It clarifies the regulatory requirements for healthcare organisations who are procuring (harvesting) patient's own cells or tissues to be used as starting materials in the manufacture of an ATMP where the subsequent ATMP manufacture occurs outside of the EU. In the event of a no deal EU exit, it will also be relevant for ATMPs manufactured in the E HTA and MHRA have agreed that the collection of blood as a starting material for an ATMP can be carried out under either a tissues and cells licence or a blood establishment licence. See the joint. Starting materials - The ATMP manufacturer (or, as appropriate, the sponsor or marketing authorisation holder) should establish quality requirements for the starting materials (specifications) which should be agreed with the supplier (s). The ATMP manufacturer should verify compliance of the supplier's materials with the agreed specifications The ATMP document also provides some specific guidance for ATMPs that is not found in other EU GMP guidance. One such area is starting and raw materials. There is a requirement that if antibiotics are used, they must not be in the final product. Guidance is also given on using cells that come from outsid . he ICH Q5E guideline concept of T highly similar (and thus comparable)
• Starting materials (Cells, vector, autologous) • Raw materials (Feeder cells, Research grade reagents) • Comparability (Complex, individual variability) • GMP (Clinical manufacturing site) • Process validation (e.g. surrogate vs. patient material) • Analytical control strategy (CQA identification , demonstrating both chain of identity and chain of custody from collection of starting material to the treatment of patients and facilitates long-term, compliant, data storage and controlled access to records
starting materials • Surrogate batches for ongoing stability • Define critical raw materials and keep samples. Cons • No independence-of-function requirement • No OOS/OOT LIR guidance • Diluted guidance on reference samples and retest-capability, and no Ann13 storage time (2y after end of trial) • Documentation requirements absen ATMP. Arzneimittel für neuartige Therapien (Advanced Therapy Medicinal Products, ATMPs) sind Arzneimittel für die Anwendung beim Menschen, die auf Genen, Geweben oder Zellen basieren. Sie bieten innovative Möglichkeiten zur Behandlung von Krankheiten und Verletzungen Date for coming into operation ATMP manufacturers should comply with these Guidelines no later than 22 May 2018. These Guidelines are specific to ATMPs. Other documents developing GMP requirements for medicinal products which are contained in Volume 4 are not applicable to ATMPs, unless specific reference thereto is made in these Guidelines starting materials (porcine mucosa , urine) have to be collected and pre- treated before initiating the final active substance manufacturing steps resulting in an active substance of the desired quality. These first steps of collection, testing and pre -treatment of the starting material may be carried out b
Most companies developed cell-based medicinal products (53%), followed by GTMPs (46%) and combined ATMPs (1%). Of respondents, 35 (51%) reported developing more than one ATMP, and 10 developers worked on different ATMP types (e.g., GTMP, CTMP, TEP, or combined ATMP) simultaneously Collection of starting materials - blood based starting materials regulated by HTA (EUTCD) or MHRA (EUBD) Movement of products intended for use in ATMP manufacture Single regulatory agency has..
such tissues and cells are used as starting materials for ATMP manufacture (European Communities (Quality and Safety of Human Tissues and Cells) 2006 (S.I.No. 158 of 2006)) - The blood legislation for collection and testing (of donors) when such blood components are used as starting materials for or used in the production processes of ATMP manufacture (European Communities (Quality and Safety. procedure solely for the collection of starting material for ATMP. manufacture. Therefore, we have examined the long-term stabil-ity of cryopreserved disaggregated tissue and cells in tissue proc. (ATMP), their unique complexity and specific nature made it necessary to draft legislation and guidance specifically tailored towards cell- and gene-based medicinal products. On 30 October 2007 the European Council formally adopted the Regulation on Advanced Therap Advanced therapy medicinal products (ATMPs) are a fast-growing field of innovative therapies. The European Union (EU) and the United States (US) are fostering their development. For both regions, ATMPs fall under the regulatory framework of biological products, which determines the legal basis for their development. Sub-classifications of advanced therapies are different between regions, while.
. For surgical tissue, an aseptic fresh-frozen workflow suitable for ATMP manufacture will be developed. Expertise from UK-Blood services, tissue banks, clinical teams and biobanks will be gathered to ensure quality and safety of tissue procurement in a robust, efficient and compliant manner Apheresis is a standard practice to obtain a larger number of CD3+ cells as a starting material for CAR-T cell production with the goal of obtaining a minimum of 0.6 × 10 9 to a target of 2 × 10 9 CD3+ T cells . Apheresis has the advantage and choice of extracting one or more components of the whole blood with help of the appropriate device and return the rest of the donation to the donor. Regulatory Requirements for Export of ATMP Starting Materials September 2019 Anne Black · Sep 2019 · External link Gene Therapy Medicinal Products Governance and Preparation Requirement
ATMP storage and distribution. Cell therapy products have very short shelf lives at ambient temperature conditions. This must be considered for the collection of starting material, transportation to the manufacturing site, shipment of the finished product to the clinical trial site and administration to the patient Furthermore, both patient to patient variability of the starting material and inherent variability of manufacturing processes often demonstrate an inherent variability causing significant heterogeneity between batches, which also relates to the challenges in testing, characterization, and control. Some things to keep in mind: Changes to a CGT/ATMP design to obtain improved product. A critical component for the successful manufacture of any advanced therapy medicinal product (ATMP) is the starting material. Many cellular therapies for the treatment of cancer have now moved to clinic, such as tumour infiltrating lymphocyte (TIL) and CAR-T cell therapies, and while apheresis collection for CAR-T therapy is a well-defined and established process, the collection of starting material for solid malignancies currently has no standardised approach within the industry.
•ATMP •Products already -quality of starting material (geographical origin, species, tissue), viral testing if appropriate-main steps of the manufacturing process dedicated to viruses inactivation/removal (ie. autoclaving) TSE aspects (for products derived from ruminants) -CEP TSE delivered by EDQM should be provided or appropriate documentation according NFG EMEA/410/01 Cells/Tissues. Regulatory Requirements for Export of ATMP Starting Materials September 2019 Scope This guidance aims to clarify the regulatory requirements for the export of human tissues and cells for use as starting materials for marketed advanced therapy medicinal products (ATMPs) and investigational ATMPs for administration at UK sites. Backgroun STARTING MATERIAL Human Blood, Tissues or Cells ATMP regulation EC 1394/2007 YES NO Cell, gene and tissue-based therapies Substantial manipulation and/or non-homologous use Transplants / Transfusions * Excludes: cutting, grinding, shaping, centrifugation, soaking in antibiotic/antimicrobial solutions, sterilization, irradiation, cel During this session the most important aspects regarding starting and raw material selection for ATMP manufacturing are going to be reviewed such as:-Differences in donor eligibility requirements, regulatory aspects to comply during donor selection and ethical considerations-Critical aspects to consider when using biological raw materials for ATMP manufacturing-Challenges to consider during vector production and control-Appropriate conditions to establish and test when using seed lots and. In this document, the terminology starting materials will be considered only in the frame of ATMPs. Unless specifically mentioned, both starting materials and raw materials will be referred to as RM hereafter. Even though excipients are not covered by the official definition of RM in this concep
INPUTS - material attributes . GMP for ATMP. Starting materials - changes cell substrate - cell factory change. viral vector - retroviral vector safety improvement. Plasmid - ex. AAV redesign - new promotor . Human cells -expected for autologous gene therapy . INPUTS - material attributes . Stringency . according to . stage of development • Optimisation • Upscaling • Tech. They may be derived from different starting materials (mainly bone marrow (BM), adipose tissue, or cord blood) and applied as fresh or cryopreserved products, in the autologous as well as an allogeneic context (Sharma et al., Transfusion 54:1418-1437, 2014; Ikebe and Suzuki, Biomed Res Int 2014:951512, 2014; Sensebé and Bourin, Transplantation 87(9 Suppl):S49-S53, 2009). In any case, they require an approved and well-defined panel of assays in order to be released for clinical use.This.
. All methods required for immunological, genetic and hematopoietic characteri-zation were established in the group before, for expansion in a clinical/research setting [7,8] and for iPSC in research projects [9,10]. Few highly selected homozygous donor In the context of ATMP, the Scientific Advice particularly frequently raises questions about comparability in the case of changes in manufacturing processes or the introduction of a new or additional production site. This may involve changes to equipment, raw materials and critical starting materials such as cells or vectors or their suppliers, scale of the manufacturing process or product stability. Such changes often occur during the early stages of product development. In such cases, an. ATMP advanced therapy medicinal product BCG bacille Calmette-Guérin GMP good manufacturing practice(s) aliquoted and used as starting material for production of a limited number of lots of a cell-based medicinal product. Containment: the concept of using a process, equipment, personnel, utilities, system and/or facility to contain product, dust or contaminants in one zone, preventing.
High-quality ATMPs start with high-quality raw materials. Both the donor cell material (apheresis product) and auxiliary raw materials such as cell culture media have a major impact on the robustness of the biomanufacturing process. Apheresis product variability is cited as the major reason ATMPs fail manufacturing runs. Most often, this is due to not hitting target therapeutic cell yields. Challenges for ATMP Development and Supply to the Patients EBE, London 2017 Christina Basford . Introduction Comparability Challenges • ATMPs at GSK • Original Strategy • Current / Future Strategy and Associated Challenges • Summary . ATMPs at GSK. Summary of CGT technologies - GSK View Vector Delivery vehicle (e.g. lenvirus , AAV) Donor Cell Ex vivo, autologous CGT product Ex vivo.
Process development for an ATMP Manufacturing Process Klaus Kühlcke, BioNTech Round table - Ddiscussion with all available speakers Vector`s used to manufacture genetically modified cells - starting material and/or API Definition of pharmaceutical quality Risk based discussion of critical quality attribute CAMP is a Vinnova funded project focussing on the science and technology required to translate ATMPs from lab to clinic, including bioprocess development, GMP production and logistics. CAMP drives collaboration between researchers, GMP competent resources, industry and hospitals. CAMP will receive 48 million SEK between 2018 and 2023
starting materials for ATMPs are regulated by the Human Tissues Authority under EU legislation and the EU Cell and Tissue Directives.26 The subsequent stages, including manufacture, storage, clinical trials and distribution, are - also under EU legislation.26 The Health Research Authority is responsible for assessment of governance and legal compliance of all project based undertaken in. DEFINING STARTING MATERIALS Annex 2 Directive 2001/83/EC EMA/CHMP/ BWP/429241 /2013 Eudralex Volume 4 Annex 14 Directive 2002/98/EC Directive 2009/120/EC Directive 2004/23/EC Ph. Eur. 8.2 01/2008/2323 HHSC Biological drugs of non-recombinant origin • substance of biological origin: micro organisms, organs, tissues of plant or animal origin cells or fluid (incl. blood, plasma or urine) of. Two arms of the company have been established to utilise the platform: Touchlight Genetics, a DNA therapeutics business developing DNA vaccine and non-viral gene therapy assets, and Touchlight DNA Services, a contract manufacturing business producing dbDNA as a critical starting material for ATMP production Unsuitable starting material, unmet quality standards of starting raw materials, manufacturing process contamination and cross-contamination, positive selection failure, overnight storage and transportation of ATMP-CD133, and miss-labelling were identified as in-process critical steps. Strategies to specifically avoid and manage those steps have been developed and documented in IMPD Standard.
While developing the CGT/ATMP, you may be excited to see the first promising results, but it is critical to document all experiments, materials, and methods carefully. Don't throw out data from experiments that were not successful, they might be useful later. Make sure you are always able to look back at the data being generated at these steps of the process, make sure it is findable. Rapid Virus Detection Platforms for Testing ATMP Products and Raw Materials Webinar Overview Selecting starting materials and subsequently testing them and process intermediates, along with virus inactivation and removing steps in manufacturing, is a combination approach applied to traditional biopharmaceuticals and advanced therapy medicinal products (ATMPs) 8.5 Starting the Reaction.. 15 8.6 Analysis.. 15 9. Short Instructions . . . . . . . . . . . . . . . .16 Microsart® ATMP Bacteria kit is designed for the direct detection of bacteria in cell cultures, cell culture derived biologicals and ATMPs (e.g. autologous transplants), based on real-time PCR (qPCR). 2. Explanation of the Test Microsart® ATMP Bacteria utilizes qPCR as the. This page contains a listing of cellular and gene therapy guidances 03/02/2017 5 General Chapter 5.2.12 Aim Raw materials of biological origin for the production of cell-based and gene therapy medicinal products Overarching general chapter covers the quality requirements of raw materials of biological origin used for the production of cell-based and gene therapy products
Home; The page is under construction PEIpro ®-GMP is manufactured according to a validated manufacturing process in compliance with GMP guidelines to ensure traceability from starting material to the final product. GMP guidelines for manufacturing of ATMPs requires that the quality of raw materials be of pharmaceutical grade when available to avoid contamination and to minimize the variability of raw material (ICH Q7 and. ATMP Manufacturing Process key; Manufacturing Starting Material & Part IV of EU GMP; Key GMP Challenges; Key Challenges in Designing QMS for ATMPs; Download the Full Program and the Speakers' Profiles. Contact Us. If you require further information about the services offered by Rephine please contact us by email at [email protected] or telephone +44 1763 853 135. Contact Information. XXVIII - Starting Material: material used in the production of the ATMP that is part of the final product, including those of biological and non-biological origin. Examples of starting materials are: cells or tissues retrieved from a donor, supports and matrices or biomaterials combined with engineered cells
The startup phase of an ATMP clinical trial constitutes an imperative strategic decision stage of the trial, laying ground for its success. Trial startup activities require not only extensive and comprehensive documentation to be developed for submission purposes and clinical site use (eg, safety instructions), but also demand much broader interactions with competent authorities, study teams, clinical sites and their pharmacy personnel than conventional non-ATMP clinical trials. Due to a. Starting materials of human and/or animal, details of their origin and safety with regard to contamination by foreign substances (e.g. mycoplasma, bacteria, TSE-risk virus safety) are required. For Cell banking system Information on the source/history/establishment and characterization/qualification of the cell bank system
Raw materials for ATMP manufacturing: regulatory and supply issues Published on September 11, 2017 September 11, 2017 • 4 Likes • 0 Comment The holder of a marketing authorisation for an advanced therapy medicinal product shall establish and maintain a system ensuring that the individual product and its starting and raw materials, including all substances coming into contact with the cells or tissues it may contain, can be traced through the sourcing, manufacturing, packaging, storage, transport and delivery to the hospital, institution or private practice where the product is used
ATMPs present unique bioprocessing challenges such as limited scalability, variable quality of starting material and an inability to sterilize the final product. ATMP developers, clinical teams and patients rely on the provision of high-quality raw materials, effective logistics support, and validated, robust clinical manufacturing processes. This talk will provide a high level overview of how. ATMPs have been studied in clinical trials during 2011-2015 (~200 CTs during 2004-2010) - first classification of gene edited cells, CAR-Ts in clinical studies in EU (6) Substantial manipulation Enzymatic digestion. Same essental function(s) in the recipient and the donor Homologous vs non-homologous use Process control for ATMPs is inherently difficult due to variability in the biologic starting material, but real-time biosensor readings could fix this by allowing adjustments during the process, she said Your GMP/GDP Information Source. With news, trainings and conferences, a comprehensive guidelines database, publications and more the ECA is the leading European training and information services provider in the GMP and GDP environment
Direct interaction with the trainer during live sessions. Participation in interactive features within sessions including polls, Q&A, break out rooms, tasks, case studies, and more. Revisiting recorded sessions with unlimited access for 30 days. Interaction with peers during live sessions and through the online forum starting materials . and . highly specialised testing . in the jurisdictions that are subject to licensing(e.g. karyotype testing, exome sequencing) can be outsourced to non GMP licensed third party, as allowed by national law, provided that: a) b) c) There is a rationale and a justification in the quality system The contract giver takes responsibilit
Primary human cells as starting material for ATMP production; Isolation and selection of target cells for ATMP manufacturing . Procurement of starting material; Processing of starting material . Density gradient centrifugation; Mechanical break-up; Magnetic-activated cell sorting (MACS) FACS ; Cell culture . Adherent (anchorage dependent) cell culture and its scale-up potential . Classical two. Since a majority of the ATMPs that progress to authorization or at least to clinical trials are manufactured from autologous mononuclear cells, starting material is currently procured by hospital- or blood bank-operated apheresis facilities creating a peculiar situation in which a product starts under one regulation—Tissues and Cells Directive—before passing to another, ATMP Regulation. Ein Wirkstoff-Startmaterial (Active Substance Starting Material) ist ein Rohma-terial, Zwischenprodukt oder Wirkstoff, der für die Produktion eines Wirkstoffes verwendet wird und der als wichtiges Strukturelement in die Struktur des Wirk-stoffes eingebaut wird. Ein Wirkstoff-Startmaterial kann ein Handelsartikel, ein von einem oder mehreren Lieferanten im Rahmen eines Lohnauftrags. •Manufacturer must ensure that all the starting materials used originate from controlled sources - GMP compliance for API & excipients •GMP & GDP audits should be carried out at manufacturers and distributors of API - QRM approach •Clarification and harmonisation of expectations of manufacturers regarding th