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Novel cellular products: How to identify indicators for quality evaluation
Poster Abstracts
T cells (expanded with anti CD3/CD28 Dynabeads®) were cryopreserved in Cryostor10® (Sigma-Aldrich) at 107cells/mL, at a rate of 1°C/min to −100°C in cryovials (0.5mL fill) using a ViaFreeze controlled rate freeze. MSCs (Rooster Bio) were cryopreserved in Cryostor10® at 5x106 cells/mL in cryovials (0.5mL fill). Samples were either thawed in a 37°C water bath or in the dry thawing system before re-culture and viability testing. There was no significant difference (p = 0.91, n = 3) between cryovials of T cells thawed in the water bath and dry thawing system, with post-thaw recovery of 97.5 ± 11.0% and 96.6 ± 2.5% respectively. Similarly, no significant difference (p = 0.78, n = 3) between vials of MSCs thawed in the two thaw systems based on post-thaw cell recovery (84.1 ± 7.1% and 82.5 ± 2.7% respectively). No significant differences were seen between any set on outward growth or proliferation studies. This work shows promising results that dry thawing can ensure effective, automated and reproducible delivery of cell therapies. Removing water baths from the thawing cycle will ensure sterile, robust, controlled and validated thawing of cryopreserved cell therapies at the point of delivery. 139 A SUCCESSFULLY IMPLEMENTED DEVIATION MANAGEMENT PROGRAM IS ESSENTIAL TO ACHIEVE AND MAINTAIN PROCESS IMPROVEMENTS J.C. Kreitzer, M. Colon Lozada, M. Hackett Quality Assurance, Moffitt Cancer Center, Riverview, Florida, United States Background: Deviation management is a necessary component to Quality Management’s process improvement goals. Implementing an integrated deviation management program supports an organization with identification, investigation, and reduction of the effects of deviations. A total quality management approach is critical as your program interfaces with other quality systems such as document control, training, equipment management or change management. Methods: First, Quality facilitates staff training which includes the concepts and importance of deviation management. Training should include methods of identification, proper documentation of deviation descriptions and immediate actions. This creates a cultural change while fostering a positive working relationship between Quality and staff. Next, Management must be actively involved with QA during the investigative and corrective action phases to ensure deviations are managed effectively. A thorough investigation and analysis using problem solving tools such as Fishbone diagrams, Pareto charts or Scatter diagrams, will lead to the root cause of the problem. And finally, consistency and support is obtained through regular interaction with Quality. Weekly meetings provide a platform for Quality and Management to ensure regulatory compliance is maintained. Results: Management collaboration has created a solid foundation to promote a climate of process improvement for all staff. This is evidenced in the improved descriptions written by staff members adding to the efficiency and management of deviations. Future plans include implementation of an automated system to further enhance deviation management. Conclusion: A deviation management program that is ineffectively managed or without the support from Management will result in inadequate results and you will face challenges meeting your compliance goals. However, when successfully executed, a deviation management program will provide a solid foundation and guide your program to continued success. 140 WILL NOT BE PRESENTED 141 NOVEL CELLULAR PRODUCTS: HOW TO IDENTIFY INDICATORS FOR QUALITY EVALUATION B. Longsomboon, A. Khan, J. Hare Interdisciplinary Stem Cell Institute, University of Miami School of Medicine, Miami, Florida, United States Background: Quality management is a requirement in laboratory operations to ensure product quality. Establishing the quality indicators to evaluate novel cellular products is challenging especially during early phase of clinical trials when products data are limited. The burden lies heavily on cell manufacturing programs to collect sufficient scientific proof of product safety, identity, and other attributes.
S65
Discussion: This study propose to identify quality indicators for novel products manufactured under clinical research setting. It is not intended for any specific product. Well-established indicators provide a systematic and data-based evaluation of the products. Quality indicators of the products under investigation are the continuing evaluation of the data outlined in the clinical trial protocols. Data for product evaluations can be extracted from the data exists in preclinical studies. At the minimum, the quality indicators should consist of 1) The manufacturing: the pre-established technique and all manufacturing specifications have provided the reproducibility and consistency, these are normally assessed with cell viability percentage and the number of cells, etc. The evaluation of manufacturing should, then, follow or expand base on the acceptable results from the pre-exiting studies. 2) Product identity: cells identification and/or characteristics are already identified. The cell identity and characteristics can be assessed using acceptable criteria and the same matrix as those previously identified. 3). Safety: the same safety measures proposed in the clinical protocols should be used as the guidelines for product evaluations. These measures usually include sterility, endotoxin and mycoplasma (for cells undergo long term cultured). It is recommended that cell manufacturing laboratories should, as the studies progress, expand to include other quality indicators, such as stability, as appropriate, however, the pre-existing data should remains as the guidelines. It is important to note also that quality evaluation is a process, it is an unending task. Conclusion: Success of clinical trial studies depends, in part, on products being used. Product quality management is critical. Properly identify the quality indicators benefits not only the ongoing quality assessments but also the quality improvement. In addition, a well-defined outcome evaluation will confirm the validity of product safery, identity and other attributes. 142 WILL NOT BE PRESENTED 143 THE STATUS OF NASCITURUS IN THE MEXICAN LEGAL SYSTEM AND ITS RELATIONSHIP WITH EMBRYONIC STEM CELLS I.O. Osadolor Bioethics, Instituto de Ciencias Jurídicas de Puebla, A.C., Puebla, Puebla, Mexico The “unborn child” is conceived unborn (“nondum natus”), is the human being at the time of his life running from the moment of conception to the moment of birth, and develops in different stages of embryo and fetus. For embryo must understand the human being from fertilization until the third month of pregnancy; fetus is understood by humans since the third month of pregnancy until delivery. Within the embryonic period we speak of different stages, any of which we are in presence of a human being in the early stages of their existence, in which there are no leaps, as it is always the same biological body, although their morphology not yet match the man adult. The embryologist Laren, a member of the Warnock Committee, which gave rise to the famous report prepared under the direction of Mary Warnock (which gave name to the report), introduced the term pre-embryo to refer to the period from fertilization until the fourteenth day of pregnancy, wherein the nesting occurs. The introduction of such a term is merely a manipulation of language to justify the scientific use of human embryos as genetic material, saving the ethical and moral seriousness of the creation and use of same for scientific research purposes. However, it should be considered that from the moment the egg and sperm fuse, the zygote is formed, which “has a unique new information structure,” which begins “to act as a single unit” developed through cell division giving way to the morula and blastocyst stages, in which the nesting of the embryo occurs; from the nesting phase begins and organogenesis and histogenesis (the formation of tissues and organs). Meanwhile, Natalia Lopez Moratalla states: “The process of a new human is fertilization. With it matter received from the parents to give a cell unit with own home or start a program of individual life characteristics is prepared; ie, able to start issuing or express the genetic language of the new individual. The breed of the parents, natural fertilization, ends in the formation of a cell with a characteristic phenotype, the zygote, which begins its vital cycle. Looking from the embryological perspective, many researchers believe that the identification of a human being, two properties are needed: the unity and oneness. The unit refers to the positive reality that is distinct from another and uniqueness is the quality of being unique (and unrepeatable). However, some authors believe that the embryo lacks personhood.
T cells (expanded with anti CD3/CD28 Dynabeads®) were cryopreserved in Cryostor10® (Sigma-Aldrich) at 107cells/mL, at a rate of 1°C/min to −100°C in cryovials (0.5mL fill) using a ViaFreeze controlled rate freeze. MSCs (Rooster Bio) were cryopreserved in Cryostor10® at 5x106 cells/mL in cryovials (0.5mL fill). Samples were either thawed in a 37°C water bath or in the dry thawing system before re-culture and viability testing. There was no significant difference (p = 0.91, n = 3) between cryovials of T cells thawed in the water bath and dry thawing system, with post-thaw recovery of 97.5 ± 11.0% and 96.6 ± 2.5% respectively. Similarly, no significant difference (p = 0.78, n = 3) between vials of MSCs thawed in the two thaw systems based on post-thaw cell recovery (84.1 ± 7.1% and 82.5 ± 2.7% respectively). No significant differences were seen between any set on outward growth or proliferation studies. This work shows promising results that dry thawing can ensure effective, automated and reproducible delivery of cell therapies. Removing water baths from the thawing cycle will ensure sterile, robust, controlled and validated thawing of cryopreserved cell therapies at the point of delivery. 139 A SUCCESSFULLY IMPLEMENTED DEVIATION MANAGEMENT PROGRAM IS ESSENTIAL TO ACHIEVE AND MAINTAIN PROCESS IMPROVEMENTS J.C. Kreitzer, M. Colon Lozada, M. Hackett Quality Assurance, Moffitt Cancer Center, Riverview, Florida, United States Background: Deviation management is a necessary component to Quality Management’s process improvement goals. Implementing an integrated deviation management program supports an organization with identification, investigation, and reduction of the effects of deviations. A total quality management approach is critical as your program interfaces with other quality systems such as document control, training, equipment management or change management. Methods: First, Quality facilitates staff training which includes the concepts and importance of deviation management. Training should include methods of identification, proper documentation of deviation descriptions and immediate actions. This creates a cultural change while fostering a positive working relationship between Quality and staff. Next, Management must be actively involved with QA during the investigative and corrective action phases to ensure deviations are managed effectively. A thorough investigation and analysis using problem solving tools such as Fishbone diagrams, Pareto charts or Scatter diagrams, will lead to the root cause of the problem. And finally, consistency and support is obtained through regular interaction with Quality. Weekly meetings provide a platform for Quality and Management to ensure regulatory compliance is maintained. Results: Management collaboration has created a solid foundation to promote a climate of process improvement for all staff. This is evidenced in the improved descriptions written by staff members adding to the efficiency and management of deviations. Future plans include implementation of an automated system to further enhance deviation management. Conclusion: A deviation management program that is ineffectively managed or without the support from Management will result in inadequate results and you will face challenges meeting your compliance goals. However, when successfully executed, a deviation management program will provide a solid foundation and guide your program to continued success. 140 WILL NOT BE PRESENTED 141 NOVEL CELLULAR PRODUCTS: HOW TO IDENTIFY INDICATORS FOR QUALITY EVALUATION B. Longsomboon, A. Khan, J. Hare Interdisciplinary Stem Cell Institute, University of Miami School of Medicine, Miami, Florida, United States Background: Quality management is a requirement in laboratory operations to ensure product quality. Establishing the quality indicators to evaluate novel cellular products is challenging especially during early phase of clinical trials when products data are limited. The burden lies heavily on cell manufacturing programs to collect sufficient scientific proof of product safety, identity, and other attributes.
S65
Discussion: This study propose to identify quality indicators for novel products manufactured under clinical research setting. It is not intended for any specific product. Well-established indicators provide a systematic and data-based evaluation of the products. Quality indicators of the products under investigation are the continuing evaluation of the data outlined in the clinical trial protocols. Data for product evaluations can be extracted from the data exists in preclinical studies. At the minimum, the quality indicators should consist of 1) The manufacturing: the pre-established technique and all manufacturing specifications have provided the reproducibility and consistency, these are normally assessed with cell viability percentage and the number of cells, etc. The evaluation of manufacturing should, then, follow or expand base on the acceptable results from the pre-exiting studies. 2) Product identity: cells identification and/or characteristics are already identified. The cell identity and characteristics can be assessed using acceptable criteria and the same matrix as those previously identified. 3). Safety: the same safety measures proposed in the clinical protocols should be used as the guidelines for product evaluations. These measures usually include sterility, endotoxin and mycoplasma (for cells undergo long term cultured). It is recommended that cell manufacturing laboratories should, as the studies progress, expand to include other quality indicators, such as stability, as appropriate, however, the pre-existing data should remains as the guidelines. It is important to note also that quality evaluation is a process, it is an unending task. Conclusion: Success of clinical trial studies depends, in part, on products being used. Product quality management is critical. Properly identify the quality indicators benefits not only the ongoing quality assessments but also the quality improvement. In addition, a well-defined outcome evaluation will confirm the validity of product safery, identity and other attributes. 142 WILL NOT BE PRESENTED 143 THE STATUS OF NASCITURUS IN THE MEXICAN LEGAL SYSTEM AND ITS RELATIONSHIP WITH EMBRYONIC STEM CELLS I.O. Osadolor Bioethics, Instituto de Ciencias Jurídicas de Puebla, A.C., Puebla, Puebla, Mexico The “unborn child” is conceived unborn (“nondum natus”), is the human being at the time of his life running from the moment of conception to the moment of birth, and develops in different stages of embryo and fetus. For embryo must understand the human being from fertilization until the third month of pregnancy; fetus is understood by humans since the third month of pregnancy until delivery. Within the embryonic period we speak of different stages, any of which we are in presence of a human being in the early stages of their existence, in which there are no leaps, as it is always the same biological body, although their morphology not yet match the man adult. The embryologist Laren, a member of the Warnock Committee, which gave rise to the famous report prepared under the direction of Mary Warnock (which gave name to the report), introduced the term pre-embryo to refer to the period from fertilization until the fourteenth day of pregnancy, wherein the nesting occurs. The introduction of such a term is merely a manipulation of language to justify the scientific use of human embryos as genetic material, saving the ethical and moral seriousness of the creation and use of same for scientific research purposes. However, it should be considered that from the moment the egg and sperm fuse, the zygote is formed, which “has a unique new information structure,” which begins “to act as a single unit” developed through cell division giving way to the morula and blastocyst stages, in which the nesting of the embryo occurs; from the nesting phase begins and organogenesis and histogenesis (the formation of tissues and organs). Meanwhile, Natalia Lopez Moratalla states: “The process of a new human is fertilization. With it matter received from the parents to give a cell unit with own home or start a program of individual life characteristics is prepared; ie, able to start issuing or express the genetic language of the new individual. The breed of the parents, natural fertilization, ends in the formation of a cell with a characteristic phenotype, the zygote, which begins its vital cycle. Looking from the embryological perspective, many researchers believe that the identification of a human being, two properties are needed: the unity and oneness. The unit refers to the positive reality that is distinct from another and uniqueness is the quality of being unique (and unrepeatable). However, some authors believe that the embryo lacks personhood.