PDA Journal of Pharmaceutical Science and Technology最新文献

In January 2023, ICHQ9 was updated to include expanded guidance on risk-based decision-making, emphasizing its application in informing science-driven and strategic decisions. The revised guidance highlights that while quality risk management can aid decision-making, it does not eliminate the industry's obligation to comply with regulatory requirements. This article introduces a framework for evaluating the risks and benefits of pre-use/post-sterilization integrity testing (PUPSIT) using risk management principles. It provides a structured approach to assess the acceptability of alternative methods to the EU Annex 1 PUPSIT requirement, which acknowledges that PUPSIT may not always be feasible due to constraints such as the filtration of small solution volumes. In such cases, Annex 1 permits alternative approaches if a comprehensive risk assessment is conducted and effective controls are implemented to mitigate the risk of non-integral filtration systems. The proposed framework considers three critical domainspatient safety, process integrity, and regulatory complianceto ensure decisions are well-informed and balanced. By applying this science- and risk-based approach, organizations can navigate PUPSIT requirements effectively, ensuring compliance while addressing operational limitations.

Topical ophthalmic solutions, suspensions, and emulsions are typically packaged in opaque or semi-transparent plastic dropper bottles. This packaging provides resistance to breakage and controlled drop size needed in ophthalmic container systems. Recent changes to general chapter USP<771> Ophthalmic Products - Quality Tests have impacted the particulate and foreign matter testing requirements for ophthalmic products dosed via topical application. The USP<771> chapter instructs that topical products undergo visual inspection for particulate matter as described in general chapter USP<790> Visible Particulates in Injections Visual inspection for particulates in the filled unit is not feasible due to lack of package transparency and therefore alternative test strategies are needed to evaluate the acceptability of the batch. Aspects of this visual inspection approach include: a statistically based sampling plan for the batch, a destructive testing process and acceptance limits based on manufacturing process capability supported with benchmark testing of competitor products to confirm manufacturing performance. Overall, the visual inspection program should include: historical trending; process monitoring; and upstream lifecycle controls for facilities, raw materials, components, and product contact equipment to meet current regulatory expectations and good manufacturing practices.

The detectability size threshold of visible particles (″visibility″ size) in the context of visual inspection of parenteral drug products has been an elusive target for several decades. The current common sense, also reflected in official guidelines, dictates that particles of different shapes and morphologies have different ″visibility″ size thresholds, that can range between hundreds and thousands of micrometers. This study demonstrates experimentally for the first time that it is possible to define a single, shape- and morphology- independent detectability size threshold, identical across particles of various types, provided that observation conditions and product attributes are kept constant. We propose that, based on the physiology of human visual perception, instead of single-dimension measures of particle size (e.g. diameter or length), such a single size-threshold requires the use of area-based size parameters (such as ″equivalent circular diameter″, or ECD. The experimental results reported here clearly demonstrate that the ″visibility″ thresholds for particles of various morphologies converge on a single ECD value. In addition, the data reported here show that product attributes, such as container configuration, fill volume etc. influence the threshold of visibility. Collectively, the findings reported in this paper provide substantial evidence and scientific rationale, as well as unanticipated prospects for standardization of visual inspection qualification practices, ultimately leading to improving pharmaceutical product quality.

This review paper explores the transformative impact of Artificial Intelligence (AI) on Continued Process Verification (CPV) in the biopharmaceutical industry. Originating from the CPV of the Future project, the study investigates the challenges and opportunities associated with integrating AI into CPV, focusing on real-time data analysis and proactive process adjustments. The paper highlights the importance of aligning AI solutions with regulatory standards and offers a set of comprehensive recommendations to bridge the gap between AI's potential and its practical, compliant, and safe application in pharmaceutical manufacturing. Emphasizing transparency, interpretability, and risk management, the research contributes to establishing best practices for AI implementation, ensuring the highest quality pharmaceutical products while meeting regulatory expectations. The conclusions drawn provide valuable insights for navigating the evolving landscape of AI in pharmaceutical manufacturing.

Leachables leached from a medical device during its clinical use are important due to the patient health-related effects they may have. Thus, medical devices are profiled for leachables (and/or extractables as probable leachables) by screening extracts or leachates of the medical device for released organic substances via non-targeted analysis (NTA) employing chromatographic methods coupled with mass spectrometric detection. Chromatographic mass spectral response factors for extractables and leachables vary significantly from compound to compound, complicating the application of assessment strategies such as the Analytical Evaluation Threshold (AET), which is the concentration threshold at or above which an extractable or leachable must be reported for quantitative toxicological risk assessment. The analytical uncertainty resulting from response variation can make interpretation of the AET difficult, potentially leading to both false positive and false negative outcomes. Furthermore, response factor variation complicates the estimation of leachables' and extractables' concentrations (quantification). This Correspondence discusses best practice recommendations for the calculation and application of the AET and for performing quantification, including a discussion of accuracy versus protectiveness.

The role of Environmental Monitoring has evolved alongside the manufacturing processes and filling technologies its aims to monitor, and so should the risk assessment tools we implement for establishing this important program. Sample site selection, appropriateness of sampling methods, sampling volumes and sampling frequencies are all important components of contamination control for a facility and must be evaluated as appropriate using a robust risk assessment. The types of environmental monitoring required for a robust program will vary based on the type of operation, frequency in which that operation is performed, and the level of risk associated to the process. Learn how to develop a meaningful risk assessment and include measurable risk rankings for 6 applicable categories in biopharmaceutical manufacturing. The process for scoring each of the 6 categories, systematic evaluation of contamination probability and example outcomes will be shared for theoretical EM sites mapped throughout an ISO 5 and 7 cleanroom area, thus ensuring adequate criteria and fair assessment are applied in each case. The methodology for this risk assessment tool will be demonstrated as suitable for environmental monitoring programs during initial site qualification, when evaluating EMPQ results, or when periodically updating the requirements for monitoring during routine operations.

Establishing a Contamination Control Strategy (CCS) is a requirement per EU Annex 1 (Aug 2022).  Once a CCS is established, the challenge becomes; "how do I ensure appropriate lifecycle management and effectiveness monitoring for my CCS?"  According to Annex 1, "The CCS should be actively reviewed and, where appropriate, updated and should drive continual improvement of the manufacturing and control methods. Its effectiveness should form part of the periodic management review."  This presentation will provide examples of how a pharma company is integrating CCS review into existing quality management system processes to ensure CCS remains updated and accurate.  Additionally, the use of tools to automate and digitize monitoring of the effectiveness of CCS will be presented.

Aseptic process simulations (APS) are traditionally performed using Tryptic Soy Broth (TSB) as a surrogate for finished product to qualify aseptic manufacturing operations. In this study, the supernatant from cell processing media was examined for bacterial and fungal growth viability to determine equivalency with TSB. With the use of cell processing media in Cell and Gene Therapy (CGT) manufacturing, can qualifying the supernatant collected from the process eliminate the need for an APS run?Supernatant was collected from cell processing media and incubated at same incubations conditions required for the APS post sterility check (Test A - 7d 20-25°C/7d 30-35°C) and at use conditions (Test B - 14 d at 35°C/5%CO/5%O2). Post incubation, growth promotion testing was performed using ATCC cultures (Ab+, Bs+, Ca+, Ec+, Sa+, Pa+ and Se+), which resulted in growth for Tests A-B and the positive inoculum control. Results concluded that the cell processing supernatant examined was equivalent to TSB, thereby implying that each cell therapy manufacturing run is aseptically self-validating. As more practical approaches emerge for APS qualifications in CGT manufacturing, this data can be used to implement alternate options to qualify a CGT manufacturing process and help establish guidelines for future cell therapy APS qualifications.

Vaccines are complex and a very diverse group of products with relatively long product life cycles. The manufacturing programs for these vaccines need to be continually updated to comply with evolving regulatory expectations. Members of the Parenteral Drug Association (PDA) Vaccines Interest Group (VIG) authored and published PDA Technical Report No. 89: Strategies for Vaccine Development and Lifecycle Management (TR 89), which seeks to provide context to vaccine developers and manufacturers regarding key aspects of new or legacy vaccines such as control strategy from process development to vaccine life cycle management, comparability and life cycle management including technical, validation, quality, and regulatory perspectives. To further explain and illustrate the concepts and topics discussed, seven relevant situations were selected as either case studies associated with changes implemented or proposed process development strategies, which are discussed in this article. The situations described are: working cell bank, modification or update of externally supplied product contact components for vaccine manufacturing, raw material change, new product at an existing site, vaccine development acceleration by leveraging existing platforms, selection and implementation of potency method, and modeling for stability forecast prediction. For each situation, the applicable key concepts from TR 89 are discussed as follows: Control Strategy, Prior Knowledge, Relying on Pharmaceutical Quality System (PQS), Classification of Parameters, Validation Approach, Use of a Risk-Based Approach, Comparability, Use of ICH Q12, and Additional Regulatory Considerations.