Aseptic processing is an important part of the pharmaceutical industry, and it can be confusing to know where to start. That’s why we’re holding this introductory session – so you can learn about ISPE, sterile manufacturing methods, and everything else related to aseptic processing! You’ll hear from experts in the field and have the opportunity to ask questions. All attendees are welcome, but this session is tailored more specifically to students, emerging leaders, young professionals, first time attendees, or those needing additional insight into all things Aseptic! This event is free to attend but has limited availability.
This session will provide state-of-the-art examples and tools for process control and quality risk management. Presentations will cover topics from Continuous Process Verification (CPV) to strategies for creating a holistic understanding of the quality system; and Annex 1 approaches to risk activities, including risk assessment tools that will enable the contamination strategy goals.
Do you know if your equipment and processes are in a state of control all year long? Our equipment and processes govern our products' quality; therefore, we regularly perform requalifications or revalidations. However, with this approach, we only see a snapshot of the state of control (maybe once a year or after two to five years) as this approach does not provide us with real-time data. Furthermore, these activities are time-consuming and lead to downtimes of several weeks. This approach also does not allow us to detect trends or problems within our processes or equipment before it may be too late, and then we have to question our products' quality.
We believe that by moving towards "Continuous Process Verification (CPV)," we can avoid the aforementioned constraints. Regulatory bodies have already defined the requirements of such an approach, e.g., in the ICH Q8 and the EMA GMP Annex 15. Let us look into the advantages of CPV by sharing our approach within the process of VPHP decontamination. We believe CPV will allow us to move away from the time-based requalifications and revalidations by ensuring a continuous state of control.
Annex 1 has gone through multiple sets of industry review, comment, and revision. With the review and revisions, the application of quality risk management and risk principles has been identified as a foundational element for developing a robust contamination control strategy (CCS). Overall CCS goals include definition of critical control points, evaluation of control effectiveness, and technical/process knowledge – all factors which can be integrated into robust risk activities and through the use of practical risk assessment strategy. This presentation will evaluate the language used in Annex 1 to describe risk activities, where those activities are required, and explore risk assessment tools that will enable the contamination strategy goals.
Participants will better understand how a holistic consideration of its own quality system can support the system’s effectiveness and compliance. The combination of several perspectives such as PQS effectiveness, quality maturity, and further ones can reliably predict inspection outcomes. Attendees will learn how the assessment can be structured and what the most important system’s features are when it comes to predict inspection outcomes for sterile facilities.
The content is the St.Gallen works on the US FDA funded project “RiskSurve” which has just been extended to a second year. The project aims at creating a comprehensive site surveillance model consolidating data from different dimensions and embedded in their relevant context. Conclusions and results for sterile facilities, especially from the first year of research, are presented. The features and accuracy of sterile specific predictive models are illustrated and compared to the non-sterile ones. The analysis is conducted on data stemming from St.Gallen’s extensive Operational Excellence research. Plant specific data are enriched with external publicly available and regulatory compliance data. Metrics have been scientifically identified with several statistical tests and validated into the predictive model.
As the demand for new drugs and medicines grows, pharma continuously looks for new ways to increase productivity, strengthening reliance on automated equipment and robotics. The next decade will shape the Facility of the Future on Automation and Robotics. In this session, these trends will be discussed. A German CDMO will share how they transformed their gloveless Robotic Aseptic Filling operations to fully digital. In another case study, we will familiarize ourselves with automation for the aseptic processing support and a vial line with fully automated lyophilizer loading with robots. These exciting presentations showcase the leading-edge technology and development of automation and are excellent examples for the Facility of the Future on Robotics. The audience will leave with a better understanding of how to achieve better production while ensuring quality and patient safety.
This presentation gives an impression of the still ongoing road to zero human interaction in filling and transportation steps to meet Annex1 specifications.
As a case study, a new lyo vial filling line will be presented beginning with the idea, moving to the planning phase, building the clean room, implementing the filling line until mediafill and first commercial product batches. Talking about lessons learned during this road will be focus of the presentation.
This presentation will give a detailed overview how robotic filling technologies can contribute to higher process safety, reliability and ulitmately highest product yield in a CDMO environment. Robotic applications can add significant benefits to a companies CCS when used and applied in compliance with pharma standards. Examples will be shown on how traditional manual operations in machine set-up and machine operation can be automated to eliminate human interventions into the aseptic areas to follow Annex 1. There will be a special focus on the impact when processing smaller batches with high value API and the flexibility given by such technologies. A comparison with pro´s and con´s is also shown between traditional filling lines and robotic filling lines.
Special focus will be on:
• Contamination control strategy
• Isolator and machine design
• Automation of manual handling steps
• Process flow for a fully automated filling line
• Annex 1 compliance
In the second Manufacturing Case Studies session, participants will be presented with multiple smaller scale manufacturing approaches. Discussion on the challenges of scaling up gene therapeutics will be presented from an operator’s perspective. The conditions to facilitate the production of ATMPs will be analyzed by one manufacturer of quickly deployable cleanroom spaces. In addition to these cases, we will hear from a manufacturer who is really focusing on improving the human condition by making life saving therapies more accessible from a financial standpoint.
This presentation will focus on how Thermo Fisher Scientific and Optima Pharma have developed innovative solutions to address the unique challenges facing gene therapy drug product manufacturing.
Thermo Fisher and Optima Pharma have partnered to leverage each's experience and expertise to design and deliver two specialized fill finish lines as part of Thermo Fisher Scientific's new, state of the art viral vector manufacturing site in Plainville, MA. This 288,000 SF facility, which is now operational, offers end-to-end viral vector and gene therapy capabilities to meet the rapidly growing and maturing needs of the gene therapy industry. Case studies of how specific challenges have been addressed via technology, equipment and single use design will be presented alongside potential new technologies that are emerging in our industry.
Major issues affecting the drug product industry include long lead times, high equipment costs, and a reliance on modified legacy technologies that introduce operational compromises. To meet the unprecedented demand for pharmaceuticals, the industry needs to adopt a more responsive, modular, technology approach that overcomes the major issues affecting the industry.
This presentation introduces a paradigm shift in aseptic Fill Finish technology. Using the backdrop of a collaboration case study between three international companies (PM Group, G-CON and Pharma Integration), each offering something very different, it describes the innovation journey from vision to solution. By starting with first principles and adopting a range of technologies such as robotics, smart manufacturing, modular design and construction, the presentation will describe how the companies combined their knowledge and skill sets, and modified existing product offerings, to design and build a flexible equipment offering that is unique within the industry.
Over the past two decades, shortages of generic, injectable medications critical to the lifesaving work of hospitals in the United States have become commonplace. Hospitals now maintain permanent drug shortage response teams that seek alternatives to unavailable drugs, a situation that poses risks to patient care. U.S. nonprofit drug company Civica Rx was created in 2018 to address the problems of:• chronic shortages of essential medicines used in hospitals every day• unpredictable price inflation of essential generic medications due to shortages• predatory pricing for certain medicines, including insulin Civica is building a 140,000 square-foot manufacturing facility in Petersburg, Virginia. This facility is the future home of Civica’s affordable insulin and numerous essential sterile injectable medicines that will be used in hospitals across the U.S. Building out Civica’s essential medicine manufacturing facility is a huge team project, with Civica Rx, CRB, groninger group, and SKAN AG coming together at a pivotal time. The new plant, with CRB leading design and construction, includes two groninger high speed filling lines – one for Ready-to-Use (RTU) syringes and one INTEGRA bulk vial line in cooperation with Swiss isolator manufacturer, SKAN.
Contamination Control Strategy is a key concept in the new Annex 1, but contamination prevention is not new to the industry. It covers all aspects of aseptic processes, starting with the selection of equipment, its qualification and routine production. But re-thinking of existing processes and retrofitting to improve them and introduction of new solutions to existing problems are also key. In this session, attendees will hear about a tool to select the right equipment, how Kaizen can be used to improve aseptic processes and how barrier systems are made even safer.
The release of the new Annex 1 has been highly prepared for the last two years. One of the question rosen was "how further and what is still missing in the contamination control for aseptic processing?". Based on this question we started to analyze issues and challenges received by customer/projects. What we did find out was that bellows similarly to the gloves are one of the weak points in the integrity of the Grade A barrier and would therefore deserve a special focus. The presentation will present the journey of an innovation, currently under international patenting path, to implement an automatic leak testing of the boothings (bellows) particularly interesting when automatic machines and isolator technology are used.
At the last Aseptic Conference, FDA regulators again mentioned they embrace new technologies.
Three case studies that showcase adoption of new technologies are mainly discussed in this presentation.
1. Retrofit of old-school isolators using rapid bio-decontamination technology, Ultra Decon Retrofit is a trend in the industry. It usually means update traditional clean booth to RABS. We integrated new technologies into 15-year old isolators to improve its productivity.
2. Scalable Cell Processing Barrier Systems for ATMP
With half suit that can rotate 360°, GMP Incubator, rapid decontamination of cell package and other integrated technologies, this barrier systems achieve robust contamination control and production scale-up for ATMPs.
3. Continuous bio-decontamination/electron beam hybrid system for RTU transfer
RTU transfer with validated contamination control has been difficult. New concept, which combines benefit of hydrogen peroxide decontamination and electron beam sterilization, is introduced in the presentation.
Owners, when sourcing a new aseptic fill line, typically solicit proposals from three or more vendors. The vendor proposals received are complex and oftentimes require additional evaluation to determine the true total cost of the equipment.
This presentation allows the attendee to walk through a structured approach to the design and completion of a technical bid evaluation (TBE) & introduces a systematic methodology for normalizing multiple proposals to estimate the true cost difference between the offers. This work achieves three primary objectives:
1) Identify gaps between each vendor’s proposal and the URS to establish an agenda for preliminary discussions between the vendors & the owner/ engineering company. These preliminary discussions may result in modifications to the URS, disqualification of non-compliant vendors, or updates to vendor proposals.
2) Differentiate vendor offerings on a performance basis to provide qualitative justifications for favoring one vendor over another.
3) Normalize commercial pricing. One vendor may include an accessory as a standard offering that a second vendor excludes but charges a premium if elected. This accessory or technological offering is required for a complete & operable installation. Pricing normalization will ensure an ‘apples to apples’ approach is truly considered at the end of the evaluation.
Are you looking for a career change? Join this Women in Pharma®-sponsored session to learn how to develop your brand and reach your goals. Hear from men and women who have successfully merged their passion with their career, and find out what kind of steps are required to make that happen for yourself. This is an opportunity to gain the skills and knowledge you need to turn your passion into a reality. With the help of industry experts, you can start moving your career in the direction you always dreamed of. This Breakfast Session is an excellent chance to connect with industry experts and network. You won’t want to miss this! ISPE Women in Pharma® (WiP) provides women in the pharmaceutical industry a forum for connecting and collaborating on technical and career advancement topics. WIP's inclusive community leverages a network of mentors, role models, and resources across all levels to foster balanced professional success. Recognizing women that make efforts to lead, coordinate, and present technical presentations that are inclusive of both women and men is a key element in the success of the industry.
Novel therapy methods require new approaches and manufacturing techniques, all with their own challenges. This session will examine how to overcome some of them through various examples and case studies. We will learn how a Virtual Reality Simulator can be used to train and monitor employees on targeted behaviors to avoid previously identified critical errors, the critical steps to take during a contamination event and how accurately identify the source of contamination, as well as cleaning processes for in lipid nanoparticle (LNP) delivery systems.
When contamination events occur, it is critical to quickly and accurately identify the source of contamination so effective corrective and preventive actions can be implemented. Currently available methods of identification range from genotypic to phenotypic, with 16S rRNA gene sequencing being the gold standard for microbial identifications. There is very little complexity in the data from phenotypic systems and the methods are highly error prone, variable, and subjective. This microbial investigation case study examines the challenges and consequences of inaccurate microbial identification methods. The identification of a Gram-positive organism during an endotoxin out-of-specification event, not surprisingly, led the company down an erroneous investigation path. Although an extensive review of historical environmental monitoring tracking and trending data was performed, an initial incorrect microbial identification proved that exercise futile. After three discarded batches, production line work stoppages, and countless months spent sampling and cleaning equipment, DNA sequencing of the offending isolate revealed a Gram-negative organism. This finding led the company down the correct path to a root cause and lessons learned regarding accurate microbial identification methods.
The advancements in lipid nanoparticle (LNP) delivery systems have been paramount in the performance, stability, safety, and eventual regulatory approval of novel drugs and vaccines, such as the mRNA COVID-19 vaccine by Moderna, Pfizer/BioNTech, and others. These encapsulated LNPs can deliver drugs using a wide range of sizes based on the LNP components and route of administration. However, the lipophilic nature and complexity of LNPs can present difficulties in the cleaning process. Laboratory cleaning models can be used to efficiently screen the optimum aqueous cleaning agent and define critical cleaning parameters. This presentation explores the concerns with cleaning pharmaceutical products utilizing LNP delivery vehicles and provides a general cleaning recommendation based on laboratory and field testing.
Advances in developing new therapies require enhancement in training methods. This presentation will address the lessons learned by applying the Meta-EA (Meta Error Analysis) risk profiling and mitigation approach in cell and gene therapy manufacturing processes. Unlike traditional risk analysis approaches, Meta-EA is able to create a differentiated objectifiable risk profile of the process by a frame-by-frame assessment of potential /error, including objectifiable risk assignments. Based on this risk profile, it’s possible to identify risk clusters and quantify the individual risks of the different failure types in relation to the overall risk. In addition, the underlying data set enabled the creation of a blueprint to map key mitigation actions to the process risk profile and design and justify targeted initiatives to control key risk clusters. As part of the mitigation, a Virtual Reality Simulator is used to subsequently train and monitor employees on targeted behaviours to avoid previously identified critical errors, thus training them to become "prepared on critical risk". Key to this is an automated feedback system generated by the VR-Simulator, which identifies individual blind spots and behavioral weaknesses related to the associated risk profile, thus improving human reliability in executing tasks with the highest criticality.
This session will explore the advancements and innovations in decontamination and single-use technology to comply with the newly revised EU GMP Annex 1. New gaseous hydrogen peroxide (H2O2) with lower percentages of peroxide have been shown to lessen downtime from off gassing following treatment and have improved material compatibilities. Furthermore, the development and validation of H2O2 cycles continue to see advancements with the use of enzyme indicators. The understanding of enzyme indicators and their possibilities continues to grow as more data about the influence of temperatures, storage conditions, timing of the reading, and degree of inactivation is gathered through experimental results. Lastly, the revised EU GMP Annex 1 maintains the importance of cross-contamination prevention and operator risk. Continued research and advancements in single-use technology show the advantages single-use presents for product loss and filling accuracy.
One of the most frequent asked question is, how to get things inside an Isolator without breaking the sterile barrier, how to protect the product but also the operators from certain substances the best possible way.
In pharma manufacturing, all is based on identifying and evaluating critical factors. Initially for the project, but also later in daily processes. It’s all about risks. Cross contamination prevention, risks for the products, but also risk for the operators.
There’s also the price of the drugs, the manufacturing costs, and the batch size. The costs inevitably lead to the question of how to avoid product loss, in other words how to get as much as product to the point of fill by achieving best possible product recovery rates and filling accuracy.
Why does single-use and ready-to-use best possibly comply to EU GMP Annex 1 Why does single-use especially make sense in dealing with new types of medicinal products like ATMPs and ADCs.
What are market standards and trends and where is pharma manufacturing moving to.
The application of biological indicators for development and validation of H2O2 biodecontamination cycles for barrier systems is common across the industry, despite their drawbacks like significant variability together with necessary incubation times. Enzyme indicators are a recent supplementary type of indicators, which are based on the decomposition of an enzyme (thermostable adenylate kinase, tAK) by H2O2. Initial experience with the use of these new indicators is currently being gained throughout the industry. However, there are still significant knowledge gaps on how to apply the indicators.
In this presentation, new experimental results that contribute to a better understanding of the indicators will be discussed. A more detailed analysis of the contributions to the variability of the results, the influence of temperatures, storage conditions, the timing of the reading after exposure and the degree of inactivation of the indicator will be given.
These results lead to a better understanding of the possibilities and limitations for the use of enzyme indicators. Practical questions such as "When to do what?" can be answered with a better data basis. This will further facilitate the use of enzyme indicators as a complementary tool to biological indicators with the goal of faster development of safer processes.
This presentation discusses how cleanrooms can address the call for improved biosafety in the newly revised EU GMP Annex I by implementing automated, efficacious, and lower-consequence gaseous hydrogen peroxide biodecontamination technology. Legacy high-concentration hydrogen peroxides containing 35-59% solutions have been the norm for gaseous biodecontamination, based on the assumption higher concentrations are more effective antimicrobials. However, higher concentration peroxides are responsible for lengthy periods of off gassing following treatment and leaching from materials which may require residue cleanup or interact with pharmaceutical products. New systems employing lower percentages of peroxide combine vapor and micro-aerosols which revolutionize how we understand and apply gaseous hydrogen peroxide. Proven through the trifecta of verification, Regulatory approval, Real-World implementation, and Scholarly publications, these new systems shorten downtime and are technologically advanced. In support of the latest Annex I revision, innovations in gaseous hydrogen peroxide, such as hybrid hydrogen peroxide, may support risk management with safer, low concentrations, improved material compatibilities, reduced downtimes, and sporicidal efficacy. All of this, coupled with lower residues compared to legacy methods traditionally employed, makes it possible to support Annex I revision goals for faster automated processes without sacrificing safety.
Lively discussion about new trends in aseptic processing and Annex 1 implications on aseptic process simulation (APS) are the two hot topics that we will discuss during this breakout session. We will dive into the latest technologies and design philosophies of SUS to help mitigate risks related to PUSPIT and product loss.
Get in contact with the experts and use the opportunity to discuss different topics in a small group with other attendees. This session is every year one of the highlights on the second day with a lot of knowledge exchanges and many times important questions are discussed and solved. Get ready and bring your questions to the breakout session.
How to Reduce the Risk of Contamination in Drug Manufacturing Group Discussion | Contaminations come in many shapes and sizes. Cross contaminations, mix-ups, microbial, and particulates are types of contaminations that can happen within a process, facility, and can cause losses of product and profit. The members of this discussion group will tackle these complex issues from different angles for different problems. As drug manufacturing changes and as monitoring technology changes, so the processes and procedures will need to change to protect the product at its critical points in operations. Each of these speakers bring a different approach: cleaning as a focus, microbial identification (and often mis-identification) as a focus, and reducing overall risks with new targeted and visual training at the point of risk focus. We will all learn much from these speakers.
Get in contact with the experts and use the opportunity to discuss different topics in a small group with other attendees. This session is every year one of the highlights on the second day with a lot of knowledge exchanges and many times important questions are discussed and solved. Get ready and bring your questions to the breakout session.