, 'square' shaped, or straight line, etc. In an embodiment as shown in Figures 7 and 8, the lower protrusions 14a have 'L' shape, 14b are straight line, and upper protrusions 14c are of 'triangle' shape.

The interior dimension of the cylindrical interior surface of peripheral wall 32 is greater than the exterior dimension of glass vial container 22, so as to permit glass vial container 22 to be positioned by protrusions 14a, 14b, and 14c.

Exemplary thermoplastic materials that may be used for manufacturing a protective sheath of the present invention include, but are not limited to, polyvinyl chloride, polypropylene, polyethylene, polycarbonate, polyester, and acrylonitrile butadiene styrene (ABS).

Removable cap 16 can comprise a metal foil, such as aluminum foil, or a polymeric sheet material. Typically, the removable cap will be adherent to the top closure of a medicament vial, such as by using an adhesive.

A method of withdrawing medicament from vial 12 within protective sheath 10 will now be described with respect to Figures 3-6.

Protective sheath 10 is arranged to be used with a diluent syringe. Such a syringe, as is well known, includes a conventional glass barrel defining a chamber which communicates at one end with a hypodermic needle having a sharpened open end. A plunger is slidably and sealingly mounted in the syringe chamber. The syringe plunger can be actuated to draw a dosage amount of diluent into the syringe chamber.

With protective sheath 10 in the position shown in Figure 6 or Figure 10(a), after removable cap 16 has been removed, the diluent syringe containing a full dosage of diluent in the chamber thereof is aligned in a way that the open end of the needle is in a position to pierce through septum 34, which is exposed at the upper end of medicament vial 12 after removable cap 16 has been removed. By pushing down on the syringe, the needle point penetrates through septum 34 and then through elastomeric stopper assembly 26 of the medicament vial 12. The user then depresses the syringe plunger so as to eject the diluent from the syringe chamber through the open end of the needle into the medicament chamber of the medicament vial 12 to be intermixed with the hazardous drug contained therein.

After the diluent has been ejected from the syringe chamber into the medicament chamber in medicament vial 12, the medicament chamber has a dosage of liquid medicament solution in the lower portion thereof and a gaseous fluid which includes saturated vapor of the hazardous material solution thereabove, both of which are retained under elevated pressure conditions by virtue of the added volume of the diluent. The syringe with the plunger held in its fully engaged position is retained with the needle in its penetrating relation. If necessary, medicament vial 12 is agitated as shown in Figure 10(b) to complete the mixing procedure required to constitute the solution. Thereafter, the user simply inverts the entire protective sheath 10 with the syringe maintained in penetrating relation as shown in Figure 10(c) and then releases the plunger. The gaseous fluid within the container remains on top of the liquid solution and the pressure thereof serves to move the liquid medicament from medicament vial 12 into the open end of the syringe needle, thus filling the syringe chamber as the syringe plunger moves downwardly. Where the liquid medicament is to be injected directly into the patient, preferably, prior to withdrawal of the needle, the operator applies a slight pressure to the plunger so as to ensure that any air in the interior of the needle is discharged there from and into medicament vial 12. This pressure is retained during the withdrawal of the needle from elastomeric stopper assembly 26 and immediately after such withdrawal; the pressure on the plunger is relieved. During the withdrawal of the needle from elastomeric stopper 26, any residual pressure within medicament vial 12 which would tend to cause aerosolizing of hazardous material from the interior of medicament vial 12 past elastomeric stopper assembly 26, from which the user needs to be protected, is performed by skirt 18.

It can also be seen from the Figure 10 that, in a typical situation where a single syringe is used both as a reconstituting syringe and as a dosage syringe, skirt 18 prevents any contact of the hazardous material which would reach the outer atmosphere onto the upper surface of septum 34 to the user's finger and/or fingertips. This insurance is provided by the upward extension of skirt 18 to close any possible space through which the user's fingers and/or fingertips could reach the upper surface of septum 34.

In situations where the reconstituting procedures are separated from the filling and injecting procedures, a typical mode of use in accordance with the principles of the present invention is set forth below, assuming first a one dosage vial 12 in protective sheath 10. The reconstituting procedure involves moving the needle of the diluent syringe through septum 34 of the elastomeric stopper assembly 26 in the manner previously described. Thereafter, the syringe plunger is depressed to eject the diluent from the syringe chamber through the open end of the syringe needle into the medicament chamber provided in medicament vial 12. When this movement of diluent has been completed, the user simply releases the plunger with medicament vial 12 retained in its upright position so that the liquid is in the lower portion of the medicament chamber and the open end of the needle is in communication with the gaseous fluid within the vial chamber.

By relieving the manual pressure acting on the syringe plunger, the gaseous fluid pressure within the vial medicament chamber thus communicates through the open end of the needle with the syringe chamber moving the syringe plunger upwardly until the pressure conditions are substantially equal and atmospheric. Here again, it will be understood that the syringe plunger has frictional contact within the barrel so that in the absence of a manual movement at the end, the syringe plunger will reach a position where only substantial atmospheric conditions are obtained.

This gaseous fluid basically is air, with perhaps some hazardous material entrained therein. After the gaseous fluid has been ejected from the syringe chamber, the syringe needle is then withdrawn from septum 34. In this way, medicament vial 12 is engaged thereon in a condition to be transported to the position of use, it being noted that the gaseous fluid and liquid medicament are now contained within the chamber of medicament vial 12 at substantially atmospheric pressure conditions.

When it is desired to utilize the liquid medicament of medicament vial 12, a dosage syringe similar to the diluent syringe is initially moved into a position wherein the syringe plunger is disposed from its fully engaged position to an extent such that the volume within the syringe chamber defined by the plunger is generally equal to the volume of the dosage. Thus, this volume of the dosage syringe chamber is initially filled with air. With the dosage syringe in this condition, the needle is penetrated through septum 34 and elastomeric stopper assembly 26 until the open end thereof communicates with the interior of the vial chamber. The syringe plunger is then depressed so as to inject the air within the syringe chamber through the open end of the needle and into the vial chamber, thus raising the pressure conditions therein. Protective sheath 10 including medicament vial 12 is then inverted, and the operator releases the syringe plunger, allowing the gaseous fluid pressure conditions acting on top of the liquid medicament within the vial chamber to pass into the open end of the needle and into the syringe chamber moving the syringe plunger downwardly, as aforesaid. Here again, basically, the syringe plunger should move into a position in which the pressure as between the syringe chamber and the vial chamber is equalized at or slightly above or near atmospheric conditions. Before withdrawing the needle, where required by the nature of the injection to be made, the operator applies a slight pressure to the syringe plunger insuring that any gaseous fluid in the needle is ejected therefrom. The syringe needle is withdrawn while the syringe is retained in this condition and immediately after withdrawal from elastomeric stopper assembly 26, the manual pressure on the syringe plunger is released. As previously indicated, any tendency for any residual pressure in the vial chamber to cause aerosolizing or any tendency of the manual pressure to cause ejection of the liquid from the open end due to changing pressure conditions as the needle end is withdrawn from elastomeric stopper assembly 26, is prevented.

Thereafter, the syringe is pulled all the way out, thus withdrawing the needle from septum 34. In this way, the filled syringe is now in a proper equilibrium condition to be used. It will be understood that the step of ejecting gaseous fluid from the needle within the vial chamber is undertaken in those situations where the liquid medicament is to be injected directly into the patient or where the liquid medicament is to be injected into an intravenous fluid bag.

It will be understood that the above procedures are easily carried out also with a multiple dosage vial forming a part of the package vial container except that the filling procedures are repeated a number of times equal to the number of dosages.

It can be seen from the above that the method of the present invention has applicability in those situations where mixing is carried out in medicament vial 12 between an ingredient originally within the vial container and an extraneously added ingredient. The two ingredients are, in the typical case, a powder material and a diluent. However, they may be two different liquid ingredients.

It will be seen that the objects of this invention have been fully and effectively accomplished. It will be realized, however, that the foregoing embodiment has been shown and described for the purpose of this invention and is subject to change without departure from such principles. It is to be understood that the illustration given are not intended to limit the scope of the invention in any manner. All the modifications encompassed to the protective sheath are within scope of the invention.

All the hazardous drugs which may be one or more of carcinogenic, teratogenic, or mutagenic and may be toxic to various organs are within the scope of the invention. Some of the hazardous drugs (with their trade names in the brackets) for which this kind of protective sheath is useful include but not limited to Aldesleukin (Proleukin), Alemtuzumab (Campath), Alitretinoin (Panretin), Altretamine (Hexalen), Amifostine, Aminoglutethimide, Amsacrine, Anastrozole (Arimidex), Arsenic Trioxide (Trisenox), Asparaginase/L-Asparaginase (Elspar), Azacytidine (Azacytidine), Azathioprime (Azathioprine), Bexarotene (Targretin), Bicalutamide (Casodex), Bleomycin/Bleomycin Sulfate (Blenoxane), Busulfan (Myleran), Capecitabine (Xeloda), Carboplatin (Paraplatin), Carmustine/BCNU (BiCNU), CCNU (Belustine), Chlorambucil* (Leukeran), Chloramphenicol, Chlornaphazin, Chlorotrianisene, Chlorozotocin, Cisplatin/Cis-Platin (Platinol), Cladribine/2-chlorode-oxyadenosine, 2CdA (Leustatin), Cyclophosphamide (Cytoxan/Neosar), Cyclosporin, Cytarabine/Cytosine Arabinoside (Cytosar-U), Dacarbazine (DTIC, DIC, DTIC-Dome), Dactinomycin/Actinomycin-D (Cosmegen), Daunomycin, Daunorubicin/Daunorubicin Hydrochloride (Cerubidine), Daunorubicin (DaunoXome), Denileukin Diftitox (Ontak), Diethylstilbesterol, Docetaxel (Taxotere), Doxorubicin (Adriamycin), Doxorubicin Hydrochloride Liposomal Injection (Doxil), Epirubicin/Epirubicin Hydrochloride (Ellence), Erlotinib, Estradiol, Estramustine (Emcyt), Ethinyl Estradiol, Etoposide (VePesid), Exemestane (Aromasin), Filgrastim, Floxuridine Fludarabine/Fludarabine Phosphate (Fludara), Fluorouracil/5-Fluorouracil (Adrucil), Flutamide (Eulexin), Fulvestrant, Ganciclovir, Geftinib, Gemcitabine (Gemzar), Gemtuzumab Ozogamicin (Mylotarg), Goserelin/Goserelin Acetate (Zoladex), Granisetron, Hydroxyurea (Droxia/Mylocel), Ibritumomab Tiuetan (Zevalin), Idarubicin (Idamycin), Ifosfamide (Ifex), Imatinib Mesylate (Gleevec), Interferon-A/lnterferon Alfa (2a, 2b) (Roferon-A, Intron-A), lnterleukin-2, Irinotecan (Camposar), Isotretinoin, Letrozole (Femara), Leuprolide/Leuprolide Acetate (Lupron/Lupron Depot), Levamisole (Ergamisol), Lomustine (CeeNu), Mechlorethamine (Mustargen), Mechlorethamine Hydrochloride Medroxyprogesterone/Medroxyprogesterone Acetate (Provera), Megestrol/Megestrol Acetate (Megace), Melphalan (Alkeran), Mercaptopurine (Purinethol), Methotrexate (Mexate/Folex), Methyl-CCNU (Semustine), Mithramycin (Mithracin), Mitomycin/ Mitomycin C (Mutamycin), Mitotane, Mitoxantrone (Novantrone), Myleran, Nafarelin Nilutamide (Nllandron), Nitrogen Mustard (Mustargen), Octreotide, Ondansetron , Oprelvekin (Neumega), Oxaliplatin, Paclitaxel (Taxol), Pamidronate. Pegaspargase, Pentostatin (Nipent), Pipobroman Plicamycin, Procarbazine/Procarbazine Hydrochloride (Matulane), Ribavirin, Rituximab (Rituxan), Sorafenib, Streptozocin/Streptozoticin (Zanosar), Tamoxifen/Tamoxifen Citrate (Nolvadex), Temozolomide (Temodar), Teniposide (Vumon), Teosulfan, Testolactone, Thalidomide, Thioguanine, Thiotepa (Thioplex), Topotecan (Hycamtin), Toremifene/Toremifene Citrate (Fareston), Trastuzumab (Herceptin), Tretinoin (Vesanoid), Triethylene Thiophosphoramide (Thiotepa), Triptorelin Pamoate (Trelstar Depot), Uracil Mustard (Uramustine), Valrubicin, Vidarabine, VinblastineA/inblastine Sulfate (Velban), VincristineA/incristine Sulfate (Oncovin), Vindesine, VinorelbineA/inorelbine Tartrate (Navelbine), VM-26, Zidovudine (Retrovir), Zoledronic acid.

STATEMENT OF CLAIMS

1. A method for determining a reason for customer churn and
predicting future instances of said customer churn, said method comprising steps of:
identifying negative sentiments among customers for different attributes;
identifying said customers who are likeiy to churn, based on said negative sentiments;
computing said customer level peer performance score;
computing network level performance score; and
computing cumulative churn score for each of said customers.

2. The method, as claimed in claim 1, wherein said method further comprises the step of displaying information about customer on said data management support system.

3. The method, as claimed in claim 1, wherein said attributes relate to at least one of:
network performance; competitor performance; and peer influence.

4. The method, as claimed in claim 1, wherein said data is at least one of:
demographic data of said customers;
data on usage of services by said customers;
customer billing information;
data about peers;
historic data about competitors;
current data about competitors;
data about network service providers of peers;
system failures within network; and
meta-data.

5. The method, as claimed in claim 1, wherein a miner module periodically finds patterns of system failures, said negative sentiments and peer influence that precede said customer churn.

6. The method, as claimed in claim 5, wherein said miner module builds models to predict said customer churn using said data.

7. The method, as claimed in claim 5, wherein said patterns identified by said miner module are stored as part of a rule base in a rules data base.

8. The method, as claimed in claim 1, wherein said rule base is used to assign a churn score to said customers.

9. A Churn Analyzer for determining a reason for customer churn and predicting future instances of said customer churn, said Churn Analyzer said further comprising a miner module and a rules data base, said Churn Analyzer comprising at least one means adapted for:
identifying negative sentiments among customers for different attributes;
identifying said customers who are likely to churn, based on said negative sentiments;
computing said customer level peer performance score;
computing network level performance score; and
computing cumulative churn score for each of said customers.

10. The Churn Analyzer, as claimed in claim 9, wherein said Churn
Analyzer is further adapted for:
identifying negative sentiments among customers for different attributes;
identifying said customers who are likely to churn, based on said negative sentiments;
computing said customer level peer performance score;
computing network level performance score; and computing cumulative churn score for each of said customers.

11. The Churn Analyzer, as claimed in claim 9, wherein said miner module periodically finds patterns of system failures, said negative sentiments and peer influence that precede said customer churn.

12. The Churn Analyzer, as claimed in claim 11, wherein said miner module builds models to predict said customer churn using said data.

13. The Churn Analyzer, as claimed in claim 11, wherein said patterns identified by said miner module are stored as part of a rule base in said rules data base.

14. The Churn Analyzer, as claimed in claim 9, wherein said rule base is used to assign a churn score to said customers.

15. The Churn Analyzer, as claimed in claim 9, wherein said miner module builds models to predict said customer churn using said data.