1. 3rd Dimension of Product Translation: Industrialization
BioMARC
3rd Dimension of Product Translation: Industrialization
Becky Rivoire, B.S., RAC
Director, BioMARC
Department of Microbiology, Immunology & Pathology
Colorado State University
Regional Training Center for Product Translation
Short-Course: Product Translation and Related Regulations
December 10, 2008

2. Translational Critical Path for Medical Product Development

3. Translational Critical Path Initiative
IND
BLA, NDA, 510k
The template we will use was published by the FDA in 2004 and updated in It is called the translational critical path initiative. It depicts the progression of a product from basic research, through a prototype to preclinical and clinical development to get to the stage of submitting an application for a commercial license. It is broken into three dimensions: safety, medical utility, and industrialization. Good laboratory Practice (GLP) falls between the prototype and preclinical stage, current good manufacturing practice (CGMP) falls between preclinical and clinical development, and good clinical practice (GCP) is followed during clinical development.
The IND application is submitted after preclinical trials and the BLA, NDA or 510k applications are submitted following Ph I/II/III clinical trials. The PDM Core is only geared to provide services to help move a product into preclinical and phase I/II clinical trials, to provide data to leverage industrial partners to move the project into a Phase III clinical trial, if appropriate.
path/whitepaper.pdf 3

4. Industrialization Physical Design
Bird’s Eye View
Physical Design
Characterization, Small Scale Production
Preclinical lot (GLP grade material)
Manufacturing Scale-up, Refined Specifications
Clinical lots (cGMP grade material)
Phase I Clinical Trial
Phase II Clinical Trial
Phase III Clinical Trial
Mass Production
Commercial lots

5. current Good Manufacturing Practice (cGMP)
cGMPs apply to the entire production process, from raw material to final product, for any approved drug, licensed biologic, or clinical trial material.

6. cGMP Continuum
(Increased compliance required at each subsequent phase)
Phase I - Manufactured under the spirit of cGMP with all procedures properly documented
Phase II - Begin to fine tune the process: develop and refine assays, perform stability studies, begin process validation for removal of impurities
Phase III – Approaching full cGMP: final release strategies formulated, products manufactured in facility where commercial production occurs
Phase I - Manufactured under the spirit of cGMP with all procedures properly documented
Phase II - Begin to fine tune the process: develop and refine assays, perform stability studies, begin process validation for removal of impurities
Phase III – Approaching full cGMP: final release strategies formulated, products manufactured in facility where commercial production occurs
Commercial Production – Manufactured under full cGMP

7. Physical Design
Process
Feasibility
Scalability

8. Quality Considerations
Production
Facilities and Equipment
Materials
Laboratory Control
Product Labeling
Guidance for Industry, Quality Systems Approach to Pharmaceutical cGMP Regulations, September 2006
21CFR211

9. Manufacturing Campaign
Documentation & Risk Assessment
Gowning
Cleaning
Environmental monitoring
Materials receipt/quarantine/release
Sterilization of media/buffers
Production run
Testing for release
Product labeling
Product storage/Accountability
Quality Assurance oversight

10. Documentation Specification Sheets
PDM Core Experience
Specification Sheets
Raw material
Equipment
Product
Master Batch Production and Control Records
Standard Operating Procedures (SOPs)
Laboratory Cleaning and Use Logs
Equipment Cleaning, MainT, Calibration and Use Logs
Distribution Records
Deviation Logs
Inspection Reports
Complaint Files
Refer to 21CFR 211, Subpart J – Records and Reports

11. Gowning ISO 8 Clean Room
Ms. Emily Stump; PDM Core Manufacturing Manager

12. Gowning ISO 7 & 5 Clean Rooms

13. Cleaning Fumigant SporKlenz Disinfectants Conflict Vesephene LpH
RACAL Respirator
Emily Stump
Jessica Mierkey

14. Environmental Monitoring
Rodac Plate Surface Sampler - Tryptic Soy Agar (TSA)

15. Environmental Monitoring
Biotest RCS Microbial Air Sampler
TSA Strips
API Strips Biomerieux Inc.
Isolate Identification
Genus:species

16. Environmental Monitoring
Metone handheld Particle Counter

17. Sterilization ISO 8 Clean Room

18. Successful Industrialization
Preclinical grade material; characterization
GLP compliant
Animal studies
Safety and efficacy
Clinical grade material; refine specifications
cGMP compliant
Human studies
Phase I – safety/dose ranging
Phase II – safety/efficacy
Phase III – safety/efficacy
Commercial grade material
Licensed facility
Licensed product

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