The Disposable Facility and Single-Use Technology – a Solution or a Revolution?
Over the last decade the application of disposables and single-use equipment has become increasingly popular. There is however a continuous discussion going on regarding the advantages and disadvantages versus a conventional stainless steel environment. Reviewing the vast literature available on this topic it becomes pretty clear that there is no single and simple argument pro or contra which could be taken as a decisive answer. It needs to be analysed in which environment, at what condition and for what purpose disposables and single-use equipment is being used. This presentation reviews and illustrates the very different arguments for the application of equipment as a consumable, including advantages and limitations of single-use technology, understanding improvement of process robustness, contribution to lean production as well as environmental impact of disposables, finally culminating in the question if this way of processing is a solution to improve biomanufacturing economy – or if it is even a revolution regarding process feasibility and elimination of constraints.
RecordedSep 18 201362 mins
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Comparability exercises are commonly required at certain milestones during drug development as well as after product registration when changes are implemented into the manufacturing process. The goal is to evaluate if the product remains highly similar (not necessarily identical) before and after the change in terms of quality and stability and have no adverse impact on safety and efficacy predicted for the patients. This assessment requires product-specific knowledge gathered through drug development, taking a totality-of-evidence approach. The different levels of information are obtained from analytical studies for characterization of the molecule, animal studies for toxicity, pharmacokinetics and pharmacodynamics for pharmacological activities, and clinical studies for safety/tolerability, immunogenicity and efficacy. This Webinar discusses strategies and considerations for analytical characterization of protein structure and function which forms the foundation of the comparability demonstration.
Observable foreign and particulate matter has for a long time been recognized as a critical quality attribute for production of injectable protein formulations. Recently, a focus shift towards these particles and even smaller particles (particulate matter or subvisible particles) has been seen from the pharmaceutical industry, academia and the different regulatory bodies. Two of the central documents in this context are:
1. The FDA Guidance for Industry on Immunogenicity Assessment for Therapeutic Protein Products1 and
Sourcing for the manufacture and control of Antibody-Drug Conjugates (ADCs) used in clinical trials requires strategic planning, establishment of a specialized support network, and execution of several interdependent tasks. ADCs are complex molecules, a fusion of a biological, the monoclonal antibody (mAb), and of small molecules, the linker and the toxic payload. Facilities of acceptable standards for the handling of high potency materials need to be engaged, and there is a limited supply currently. This is further complicated by the fact that there is not one contract facility that has fully integrated services, a “one-stop shop” capable of mAb production, linker and/or payload synthesis, conjugation of mAb to linker-payload to make the Drug Substance, and finally, formulation of the ADC to make the Drug Product. Strategizing the best outsourcing practices for producing and testing ADCs, and establishing guiding principles for externalization to ensure the selection of the right CMOs for ADC outsourcing and technology transfer, will be further discussed.
Continuous bioprocessing offers potential to enhance productivity and product quality uniformity while simultaneously decreasing facility footprint and associated operational overhead. Advances in technology and increasing commercial pressures are leading to an increased interest in continuous processing across the biopharmaceutical sector. A number of companies are exploring and advancing continuous bioprocessing and this presents a range of opportunity and challenges, including the use of Process Analytical Technology (PAT) for process characterization, process control, and process robustness, in support of a Rapid Product Release (RPR) strategy.
Single-Use Process Analytical Technologies (PAT) tools have a great potential to not only increase process understanding at the seed stage but also simplify cell culture operations. By utilizing PAT, the risk from bioburden or contamination can be significantly reduced and the overall operating efficiency increased. In fact, PAT also provides a data-driven platform to integrate Process Development and Manufacturing Operations that can mitigate risks associated with technology/process transfer.
The FDA’s Office of Pharmaceutical Quality (OPQ) is working to encourage the development and adoption of emerging technologies in the pharmaceutical industry that have potential to enhance drug product quality. To achieve this goal, OPQ established the emerging technology team (ETT) program and focuses on advancing regulatory science for emerging technologies. OPQ has identified Continuous Manufacturing as one such emerging technology which has the potential to increase the efficiency, flexibility, agility, and robustness of pharmaceutical manufacturing. The ETT provides industry early engagement opportunities with FDA to receive feedback on potential technical and regulatory issues and FDA’s recommendations for regulatory submission content related to continuous manufacturing and other emerging technologies. In addition, OPQ has started a regulatory science and research program on continuous manufacturing to address remaining gaps in our knowledge and experience. Our research program is currently focused on the following areas in (1) integrated process modeling, (2) understanding of the impact of material properties, and (3) implementation of advanced process control strategies and real time release testing. The results and knowledge developed in this program can be utilized to support the implementation of continuous manufacturing and to ensure that FDA regulatory policies reflect state-of-the-art manufacturing science.
Monoclonal antibodies (mAbs) represent a big portion of therapeutic proteins. Mass spectrometry (MS) coupled with modern separation technologies has become an essential tool in characterization of mAbs within the Quality by Design (QbD) paradigm during development. In this article, we use case studies to discuss the application of MS analysis in clone selection, optimization of fermentation conditions, development of purification and formulation. Specifically, simultaneously detect and monitor variants due to incomplete leader sequence processing, accurately determine afucosylation level of N-glycosylation, characterize host cell proteins (HCPs), identify degradation pathways and critical quality attributes (CQAs) will be discussed.
During the past decade, continuous processing has steadily gained traction within pharmaceutical industry. The smaller footprint, the reduction or minimization of technology transfer and overall flexibility of these systems generate the economic drivers for change. The advancement of technology, such as integration of process equipment and process analytical technology (PAT) enables concentrated process understanding and effective process control for these systems. There are an increasing number of joint efforts from industries, academia and regulatory agencies in this area. Continuous manufacturing implementations for commercial products are beginning to emerge as companies begin to turned this vision into reality.
Among all the process analyzers, NIR is still one of the most widely used platform PAT tools in continuous processes. Some critical aspects should be considered for NIR (or other common PAT tools) implementation in continuous processes.
Because of worldwide demographic changes a dramatic increase of the geriatric population is expected in the next decades. While pediatric drug delivery principles are becoming integrated into the development of new medicines, drug developers are less prepared to appropriately address the specific needs of this booming patient population. This webinar tries to give an overview about the possible drug delivery strategies addressing old age dependent differences. There will be specifically focused on how patient convenience and compliance can be improved, how disease specific drug delivery strategies can help geriatric patients, and how learnings from pediatric drug development can be used as a platform towards geriatric drug delivery.
Peter will share experiences and observations how the scientific high-tech community, can benefit from adopting paperless processes in the laboratory. Is it because paper doesn’t require any significant investment budget, or is it the low barrier to access, since paper even works without power or the need to have access to an information infrastructure, or is it just simply that the “what’s in it for me” question hasn’t been answered satisfactorily for the scientists?
Cross-functional collaboration between research, development, quality assurance and manufacturing is all about optimising and integrating multi-discipline distributed processes from start-to- finish. A paperless electronic record keeping system will add significant value to support these goals. LIMS, SDMS, LES and ELN products all reduce variability, transcription errors. Do we believe that traditional paper based systems could ever support these complex processes?
Though single-use technology and the general use of disposables are widely accepted and applied both in process development, pilot plant and selected production processes, they are not in general a reasonable choice at any scale or application. Notably process chromatography is considered a critical unit operation regarding feasibility to single-use application with the chromatographic matrix assumed to be the typical cost driver. But is this really true? The answer to this quite ambivalent: it depends! Numerous young and innovative companies have developed new and/or alternative products which can help to significantly reduce the costs of goods, thus providing an interesting basis for single-use applications. After all, taking into account reasonable scales and suitable manufacturing targets, the doors have been opened widely due to the supply of appropriate low-cost matrices and feasible hardware.
The spread of counterfeit and substandard medicines is a global threat to public health. The sources of most counterfeit medicines found globally were traced to Asia. Although many of these products were found outside the region, many Asian countries are at high risk of exposure to them. There is a need for easy and affordable tools for screening medicines. Handheld Raman devices have gained increasing interest as such tools. Many of the devices available share some advantages in the detection of counterfeit medicines but there are challenges in the detection of substandard products. Fixed-dose combination medicines present even greater challenges.
Microbiological methods play a critical role in ensuring safety and efficacy of drugs and biologics. Most microbiological methods are described in compendia and do not need method validation. However, rapid microbiological methods and other alternate methods require full validation. Due to large inherent variability and complexity of microbiological methods, there are challenges in validation of such methods. This webinar will discuss, ways of performing validation of microbiological methods, with a view to achieving regulatory compliance.
The article considers the opportunities for risk based change in facility design through quality by design (QbD) and advances in PAT. It suggests that the inclusion of a mix of biopharmaceutical products alongside oral solid dose products could work based on a manufacturing dancefloor concept. Further that both upstream and downstream may be considered in a new light with the potential for in-process real-time testing and approval significantly reducing or withdrawing entirely the need for work-in-progress (WIP) inventory and quarantine storage needs as supply chain management processes integrate.
The webinar will give an overview about general drug delivery requirements for paediatric drug products and current discussions concerning the EU and US regulations.
In-depth Case Studies featuring Patient-centric Paediatric formulations, will also be presented.
Today use of the term “single use technologies” can be considered as being synonymous with the modern biotech industries. Based on the proliferation of companies now specialising in providing solutions to pretty much anyone anywhere, along with the intensive level of marketing and industry discussion, it is clear to see that the sector has progressed significantly over the years. The ability to purchase systems and technologies off the shelf as a consumable, rather than invest in significant capital infrastructure, better facilitates small enterprises to perform small and pilot GMP scale manufacture in-house. Organisations are able to leverage the experience of the manufacturers in the development of these products. The concept of single use technologies has been proven to produce solutions which are compliant and work. However, there still are questions around regulatory guidance for single use technologies.
Within the development of rapid screening methods to secure the global supply chain, the FDA’s Division of Pharmaceutical Analysis (DPA) has been building Raman spectral libraries for verification of pharmaceutical materials, in conjunction with handheld instruments in the field. Focusing on finished products, we evaluate the spectral library for method specificity, showing high specificity for drugs containing different active ingredients.
Combining the process of tableting with a multiple unit pellet system requires the protection of the drug release controlling coating as well as the limitation of segregation of the tableting mixture in order to provide mass and content uniformity. Limiting pellet size and fraction (ideally 50 – 60 % w/w), using concave tooling and of course applying flexible coatings at high layer thickness are best precaution to prevent damage of the drug release controlling coating.
Introduction on what are considered as acceptable extractable and leachable data for submissions. The talk will focus on extractable and leachable study design considerations with examples on single project level. Also, discuss how to evaluate and leverage supplier data if they are available to you. Close with discussion on how to simplify and reduce numbers of E&L studies on entire project or multiple products/lines/buildings level.
Thomas Rades and Anette Müllertz - University of Copenhagen, Denmark
Lipid Based Drug Delivery Systems: On the importance of supersaturation and precipitation
In this presentation we will review the formulation of lipid based drug delivery systems (LbDDS), with a focus on the importance of supersaturation of the drug in the LbDDS as well as on the importance of precipitation and the physical nature of the precipitate during in vitro lipolysis.
Work from research will be summarised and a perspective will be given on the consequences of supersaturation and precipitation on the future development of LbDDS.
The Journal for Asia's Pharmaceutical and Biopharmaceutical Industry
BioPharma Asia aims to keep its 30,000 readers abreast of all developments in the areas of Drug Development, Drug Delivery, Manufacturing, Quality Assurance, Outsourcing and Regulatory Affairs, with only the highest quality articles, written by the most respected authors, associated with only end-user companies. This ensures that the information will always be guaranteed to remain timely, informative and above all totally unbiased.