Vial Preparation Research Articles

Investigation of operational fundamentals for vacuum-assisted headspace high-capacity solid-phase microextraction and gas chromatographic analysis of semivolatile compounds from a model solid sample.

Vacuum-assisted headspace solid-phase microextraction (Vac-HS-SPME) is a technique used to enhance SPME sampling of semi-volatile organic compounds. Here, it was combined with a high-capacity SPME Arrow, which features a larger volume of extraction phase and a more rugged configuration than traditional extraction fibers. An in-depth assessment of the critical parameters was conducted to achieve optimal extraction of representative compounds from a model solid sample matrix (Ottawa sand). Operational fundamentals investigated included the types of seals needed to create a leak-free environment under vacuum conditions; the magnitude of the vacuum applied and time needed to activate the Vac kinetics; order of sample vial preparation methods (VPMs); and other standard variables associated with extract analysis by gas chromatography-mass spectrometry. When exploring the limits of sample VPMs, results indicated an ideal workflow requires the solid sample to be spiked before sealing the vial, allow the sample to rest overnight, then apply vacuum at a pressure of -677mbar (out of -789mbar maximum possible vacuum with pump and compressor used), exerted on the vial for 90 s. This work provides the necessary workflow for the optimization of Vac-HS-SPME sampling of analytes from solid matrices.

Critical parameters for highly efficient and reproducible polyelectrolyte multilayer coatings for protein separation by capillary electrophoresis

Since the introduction of polyelectrolyte multilayers to protein separation in capillary electrophoresis (CE), some progress has been made to improve separation efficiency by varying different parameters, such as buffer ionic strength and pH, polyelectrolyte nature and number of deposited layers. However, CE is often overlooked as it lacks robustness compared to other separation techniques. In this work, critical parameters for the construction of efficient and reproducible Successive multiple ionic-polymer layers (SMIL) coatings were investigated, focusing on experimental conditions, such as vial preparation and sample conservation which were shown to have a significant impact on separation performances. In addition to repeatability, intra- and inter-capillary precision were assessed, demonstrating the improved capability of poly(diallyldimethylammonium chloride) / poly(sodium styrene sulfonate) (PDADMAC / PSS) coated capillaries to separate model proteins in a 2 M acetic acid background electrolyte when all the correct precautions are put in place (with run to run%RSD(tm) < 1.8%, day to day%RSD(tm) < 3.2% and cap to cap%RSD(tm) < 4.6%). The approach recently introduced to calculate retention factors was used to quantify residual protein adsorption onto the capillary wall and to assess capillary coating performances. 5-layer PDADAMAC / PSS coatings led to average retention factors for the five model proteins of ∼4×10−2. These values suggest a relatively low residual protein adsorption leading to reasonably flat plate height vs linear velocity curves, obtained by performing electrophoretic separations at different electrical voltages (-10 to -25 kV).

A Novel MATLAB®-Algorithm-Based Video Analysis to Quantitatively Determine Solution Creeping in Intact Pharmaceutical Glass Vials

During the filling process of a biopharmaceutical drug product (DP), a liquid DP film might creep up the inner vial wall which is barely discernible, appears as milky-white haze after lyophilisation and is known as fogging. Creeping and fogging are mainly dependent on the primary packaging material surface and its hydration, vial preparation process as well as DP composition. The occurrence of both can impede visual inspection and might lead to DP rejection. Hence, our studies focused on the early detection of liquid solution and glass vial surface interaction directly after filling. For a fast and highly sensitive evaluation a novel video-based analysis was used. To our knowledge, this is the first time a MATLAB®-algorithm-based video analysis was applied to quantitatively determine creeping time-resolved. Furthermore, creeping in dependence of vial processing sites, surfactant type and concentration, filling temperature, and vial format were investigated. The results were verified using orthogonal conventional methods such as surface tension, wetting behaviour, and contact angle measurements, as well as ToF-SIMS, ICP-MS, and SEM. Additionally, the methods applied were assessed regarding their cross-validation capability. The observations indicate that the vial preparation process can have a pronounced impact on alteration of the glass vial surface and related creeping behaviour of the filled solution.

Setting up an Office Allergy Practice: Current Recommendations for Sterility and Supervision

Discuss optimal conditions for the office delivery of allergy immunotherapy with regard to medical personnel supervision and techniques for sterility of antigen vial preparation and delivery. The revised USP 797 pharmaceutical compounding guidelines, combined with allergen extract preparation directions provide clear instructions for the general supervision and oversight of allergen preparation for immunotherapy. Sterility of antigen vial preparation and supervision of office personnel delivering and preparing allergy immunotherapy are critical points of competency allowing for safe and effective delivery of allergy immunotherapy in the office setting.

Evaluation of Physician Knowledge of the Key Safety Information for Aflibercept in Canada: Evaluation of Risk-Minimization Measures.

As part of the risk-management plan (RMP) for aflibercept, materials have been developed to educate physicians in Canada on the key safety information and safe use for aflibercept. The objectives of this study were to assess whether physicians in Canada received and reviewed the aflibercept educational materials (i.e. vial preparation instruction card, intravitreal injection procedure video, and product monograph) and to evaluate their knowledge of key safety information. Retinal specialists and ophthalmologists who prescribe and/or administer aflibercept were recruited to complete a survey. Physicians could complete and return a paper questionnaire by mail or complete the questionnaire online via a study website. Of the 308 physicians invited to participate in the survey, 95 (31%) completed the questionnaire. Nearly all physicians (98%) reported receiving at least one of the educational materials. The proportion of correct responses to individual questions on storage and preparation of aflibercept ranged from 54 to 98%. Physician knowledge was high on the recommended dose of aflibercept (91%), dose preparation (91-96% on individual items), and dosing guidelines (75-95% on individual items). Most physicians knew the contraindications for aflibercept (89%) and that aflibercept should not be used in pregnancy unless clearly indicated by medical need in which benefits outweigh risks (60%); 21% responded more conservatively that aflibercept should never be used in pregnancy. Knowledge was high for most questions about injection procedures (91-99% on individual items); however, fewer physicians (24%) correctly reported that the eye should be covered with a sterile drape. Knowledge was high for possible side effects (89-100% on individual items) and actions to take in relation to the potential for increased intraocular pressure (86-93% on individual items). Nearly all physicians (98%) reported having received the product monograph, and most (82%) reported having received the vial preparation instruction card; nearly half (46%) reported having received the intravitreal injection procedure video. Physicians' knowledge of the most important topics was high. Knowledge varied for topics that are less frequently encountered (e.g. use in women of childbearing potential) and for recommendations that are not standard medical practice in Canada (e.g. use of sterile drape).

Influence of preparation parameters on the synthesis of plastic scintillation microspheres and evaluation of sample preparation

Plastic scintillation microspheres (PSm) are solid dispersions of fluorescent solutes encapsulated in a polymeric matrix; they are used to measure β and α decay of radionuclides. Since organic solvent evaporation/extraction methods have been successfully employed to produce PSm, this work evaluates the influence of different parameters (i.e., polystyrene (PS) and polyvinyl alcohol (PVA) concentrations, temperature, stirring speed and the organic/aqueous phase ratio) on the final size of the PSm; and the relationship between this final size and the radiometric capacities of the PSm in relation to emitters of both beta (3H, 14C and 90Sr/90Y) and alpha (241Am) radiation.The results show that when the concentration of PVA is increased, the size of the PSm decreases; meanwhile, an important decrease in particle size is also achieved when the PS concentration is decreased. For almost all the parameters evaluated, the resultant PSm were smoothed and spherical. However, when temperature was increased, the particle size increased and the PSm eventually became amorphous and porous. The observed decrease in particle size correlated with an increase in radiation detection efficiency and a movement in the positioning of the spectra at lower energy values.We also evaluated the reproducibility of the vial preparation for 3H measurements and confirmed that small variations in the quantity of PSm and preparation of different vials by different experimenters did not influence the radiometric capacities.

WE‐G‐BRA‐09: Microsphere Brachytherapy Failure Mode and Effects Analysis in a Dual‐Vendor Environment

Purpose:To improve the safety and quality of a dual‐vendor microsphere brachytherapy program with failure mode and effects analysis (FMEA).Methods:A multidisciplinary team including physicists, dosimetrists, a radiation oncologist, an interventional radiologist, and radiation safety personnel performed an FMEA for our dual‐vendor microsphere brachytherapy program employing SIR‐Spheres (Sirtex Medical Limited, Australia) and Theraspheres (BTG, England). We developed a program process tree and step‐by‐step instructions which were used to generate a comprehensive list of failure modes. These modes were then ranked according to severity, occurrence rate, and detectability. Risk priority numbers (RPNs) were calculated by multiplying these three scores together. Three different severity scales were created: one each for harmful effects to the patient, staff, or the institution. Each failure mode was ranked on one or more of these scales.Results:The group identified 164 failure modes for the microsphere program. 113 of these were ranked using the patient severity scale, 52 using the staff severity scale, and 50 using the institution severity scale. The highest ranked items on the patient severity scale were an error in the automated dosimetry worksheet (RPN = 297.5), and the incorrect target specified on the planning study (RPN = 135). Some failure modes ranked differently between vendors, especially those corresponding to dose vial preparation because of the different methods used. Based on our findings, we made several improvements to our QA program, including documentation to easily identify which product is being used, an additional hand calculation during planning, and reorganization of QA steps before treatment delivery. We will continue to periodically review and revise the FMEA.Conclusion:We have applied FMEA to our dual‐vendor microsphere brachytherapy program to identify potential key weaknesses in the treatment chain. Our FMEA results were used to improve the effectiveness of our overall microsphere program.

ПОРАЖЕНИЕ ЯРОВОЙ ПШЕНИЦЫ ВРЕДНЫМИ ОРГАНИЗМАМИ В УСЛОВИЯХ ПРЕДБАЙКАЛЬЯ В ЗАВИСИМОСТИ ОТ СРОКОВ СЕВА И ПРИМЕНЕНИЯ РЕГУЛЯТОРОВ РОСТА

The conditions of South Siberia region are favorable for the propagation of r-strategy harmful organisms. The authors investigated the influence of sowing time (early — April 26, and usual for this region — Mai 19), presowing seed treatment by the Vial preparation and Humate 80 and Krezacin growth regulators on the damage of spring wheat sowings of the Tulunskaya 12, Iren’, Novosibirskaya 29 by the root rot, wheat leaf bloch, cereal leaf beetle (larva phase), wheat thrips (larva phase), grey cereal noctuid (larva phase). The authors estimated the species composition of weeds, their number, an accumulation of green mass and wheat harvest. The investigations were made on experimental field of the Irkutsk State Agricultural Academy and in practical conditions in other zones of Pre-Baikal region. After early sowing without presowing treatment the authors observed the reduction of spreading of root rot (13.84 %) and ear bloch (13.33 %), also observed the decrease of leaves damages by cereal leaf beetle (2.3 times), corn damages by wheat thrips (6.5 times) and grey cereal noctuid (3.8 times). The weed’s biomass was decreased to 6-8 times. The productivity of spring wheat was raised by 15-40 %. The application of growth regulator-adaptogen (instead of seed treatment) permits to obtain the good and early sprouts, that also permit to increase the competitiveness of cultural plants and to weaken the harmful effect of phytopathogens, phytophages and weeds.

In‐Office Safety: Are You Putting Your Patient at Risk?

Program Description: This one-hour miniseminar will focus on three important office procedures: Compounded pharmaceuticals: Many office-based pharmaceuticals are used by otolaryngologists daily. Otolaryngologists need to know what common drug preparations are compounded for use in the office. This 15-minute segment will provide tips to physicians to ensure their pharmaceuticals are safe. Allergy vial preparation and injections: A 15-minute presentation will explore current allergy practices and emphasize current safety concerns. Sterilization and safe use of equipment: Best evidence and recommendations for safe equipment reuse and sterilization techniques for office based procedures will be reviewed during this 15-minute segment. Educational Objectives: 1) Recognize the dangers associated with the use of compounded pharmaceuticals in the office and safe practices for use of these substances. 2) Implement recommendations for enhancing safe allergy practice, including vial preparation, advancement, and office injections. 3) Apply safe sterilization and device reuse and hygienic practice for the office and steps to implement safe office practice.

Prospective Evaluation Of Rate Of Systemic Reactions To Immunotherapy As Part Of A Comprehensive Allergy Practice Quality Improvement Project

RATIONALE: There is limited published prospectively-collected data on the rate of immunotherapy systemic reactions (ISR). Rates of reactions using a particular specific technique of vial preparation and administration (e.g. using shared-specific vial immunotherapy, SSV, compared to customized patient-specific vials) are not well known.

Injectable immunotherapy: recommendations for safe allergen vial preparation in the office setting

To review the proper technique for preparing allergen vials to be used in subcutaneous immunotherapy in the office setting, examine the potential for bacterial contamination during mixing and handling and associated risk factors and review the data relevant to contamination during vial mixing. Existing literature on the subject of safe vial preparation suggests that the incidence of bacterial contamination of allergen vials is very low. Historically, there is no report of bacterial infection for subcutaneous immunotherapy using vials prepared in the office setting or otherwise when using the proper sterile technique. In-office compounding of vials is a safe practice with literature to support continuing this practice of preparation.

Can we use the CO2concentrations determined by continuous‐flow isotope ratio mass spectrometry from small samples for the Keeling plot approach?

A common method to estimate the carbon isotopic composition of soil-respired air is to use Keeling plots (delta(13)C versus 1/CO2 concentration). This approach requires the precise determination of both CO2 concentration ([CO2]), usually measured with an infrared gas analyser (IRGA) in the field, and the analysis of delta(13)C by isotope ratio mass spectrometry (IRMS) in the laboratory. We measured [CO2] with an IRGA in the field (n = 637) and simultaneously collected air samples in 12 mL vials for analysis of the 13C values and the [CO2] using a continuous-flow isotope ratio mass spectrometer. In this study we tested if measurements by the IRGA and IRMS yielded the same results for [CO2], and also investigated the effects of different sample vial preparation methods on the [CO2] measurement and the thereby obtained Keeling plot results. Our results show that IRMS measurements of the [CO2] (during the isotope analysis) were lower than when the [CO2] was measured in the field with the IRGA. This is especially evident when the sample vials were not treated in the same way as the standard vials. From the three different vial preparation methods, the one using N2-filled and overpressurised vials resulted in the best agreement between the IRGA and IRMS [CO2] values. There was no effect on the (13)C-values from the different methods. The Keeling plot results confirmed that the overpressurised vials performed best. We conclude that in the cases where the ranges of [CO2] are large (>300 ppm; in our case it ranged between 70 and 1500 ppm) reliable estimation of the [CO2] with small samples using IRMS is possible for Keeling plot application. We also suggest some guidelines for sample handling in order to achieve proper results.

MRAST to Quantify Allergy and Initiate Immunotherapy

Objective Aim to quantify mRAST by comparing it with skin testing (SPT and MQT) among patients with clinically diagnosed AR for both diagnosis of inhalant allergy and initiation of immunotherapy. Methods A prospective randomized controlled study was designed to recruit patients with allergic rhinitis selected for screening for the initiation of immunotherapy from our outpatient clinic. Multi-testTM skin prick testing (SPT), modified quantitative testing (MQT) and blood taken for mRAST was performed on all recruited subjected at the same setting. SPT, MQT and mRAST grading of common allergens were tested for their correlations. Results 21 patients (12 male, 9 female) were recruited between May 2006 and Dec 2007. After comparing results from all 3 tests, 262 sets of allergens were available for analysis. We found that there was significant correlation between SPT and mRAST results (r=0.504, p&lt;0.01). Similarly mRAST grading also correlated significantly with MQT grading ((r=0.51, p&lt;0.01). Conclusions With good correlations between mRAST grading and MQT grading, in vitro testing could be the preferred mode of quantification for vial preparation during initiaition of immunotherapy. Patient would experience less pain and had no anaphylaxis risk. Both initiation and follow-up of patient undergoing immunotherapy would be easier.

Impact of newly revised sterile medication compounding guidelines USP 〈797〉 on allergy vial preparation

To highlight newly revised guidelines on sterile medication compounding released by the United States Pharmacopeia (USP 797) in December 2007, and the implications on immunotherapy vial preparation. A policy review. The newly revised USP chapter on sterile medication guidelines was released December 2007 and becomes effective June 2008. The revised USP 797 now has specific guidelines addressing immunotherapy vial preparation that are a significant change from the previous version. The revised guidelines should be a useful tool for clinicians who are developing and setting office mixing standards. Offices preparing immunotherapy vials should consider formalizing and implementing vial preparation guidelines. These guidelines should be based on expert opinion, experience, and scientific literature.

Potential errors in the measurement of anesthetic partial pressure in blood.

Vials of 2 ml nominal volume (1.95 ml by water displacement) are used with silicone, Teflon-faced septa (Phase Separations Ltd., Deeside, TJnited Kingdom) in their caps. They are prepared shortly before sampling by first flushing with oxygen and then partially evacuating them to a pressure of approximately 150 mmHg using a needle and syringe. This provides sufficient oxygen to saturate any sample, but the pressure within the Vial will remain subatmospheric even after warming, humidification, or movement of nitrous oxide. Exactly 1 ml blood is injected through the septum, and the vial is placed in a motorized roller in a water bath at 37°C. After 30 min, the vial contents are brought to atmospheric pressure by penetrating the septum with a hollow needle and entraining air. This reduces the concentration of anesthetic in the headspace, but its partial pressure is unaffected and remains in equilibrium with the blood. The vial is rotated in the water bath for another minute to disrupt bubbles in the headspace, and then the headspace is sampled and analyzed in a gas chromatograph. A portion (0.5 ml) of the bloodis transferred to a second prepared vial that is then processed in the same way. We calculate the blood gas coefficient (Al, for each anesthetic from the second vial equilibration using a relationship derived from conservation of mass during equilibration:

Contrast medium-induced pulmonary edema is aggravated by silicone contamination in rats.

To examine the effect of silicone contamination, which occurs in clinical settings during vial preparation with disposable syringes, on contrast medium-induced pulmonary edema in rats. Ioxaglate, ioversol, and iohexol, silicone-containing physiologic saline solutions, and three silicone-containing contrast media were separately, intravenously injected at 1.5 mL/min in rats. Pulmonary edema was evaluated as changes in the relative lung weight and in the water, sodium, and potassium contents of the lung. Intravenous injection of ioxaglate induced marked pulmonary edema, even with a dose of only 4 g of iodine per kilogram of body weight. In contrast, ioversol and iohexol induced significant pulmonary edema only after the injection of large doses (6 g of iodine per kilogram; P < .05). The injection of 4 microL/mL silicone-containing physiologic saline at a dose of 18.75 mL/kg also produced marked pulmonary edema, whereas doses of 6.25 and 12.5 mL/kg showed no significant influence. The addition of an ineffective dose (12.5 mL of physiologic saline per kilogram of body weight) of silicone in contrast medium substantially aggravated the pulmonary edema induced by the contrast medium alone; this phenomenon was also confirmed with morphologic observation. Ionic contrast media are more toxic to the endothelial cells than are nonionic contrast media. Silicone contamination might be one of the causes of pulmonary edema after intravenous injection. However, caution must be exercised in extrapolating these results to humans.