PDA Journal of Pharmaceutical Science and Technology最新文献

The use of amplified adenosine trisphosphate (ATP) bioluminescence has been established within AstraZeneca as a technique for assessing the sterility of drug product formulations. A platform validation was generated that challenged the technology with a range of organisms and inoculum levels, and the approach to onboarding additional drug products has been designed to maximize the understanding of the drug product behavior when samples may be limited during the development phases of the life cycle of a drug product. Many activities to support sterility assurance take place during product development. However, sterile material manufactured under Good Manufacturing Practice (GMP) conditions may not always be available, for example, during studies to understand the bacterial retention of sterilizing grade filters. In cases of bactericidal products, the use of surrogates may be justified if they are suitably representative of the final drug product formulation. It may not be possible to secure GMP facility access to prepare such surrogate formulations; in those cases, the principles of GMP may be applied in a controlled laboratory setting. The rapid sterility test was used to provide the sterility assurance of the prepared surrogate material. In this case study, the application of amplified ATP bioluminescence sterility testing enabled a fast response to ensure mitigations could be executed in a timely manner. This meant that overarching project plans could be met. The case study also provides information on the rapid identification technique used to identify the slow growing and difficult to recover organism, which allowed faster indication of a nonsterile material. The example also highlights some of the aspects of the challenges of culturing microorganisms and the value of modern techniques in their ability to indicate a quality drift. Dermacoccus nishinomiyaensis was isolated from the test article, and throughout the investigation, it was not possible to culture this organism on standard tryptic soya agar.

With machine learning (ML), we see the potential to better harness the intelligence and decision-making abilities of human inspectors performing manual visual inspection (MVI) and apply this to automated visual inspection (AVI) with the inherent improvements in throughput and consistency. This article is intended to capture current experience with this new technology and provides points to consider for successful application to AVI of injectable drug products. The technology is available today for such AVI applications. Machine vision companies have integrated ML as an additional visual inspection tool with minimal upgrades to existing hardware. Studies have demonstrated superior results in defect detection and reduction in false rejects, when compared with conventional inspection tools. ML implementation does not require modifications to current AVI qualification strategies. The utilization of this technology for AVI will accelerate recipe development by use of faster computers rather than by direct human configuration and coding of vision tools. By freezing the model developed with artificial intelligence tools and subjecting it to current validation strategies, assurance of reliable performance in the production environment can be achieved.

A previously unreported particle type was observed during routine visual vial inspection of a liquid drug product and suspected to be the result of vial delamination. Delamination is the corrosive attack on the interior surface of a glass container resulting in the release of thin flake-like glass particles, lamellae, into solution. It is a major concern for pharmaceutical companies, especially for parenteral solutions, and drug programs with a high risk for delamination are typically monitored for lamellae formation through long-term stability studies. Although these particles observed resembled lamellae (i.e., thin, reflecting light, buoyant) they were not the result of glass delamination. In this study, the authors describe a previously unreported particle type and provide a detailed comparison with known lamellae exposed to the same drug formulation. The chemical, elemental, and morphological characteristics of the particles and respective vials are described in detail. Overall, the particles' high organic and low silica elemental signature, along with no signs of delamination on the glass vial inner surface demonstrate that this lamellae-like observation is a novel particle form that can be distinguished from lamellae formed from vial glass delamination.

In the wake of a series of outbreaks of finished pharmaceutical product-related Burkholderia cepacia complex (Bcc) human infections worldwide, the United States Food and Drug Administration (FDA) in 2017, and subsequently in 2021, issued advisory notifications to the pharmaceutical industry for stringent Bcc testing requirements for pharmaceutical manufacturing processes and for finished pharmaceutical products prior to release to the marketplace. The advisory notifications highlight non-sterile aqueous finished pharmaceutical products as being a major culprit associated with many of these human infection events. As such, there has been a significant number of Bcc-contaminated finished product recalls resulting in company revenue losses, delayed finished product release, finished product shortages for patients, and manufacturing plant shutdowns coupled with company reputational damage. With many of the finished product recall events, pharmaceutical grade water and/or manufacturing facility water distribution systems were identified as the primary origin source of Bcc contamination. Testing and monitoring regimes currently employed to identify Bcc contamination of water associated with pharmaceutical manufacturing are often limited by costly, laborious, lengthy, and nonspecific traditional microbial culture-based methodologies. Presently FDA approved, European Conformity (CE) marked, and International Organization for Standardization (ISO) standard microbial culture-independent rapid, quantitative, specific, and sensitive nucleic acid diagnostics (NAD) methodologies are now gaining greater widespread acceptance in their routine usage in testing laboratories. Here we present the development of a rapid (<4 hours from sample in to result out) single test culture-independent Bcc NAD method, incorporating a quantitative real-time polymerase chain reaction (qPCR) assay. This method can be used for the detection and simultaneous identification of all 24 Bcc species currently assigned, directly from water samples. This culture-independent Bcc NAD method is validated to the testing method equivalent of the ISO/TS 12869:2019 standard, which is a widely used rapid culture-independent NAD method for detecting Gram-negative Legionella species in water.

The recent emergence of new drug technologies such as messenger ribonucleic acid-based vaccines developed to fight the outbreak of the COVID-19 global pandemic has driven increased demand for delivery solutions capable of withstanding deep cold storage conditions down to -50°C, and even down to -80°C. Although significant data exist for deep cold storage in vials, little evidence is available for pre-filled syringes. Because pre-filled syringes serve as both the storage container and the delivery mechanism, there are additional risks to performance that must be evaluated, such as plunger gliding performance, syringe lubrication, silicone layer stability, and container closure integrity (CCI). In the present study, a comprehensive assessment of functional and physical performances of pre-filled syringes (PFS filled with water) was performed after one or multiple freeze/thaw (F/T) cycles between ambient temperature and various temperature cycles including -40°C, -50°C or -80°C for both 'staked needle' and 'luer lock' configurations. The experiments were guided by historical normative methods such as ISO 11040-4 and USP <1207> and combined with headspace gas analysis for barrel-stopper tightness testing. In addition, they were complemented with a novel approach, namely in situ real-time optical imagery, to track plunger stopper movement during the F/T cycle. The findings indicated that there is no significant impact on the functional performances from F/T down to -80°C, whereas no CCI risk was found after F/T down to -50°C.