Are you choosing the right excipients for your high risk application? Find out how to select the right excipients and enable your process optimization to improve the total cost of ownership.
In this webinar, you will learn:
• Selection of right excipients for high risk formulation is very critical step
• Low Endotoxin and low bioburden limits are important aspect while selecting raw materials
• Strong regulatory support is crucial for high risk formulation
Excipients selection for high risk formulations like parenteral and ophthalmic applications is very challenging. Excipients should be inert with high purity for such dosage forms because trace amounts of impurities present in excipients can interact with active pharmaceutical ingredient (API) which results in instability of the formulation. This presentation discusses how to select the right excipients for high-risk applications and gives guidance for process optimization by choosing the best combination of filters and excipients to improve the total cost of ownership.
Quality must be built into the product, it cannot be inspected into it. The Pharmaceutical industries are experiencing a “knowledge and experience deficit” regarding the use of QbD concepts.
FDA’s emphasis on quality by design began with the recognition that increased testing does not improve product quality (this has long been recognized in other industries).In order for quality to increase, it must be built into the product. To do this requires understanding how formulation and manufacturing process variables influence product quality.Quality by Design (QbD) is a systematic approach to pharmaceutical development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.
This presentation - Part III in the series- deals with the concepts of critical material attributes, critical process parameters , their linage to the the critical Quality attributes of the Product and Quality Risk Management and its pivotal role in the QbD process.Concepts of control strategy are also discussed briefly.
This presentation was compiled from material freely available from FDA , ICH , EMEA and other free resources on the world wide web.
Speaker at seminar "The Pharmaceutical quality system: ICH Q8/ICH Q9" - University of Parma, 18 May 2012.
Describing steps, tools, and approaches developed for application of QbD to manufacturing processes that have analogous application to the development and use of analytical methods.
Selecting the right aseptic filter for your process can be complicated: today’s biomanufacturer has many filter choices each offering distinct benefits. Understanding the specific needs for individual operations, in terms of flux, capacity, bioburden reduction or sterilizing performance, gamma or thermal compatibility and single or multi-use will inform decisions that have implications for the life of the process. This webinar will provide general customer guidance and explain the benefits and disadvantages of different options to help guide customers to the most appropriate filter for their operation.
In this webinar, you will learn:
- How filter design impacts performance
- Important criteria for filter selection
- New choices and options to maximize productivity for biomanufacturers
QbD is new concept in pharmaceutical industries which is beneficial for producing and maintaining quality in product. With help of QbD a quality is built in product during manufacturing.
Innovation in Filter Validation and Technology TransferMilliporeSigma
Regulatory and manufacturing requirements exist to perform product-specific microbial retention testing on sterilizing filters. The implementation of a Quality by Design approach to microbial retention testing supports a paradigm that would obviate the need for product-specific testing for early stage products that do not have the quantity of material required to easily and efficiently perform such testing. Process and product parameters were varied to determine their effect on microbial retention.
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: www.emdmillipore.com/mlab
Quality must be built into the product, it cannot be inspected into it. The Pharmaceutical industries are experiencing a “knowledge and experience deficit” regarding the use of QbD concepts.
FDA’s emphasis on quality by design began with the recognition that increased testing does not improve product quality (this has long been recognized in other industries).In order for quality to increase, it must be built into the product. To do this requires understanding how formulation and manufacturing process variables influence product quality.Quality by Design (QbD) is a systematic approach to pharmaceutical development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.
This presentation - Part III in the series- deals with the concepts of critical material attributes, critical process parameters , their linage to the the critical Quality attributes of the Product and Quality Risk Management and its pivotal role in the QbD process.Concepts of control strategy are also discussed briefly.
This presentation was compiled from material freely available from FDA , ICH , EMEA and other free resources on the world wide web.
Speaker at seminar "The Pharmaceutical quality system: ICH Q8/ICH Q9" - University of Parma, 18 May 2012.
Describing steps, tools, and approaches developed for application of QbD to manufacturing processes that have analogous application to the development and use of analytical methods.
Selecting the right aseptic filter for your process can be complicated: today’s biomanufacturer has many filter choices each offering distinct benefits. Understanding the specific needs for individual operations, in terms of flux, capacity, bioburden reduction or sterilizing performance, gamma or thermal compatibility and single or multi-use will inform decisions that have implications for the life of the process. This webinar will provide general customer guidance and explain the benefits and disadvantages of different options to help guide customers to the most appropriate filter for their operation.
In this webinar, you will learn:
- How filter design impacts performance
- Important criteria for filter selection
- New choices and options to maximize productivity for biomanufacturers
QbD is new concept in pharmaceutical industries which is beneficial for producing and maintaining quality in product. With help of QbD a quality is built in product during manufacturing.
Innovation in Filter Validation and Technology TransferMilliporeSigma
Regulatory and manufacturing requirements exist to perform product-specific microbial retention testing on sterilizing filters. The implementation of a Quality by Design approach to microbial retention testing supports a paradigm that would obviate the need for product-specific testing for early stage products that do not have the quantity of material required to easily and efficiently perform such testing. Process and product parameters were varied to determine their effect on microbial retention.
To learn more about this topic or collaborate with our technical experts, schedule an in-person or remote visit at our M Lab™ Collaboration Centers: www.emdmillipore.com/mlab
Medicinal products must comply with their approved specifications before they are released into the market. Compliance with release specifications can be demonstrated by performing a complete set of tests on the active substance and/or finished product, according to the approved specifications. Under certain conditions, an alternative strategy to systematic end product testing is possible. So far this concept has been mainly applied to sterility testing of terminally sterilised products and has become associated with parametric release applications. Recent guidelines adopted in the ICH context (ICH Q8, Q9 and Q10) have made it possible to apply a similar release decision process to tests other than sterility, this approach has been called Real Time Release Testing (RTRT).
RTRT is a system of release that gives assurance that the product is of intended quality, based on the information collected during the manufacturing process, through product knowledge and on process understanding and control. RTRT recognises that under specific circumstances an appropriate combination of process controls (critical process parameters) together with pre-defined material attributes may provide greater assurance of product quality than end-product testing and the context as such be an integral part of the control strategy. The RTRT principle is already authorised for use as an optional alternative to routine sterility testing of products terminally sterilised in their final container i.e. parametric release. Enhanced product knowledge and process understanding, the use of quality risk management principles and the application of an appropriate pharmaceutical quality system, as defined within ICH Q8,Q9 and Q10 provide the platform for establishing RTRT mechanisms for other applications, for new products as well as established marketed products. Release of a product can be a combination of a RTR approach for certain critical quality attributes (CQAs) and a more conventional evaluation for other CQAs (partial RTR).
This presentation deals with the concepts of Real Time Release Testing. This presentation was compiled from material freely available from FDA , ICH , EMEA and other free resources on the world wide web.
In this webinar, you will learn:
Sources of endotoxin contamination
Contamination control strategy
Endotoxin removal strategies
Detailed description:
Endotoxin, a lipopolysaccharide (LPS), is a type of pyrogen and is a component of the exterior cell wall of Gram-negative bacteria. To ensure safety on patient’s endotoxin content in the drug should always be controlled. In a biological processing it may emanate from facility, utility, raw materials, process, and personnel. In this webinar we discuss the regulatory norms, strategies for prevention & removal of endotoxin to ensure that the final drug product is safe.
FDA’s emphasis on quality by design began with the recognition that increased testing does not improve product quality (this has long been recognized in other industries).In order for quality to increase, it must be built into the product. To do this requires understanding how formulation and manufacturing process variables influence product quality.Quality by Design (QbD) is a systematic approach to pharmaceutical development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.
This presentation - Part V in the series- deals with the concepts of Control strategy and PAT. This presentation was compiled from material freely available from FDA , ICH , EMEA and other free resources on the world wide web.
Successful Drug Development with Synthetic Lipids: Critical Aspects and Strat...MilliporeSigma
Lipid-based formulations and lipid nanoparticles are administration strategies of increasing importance in the pharmaceutical world. On the way to a successful drug product registration, there are numerous challenges to be overcome – from formulation development to meeting regulatory requirements and submission. In particular, care must be taken to choose appropriate lipids with respect to their type, source and quality, as these factors greatly affect the performance of the final formulation and also play a role in financial considerations.
In this webinar, you will:
● Explore critical aspects relating to synthetic lipids as raw materials for lipidic formulations
● Learn strategies to minimize risk when choosing lipidic raw materials for drug product development
● Gain insights into tailored manufacturing and lipids with optimized properties such as conjugation of targeting moieties
Successful Drug Development with Synthetic Lipids: Critical Aspects and Strat...Merck Life Sciences
Lipid-based formulations and lipid nanoparticles are administration strategies of increasing importance in the pharmaceutical world. On the way to a successful drug product registration, there are numerous challenges to be overcome – from formulation development to meeting regulatory requirements and submission. In particular, care must be taken to choose appropriate lipids with respect to their type, source and quality, as these factors greatly affect the performance of the final formulation and also play a role in financial considerations.
In this webinar, you will:
● Explore critical aspects relating to synthetic lipids as raw materials for lipidic formulations
● Learn strategies to minimize risk when choosing lipidic raw materials for drug product development
● Gain insights into tailored manufacturing and lipids with optimized properties such as conjugation of targeting moieties
Medicinal products must comply with their approved specifications before they are released into the market. Compliance with release specifications can be demonstrated by performing a complete set of tests on the active substance and/or finished product, according to the approved specifications. Under certain conditions, an alternative strategy to systematic end product testing is possible. So far this concept has been mainly applied to sterility testing of terminally sterilised products and has become associated with parametric release applications. Recent guidelines adopted in the ICH context (ICH Q8, Q9 and Q10) have made it possible to apply a similar release decision process to tests other than sterility, this approach has been called Real Time Release Testing (RTRT).
RTRT is a system of release that gives assurance that the product is of intended quality, based on the information collected during the manufacturing process, through product knowledge and on process understanding and control. RTRT recognises that under specific circumstances an appropriate combination of process controls (critical process parameters) together with pre-defined material attributes may provide greater assurance of product quality than end-product testing and the context as such be an integral part of the control strategy. The RTRT principle is already authorised for use as an optional alternative to routine sterility testing of products terminally sterilised in their final container i.e. parametric release. Enhanced product knowledge and process understanding, the use of quality risk management principles and the application of an appropriate pharmaceutical quality system, as defined within ICH Q8,Q9 and Q10 provide the platform for establishing RTRT mechanisms for other applications, for new products as well as established marketed products. Release of a product can be a combination of a RTR approach for certain critical quality attributes (CQAs) and a more conventional evaluation for other CQAs (partial RTR).
This presentation deals with the concepts of Real Time Release Testing. This presentation was compiled from material freely available from FDA , ICH , EMEA and other free resources on the world wide web.
In this webinar, you will learn:
Sources of endotoxin contamination
Contamination control strategy
Endotoxin removal strategies
Detailed description:
Endotoxin, a lipopolysaccharide (LPS), is a type of pyrogen and is a component of the exterior cell wall of Gram-negative bacteria. To ensure safety on patient’s endotoxin content in the drug should always be controlled. In a biological processing it may emanate from facility, utility, raw materials, process, and personnel. In this webinar we discuss the regulatory norms, strategies for prevention & removal of endotoxin to ensure that the final drug product is safe.
FDA’s emphasis on quality by design began with the recognition that increased testing does not improve product quality (this has long been recognized in other industries).In order for quality to increase, it must be built into the product. To do this requires understanding how formulation and manufacturing process variables influence product quality.Quality by Design (QbD) is a systematic approach to pharmaceutical development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.
This presentation - Part V in the series- deals with the concepts of Control strategy and PAT. This presentation was compiled from material freely available from FDA , ICH , EMEA and other free resources on the world wide web.
Successful Drug Development with Synthetic Lipids: Critical Aspects and Strat...MilliporeSigma
Lipid-based formulations and lipid nanoparticles are administration strategies of increasing importance in the pharmaceutical world. On the way to a successful drug product registration, there are numerous challenges to be overcome – from formulation development to meeting regulatory requirements and submission. In particular, care must be taken to choose appropriate lipids with respect to their type, source and quality, as these factors greatly affect the performance of the final formulation and also play a role in financial considerations.
In this webinar, you will:
● Explore critical aspects relating to synthetic lipids as raw materials for lipidic formulations
● Learn strategies to minimize risk when choosing lipidic raw materials for drug product development
● Gain insights into tailored manufacturing and lipids with optimized properties such as conjugation of targeting moieties
Successful Drug Development with Synthetic Lipids: Critical Aspects and Strat...Merck Life Sciences
Lipid-based formulations and lipid nanoparticles are administration strategies of increasing importance in the pharmaceutical world. On the way to a successful drug product registration, there are numerous challenges to be overcome – from formulation development to meeting regulatory requirements and submission. In particular, care must be taken to choose appropriate lipids with respect to their type, source and quality, as these factors greatly affect the performance of the final formulation and also play a role in financial considerations.
In this webinar, you will:
● Explore critical aspects relating to synthetic lipids as raw materials for lipidic formulations
● Learn strategies to minimize risk when choosing lipidic raw materials for drug product development
● Gain insights into tailored manufacturing and lipids with optimized properties such as conjugation of targeting moieties
Endotoxin Control and Clearance in BiomanufacturingMilliporeSigma
In this webinar, you will learn:
Sources of endotoxin contamination
Contamination control strategy
Endotoxin removal strategies
Detailed description:
Endotoxin, a lipopolysaccharide (LPS), is a type of pyrogen and is a component of the exterior cell wall of Gram-negative bacteria. To ensure safety on patient’s endotoxin content in the drug should always be controlled. In a biological processing it may emanate from facility, utility, raw materials, process, and personnel. In this webinar we discuss the regulatory norms, strategies for prevention & removal of endotoxin to ensure that the final drug product is safe.
Process equipment characterization – how standardized extractables data suppo...MilliporeSigma
View the recording here: https://bit.ly/35KIwBb
Biopharmaceutical Industry recently increased adoption of Single-Use systems and components in manufacturing process operations. Drug manufacturers are responsible for the characterization of SU components and systems used for the production to ensure patient safety. SUS Suppliers are encouraged by BPOG and BPSA to provide comprehensive extractables data package to support drug manufacturer’s E&L assessments.
This webinar will give an overview of the E&L evaluation workflow and practical study approaches from both supplier and end-user perspective, in accordance with the latest industry’s standards and upcoming USP <665> requirements. Case studies will be presented on how the data from suppliers are used to mitigate risk associated to SU materials, highlighting the key role of collaboration between the supplier and the drug manufacturer.
Process equipment characterization – how standardized extractables data suppo...Merck Life Sciences
View the recording here: https://bit.ly/35KIwBb
Biopharmaceutical Industry recently increased adoption of Single-Use systems and components in manufacturing process operations. Drug manufacturers are responsible for the characterization of SU components and systems used for the production to ensure patient safety. SUS Suppliers are encouraged by BPOG and BPSA to provide comprehensive extractables data package to support drug manufacturer’s E&L assessments.
This webinar will give an overview of the E&L evaluation workflow and practical study approaches from both supplier and end-user perspective, in accordance with the latest industry’s standards and upcoming USP <665> requirements. Case studies will be presented on how the data from suppliers are used to mitigate risk associated to SU materials, highlighting the key role of collaboration between the supplier and the drug manufacturer.
Endotoxin Control and Clearance in BiomanufacturingMilliporeSigma
In this webinar, you will learn:
Sources of endotoxin contamination
Contamination control strategy
Endotoxin removal strategies
Detailed description:
Endotoxin, a lipopolysaccharide (LPS), is a type of pyrogen and is a component of the exterior cell wall of Gram-negative bacteria. To ensure safety on patient’s endotoxin content in the drug should always be controlled. In a biological processing it may emanate from facility, utility, raw materials, process, and personnel. In this webinar we discuss the regulatory norms, strategies for prevention & removal of endotoxin to ensure that the final drug product is safe.
Grove Advanced Chemicals: Let Nature Take Care of Nature.
Grove is a company dedicated to the water treatment industry and specializes in the application of organic biodegradable coagulants from vegetal origin.
Considerations to Extractables and Leachables Testing SGS
How to organize Extractables Assessments? FDA continues to issue Warning Letters to companies that fail to properly complete Design Verification, Design Validation, and Process Validation, and recently to include failures of manufacturers in Risk Management. The evaluation of extractables and leachables has become an increasingly important aspect in the Quality by Design (QbD) initiative of the FDA in the area of drug product design, including materials used in the drug product production process and container and closure systems used for product packaging. This presentation provides general approaches and practical aspects in E&L testing.
Overcoming Challenges in Ophthalmic Formulations through Polymer Selection – ...Merck Life Sciences
Ophthalmic drug formulations are growing in importance due to the increased prevalence of eye-related disorders such as diabetic retinopathy and macular degeneration. However, ocular drug delivery is challenging due to unique anatomical and physiological barriers.
The low ocular bioavailability (<10%) of conventional ophthalmic formulations is driving the need for novel approaches to improve the delivery of the desired concentration, at the site of action, at a controlled rate.
This whitepaper provides an overview of polymers that can be used in ophthalmic formulations and highlights the advantages offered using polyvinyl alcohol (PVA) through case studies.
Find more information about excipients for liquid formulations on our website: https://www.sigmaaldrich.com/products/pharma-and-biopharma-manufacturing/formulation/liquid-formulation
Specialized in custom synthesis of organic molecules. Broad experience of working on multiple business models - FTEs, FFS, Milestone services of pharmaceutical industry.
Commited to deliver highest quality products in a timely manner and value to the customers.
The Viscosity Reduction Platform: Viscosity-reducing excipients for improveme...Merck Life Sciences
Protein viscosity is a major challenge in preparing highly concentrated protein formulations suitable for subcutaneous injection. Recently, the Viscosity Reduction Platform (VRP) was introduced and its technical key features and benefits for formulations were discussed. However, highly viscous solutions do not only pose a challenge when administering a drug to a patient, they can also impose technical limitations in the manufacturing process.
This white paper evaluates the effect of the excipients in the Viscosity Reduction Platform on ultrafiltration processes used to produce a highly concentrated formulation of a monoclonal antibody (mAb). Two filtration methods are demonstrated in this work.
Find more information about the Viscosity Reduction Platform on our website: https://www.sigmaaldrich.com/products/pharma-and-biopharma-manufacturing/formulation/viscosity-reduction-platform
Use of Excipients in Downstream Processing to Improve Protein PurificationMerck Life Sciences
Excipients are used to improve the stability of protein-based therapeutics by protecting the protein against a range of stress conditions such as temperature changes, pH changes, or agitation. Similar stresses are applied to proteins during downstream purification. Shifts in pH during Protein A chromatography, subsequent incubations at low pH for virus inactivation, and changes in conductivity in ion exchange chromatography can lead to aggregation, fragmentation, or other chemical modifications of the therapeutic protein. Given the potential impact on the protein’s structural integrity, there is a need for approaches to reduce the risk presented by the conditions during downstream processing. For example, integration of a solution to prevent aggregation of proteins would be a more efficient strategy than implementing steps to remove multimeric forms.
This white paper highlights the results from a recent paper by Stange et. al., in which protein stabilizing excipients such as polyols, sugars, and polyethylene glycol (PEG4000) were used as buffer system additives. Effect of the excipients on elution patterns, stabilization of the monomer antibody, host-cell protein removal, virus inactivation rates and binding capacity of cation exchange chromatography were explored.
Exploring the protein stabilizing capability of surfactants against agitation...Merck Life Sciences
Agitation of therapeutic protein solutions during manufacturing, shipping and handling is one of the major initiators for protein aggregation and particle formation during the life history of a protein drug. Adsorption of protein molecules to liquid-air interfaces leads to the formation of highly concentrated protein surface films. The rupture of these protein films due to various mechanical processes can then result in the appearance of protein aggregates and particles in the bulk solution phase.
One technique to stabilize proteins against stress induced by liquid-air interfaces is the use of non-ionic surfactants. About 91% of antibody formulations commercially available in 2021 contained a surfactant. Polysorbate 20 and 80, composed of a hydrophilic polyoxyethylene sorbitan and hydrophobic fatty acid esters, made up the largest part being employed in 87% of said formulations.
Despite their frequent use in parenteral drug products, concerns have been raised for decades about the application of polysorbates as surfactants in biopharmaceutical formulations. Autoxidation of polysorbate, caused by residual peroxides in polysorbates, can damage the proteins and can further drive the oxidative degradation of polysorbate. Chemical and enzymatic hydrolysis of polysorbate may lead to the formation of free fatty acid particles, which may become visible; and both mechanisms eventually lead to the reduction in polysorbate concentration. Therefore, the purpose of the current study was to compare various molecules for their capabilities to reduced agitation-induced protein aggregation and particle formation; and furthermore, investigate their underlying protein stabilizing mechanisms.
The Viscosity Reduction Platform: Viscosity Reducing Excipients for Protein F...Merck Life Sciences
Protein viscosity is one of the major obstacles in preparing highly concentrated protein formulations suitable for subcutaneous injection.
This whitepaper examines how combining an amino acid with a second viscosity-reducing excipient circumvents adverse effects on protein stability and improves viscosity-reducing capacity.
To find more information about the Viscosity Reduction Platform, please visit our website: https://sigmaaldrich.com/products/pharma-and-biopharma-manufacturing/formulation/viscosity-reduction-platform
Characterization of monoclonal antibodies and Antibody drug conjugates by Sur...Merck Life Sciences
Watch the presentation of this webinar: https://bit.ly/3Pjpjvr
Highlights of this webinar:
- Surface plasmon resonance as a powerful tool for biologic characterization including mAbs and ADCs.
- SPR allows rapid binding analysis in real time without using labels for SARS-CoV-2 receptor binding domain mutations.
- Kinetic data is indicative of possible neutralizing activity allowed assessment of neutralizing ability of therapeutic monoclonal antibodies.
- The application can provide preliminarily efficacy information and facilitated mAbs/ACDs candidate selection process
Detailed description:
Characterization of therapeutic monoclonal antibodies (mAbs) or Antibody drug conjugates (ADCs) is challenging due to their ability to bind to a variety of proteins via their Fc and Fab domains, giving rise to diverse biological functions associated with each domain. The Fc domain of mAbs interacts with Fc receptors with varying affinities, which can influence biological processes such as Complement-dependent cytotoxicity (CDC) and Antibody-dependent cellular cytotoxicity (ADCC), transcytosis, phagocytosis, and/or serum half-life.
An important characteristic of an antibody is its Fc effector function. Antibodies can be engineered to obtain desired binding of the Fc region to Fc receptors expressed on effector cells. Hence, it is crucial to evaluate the binding interaction of mAbs/ADC with Fc receptors in the early phase of drug development to understand the potential biological activity of the product in vivo.
Surface Plasmon Resonance (SPR) is a powerful technique to establish binding kinetics in real-time, label free, and high sensitivity with low sample consumption. Along with target antigen binding, it is crucial to evaluate the binding interaction of antibodies and ADCs with Fc receptors. Our SPR case studies investigated the impact on binding kinetics of ADCs with different linkers and the binding interactions of SARS-CoV-2 spike protein variants and evaluated the neutralizing ability of therapeutic mAbs. SPR characterisation can be facilitated in all stages of the product life cycle to ensure the quality and safety of mAbs and ADCs.
The Role of BioPhorum Extractables Data in the Effective Adoption of Single-U...Merck Life Sciences
Regulatory expectation does require patient safety evaluations with supporting data for manufacturing components that directly come into contact with drug manufacturing process streams. Readily available extractables data can help manufacturers using singleuse technology to accelerate product qualifications, risk assessments and process optimization
This white paper guides you on how to save time and resources with supplier-provided single-use system extractables data and gives you an overview about the overall strategy for Extractables & Leachables. At the end you will find a case study.
Find more information about filters and single-use components on our website: https://www.sigmaaldrich.com/DE/en/services/product-services/emprove-program/emprove-filter-and-single-use-component-portfolio
Watch the recording of this presentation here: https://bit.ly/3zTOpe4
Detailed description:
SARS-CoV-2 showed us that technology supports us during our inspection activity even if on-site visits are not possible. Travel restrictions of various kinds will remain a risk in the future. The use of new technologies has shown that inspections and audits can be carried out despite these restrictions. We will focus on what possibilities the new technologies offer and take a look at the future of inspections and audits.
In this webinar, you will learn:
• Regulatory overview of remote audits
• The technologies needed to support the audit process
• What types of inspections are possible with the use of these technologies
• How audits may look in the future
Presented by:
Daniel Buescher, Product Manager - Digital Solutions
Moving your Gene Therapy from R&D to IND: How to navigate the Regulatory Land...Merck Life Sciences
Watch the recording of this presentation here: https://bit.ly/3SqOsoP
Novel therapies, including cell and gene therapies, continue to be central to innovation in healthcare and represent the fastest growing area of therapeutic medicine. As a consequence, the number of gene therapies undergoing clinical trials has increased significantly in the last five years.
Manufacturing processes for these novel therapeutics are very complex with a high risk of contamination. Regulatory agencies world-wide have responded by issuing guidance to outline their expectations for development and manufacture of cell and gene therapies. Currently, regulatory guidance is not harmonized globally and can often lead to confusion within industry and increased risk of non-compliance.
In this webinar, we'll answer:
• Which regulatory guidelines do you need to comply for your INDs?
• When do you start implementing GMPs and validated assays?
• How do you get your QC testing strategy ‘right the first time’?
• How do you ensure testing is not your rate limiting step for the IND submission?
Presented by:
Manjula Aysola, Senior Regulatory Consultant
Dr. Alison Armstrong, Sr. Director, Technical and Scientific Solutions
Identity testing by NGS as a means of risk mitigation for viral gene therapiesMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3RijkHC
Detailed description:
Imagine you’ve just completed a manufacturing run for your viral vector. Identity testing is performed to confirm the vector sequence. But when the results come back the data reveals unexpected sequence variants! With an appropriate risk mitigation testing strategy, this situation can be prevented.
The situation described above is not hypothetical, and happens more that you think, costing valuable time and resources.
Investigatory testing has shown that sequence variants present in starting materials (e.g. plasmids) are likely to make their way to the final product. Adequate identification of low-level variants with an appropriately sensitive method is critical in ensuring the quality of the final product. A risk-based testing strategy, in the context of identity, for viral vector manufacturing will be presented, focusing on key testing points. NGS assays for identity and variant detection will be highlighted due to their extremely sensitive nature compared to traditional approaches.
In this webinar, we'll explore:
• Regulatory requirements for identity testing
• NGS applications for identity testing as compared to traditional methods
• A case study on the impact of not establishing a proper risk-based testing strategy
Presented by: Bradley Hasson, Director of Lab Operations for NGS Services
Latest advancements of melt based 3D printing technologies for oral drug deli...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3A2WcH4
The application of polymer excipients in 3D printing manufacturing is usually limited due to the concerns of filament strength, high processing temperature and large scale manufacturing.
Latest technology developments are targeting a direct melt deposition to simplify the process and enable a constant and efficient process. Two different processing approaches will be presented:
The advanced melt drop deposition, where individual three dimensional geometries can be created by depostition of polymer droplets and the MED® 3D printing technology which allows by precise layer-by-layer deposition to produce objects with well-designed geometric structures.
In this webinar, you will learn:
• Latest advancements of melt based 3D printing approaches
• Application examples for the individual technologies
• Deep dive in the MED® 3D printing technology to design dedicated drug release profiles
Presented by:
Dr. Thomas Kipping, Head of Drug Carriers
Dr. Xianghao Zuo, Deputy Director of R&D, Triastek
CAR-T Manufacturing Innovations that Work - Automating Low Volume Processes a...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3NDNIKe
Automated, fit-for-purpose tools are essential in CAR-T processing to support sustainable manufacturing of clinical and market-approved cell therapy products. This webinar will discuss how the ekko™ Acoustic Cell Processing System uses acoustic technology as a touchless approach to manipulate cells, enabling a modular tool across the CAR-T manufacturing workflow. Typical performance of templated ekko™ System processes for DMSO washout of leukapheresis material, low volume and high cell concentrate for electroporation preparation, and harvest of expanded T cells will be reviewed.
This webinar will also give an early glimpse at the ekko™ Select System for unmatched T cell selection.
In this webinar, you will:
• Uncover how the ekko™ System supports the broad industrialization of cell therapy, with particular focus on how to achieve low volume, high concentrate cell product for critical transduction and transfection steps
• Discover how ekko™ System for wash and concentrate processes throughout the cell therapy workflow achieve high cell recovery, viability, and effective residual removal
• Preview to ekko™ Select, our cell therapy selection platform, to achieve unmatched ease-of-use with direct processing from leukopaks reducing the need for preparation steps
Presented by:
Benjamin Ross-Johnsrud, Acoustic Technology Expert
Robert Scott, Mechanical Engineer III
Viral safety of biologics: What's changing with the ICH Q5A revision?Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3t7X9tg
How does the ICH Q5A revision impact viral safety strategies for biologics?
Biologics continue to grow at a fast pace. Manufactured using cell lines of human or animal origin, these are at risk of viral contamination making safety strategies critical. A comprehensive risk mitigation strategy using multiple orthogonal measures is a regulatory expectation. ICH Q5A, the globally-harmonized guideline outlines the expectations. ICH Q5A is currently being revised to address recent scientific advancements including novel therapeutic modalities, new manufacturing paradigms, updates in viral clearance applications, and alternate detection technologies. We’ll discuss the expected changes and potential impact on viral safety strategies with case studies and examples.
In this webinar, you will learn about:
• The Importance of virus testing in biologics products
• Regulatory landscape, expectations for the Q5A revision
• What's new and changing
• Examples of alternate testing schedules, impact on viral clearance
Presented by:
Manjula Aysola, Senior Regulatory Consultant
Alison Armstrong, PhD, Sr. Director, Technical and Scientific Solutions
Improve Operational Efficiency by Over 30% with Product, Process, & Systems A...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3adaxWh
When implementing new automation systems, organizations must consider things like deployment time, user adoption, and costs.
They must also consider the cost of doing nothing – that is, what competitive advantage is lost in standing still? What time and quality is lost in repetitive, manual tasks rather than an automated, digital workflow? What operational efficiencies are lost?
In this webinar we examine how a product, process, and system agnostic automation platform can be deployed faster than traditional system specific software while bringing greater operational efficiencies (in many cases over 30% improvement).
To remain competitive in the market, biopharma manufacturers must adopt automation and digital technologies, but most plants still have island of automation consisting of independently functioning, standalone unit operations. This results in operational inefficiency, regulatory concerns, and a poor understanding of the process and product life cycle.
Taking the first, right step must include considering risks, costs, timelines, and technology alternatives. Traditional automation approaches tied to specific systems, processes, and products are, by their nature, limited; while an agnostic platform will address current biomanufacturing business challenges and ensure future readiness. With the right platform, a phased automation implementation can yield operational efficiency gains of up to 30% and improved product quality and regulatory compliance.
In this webinar, let's explore:
• Challenges of automation and digital technology adoption
• What a product, process, and system agnostic platform entails
• Applications and benefits of a process orchestration platform
• Ensuring future readiness with process orchestration
Presented by:
Braj Nandan Thakur, Global Product Manager - Automation
Insights from a Global Collaboration Accelerating Vaccine Development with an...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3Nbb5ug
Get insights and best practices from a multinational team establishing a platform for vaccine production. See how a long-term collaboration on a bench-scale process used to produce a Virus Like Particle (VLP) vaccine for SARS-CoV-2 was successfully converted to a robust GMP-compatible, scalable process.
The COVID-19 pandemic further emphasized the need for collaboration in the development of urgently needed vaccines and therapeutics. In this webinar, we take you behind the scenes of our collaboration with Technovax and Innovative Biotech in which a scalable VLP vaccine platform was optimized for use in a production facility in Nigeria in response to the need for local production of SARS-CoV-2 vaccines. The flexibility and robustness of the platform will enable its rapid deployment to support the West African pandemic readiness program. Initial development of the VLP process began in late 2019 and by March 2020, was already adapted for production of a SARS-CoV-2 vaccine.
In this webinar, you will learn:
• About building a priceless collaborative network with integrated solutions
• Virus-Like Particle Vaccines
• Process Development Overview and Challenges
• Pre-clinical Results and Next Steps
Presented by:
Jose M. Galarza, PhD,
President and Founder of TechnoVax
Naomi Baer,
Business development consultant, Emerging Biotech, BioProcess division
Youssef Gaabouri, Eng. ,
Associate Director, Head of Sales Middle East & Africa, BioProcess division
Risk-Based Qualification of X-Ray Sterilization for Single-Use SystemsMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3vQf0qv
In the single-use bioprocess industry, X-ray irradiation warrants consideration as an alternate sterilization technology. Using a risk-based qualification testing strategy is important when evaluating and implementing equivalent ionizing irradiation sterilization methods.
The urgent need for life-saving therapies as a result of the global pandemic has reinforced the criticality of flexibility in pharmaceutical manufacturing, including sterilization. The single-use bioprocess industry traditionally has employed gamma irradiation sterilization. X-ray irradiation is being considered as an additional sterilization technology for business and supply continuity. We will share a risk-based qualification testing strategy including Extractables and data generated to support comparability of gamma irradiation and X-ray irradiation as equivalent ionizing irradiation sterilization methods.
In this webinar, you will learn about:
• The comparison of gamma and X-ray irradiation sterilization
• A risk-based qualification test strategy
• Data evaluation of gamma versus X-ray sterilized single-use components
Presented by:
Monica Cardona,
Global Senior Program Manager
Paul Killian, Ph.D.,
R&D Director, Analytical Technologies
Rapid replication competent adenovirus (rRCA) detection: Accelerate your lot ...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3MJ4u9V
Testing for presence of replication competent adenovirus (RCA) is a key component to ensure patient safety and a requirement for all biologicals manufactured using adenoviral vectors. For many adenoviral-based products, the RCA assay is a rate-limiting assay for lot release.
Join this webinar to learn about a rapid RCA detection assay currently in development, which combines a 7-day culture assay with a highly sensitive molecular endpoint specific for RCA. The method can detect presence of as little as 1 RCA in adenoviral vector material at an approximate concentration of 5x107 - 2x108 vector particles (VP)/mL, making it a suitable method to meet regulatory requirements while accelerating your lot release timelines.
In this webinar, you will learn about:
• Regulatory framework for adenoviral vector products
• Considerations for lot release testing of adenoviral-based therapies
• Advantages of a rapid method for RCA testing on production lot material
Presented by:
Axel Fun, Ph.D.,
Principal Scientist
Alberto Santana, MBA,
Product Manager, Biologics Biosafety Testing
The High Intensity Sweeteners Neotame and Sucralose: 2 Ways to ace the Patien...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3vQyN7K
Bitter medicines are an important issue, especially for pediatric applications. As several APIs have bitter tasting components, high intensity sweeteners for taste optimization are of great interest. Join our webinar to discover our new sweetener toolbox enabling safe and stable formulations.
Mask bitter aftertaste for a sweeter pill to swallow! Patients’ compliance and the therapeutic benefit are supported by a pleasant taste of pharmaceutical formulations. With the high intensity sweeteners Neotame and Sucralose, you have efficient tools at hand which are superior to other sweeteners in many aspects:
• excellent sugar-like taste profile
• outstanding sweetness factors
• use effectiveness
• enhanced stability
We will present our new toolbox of two high performance sweeteners and focus on aspects of stability, safety, the application in various dosage forms, and market perception.
In this webinar, you will learn:
• How to optimize the patients' taste experience of your pharmaceuticals
• How sweeteners can be differentiated by their sensory profiles and features
• How our new product offering Neotame can be effectively used in your targeted formulations
Presented by:
Almut von der Brelie,
Senior Manager Strategic Marketing
Excipients for Solid Applications
The Developability Classification System (DCS): Enabling an Optimized Approac...Merck Life Sciences
This whitepaper by Dr. Daniel Joseph Price outlines how poorly soluble drug formulations can be designed using the developability classification system (DCS).
The DCS identifies the root cause of low solubility and enables lean, cost-effective and effective formulations to be developed.
#solubility #pharmaceuticalmanufacturing #oralsoliddosage #drugdevelopment
In this webinar, you will learn about:
The advantages of using advanced intermediates to develop ADC therapies
How to increase ADC solubility and efficiency
Fast, small-scale ADC library generation
Seamless supply chain with reduced complexity and regulatory support
The ADCore product line offers versatile intermediates that simplify the synthesis of common ADC payloads (dolastatins, maytansinoids, and PBDs) by greatly reducing the number of synthetic steps. This translates to savings in development and manufacturing costs and shorter timelines to the clinic. To address the poor solubility of many ADC payloads, ChetoSensar™ was developed to significantly increase the hydrophilicity of the drug linker, which has been shown to also substantially increase the efficacy of ADCs and broaden the therapeutic window.
Lastly, the ADC Express™ service leverages conjugation chemistry and analytical expertise to help design and quickly synthesize sets of potential ADC therapies suitable for screening to simplify candidate selection and get ADC therapies to market faster.
CHAPTER 1 SEMESTER V - ROLE OF PEADIATRIC NURSE.pdfSachin Sharma
Pediatric nurses play a vital role in the health and well-being of children. Their responsibilities are wide-ranging, and their objectives can be categorized into several key areas:
1. Direct Patient Care:
Objective: Provide comprehensive and compassionate care to infants, children, and adolescents in various healthcare settings (hospitals, clinics, etc.).
This includes tasks like:
Monitoring vital signs and physical condition.
Administering medications and treatments.
Performing procedures as directed by doctors.
Assisting with daily living activities (bathing, feeding).
Providing emotional support and pain management.
2. Health Promotion and Education:
Objective: Promote healthy behaviors and educate children, families, and communities about preventive healthcare.
This includes tasks like:
Administering vaccinations.
Providing education on nutrition, hygiene, and development.
Offering breastfeeding and childbirth support.
Counseling families on safety and injury prevention.
3. Collaboration and Advocacy:
Objective: Collaborate effectively with doctors, social workers, therapists, and other healthcare professionals to ensure coordinated care for children.
Objective: Advocate for the rights and best interests of their patients, especially when children cannot speak for themselves.
This includes tasks like:
Communicating effectively with healthcare teams.
Identifying and addressing potential risks to child welfare.
Educating families about their child's condition and treatment options.
4. Professional Development and Research:
Objective: Stay up-to-date on the latest advancements in pediatric healthcare through continuing education and research.
Objective: Contribute to improving the quality of care for children by participating in research initiatives.
This includes tasks like:
Attending workshops and conferences on pediatric nursing.
Participating in clinical trials related to child health.
Implementing evidence-based practices into their daily routines.
By fulfilling these objectives, pediatric nurses play a crucial role in ensuring the optimal health and well-being of children throughout all stages of their development.
Telehealth Psychology Building Trust with Clients.pptxThe Harvest Clinic
Telehealth psychology is a digital approach that offers psychological services and mental health care to clients remotely, using technologies like video conferencing, phone calls, text messaging, and mobile apps for communication.
CRISPR-Cas9, a revolutionary gene-editing tool, holds immense potential to reshape medicine, agriculture, and our understanding of life. But like any powerful tool, it comes with ethical considerations.
Unveiling CRISPR: This naturally occurring bacterial defense system (crRNA & Cas9 protein) fights viruses. Scientists repurposed it for precise gene editing (correction, deletion, insertion) by targeting specific DNA sequences.
The Promise: CRISPR offers exciting possibilities:
Gene Therapy: Correcting genetic diseases like cystic fibrosis.
Agriculture: Engineering crops resistant to pests and harsh environments.
Research: Studying gene function to unlock new knowledge.
The Peril: Ethical concerns demand attention:
Off-target Effects: Unintended DNA edits can have unforeseen consequences.
Eugenics: Misusing CRISPR for designer babies raises social and ethical questions.
Equity: High costs could limit access to this potentially life-saving technology.
The Path Forward: Responsible development is crucial:
International Collaboration: Clear guidelines are needed for research and human trials.
Public Education: Open discussions ensure informed decisions about CRISPR.
Prioritize Safety and Ethics: Safety and ethical principles must be paramount.
CRISPR offers a powerful tool for a better future, but responsible development and addressing ethical concerns are essential. By prioritizing safety, fostering open dialogue, and ensuring equitable access, we can harness CRISPR's power for the benefit of all. (2998 characters)
CHAPTER 1 SEMESTER V PREVENTIVE-PEDIATRICS.pdfSachin Sharma
This content provides an overview of preventive pediatrics. It defines preventive pediatrics as preventing disease and promoting children's physical, mental, and social well-being to achieve positive health. It discusses antenatal, postnatal, and social preventive pediatrics. It also covers various child health programs like immunization, breastfeeding, ICDS, and the roles of organizations like WHO, UNICEF, and nurses in preventive pediatrics.
Health Education on prevention of hypertensionRadhika kulvi
Hypertension is a chronic condition of concern due to its role in the causation of coronary heart diseases. Hypertension is a worldwide epidemic and important risk factor for coronary artery disease, stroke and renal diseases. Blood pressure is the force exerted by the blood against the walls of the blood vessels and is sufficient to maintain tissue perfusion during activity and rest. Hypertension is sustained elevation of BP. In adults, HTN exists when systolic blood pressure is equal to or greater than 140mmHg or diastolic BP is equal to or greater than 90mmHg. The
How many patients does case series should have In comparison to case reports.pdfpubrica101
Pubrica’s team of researchers and writers create scientific and medical research articles, which may be important resources for authors and practitioners. Pubrica medical writers assist you in creating and revising the introduction by alerting the reader to gaps in the chosen study subject. Our professionals understand the order in which the hypothesis topic is followed by the broad subject, the issue, and the backdrop.
https://pubrica.com/academy/case-study-or-series/how-many-patients-does-case-series-should-have-in-comparison-to-case-reports/
Navigating Challenges: Mental Health, Legislation, and the Prison System in B...Guillermo Rivera
This conference will delve into the intricate intersections between mental health, legal frameworks, and the prison system in Bolivia. It aims to provide a comprehensive overview of the current challenges faced by mental health professionals working within the legislative and correctional landscapes. Topics of discussion will include the prevalence and impact of mental health issues among the incarcerated population, the effectiveness of existing mental health policies and legislation, and potential reforms to enhance the mental health support system within prisons.
The dimensions of healthcare quality refer to various attributes or aspects that define the standard of healthcare services. These dimensions are used to evaluate, measure, and improve the quality of care provided to patients. A comprehensive understanding of these dimensions ensures that healthcare systems can address various aspects of patient care effectively and holistically. Dimensions of Healthcare Quality and Performance of care include the following; Appropriateness, Availability, Competence, Continuity, Effectiveness, Efficiency, Efficacy, Prevention, Respect and Care, Safety as well as Timeliness.
Deep Leg Vein Thrombosis (DVT): Meaning, Causes, Symptoms, Treatment, and Mor...The Lifesciences Magazine
Deep Leg Vein Thrombosis occurs when a blood clot forms in one or more of the deep veins in the legs. These clots can impede blood flow, leading to severe complications.
Deep Leg Vein Thrombosis (DVT): Meaning, Causes, Symptoms, Treatment, and Mor...
Excipients selection for high risk formulations Smita Rajput
1. The life science business of Merck KGaA,
Darmstadt, Germany operates as
MilliporeSigma in the U.S. and Canada.
Excipients
Selection for
High Risk
Formulations
Dr. Smita Rajput
Field Marketing Manager, Actives & Formulation
India, South East Asia & Oceania
2. 2
Field Marketing Manager, Actives & Formulation, India, S.E.A & Oceania
Dr. Smita Rajput
• 8 years of experience in Pharmaceutical Product
Development
• Expertise in formulation development of
Complex Injectable and Ophthalmic Segment.
With her expertise, she provide consultations for
selection of Excipients in the injectable and
ophthalmic segment
• She has the credit of 5 patents and 7
international publications in different complex
formulation areas
• For working experiences, she was previously
with Dr. Reddy’s, Cadila Healthcare, and Johnson
& Johnson for few years
3. The life science business
of Merck KGaA, Darmstadt,
Germany operates as
MilliporeSigma in the U.S.
and Canada
6. 488
402
152
72
44
86
572
619
238
96
61
108
0
100
200
300
400
500
600
700
Oral Injectable Topical Ocular Nasal Other
(pulmonarty,
implantable,
etc)
Market Size (in Billion $)
2018 2023
3,2%
Source : Marketsandmarkets
Injectable drug delivery is
the second-fastest-growing
segment in the drug
delivery technology market
and is expected to grow at
a CAGR of 9.0% to reach
USD 619.21 billion by
2023.
Injectable will
dethrone oral
dosage form
within 2023
Injectable drugs market – April 2019
6
9,0%
9,4%
6,0%
6,8%
CAGR
2018/2023
7. Pharmaceutical excipients are any substance other than the active drug
substance which has been appropriately evaluated for safety and is included in
a drug delivery system.
Excipient Basic Understanding
7
Processing aids in Manufacture Process
Protect, support or enhance stability, bioavailability
Modulation of Drug Release
Enhance effectiveness of the drug product
Inert and should not have pharmacological action
Desired functionality/Multifunctionality
8. 8
Pharmaceutical Development : Excipient Role
QTPP CQA
CMA of API
and Excipients
(Quality & Quantity)
Manufacturing
process and
CPP
Control
Strategy
QTPP: Quality target product profile CQA: Critical quality attributes
CMA: Critical material attributes CPP: Critical process parameter
Excipient selection based on specific/targeted/expected function
Critical material attributes in excipient should be considered while
developing finished product
Excipient composition may have direct impact on CQA’s of DP
9. Inert and high purity
Low bioburden and low endotoxin
Unaffected by sterilization or manufacturing process
Salient Features for High Risk Formulation
9
10. Different Types of High Risk Formulations
10
General injectables –
SVP,LVP and
Ophthalmic
Lipid Drug delivery
systems
Injectable formulation of
API, water, organic
cosolvents and surfactants.
High value low volume
products.
A liposome is a spherical
vesicle with lipid bilayer and
is used as a vehicle for
administration of nutrients
and pharmaceutical drugs.
Polymeric microspheres have
advantages as ability to
encapsulate a variety of drugs,
biocompatibility, high
bioavailability and sustained drug
release characteristics.
Polymer based drug
delivery system
11. Excipients Categories for High Risk Formulation
Viscosity
modifier
Buffer
Pre-
servative
Isotonicity
adjuster Anti-
oxidant
Stabilizer Solubilizer
Common requirements for raw materials quality
Pharma quality
Low bioburden, Low endotoxins
IPEC-PQG GMP manufacturing
Specific excipients are applicable to particular dosage forms like
suspensions, emulsions, liposomes, lyophilized or microsphere preparations
11
13. Perspective of the Formulator
Development Challenges for High Risk Formulations
13
Particulate
matter
Microbial
purity
No
interaction
with API
Solubility
enhance-
ment
Trace
amount of
impurities
Stability
Process
optimiza-
tion
14. Perspective of the Formulator
Development Challenges for High Risk Formulations
14
Particulate
matter
Microbial
purity
No
interaction
with API
Solubility
enhance-
ment
Trace
amount of
impurities
Stability
Process
optimiza-
tion
15. FDA Sterile Injectable Drug Recalls 2008-2012
15
Particulate Matter: How does the Reality look like?
22%
22%
9%
47%
Lack of sterility assurance
Visible particles
Impurities/Degradation
Other*
*Includes crystallization, discoloration,
failed pH, impurities/degradation
products and storage temperature
excursions
Steven Lynn, FDA Office of Manufacturing and
Product Quality, March 14, 2013.
Raw materials
API
Excipients
WFI
Filter
Equipment
Tubings and gaskets
Container closure
Unstable formulation
Root Cause
19. Perspective of the Formulator
Development Challenges for High Risk Formulations
19
Particulate
matter
Microbial
purity
No
interaction
with API
Solubility
enhance
ment
Trace
amount of
impurities
Stability
Process
optimiza
tion
20. 20
Low bioburden with controlled limits
on TAMC and TYMC
Low endotoxin level
Emprove® Expert : Taking care of Microbial Purity
21. Emprove® for Chemicals
21
Addressing High Risk by Emprove® Expert
ESSENTIAL
▪ Designed for
moderate risk levels
▪ Former
EMPROVE® exp
EXPERT
▪ Addresses higher risk
applications
▪ Former EMPROVE® bio
▪ Lowest
microbiological and
endotoxin levels
specified
API
All products produced in Europe according to the ICH Q7 guideline
22. 22
Emprove® Program: Facilitates Risk Assessment
EMPROVE® Dossier
Library:
Material Qualification Dossier
Quality Management Dossier
Operational Excellence
Dossier
EMPROVE® Portfolio:
chemicals, filters and single use
components to make, purify and
formulate drugs
EMPROVE®
Raw Materials
Risk-adjusted
Portfolio
EMPROVE®
Suite allows
online Access
to Dossiers
EMPROVE®
Filtration and
Single Use
Program being
rolled out
EMPROVE® dossiers
support Qualification,
Risk Assessment and
Process Optimization
EMPROVE® Program:
addresses existing and
anticipated regulatory
requirements and expectations
EMPROVE® Suite:
answers to regulatory questions
for around 400 products
available 24/7
EMPROVE® program supports drug manufacturers’
qualification, risk mitigation and process optimization efforts.
Industry-leading documentation drives confidence
in the transparency and control of our products.
23. Preservatives
23
Preservative selection based on pH of maximum microbial activity
Mixture can be used to target complete microbial population
2
Approximate pH ranges
3 4 5 6 7 8 9
Benzoic Acid
Benzyl Alcohol
Boric Acid
Chlorobutanol
Methyl Paraben & Propyl Paraben
Phenol
Sorbic Acid
Benzyl Benzoate
Thimerosal
Benzalkonium Chloride
25. Perspective of the Formulator
Development Challenges for High Risk Formulations
25
Particulate
matter
Microbial
purity
No
interaction
with API
Solubility
enhance-
ment
Trace
amount of
impurities
Stability
Process
optimiza-
tion
26. Functional group Incompatibilities Possible type of reaction
Primary amine Mono and disaccharides Maillard reaction
Ester, cyclic lactose Basic components
Ring opening, ester-base,
hydrolysis
Aldehyde Amine, carbohydrates
Aldehyde-amine, Schiff base or
glycosylamine formation
Carboxyl Bases Salt formation
Alcohol Oxygen
Oxidation to aldehydes and
ketones
Sulfhydryl Oxygen Dimerization
Phenol Metals Complexation
Interaction & Incompatibility of Excipients
26
27. Benzyl Alcohol
27
Photochemical oxidation
products of Benzyl Alcohol
Benzaldehyde impurity present in Benzyl
alcohol interacts with oxidation prone Benzyl
alcohol as well API.
Source: Kishore Hotha et al, (2016) Drug-Excipient Interactions:
Case Studies and Overview of Drug Degradation Pathways,
American Journal of Analytical Chemistry, 7, 107-140
28. We Take Care of Benzyl Alcohol Purity
28
100981, 100987 and
137043, 137120
Emprove® Essential &
Expert
Not for Neonates & with
caution in children
Applications
Oral
Injectable
Topical
Nasal
Benzaldehyde :
<0.05%
Emprove® Expert
grade
100987
Benzaldehyde :
<0.01%
Emprove® Expert
grade
137043
Pharmacopeia limits for Benzaldehyde
(USP & Ph.Eur): <0.15%
Lower level of benzaldehyde impurity is important for oxidation prone API.
Benzaldehyde impurity does have negative impact on
drug release of microsphere preparations.
29. Perspective of the Formulator
Development Challenges for High Risk Formulations
29
Particulate
matter
Microbial
purity
No
interaction
with API
Solubility
enhance-
ment
Trace
amount of
impurities
Stability
Process
optimiza-
tion
31. 31
Meglumine: Solubility Enhancement and Stabilizer
Derivative of sorbitol in which the hydroxyl group in position 1 is replaced by a
methylamino group
White crystalline powder; melting at 130°C
pKa value: 9.52
Solubility in water: 1000 mg/ml
Organic base
used as
pH-adjusting agent,
solubilizing agent,
buffering agent,
stabilizing agent,
counter-ion,
scavenger for formaldehyde impurity
32. 32
Meglumine : Improve the Stability
Source: Fujita, M., Ueda, T., Handa, T., (2009) Generation of Formaldehyde by Pharmaceutical Excipients
and Its Absorption by Meglumine. Chem. Pharm. Bull. 57, 1096-1099.
Many excipients
contain
formaldehyde as
an impurity
Major excipients used in
formulations have been
shown to generate
formaldehyde during storage
(including, Polyols, HPMC,
Polysorbates, Poloxamers,
PEGs)
Formaldehyde can
react with amine
groups and
electron-rich
groups of the API!
Meglumine acts as
a formaldehyde
scavenger
33. 33
HP-β-Cyclodextrin : Solubility Enhancement
Enhance API solubility
Enhance API stability
Enhance corneal penetration
Reduce local irritation
Cyclodextrin HPB at concentration of 12.5% well tolerated*
Cyclodextrin HPB EMPROVE® EXPERT Ph.Eur.,NF – item 1.42020.2500
*EMA/CHMP/333892/2013
Marketed Eye drops with
HP-β-Cyclodextrin
Diclofenac sodium eye drop
Indomethacin eye drops
34. Why use Cyclodextrin HPB*?
34
*Hydroxypropyl-beta-CD,
official compendial name: Hydroxypropyl-Betadex
SzejtliJ. Past, present and future of cyclodextrinresearch. Pure ApplChem2004;76:1825-45
Davis ME, Brewster ME. Cyclodextrin-based pharmaceutics: past, present and future. Nat Rev Drug Discov2004;3:1023-35.
In comparison to other cyclodextrins:
Optimal cavity size:
“not too small and not too large”
Hydrophilic derivative of beta-CD:
Better soluble than the “parent”
beta-CD
Lower toxicity than the “parent”
beta-CD
35. Protein Formulation with Cyclodextrin HPB
35
Example 1: Ovine growth hormone
Solubilization with hydroxypropyl-beta-cyclodextrin facilitates physiological pH of 7.4
without cyclodextrin, an extreme pH of 11 is used which results in pain upon i.v. injection
Example 2: Interleukin-2
Hydroxypropyl-beta-cyclodextrin prevents aggregation after the reconstitution of lyophilized
formulation
Example 3: Bovine insulin
With hydroxypropyl-beta-cyclodextrin, a parenteral insulin formulation is stable for 1 year at room
temperature
With the usual pH 7.4 buffer (without cyclodextrin), precipitation occurred after 2 weeks of storage
Source: Brewster, M., M. Hora , et al. (1991). "Use of 2-Hydroxypropyl-β-cyclodextrinas a Solubilizingand Stabilizing Excipient for
Protein Drugs." Pharmaceutical Research 8(6): 792-795.
36. Perspective of the Formulator
Development Challenges for High Risk Formulations
36
Particulate
matter
Microbial
purity
No
interaction
with API
Solubility
enhance-
ment
Trace
amount of
impurities
Stability
Process
optimiza-
tion
37. Tris (hydroxymethyl) aminomethane High Purity
37
Tris: Polyoxymethylene (POM) Impurity
Highly concentrated Tris solutions (> 20%) Precipitation of POM
Product Product No Description
Tris 108307
Tris(hydroxymethyl)aminomethane high purity
EMPROVE® EXPERT Ph Eur,BP,JPC,USP,ACS
Our Limits Pharmacopiea
Polyoxymethylene (ppm) ≤ 50 ≤ 200
Industry-leading low levels specified!
Specification:
38. Product Name Parteck® SI 400 LEX (Sorbitol)
Ph Eur,BP,NF,JP
D(-) – Mannitol Emprove® Expert
Product Code 111597 137096
Pharmacopeia Limits ≤ 0.2, 0.3 ≤ 0.2
Our Limits ≤ 0.11 ≤ 0.05
Reducing Sugar Content : an Impurity
38
Maillard Reaction with
amine drugs
Glycation Reaction with
primary protein amine
group
Reduction in
drug potency and
discoloration
40. Formaldehyde
40
API with primary
or secondary
amine
Formaldehyde
impurity in PEG
300 &
Polysorbate 80
Formaldehyde adduct of API
Source: Munir Nassar et al; (2004) Influence of Formaldehyde Impurity in Polysorbate 80 and PEG‐300 on the Stability of a
Parenteral Formulation of BMS‐204352: Identification and Control of the Degradation Product, Pharmaceutical Development
& Technology, 9(2)
A direct relationship between the levels of formaldehyde in the excipients and the
formation of the formaldehyde adduct as a degradant
Formaldehydes present in the excipients react with amine containing compounds to form
degradants
Control Strategy: A limit test on the formaldehyde content in polysorbate 80 and PEG 300
can be set as part of a strategy to limit the formation of the degradation product
We specifies limit for formaldehyde in polysorbate and PEG 3000
41. Perspective of the Formulator
Development Challenges for High Risk Formulations
41
Particulate
matter
Microbial
purity
No
interaction
with API
Solubility
enhance-
ment
Trace
amount of
impurities
Stability
Process
optimiza-
tion
42. 42
Trehalose in Liposomal Formulation
Source: Bianca Sylvester et al (2018) Formulation Optimization of Freeze-Dried Long-Circulating Liposomes and In-Line Monitoring of the
Freeze-Drying Process Using an NIR Spectroscopy Tool Journal of Pharmaceutical Sciences, 107(1), 139-148
Lyoprotectant:
lipid molar ratio
Control Trehalose Sucrose Sucrose+Mannito
l
Before
freeze
drying
Particle size (nm)
3:1 536.2±42 353.45 ± 18 345.12 ± 25 397.33 ± 23 103 ± 11
5:1 119.55 ± 31 127.93 ± 36 174.0 ± 22
8:1 237.82 ± 24 259.22 ± 12 218.31 ± 16
PDI 0.482± 0.036
3:1 0.323 ± 0.025 0.319 ± 0.033 0.297 ± 0.011 0.104 ± 0.028
5:1 0.123 ± 0.029 0.173 ± 0.053 0.189 ± 0.056
8:1 0.299 ± 0.017 0.243 ± 0.009 0.225 ± 0.013
Encapsulated Drug
(%)
3:1 56.02 ± 0.303 64.07 ± 0.461 62.05 ± 0.319 59.79 ± 0.260 100
5:1 79.23 ± 0.229 73.62 ± 0.189 75.50 ± 0.435
8:1 68.43 ± 0.502 67.61 ± 0.355 65.49 ± 0.192
Residual moisture
(%)
3:1 0.92±0.04 2.86 ± 0.07 3.05 ± 0.09 2.69 ± 0.03 N/A
5:1 0.59±0.05 1.17 ± 0.08 1.89 ± 0.10 1.52 ± 0.06 N/A
8:1 0.67±0.02 1.37 ± 0.05 1.73 ± 0.07 1.71 ± 0.06 N/A
Trehalose is
suitable for
liposomal
formulation
considering
process and
stability of final
formulation
Nanocort®: Liposomal prednisolone for acute manifestations of inflammatory diseases and Cancer and under
Clinical Phase II
43. 43
Trehalose in Liposomal Formulation
Nanocort®: Liposomal prednisolone for acute manifestations of inflammatory diseases and Cancer
Clinical Phase II
No Cryoprotectant With Mannitol With Trehalose
Crystallization
Source: Bianca Sylvester et al (2018) Formulation Optimization of Freeze-Dried Long-Circulating Liposomes and In-Line Monitoring of the
Freeze-Drying Process Using an NIR Spectroscopy Tool Journal of Pharmaceutical Sciences, 107(1), 139-148
44. 44
Trehalose in Ophthalmic Formulations
1. HU00701 Eye Drop (Nanocomposite eye drop): Phase 3
Contains: Cyclosporine and trehalose
Indication: Dry eye syndrome
Company: Huons Global Co. Ltd.
2. Cenegermin Ophthalmic Solution: Marketed in USA
Contains: Cenegermin-bkbj and trehalose
Indication: Eye Diseases, Corneal neurotrophic keratitis
Company: Dompe Farmaceutici S.p.A.
3. Thealoz Duo® Eyedrop: Marketed in France, Canada
Contains: Trehalose
Indication: Dry Eye syndrome
Company: Thea
4. Trehalube® Eye Drops : Marketed in India
Contains : Trehalose and Sodium hyaluaronate
Indication: Dry Eye Syndrome
Company: Micro Labsc
Mechanism of Action of Trehalose
Rehydrate Tear Film
Protect Against Future Irritation
Support Homeostasis of Tear Film
Trehalose Dihydrate
45. Need for RTU
We can be your partner
Lyophilized to Liquid Ready to Use Solutions (RTU)
45
Stability Patient safety LCM
Dispensing Safe alternative
Excipients play vital role
Lactic
Acid
Poloxamer
188
API is unstable in aqueous media
API is soluble in acidic media
API is soluble and stable in
poloxamer 188
Same surfactant action like
polysorbate
More stable than polysorbate
46. Perspective of the Formulator
Development Challenges for High Risk Formulations
46
Particulate
matter
Microbial
purity
No
interaction
with API
Solubility
enhance-
ment
Trace
amount of
impurities
Stability
Process
optimiza-
tion
47. Improve Throughput of your Liquid Solutions
47
Sterile filtration with Right Filter
High flux rates in sterile filtration can
mean substantial cost savings for the
manufacture of ophthalmic solutions.
Millipore Express® SHF membranes
achieved up to 2 ½ times better
thoughput through filters than
competitive filters.
48. Chose the Right Filter
48
Improve Benzalkonium Chloride Filtration
Many preservatives do usually bind or are
adsorbed by membrane filters which
cause a loss of the appropriate amount of
preservatives in the final product.
The test results with a 0,01 %
Benzalkonium Chloride (BAK) solution
showed the lowest BAK binding = lowest
BAK loss in final product
Test membranes have been been all 0.2
mm sterilizing-grade and composed of
either PES or polyvinylidendiflupride
(PVDF)
®
49. Viscosity Profile of Different Grades of PVA
Ophthalmic Drug Delivery System
49
PVA polymer:
According to US FDA
llD database
- 1.4 % (w/v)
50. 50
Aseptic Sterile Filtration of PVA solution
Ophthalmic Drug Delivery System
0
5000
10000
15000
20000
25000
30000
35000
PVA 4-88 PVA 5-88 PVA 8-88 PVA 18-88PVA 26-88PVA 28-99PVA 40-88
Vmax
(L/m
2
)
Vmax
PVDF
PES
PVA polymer solution can be sterile filtered using 0.2 µm both PVDF and PES
membranes. However, PES filters are showing better results regrading Vmax and
mean flux.
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
PVA 4-88 PVA 5-88 PVA 8-88 PVA 18-88 PVA 26-88 PVA 28-99 PVA 40-88
Mean
Flux
(L/m
2
/h)
Mean Flux
PVDF
PES
Polyvinyl Alcohol - Role in Ophthalmics
52. Perspective of the Formulator
Development Challenges for High Risk Formulations
52
Particulate
matter
Microbial
purity
No
interaction
with API
Solubility
enhance-
ment
Trace
amount of
impurities
Stability
Process
optimiza-
tion
TUPP and GMP
manufacturing
Paper free packaging
Emprove® Expert
Benzyl Alcohol
Meglumine
HP-β-Cyclodextrin
Control on
Reducing sugar
Formaldehyde
Trehalose
Low binding of
preservative with high
throughput: PES filter
Preservatives