PDA Journal of Pharmaceutical Science and Technology最新文献

The BIOSECURE Act, along with the recent election, stands to influence the reshoring of biomanufacturing activities in the United States, significantly impacting the growth of international technology transfers. However, these technology transfers are complex, requiring careful coordination across regulatory, quality, operations, and technical disciplines. When executed between international sites, these transfers become even more intricate due to varying regulatory requirements, compliance landscapes, and operational constraints. The resultant stress placed on people, processes, and technology results in an increased likelihood of misalignment, knowledge gaps, and inefficiencies that can negatively impact project timelines, budget, and ultimate product quality. In this poster, we will discuss a refined International Technology Transfer Playbook that we have developed to successfully approach technology transfer planning and execution. Included are strategies for comprehensive scope planning, successful knowledge and process transfer, risk management, validation, operational infrastructure, and training/proficiency requirements, which lay the groundwork for successful project delivery. Through practical examples, we will illustrate how this framework leads to successful outcomes for both companies and patients. Through deliberate planning and coordination, companies can accelerate commercialization timelines while maintaining product quality and compliance, extending their reach in global markets.

Lyophilization, the process of dehydrating a material at low temperature and reduced pressure, is used to extend the shelf life of biologic drug products. Because the object is extended shelf life, long-term performance testing of any lyophilization containment system is essential. That testing must include not only measurement of container closure integrity (CCI), but measurement of system ability to maintain drug product water content. Both parameters depend upon stopper composition. This presentation discusses a strategy for two-year evaluation of four types of lyophilization stoppers (two bromobutyl elastomers, two chlorobutyl elastomers) in both 13 mm and 20 mm sizes, paired with borosilicate glass vials and aluminum seals. Lyophilization was performed in a commercial chamber using a solution blend of 20 mg/ml mannitol and 40 mg/ml sucrose - nitrogen backfill was to 11.6 psi. Evaluation comprised: - CCI (unsealed) - ability to maintain vacuum (24 hrs) - CCI (sealed) - ability to maintain vacuum - water vapor pressure in headspace - water content of cake - water content of stopper. The strategy proved effective in demonstrating that while all systems maintained acceptable CCI and water levels, composition of stopper does influence water level of drug product.

A comparative study of Polysorbate adsorption to membrane filters for Fill & Finish applications, considering a potentially upcoming restriction of the use of PFAS based membranes, such as PVDF.

With increased demand on sealed packed, pre-sterilized ready-to-use (RTU) components like Syringes & Vials, the ebeam technology is used as Annex 1 compliant transfer technology with surface sterilization for transfer of the RTU to higher grade A environment like Isolator.

There is an understanding of how cleaning processes for pharmaceutical equipment used in aseptic operations are implemented not only for controlling drug product cross-contamination, but also for the initial reduction in bioburden prior to sterilization. However, there is limited guidance on bioburden limits for product-contact surfaces on equipment used to manufacture non-sterile products. This lack of information and regulatory requirements prompts questions on whether it is necessary to have a separate sanitization or disinfection step after cleaning of equipment product-contact surfaces for nonsterile drug manufacturing. Per USP <1115>, microbial limits and the design for cleaning and other associated processes should be based on risks assessed and the level of control necessary based on the product. It would be beneficial to implement processes that can address both product residual and microbial contamination of equipment surfaces. Multiple factors play into the design of an effective and efficient cleaning process. When adequate controls are implemented for the cleaning process and its associated factors, a separate sanitization or disinfection process may not be needed for product-contact surfaces when data is able to demonstrate that the cleaning process and the other preventive measures are able to control microbial contamination of those surfaces.

Analytical testing and an appropriate sampling method are instrumental in confirming that equipment surfaces have been adequately cleaned during cleaning validation or verification activities. Surface swab sampling is performed manually by directly holding the swab (hand swabbing) or attaching the swab to the end of an extension pole (remote swabbing). This study evaluated the performance of a prototype automated swabbing device constructed from configurable microcontrollers, microelectronics, and electromechanical components against representative manual sampling methodologies. Automated swab sampling of pharmaceutical manufacturing equipment offers several advantages over hand swabbing or remote swabbing, including decreased variability, the necessity for swab qualification of operators, increased accuracy versus remote swabbing, and decreased risk to personnel. To determine if automated swabbing can replace the current state of the art in manual swabbing, The Hyde Analytical Laboratory performed a comparative analysis of manual swabbing methods, hand and remote, and an automated swabbing method using a prototype device developed by Swabbot Solutions. This case study tested the three swabbing methods using multiple replicates, concentrations, representative soils, and controls to gauge the relative recovery performance of the accuracy and variability of each method.

Annex 1 encourages pharmaceutical companies to adopt new and innovative technologies in order to streamline their manufacturing processes. As well, companies are continually looking to create more sustainable laboratories. Using microfluidics and centripetal force, a new BET platform allows for assay set up in 85% of the time it takes to set up a traditional 96-well microplate; and is fully automated. It increases efficiency and assures precise and accurate results, allowing manufacturers to meet Annex 1 and sustainability goals while remaining in full compliance with regulations to assure patient safety. Addition to Annex 1, the USP has now accepted a new chapter, USP < 86> which will allow users to implement non-animal derived reagents compared to horseshoe crab blood extract (LAL). In this session, we'll review a case study demonstrating acceptable and comparable results using traditional LAL reagents versus non-animal derived reagents on real world samples using a microfluidic platform. This will demonstrate to the audience who are looking at sustainable testing options with new technology that these reagents are suitable for use on pharmaceutical products.

The role of the microbiologist during product development of medicines ensures patient safety during clinical trials and also the continuation of microbial control through the commercialization of the new product. Microbiological expertise, insight, and cGMP input for new product development is needed for formulation, manufacturing, packaging, and monitoring, plus testing of in-process materials and the finished dosage form as well as stability. Risk assessment and evaluation of potential microbial contamination origin(s) support a phase-appropriate, broad end-to-end analytical approach to microbiological contamination control strategy. The ultimate beneficiary of this robust oversight and management of quality is the patient. Using knowledge and risk assessment along with experience (of nonsterile and sterile drug product development) provide for a balanced approach to microbiological quality in medicines. This paper will discuss more specific area detail to consider for the role of a microbiologist in nonsterile drug product development.

Companies are implementing barrier systems, RABS and isolators, to align with Annex 1 requirements. The implementation of a new filling line requires a cross-functional team of highly skilled staff to ensure success. Even more critical is the importance of having skilled aseptic processing operators to run the filling lines. Companies used to put in the "A team" staff when they implemented a new, barrier system. In a post-covid world, the reality is that staffing in operations has been impacted and there are sometimes less "A team" operators to tackle these critical tasks. The importance of ensuring that the staff in place has adequate and thorough aseptic behaviors training is crucial for contamination control on the lines. This talk will highlight concerns and issues with lack of experienced staff and operators in place to qualify and operate the barrier systems and describe solutions to ensure proper competencies and aseptic behaviors training are in place.