Compounding Parenteral Products in Pediatric Wards-Effect of Environment and Aseptic Technique on Product Sterility.

Parenteral products must be compounded using an aseptic technique to ensure sterility of the medicine. We compared the effect of three clinical environments as compounding areas as well as different aseptic techniques on the sterility of the compounded parenteral product. Clinical pharmacists and pediatric nurses compounded 220 samples in total in three clinical environments: a patient room, a medicine room and biological safety cabinet. The study combined four methods: observation, environmental monitoring (settle plates), monitoring of personnel (finger dab plates) and sterility testing (membrane filtration). Of the compounded samples, 99% were sterile and no significant differences emerged between the clinical environments. Based on the settle plates, the biological safety cabinet was the only area that fulfilled the requirements for eliminating microbial contamination. Most of the steps on the observation form for aseptic techniques were followed. All participants disinfected their hands, wore gloves and disinfected the septum of the vial. Non-contaminated finger dab plates were mostly detected after compounding in the biological safety cabinet. Aseptic techniques were followed relatively well in all environments. However, these results emphasize the importance of good aseptic techniques and support the recommendation of compounding parenteral products in biological safety cabinets in clinical environments.

Microscopic evaluation of pharmaceutical glass container-formulation interactions under stressed conditions.

Chemical incompatibility of the formulation with glass container can adversely impact the quality of parenteral products. The objective of this study is to investigate formulation-glass interactions at the inner surface of the glass containers that lead to the generation of particulates under stressed conditions (i.e., combinations of high pHs, temperatures and prolonged exposure selected to purposely cause failure of glass containers) using advanced microscopic techniques. The optical, electron microscopy and X-ray spectroscopy were used in tandem to investigate the nature of these interactions at the vial inner surface. These interactions were characterized by surface roughness and reaction zones on the inner surface of the vials and particulates in the formulation using two commercially available pharmaceutical glass containers (Vials 1 and 2). A nanoscale level examination of the inner surface of Vial 1 revealed layers flaking off from the inner surface of the vial resulting in typical particulate generation, while the reaction zone on the inner surface of Vial 2 exhibited a different layered structure. The results suggest that particulates observed in Vials 1 and 2 were generated through different failure modes.

Qualitative risk assessment of follicle stimulating hormone injectable products.

BACKGROUND: Gonadotropin injections for fertility treatment regimens are usually self-injected, typically over 8-12 days during the assisted reproductive technology cycle. Parenteral gonadotropins are available in different formulations and administered through various systems. A user experience study and risk assessment were performed to evaluate different product types for risks to the patient when preparing and administering injections. METHODS: Nine women of child-bearing age each prepared and administered injections of six products representing single- and multidose vials of menotropin for reconstitution (Merional® and Menopur®), follicle stimulating hormone (FSH) reusable pen injectors with (Puregon®), and without cartridges (Gonal-f®), and single-use FSH pre-filled pens (Bemfola®). Risk assessments based on user feedback were made with reference to EU regulations for implementing practices for safe use of injectable products. RESULTS: Products requiring reconstitution with diluent in glass ampoules were associated with medium risk for sharps injury and a lower level of user confidence. Pen injectors were considered easy-to-use, with a low risk of sharps injury. Single-use pens were associated with the lowest risk of dosing errors. CONCLUSIONS: The study identifies differences in the risks for both sharps injuries and dosing errors between FSH delivery options that practitioners should consider when making a treatment choice.

Sequence-based identification of microbial contaminants in non-parenteral products

ABSTRACT Phenotypic profiles for microbial identification are unusual for rare, slow-growing and fastidious microorganisms. In the last decade, as a result of the widespread use of PCR and DNA sequencing, 16S rRNA sequencing has played a pivotal role in the accurate identification of microorganisms and the discovery of novel isolates in microbiology laboratories. The 16S rRNA region is universally distributed among microorganisms and is species-specific. Accordingly, the aim of our study was the genotypic identification of microorganisms isolated from non-parenteral pharmaceutical formulations. DNA was separated from five isolates obtained from the formulations. The target regions of the rRNA genes were amplified by PCR and sequenced using suitable primers. The sequence data were analyzed and aligned in the order of increasing genetic distance to relevant sequences against a library database to achieve an identity match. The DNA sequences of the phylogenetic tree results confirmed the identity of the isolates as Bacillus tequilensis, B. subtilis, Staphylococcus haemolyticus and B. amyloliqueficians. It can be concluded that 16S rRNA sequence-based identification reduces the time by circumventing biochemical tests and also increases specificity and accuracy.

RESUMO Os perfis fenotípicos para identificação microbiana são incomuns para micro-organismos raros, de crescimento lento e exigentes. Na última década, em resultado do uso generalizado de PCR e sequenciação de DNA, a sequenciação do rRNA 16S tem desempenhado papel crucial na identificação precisa do micro-organismo e a descoberta de novos isolados em laboratórios de microbiologia. A região de rRNA 16S é universalmente distribuída entre micro-organismos e é espécie-específica. A genotipagem foi realizada sobre os organismos isolados a partir de formulações farmacêuticas não parenterais. O DNA foi separado dos cinco isolados obtidos a partir das formulações. As regiões alvo dos genes de rRNA foram amplificados por PCR e sequenciados utilizando os iniciadores adequados. Os dados dos sequência foram analisados e alinhados na ordem crescente de distância genética de sequências relevantes contra biblioteca de dados para obter a identidade. A sequência de DNA de árvores filogenéticas confirma a identidade dos isolados como Bacillus-tequilensis, B. subtilis, Staphylococcus haemolyticus e B. amyloliqueficians. Pode-se concluir identificação baseada na sequência do rRNA 16S reduz o tempo por evitar testes bioquímicos e também aumenta a especificidade e a precisão.

Parenterals laboratory course to reduce microbial contamination rates in media fill tests performed by pharmacy students.

OBJECTIVES: To evaluate microbial contamination rates of low- and medium-risk level media fill tests performed by pharmacy students near the beginning and end of a parenterals laboratory course in the second- professional year of a doctor of pharmacy (PharmD) program. METHODS: Students enrolled in a required parenterals laboratory class (N = 84) participated in this study. The aseptic technique procedures performed at the beginning of the course were identical to the procedures performed at the end of the course and included 3 low-risk level media-fill tests and a medium-risk level media-fill test. Single-strength trypticase-soy broth (TSB) was substituted for the drug and was used to detect microbial contamination for all manipulations. RESULTS: The baseline and end-of-course contamination rate was 21 of 504 syringes and 0 of 498 syringes, respectively (p < 0.001). Eighteen of 84 students at baseline and 0 of 83 students near the end of the course produced one or more contaminated syringes (p < 0.001). Of the 21 contaminated syringes at baseline, low-risk manipulations accounted for 14 and medium-risk manipulations accounted for 7. Of the low-risk procedures, the ampule produced the highest contamination rate (11 syringes), followed by the vial (2 syringes) and the reconstitution (1 syringe). CONCLUSIONS: This study demonstrated a decreased rate of microbial contamination during the manipulation of parenteral products and a corresponding improvement in aseptic technique skills among pharmacy students enrolled in a parenterals laboratory course. The most sensitive tests for poor aseptic technique and bacterial contamination were medium-risk manipulations and low-risk manipulations involving an ampule.