University of Minnesota Facility Design

Diane Kadidlo MT(ASCP) Facility DirectorUniversity of MinnesotaMolecular and Cellular Therapeutics

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Molecular and Cellular Therapeutics University of Minnesota

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OverviewFacility – 40,000 square feet

ISO Class Production Clean Rooms – 20

Total Operational Staff – 37

Therapeutic Product Classes Supported – 4

18 INDs (14 internal; 4 external)

Over 900 products produced annually

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Molecular and Cellular Therapeutics (MCT) Est.1992

Translate basic discovery to clinical trials, across a wide array or therapeutic classes

Develop and manufacture therapeutic products meeting Good Manufacturing Practices (cGMPs) and current Good Tissue Practices (cGTPs)

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Molecular and Cellular Therapeutics (MCT) Est.1992

Support Phase I/II/III clinical trials of molecular and advanced cell-, tissue-, gene-based, protein, drug therapies for researchers and external contracts

Manufacturing Units

Cell Therapy Laboratory

Protein Production

Pancreatic Islet Transplant

Pharmaceutical SynthesisSlide 5

Production Capabilities

Hematopoietic TransplantBone Marrow, Peripheral Blood, Cord Blood

Pancreatic Islet TransplantImmunoadoptive Therapies

Natural Killer CellsT Regulatory CellsMesenchymal Stem CellTumor Vaccine

Cardiac RepairBone Marrow MononuclearCardiac Derived Cells

Monoclonal Antibodies/ProteinsActive Pharmaceutical Ingredients (API

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Upper Level (10,000 Sq feet)

5500 Sq ft Clean Space

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MCT Renovation

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Lower Level

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Core Activities

Quality and ComplianceFacility

Control of Critical SystemsEquipment Management

OperationsProduct Development

FinanceProgram Budgets/Forecasts/Cost Accounting

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MCT Organizational Structure

Scientific Director Dr. Mark Paller, MD

Facility Medical DirectorDr. David McKenna, MD

Facility DirectorDiane Kadidlo

Director of IND/IDE Assistance ProgramHarvey Arbit, PhD

ManagersQuality AssuranceFacility & MaterialsOperationsFinance

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Quality Assurance

All 4 Programs (Cell, Islet, Mono aby, API) comply with one Quality Program

Common Quality PlanType V Drug Master File

Centralized QA SystemsDocument Control SystemEquipment ManagementRecord KeepingLot ReleaseAudits

StaffingQuality Manger2 QA Staff

Quality Steering Committee

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Facilities and Services

o Security• Limited Access – Electronic Card Key

o Facility Design• Controlled Environment Areas (ISO Class 5 and 7)• Single pass, isolated differential air pressure rooms,

negative pressure capabilitieso Central Alarm Monitoring

o Equipmento Critical Systems – Heating, Ventilation & Air Conditioning

o Materials and Inventory Managemento Equipment

• Calibration & Preventative maintenance• IQ/OQ/PQ

o Product Development• Project Management

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LOWER LEVEL LOWER LEVEL 7,000 Sq ft Clean Space7,000 Sq ft Clean Space

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University of Minnesota Medical Center, Fairview Clinical Cell Therapy Laboratory

Established 1979 in support of the Blood and Marrow Transplant Program at the University of Minnesota. Moved to MCT Facility 1996

Processes more than 1500 human bone marrow, peripheral blood, umbilical cord blood and tissues annually

Provide translational development expertise for bringing novel cell engineering techniques from research to clinical applications

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UMMC Cell Therapy Lab Clinical Operations - GTP Production

3300 sq ft, separate air handling systemUnclassified space meets the requirements for Class 100,000Clinical production not requiring extensive manipulation. Processes: cryopreservation, positive and negative selection.

Auto/Allo PB, CB & Bone Marrow

Closed system processes – products in bags; biological safety cabinets

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GMP Production

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Production Area Characteristics

Class 10,000 (ISO 7) Clean Suite ISO 5 Biological Safety CabinetsSingle pass, isolated differential air pressure rooms, negative pressure capabilitiesTerminal HEPA Filtration, 20-70 Air Changes/Hr Clean Room surfaces, epoxy liquid flooring coved base, reinforced resinous wall surfacing, and epoxy painted veneer plaster ceilings

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PersonnelMaterialsProductWaste

•Uni-directional workflow

•Production in biosafety cabinets or within closed systems.

•Personnel and product exit through the degowning rooms.

Process Flow

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Environmental Controls

SanitizationContract for janitorial services (non Class 10,000)Programs cleans production suites

Environmental MonitoringWeekly surface testingMonthly viable particlesQuarterly mold and non-viable particles

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