The Krembil Good Manufacturing Practice Cell Facility

The Krembil Cell Facility at St. Michael’s Hospital is certified for the processing and manufacturing of Good Manufacturing Practice (GMP) -grade cell products intended for preclinical research, investigator-initiated cell therapy trials, and eventual therapeutic use.

The facility includes a fully equipped clean room suite designed and established under ISO designation 7/ Class 10,000 classification, ensuring orderly flow of raw materials, processes and personnel. The operation of the clean room suite is in compliance with the guideline of the FDA for GMP operations with special emphasis on processing and manufacturing of cell and cell products. Quality control and quality assurance programs, which establish a Quality System approach to control collection, processing, storage and release of cell and cell therapy products and also address the following elements: a) facilities (design, access and maintenance); b) equipment (purchase, use and maintenance); c) materials (specifications, purchase, storage and use); d) quality assurance (quality control, validation, qualification and document control). For example, various critical facility parameters, critical controls and laboratory equipment are continuously monitored via REES alarm system, with onsite surveillance and automated data collection. For the facilities it is of paramount importance to prevent potential contamination, both microbiological and by endotoxins due to defects in environmental conditions, handlers, culture containers, or raw materials, or crossed contamination with other products prepared in the same clean room suite. Therefore, quality assurance programs are in place to do microbiological monitoring and take corrective measures when needed as well as endotoxins monitoring of products before release. High Efficiency Particular Absorbing (HEPA) filters are used to prevent airborne cross-contamination as well as separate handling of materials from different patients, etc. therefore the clean room is monitored for air purity based on the number of particles. Other parameters such as temperature, humidity, and pressure are monitored because of their potential impact on particle generation and microorganism proliferation. The technical staff is especially trained in basic hygiene measures required for manipulation in clean room and have adequate qualification for both the conduct and surveillance of all activities.

The Krembil Cell Facility has been one of the sites in a number of clinical trials.

Cell Therapy for advanced diabetic kidney disease (Can-SOLVE CKD).

A 2 centre, phase 1b safety study. Autologous endothelial progenitor-like cells will be isolated, cultured and harvested at the cell facility for intravenous injection in patients with advanced diabetic kidney disease. A total of 82 patients will be enrolled for this trial.

The ENACT study. The Enhanced Angiogenic Cell Therapy-Acute Myocardial Infarction Trial (ENACT-AMI).

This trial is ongoing. We receive the blood mononuclear cells, do further isolation of angiogenic cells, cell culture, genetic engineering (transfection), if necessary, and final product preparation for delivery. So far, 20 patients have been enrolled and treated. This cell facility has prepared 6 final products for the trial.

TEVA DREAM-HF study.

TEVA DREAM-HF C41750-3100, a double-blind, randomized, sham-procedure-controlled, parallel-group efficacy and safety study of allogenic mesenchymal precursor cells (CEP-41750) in patients with chronic heart failure due to left ventricular systolic dysfunction or either ischemic or nonischemic etiology. We will receive and prepare the mesenchymal stem cells for delivery for this trial.

AlloCure ACT-AKI study (protocol# AC 6071103).

A Randomized, Multicenter, Double-Blind, Placebo-Controlled Study of AC607 (allogenic human mesenchymal stem cells) for the Treatment of Acute Kidney Injury in Cardiac Surgery Subjects. The allogenic human mesenchymal stem cells were received, stored and prepared at The Krembil Cell Facility for the Allocure trial. A total of 10 patients were enrolled and treated at our institution.

Pulmonary Hypertension: Assessment of Cell Therapy (PHACeT Trial).

A single-centre, phase I study, tests the benefits of genetically-modified endothelial stem-like cells harvested from the Pulmonary Arterial Hypertension (PAH) patient’s own blood for the treatment of this fatal respiratory disease. A therapeutic gene is delivered into the lung by transplanting genetically engineered endothelial precursor cells into the lungs to engraft the small pulmonary arteries which are severely damaged in this disease.

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