®cGMP, cGTP Facility Design for Production of Human Cells, Tissues and Tissue based products Presented by Kris Chatrathi atInternational Society for Pharmaceutical Engineering-Midwest Chapter October 11, 2011 www.burnsmcd.com/pharma
® Replacement Cartilage• Mimics usual cartilage environment – Cartilage cells – Collagenous scaffold The close up image of cells in the replacement cartilage
® Engineering Bone Grafts• Change stem cells into bone cells – with proper growth factors in cell culture media A 3D calcium phosphate scaffold From Becton Dickinson
® Replacement Cells for DiabetesIn vivo Islet of Langerhans in Pancreas
® A New Bladder To make a bladder a scaffold, along with several different types of cells, are needed.
Transplants That Match the Patient ®1. Remove cells from patient.2. Grow in culture with or without biomaterials.3. Give appropriate chemicals to make cells do what is needed.4. Replace into patient.
® FDA• CBER (Center for Biologics Evaluation and Research): vaccines, blood and blood products, human tissue/tissue products for transplantation, cell therapy, gene therapy, donor screening tests for blood and tissue safety, devices – Office of Cellular, Tissue and Gene Therapies• Draft Guidance for Industry: Current Good Tissue Practice (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue- Based Products (HCT/Ps)
® cGMP• Ensure Products are Manufactured by a Controlled Auditable Process• cGMP elements – Facilities and Equipment – Personnel and Training – Documentation and Validation – SOP and Error Management – Process Control – Labeling – Auditing
® cGMP/cGTP Focus• Guidance recommendations are focused on preventing infectious disease contamination and cross contamination (including mix-ups) during manufacture• Prevention of the introduction, transmission, or spread of communicable diseases• Evaluate the type of area that a task would require in order to prevent contamination or cross- contamination• Procedures must be established and maintained to prevent contamination or cross-contamination
® Facility User Requirement Specification• Scope• Facility and Process Description• User Requirements: – Barriers, physical barriers to ensure particulate and microbial level do not exceed defined limits – Construction, floors, walls, ceilings and finishes – Atmosphere, requirements for the monitoring and control in classified areas – Processing Equipment – Auxiliary Services – Material Handling and Storage Requirements – Laboratory Functional Requirements
® CFD Objectives• Objective of Baseline Analyses – Simulate flow in lab room – Examine flow environment near bio safety cabinets • Understand impact of installation of cabinet near returns • Determine if room air flows onto interior work surface
® CFD Scope•Scope of Baseline Analysis -Build room and cabinets using supplied data -Define model constraints and parameters •Supply and return flows from TAB report •Balance of airflow exits through gaps around doors -Run cabinet characterization simulation -Run full lab room simulation
® CFD Results• Results – Flow travels from supplies to returns; little mixing occurs – Exhaust flow at cabinet is significant relative to supplies – Air stagnates along wall opposite the returns – Location of cabinet near return creates bias at air curtain • ISO-7 room air extends into cabinet on upstream side • ISO-7 air region extends 19.7 inches into cabinet • Peak air speed at curtain is 80 FPM at center of cabinet (20% reduction) – Increasing air changes/hr will likely increase bias at air curtain
® CFD Results Continued• Other Considerations/Recommendations – Air passing by the cabinets has already passed over the incubators, tables, and occupants – Very low air velocities near the incubators and along the wall opposite the returns could likely be improved • Create an array of overhead diffusers and install returns around perimeter
® Contaminant Study – ComparisonBio Safety Cabinet in Standard Room Bio Safety Cabinet in Lab Room Room air extends 6.9” from Room air extends 19.7” from front of unit @ 4” from sidewall front of unit @ 4” from sidewall