Patricia Chimot-Marolle our Senior Regulatory Affairs & Quality Support Manager has participated to the RegMedNet “ask the expert” feature on raw material validation.
Read her and three other experts’ views on several Raw Materials topics ranging from important characteristics or challenges associated with qualifying raw materials to future developments in the following link.
Our R & D team published a paper “One-time optimization of advanced T cell culture media” in Frontiers in Bioengineering and Biotechnology.
Paul and Sebastian implemented a machine learning framework to overcome common challenges in cell and gene therapy such as high variability of heterogeneous data and strong sample size limitation. The introduction of a machine learning pipeline resulted in a one-time optimized T cell culture medium and is advantageous when working with heterogeneous biological material.
Read the paper in Frontiers in Bioengineering and Biotechnology (free access)
Freiburg, Germany, 2 July, 2021 The life science group Sartorius, through its subgroup Sartorius Stedim Biotech, acquired a majority stake in the raw material manufacturer CellGenix GmbH. CellGenix will continue to be led by Felicia Rosenthal, the company’s CEO and co-founder.
Founded in 1994 at the University Medical Center of Freiburg, CellGenix is a leading raw material supplier for the cell and gene therapy market. The company produces and markets cell culture components, such as growth factors, cytokines, and media in GMP quality for developing and manufacturing cell and gene therapy products. The company is based in Freiburg, Germany, and has a subsidiary near the biotechnology hub in Boston, Massachusetts, USA.
Sartorius has initially acquired 51 percent of CellGenix, which has been privately owned until now, for around 100 million euros in cash. At the beginning of 2023 and 2026, Sartorius plans to acquire the remaining shares of CellGenix.
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“For us, Sartorius is an ideal partner with a highly complementary product portfolio that will accelerate our development with its global sales team, enabling us to usher in our next phase of growth,” said Felicia Rosenthal.
“CellGenix has an excellent reputation on the market and brings in high technological expertise and considerable regulatory experience in one of the fastest-growing fields of the biopharma sector. Together, we will support our customers even better in fast-tracking their drug candidates efficiently through the various steps in the development of medicines so that innovative therapies can reach patients faster,” added René Fáber, member of the Executive Board for the Bioprocess Solutions Division of Sartorius.
Sartorius plans to expand the Freiburg site substantially and to establish it as a center of excellence within the group in the areas of development and manufacture of quality critical raw materials for the cell and gene therapy market.
About CellGenix
CellGenix is a leading global supplier of high quality raw and ancillary materials for the expanding market of cell and gene therapy and regenerative medicine. CellGenix develops, manufactures and markets human cytokines, growth factors, and other recombinant cell culture components in preclinical and GMP quality as well as proprietary serum-free media for further manufacturing of ATMPs. As a former ATMP developer and manufacturer, in more than two decades CellGenix gained in-depth cell processing knowledge and superior regulatory expertise. With this unique background, CellGenix understands the high requirements their customers are facing during product development and the regulatory approval process. To meet the increasing demand of GMP quality raw materials for ATMP manufacturing CellGenix has recently expanded manufacturing capacity, built additional R&D and QC laboratories, and warehouse space. The upgrade also introduced state-of-the-art, automated, large-scale capacities for recombinant protein products in the existing GMP facilities.
About Sartorius
The Sartorius Group is a leading international partner of life science research and the biopharmaceutical industry. With innovative laboratory instruments and consumables, the Group’s Lab Products & Services Division concentrates on serving the needs of laboratories performing research and quality control at pharma and biopharma companies and those of academic research institutes. The Bioprocess Solutions Division with its broad product portfolio focusing on single-use solutions helps customers to manufacture biotech medications and vaccines safely and efficiently. The Group has been annually growing by double digits on average and has been regularly expanding its portfolio by acquisitions of complementary technologies. In fiscal 2020, the company earned sales revenue of some 2.34 billion euros. At the end of 2020, nearly 11,000 people were employed at the Group’s approximately 60 manufacturing and sales sites, serving customers around the globe.
For more information contact:
CellGenix
Evelien Nijssen
Team Leader Marketing
+49 (0)761 88889 434
nijssen@cellgenix.com
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Take a look at what recent advancements have been made for CAR-T therapies, including different strategies that could help overcome various manufacturing
obstacles. Explore how the use of serum-free media has gained traction, especially when considering commercial-scale manufacturing.
Register here to read the complete eBook on RegMedNet
CellGenix, a global manufacturing leader of GMP-grade raw materials for cell therapy, gene therapy and tissue-engineered products, is pleased to announce the appointment of Daniel Spatz as Vice President Sales, Marketing & Logistics and member of the management team.
Daniel joined CellGenix in 2021 as Head of Marketing & Sales and Logistics. As Vice President Sales, Marketing & Logistics Daniel will now be responsible for the entire global sales and marketing, logistics and customer service organization. He will contribute to further strengthening CellGenix’ global presence as premium raw material supplier.
As part of the ‘Women to Watch’ series by RegMedNet our CEO Felicia Rosenthal is at their spotlight on International Women’s Day.
As one of the co-founders and first General Manager Felicia Rosenthal has led CellGenix since 1994. She studied medicine at the University of Mainz and the University College of London, completed a post-doctoral fellowship at Memorial Sloan Kettering Cancer Center, New York, and received her habilitation for work with retroviral gene transfer in cancer immunotherapy. Felicia obtained her medical specialisation in laboratory medicine.
Felicia also holds an executive MBA degree from the WHU Koblenz and J.L. Kellogg Graduate School of Management at the Northwestern University, Chicago.
Read the interview
Together with Phacilitate we developed a survey with over 30 cell and gene therapy professionals to find out what the prominent challenges are with regards to raw materials and how the industry is approaching automation of raw material processes. This article presents the results as well as some perspectives from Bluebird Bio, Cellex Cell Professionals and others.
Read the article & view the infographic
The manufacture of cell and gene therapies (CGT) is particularly sensitive and requires a comprehensive understanding of the materials used in the manufacturing process to ensure a safe, efficacious, and high-quality product. Successful CGT manufacturing is therefore dependent on the use of high-quality raw materials (ancillary materials according to the USP). The manufacturing of raw materials for CGT manufacturing is however not well regulated and is not supervised by any health authority. Despite arising guidance in this area existing guidelines are, essentially, recommendations rather than guidelines. Geographical discrepancies make regulatory considerations even more complex. Each region has its own regulatory agencies that view CGT manufacturing in a different way. Getting a clear understanding of regulatory requirements around the quality of raw materials can therefore be challenging.
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Consequently, we advise to choose raw materials that comply to all global regulatory guidelines. Current existing guidelines are:
An additional challenge arises from the fact that all current regulations and guidance documents are not aimed at the manufacturers of the raw materials. Instead, they assign ultimate responsibility for quality and suitability of the raw materials to the user, the CGT manufacturer. Raw material suppliers and the quality of their products is not certified by regulatory bodies, the user himself is responsible to verify compliance to quality standards. As one result, most CGT manufacturers decide to perform identity and purity testing as raw material control tests. Potency testing for raw materials is however difficult, especially since there is a large variability and poor comparability of available biological assays.
Standardization of quality requirements of raw materials would bring much needed regulatory harmonization. Until such quality standards are set, CGT manufacturers need to work in close cooperation with their supplier to get the necessary support. Raw material suppliers should offer full transparency to mitigate the risk to an acceptable level. They can do this by providing:
1) Detailed batch specific test results on the Certificate of Analysis (CoA)
Detailed batch specific test results make it easier for both the CGT manufacturer and the regulatory agencies to assess the raw material product quality as well as regulatory compliance. It in addition makes it easier to compare raw materials from different batches or suppliers. Batch specific test results including their validated test methods should cover identity, quantity, purity and impurities, and safety.
2) The possibility to audit the manufacturing site
Audits allow CGT manufacturers to ensure that the raw material supplier has a clearly defined system for quality monitoring in place. This will help to determine if they are compliant with local and global quality requirements.
3) Comprehensive product-specific documentation (e.g. Drug Master Files (DMF), Regulatory Support Files, TSE certificates, & customized documentation for regional authorities)
Being able to provide product-specific documentation for critical raw materials to authorities speeds up the regulatory approval process. Since regional authorities can ask for varying documentation, we recommend choosing a raw material supplier that is able to offer customized documentation on request.
4) Documentation on product stability & consistency studies performed by Quality Control
Extensive stability studies should be conducted by the raw material supplier to determine the maximum shelf life for all raw materials and recommended storage conditions. These studies ensure that the raw materials remain consistent throughout the recommended storage times under appropriate storage conditions. To ensure the quality and consistency of raw materials, consistency studies should in addition be performed by the raw material supplier. The importance of batch-to-batch consistency of critical raw materials is also emphasized in Ph. Eur. General Chapter 5.2.12 [3] and ISO Technical Standard-20399 [4].
5) Well defined animal-derived component-free (ADCF) policy
Materials of biological origin, particularly of human or animal origin, can present risks, including transmission of adventitious agents or introduction of biological impurities. This does not necessarily limit the use of animal-derived components for manufacturing raw materials. The main purpose of defining ADCF is to provide necessary information for a user’s risk assessment of raw materials. ISO Technical Standard-20399 [4] defines two ADCF levels:
6) Change notifications prior to relevant product changes
Changes related to product specifications, labels, formulation, packaging, expiry dates or the production process should be communicated well in advance. This ensures that the CGT manufacturer can put the necessary preparations in place without causing delays in their production process.
To help improve existing regulatory guidance we are actively involved in many regulatory initiatives and discussions. Together with the USP we have written the first version of USP chapter <92> [2]. We were also actively involved in the discussions for the setup of Ph. Eur. General Chapter 5.2.12 [3] and contributed to the ISO Technical Committee TC276. This committee issued the first global guidance for raw materials suppliers and users – ISO Technical Standard 20399 [4] – which is currently being processed into an ISO standard to improve global reach and acceptance. The guidance provides general requirements and guidance to ensure the quality and consistency of raw materials used in CGT manufacturing.
An initiative in which we are currently involved is one from the Alliance for Regenerative Medicine (ARM). They approached the European Directorate for the Quality of Medicines (EDQM) about the possibility of setting up a certification scheme for raw materials according to European Pharmacopoeia (Ph. Eur. General Chapter 5.2.12 [3]). This initiative is of critical importance because compliance to this general chapter is already demanded by regulators. Hence, a certification scheme would ease the regulatory burden for CGT manufacturers.
Another initiative that we are involved in is from the European Medicines Agency (EMA), who is evaluating the possibility of introducing a master file system in Europe. Drug Master Files (DMF) for raw materials are currently only available in the USA and Japan. A DMF is a regulatory instrument that provides confidential detailed information about the manufacturing conditions of a raw material (product’s chemistry, manufacture, raw materials used, stability, purity, impurity profile and packaging). It enables the raw material manufacturer to protect its intellectual property by allowing the FDA (or PMDA in Japan) to review the information in support of a third party’s submission. Using the detailed information provided in a DMF, the FDA can make a thorough assessment of the raw material’s quality and lot-to-lot consistency. Because of its great value to CGT manufacturers we have submitted eCTD DMFs to the FDA for our serum-free media and the large majority of our GMP cytokines. We currently offer the largest collection of eCTD DMFs for cytokines and growth factors.
Although these initiatives are promising, we propose that special workgroups should be set up that work on setting global quality standards for raw materials for CGT manufacturing. This would help reaching more global alignment between regulatory agencies.
References
1. USP General Chapter <1043> Ancillary materials for cell, gene, and tissue-engineered products Crossref
2. USP General Chapter <92> Growth factors and cytokines used in cell therapy manufacturing Crossref
3. Ph. Eur. General Chapter 5.2.12 Raw materials of biological origin for the production of cell-based and genet therapy medicinal products
4. ISO/TS 20399-1:2018 Biotechnology – Ancillary materials present during the production of cellular therapeutic products – Part 1: general requirements. ISO/TS 20399-2:2018 Biotechnology – Ancillary materials present during the production of cellular therapeutic products – Part 2: Best practice guidance for ancillary material suppliers. ISO/TS 20399-3:2018 Biotechnology – Ancillary materials present during the production of cellular therapeutic products – Part 3: Best practice guidance for ancillary material users Crossref
BIO
Bernd Leistler
Bernd Leistler has a long track record as protein specialist. He joined CellGenix in 2003 and is currently responsible for all GMP and preclinical cytokine products for further manufacturing use, as well as process development for protein production which includes new packaging formats. Following his degree in chemistry he completed his dissertation on the structure, function, folding and assembly of oligomeric proteins. His professional career started at a leading manufacturer of diagnostic autoantibody immunoassays, where he managed the Biotechnology Department and developed it as a corporate service unit for recombinant and conventional human autoantigens and allergens.
Authorship & Conflict of Interest
Contributions: All named authors take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Acknowledgements: None.
Disclosure and potential conflicts of interest: Bernd Leistler is an employee of CellGenix GmbH. The author declares that they have no other conflicts of interest.
Funding declaration: The author received no financial support for the research, authorship and/or publication of this article.
Copyright: Published by Cell and Gene Therapy Insights under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.
Attribution: Copyright © 2020 CellGenix GmbH. Published by Cell and Gene Therapy Insights under Creative Commons License Deed CC BY NC ND 4.0.
Article source: Invited.
Revised manuscript received: Nov 19 2020; Publication date: Dec 1 2020.
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Speed up your serum-free culture with CellGenix® TCM
CellGenix’ superior T Cell Medium shows several benefits for your T cell culture:
– No need to add serum at any time
– High cell yield already early on
– T cell products with an early-memory phenotype
– High proportion of polyfunctional cells
We invite you to watch the video for more details.
Freiburg, Germany, October 8, 2020 – CellGenix GmbH, a pioneer for GMP grade reagents and a leading global supplier of high quality raw and ancillary materials for cell and gene therapies, announces the completion of the second phase of their facility expansion. CellGenix has reconstructed and expanded their production facility for cytokines and implemented a state-of-the art automated filling and freeze-drying line.
By implementing an automated filling and freeze-drying line and increasing bulkware production footprint, finished product capacity for cytokines is substantially increased. This continues to enable CellGenix to meet the fast-growing demand for critical raw and ancillary materials as more customers reach late-stage clinical development and commercialization of their cell and gene therapies. Scaling up from phase I or II clinical trials to large-scale commercial manufacturing, the demand for GMP cytokines often rises by several magnitudes. Consequently, a secure supply chain is imperative. A delay in delivery or change in product quality could lead to delays in production, not only increasing costs but also putting precious patient samples in jeopardy.
The newly designed and expanded facility enables CellGenix to streamline their production processes. The automated filling process also provides increased accuracy and reduced risks, which further increases the safety of their preclinical and GMP cytokines. The automated filling, stoppering and capping system (operates under an Open Restricted Area Barrier System (ORABS) and) is compliant with EU GMP Annex 1 for the manufacture of sterile medicinal products, also taking into account the new version which is currently under revision.
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In a first expansion phase in 2018 CellGenix added additional space and personnel in its quality control, R&D, logistics and warehouse departments. By finishing both expansion phases, CellGenix has further strengthened their position as a leading supplier for large scale manufacturing in the cell and gene therapy space.
“The expansion of our facility is a result of the robust, sustainable, and profitable growth, generated by long standing and trustful customer relationships we achieved over many years. CellGenix is now well prepared for the future growth of the cell and gene therapy market. It supports our goal to further establish CellGenix as a key provider in the fight against disease, preferred supplier or raw and ancillary materials and trusted partner for large scale manufacturing of cell and gene therapies.” Felicia Rosenthal, Chief Executive Officer at CellGenix.
About CellGenix
CellGenix is a leading global supplier of high quality raw and ancillary materials for the expanding market of cell and gene therapy and regenerative medicine. CellGenix develops, manufactures and markets human cytokines, growth factors, and other recombinant cell culture components in preclinical and GMP quality as well as proprietary serum-free media for further manufacturing of ATMPs. As a former ATMP developer and manufacturer, in more than two decades CellGenix gained in-depth cell processing knowledge and superior regulatory expertise. With this unique background, CellGenix understands the high requirements their customers are facing during product development and the regulatory approval process. To meet the increasing demand of GMP quality raw materials for ATMP manufacturing CellGenix has recently expanded manufacturing capacity, built additional R&D and QC laboratories, and warehouse space. The upgrade also introduced state-of-the-art, automated, large-scale capacities for recombinant protein products in the existing GMP facilities. CellGenix is headquartered in Freiburg, Germany and operates a subsidiary near Boston in Portsmouth, USA.
For more information contact:
CellGenix GmbH
Am Flughafen 16
79108 Freiburg, Germany
Prof. Dr. Felicia M. Rosenthal
CEO
rosenthal@cellgenix.com
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