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Record W2539044895 · doi:10.2337/db16-0234

National Institutes of Health–Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities

2016· article· en· W2539044895 on OpenAlexafffund
Camillo Ricordi, Julia Goldstein, Appakalai N. Balamurugan, Gregory L. Szot, Tatsuya Kin, Chengyang Liu, Christine W. Czarniecki, Barbara Barbaro, Nancy D. Bridges, Jose Cano, William R. Clarke, Thomas L. Eggerman, Lawrence G. Hunsicker, Dixon B. Kaufman, Aisha Khan, David-Erick Lafontant, Elina Linetsky, Xunrong Luo, James F. Markmann, Ali Naji, Olle Korsgren, José Oberholzer, Nicole A. Turgeon, Daniel Brandhorst, Xiaojuan Chen, Ji Lei, Ling‐Jia Wang, Joshua J. Wilhelm, Jamie Willits, Xiaomin Zhang, Bernhard J. Hering, Andrew M. Posselt, Peter G. Stock, A. M. James Shapiro

Bibliographic record

VenueDiabetes · 2016
Typearticle
Languageen
FieldMedicine
TopicPancreatic function and diabetes
Canadian institutionsUniversity of Alberta
FundersNational Center for Advancing Translational SciencesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Allergy and Infectious DiseasesUniversity of AlbertaFeinberg School of MedicineLeonard M. Miller School of Medicine, University of MiamiPerelman School of Medicine, University of PennsylvaniaNovo Nordisk FondenUniversity of California, San FranciscoUniversity of Illinois at Urbana-ChampaignUniversity of MinnesotaNorthwestern UniversityEmory UniversityNational Center for Research ResourcesLeonard M. Miller School of MedicineUniversity of PennsylvaniaFaculty of Medicine and Dentistry, University of AlbertaUniversity of Miami
KeywordsTransplantationMedicineClinical trialProduct (mathematics)Good manufacturing practiceManufacturing engineeringOperations managementEngineeringSurgeryInternal medicineRegulatory affairs

Abstract

fetched live from OpenAlex

Eight manufacturing facilities participating in the National Institutes of Health-sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for the manufacture of allogeneic purified human pancreatic islet (PHPI) product evaluated in a phase 3 trial in subjects with type 1 diabetes. Manufacturing was controlled by a common master production batch record, standard operating procedures that included acceptance criteria for deceased donor organ pancreata and critical raw materials, PHPI product specifications, certificate of analysis, and test methods. The process was compliant with Current Good Manufacturing Practices and Current Good Tissue Practices. This report describes the manufacturing process for 75 PHPI clinical lots and summarizes the results, including lot release. The results demonstrate the feasibility of implementing a harmonized process at multiple facilities for the manufacture of a complex cellular product. The quality systems and regulatory and operational strategies developed by the CIT Consortium yielded product lots that met the prespecified characteristics of safety, purity, potency, and identity and were successfully transplanted into 48 subjects. No adverse events attributable to the product and no cases of primary nonfunction were observed.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.044
Threshold uncertainty score0.457

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.081
GPT teacher head0.354
Teacher spread0.272 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations197
Published2016
Admission routes2
Has abstractyes

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