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Clinical Research involving Advanced Therapies: impacts of RDC nº 836, December 2023 - ANVISA / Brazil




In order to provide greater safety and quality to human cells used in clinical research and advanced therapies, Resolution of the Collegiate Board of Directors – RDC nº 836 was published on December 18, 2023, addressing the subject. 


The regulation establishes Good Practices in Human Cells for Therapeutic Use and Clinical Research in the country, representing a significant milestone for the sector that was advancing with little regulation.  


The RDC presents, in clear and objective language, the minimum requirements regarding good practices, biosafety, and hygiene in the facilities where Advanced Therapy products will be handled, cultured, distributed, stored, and disposed of. Additionally, it defines responsibilities, assigning to Cellular Processing Centers the elaboration of checklists and the implementation of adequate tools for managing processes and care related to therapies and the involved patients. 


Among the points worth highlighting is the definition of the minimum technical-sanitary requirements that Cell Processing Centers (CPCs) must meet. Laboratories processing bone marrow and peripheral blood, umbilical cord and placental blood banks, as well as cell technology centers, must be classified as CPCs. Such establishments must have adequate physical infrastructure, equipment, techniques, and human resources, and may have as their responsibilities the recruitment and selection of donors, including clinical and laboratory screening, collection and processing, as well as the provision of human-origin cells for therapeutic use, and must have a sanitary license issued by the competent health surveillance authority. 


The Resolution also establishes and details the entire quality framework to which CPCs must adhere. It determines that CPCs are responsible for ensuring the quality and safety of cells made available for therapeutic use and clinical research, and may only offer human cells in accordance with Good Practices in Human Cells. Thus, the resolution aims to ensure the adoption and implementation of Good Practices by the centers. 


Good practice in Human Cells, in turn, ensure that cells are obtained, transported, processed, stored, and made available according to the necessary quality and safety standards for the proposed therapeutic application and/or clinical research.  

It requires that qualification and validation actions be implemented by CPCs to demonstrate that all processes defined as critical are under control, with the description and documentation integrated into a master validation plan. Any alteration that may influence the quality of the products must also undergo validation. 


It establishes requirements related to biosafety and hygiene in CPCs and the expected quality standards, including the definition of analysis parameters and analytical methods, sampling procedures, and environmental monitoring, requirements for equipment, personnel, and physical structure, with criteria for adequacy, preventive and corrective maintenance, records, specificities, and contingency plans. 


The regulation also establishes the minimum physical infrastructure necessary for carrying out CPC activities. It is mandatory to segregate administrative areas, reception of biological material, cell processing, cell storage, and quality control. Norms and specificities are established for each area, with environmental control defined to each of them. Specific care is also directed towards the cryopreservation room and/or liquid nitrogen storage. 


The requirements for donor selection and exclusion, as well as laboratory screening, are described in the document and must be incorporated into the operational procedures of the CPC, with criteria for donor selection and exclusion through clinical screening, laboratory testing, and other related tests, in order to ensure the protection of the donor and the safety of the recipient. Mandatory tests for detecting markers of transmissible infections in donors are described, which must always use in vitro diagnostic products registered with Anvisa, with control of allogeneic and autologous cell donors, living or deceased. Procedures for serological and NAT testing, post-marketing surveillance, ABO and RhD typing, irregular antibody detection, as well as the presentation of abnormal results to the donor, are equally defined in the resolution. 


For basic research, education, training, quality control, or process validation purposes, the provision of advanced therapies should only occur upon documented request from the professional or institution that will use them. The processing of biological materials must ensure that no cross-contamination or mix-up occurs. Other aspects covered by this RDC include monitoring and recording the time between the collection of biological material and the start of processing or fresh cell infusion, and maintaining product viability through controlled and monitored cryopreservation. Regarding the packaging and labeling of the final product, it is imperative to preserve sterility, cell integrity, and stability, as well as label inviolability and integrity throughout storage. During this cell storage, processes must be instituted to ensure the maintenance of quality and safety, observing appropriate temperature conditions for each biological material, the specificities of the cryopreservation process and DNA samples, as well as adequate procedures for quarantines. 


Technical complaints and adverse events occurring from the collection process to the supply and use of the product must be appropriately documented. CPCs should have mechanisms to identify, investigate, and implement corrective and preventive actions. Technical complaints related to equipment, instruments, materials, reagents, and in vitro diagnostic products used must be reported to the National Health Surveillance System. Notification of cases reactive to markers of blood-borne infections detected during donor selection and those observed in recipients after transplantation is mandatory. 


In summary, the publication of this Resolution will certainly guide the development and contribute to the advancement of advanced therapies. 

 

See the full and original Resolution. Click here

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