3rd Dimension of Product Translation: Industrialization

Becky Rivoire, B.S., RACDirector, BioMARC

Department of Microbiology, Immunology & PathologyColorado State University

Regional Training Center for Product TranslationShort-Course: Product Translation and Related Regulations

December 10, 2008

BioMARC

Translational Critical Path for Medical Product Development

http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.html

Translational Critical Path Initiative

IND BLA, NDA, 510k

www.fda.gov/oc/initiatives/critical path/whitepaper.pdf

Industrialization

• 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

Bird’s Eye View

cGMPs apply to the entire production process, from raw material to final product, for any approved drug, licensed biologic, or clinical trial material.

current Good Manufacturing Practice (cGMP)

cGMP Continuum

Phase III – Approaching full cGMP: final release strategies formulated, products manufactured in facility where commercial production occurs

Commercial Production – Manufactured under full cGMP

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

(Increased compliance required at each subsequent phase)

Physical Design

• Process

• Feasibility

• Scalability

Quality Considerations

• Production

• Facilities and Equipment

• Materials

• Laboratory Control

• Product Labeling

Guidance for Industry, Quality Systems Approach to Pharmaceutical cGMP Regulations, September 2006 http://www.fda.gov/CDER/guidance/7260fnl.htm

21CFR211http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=211

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

Documentation• 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

PDM Core Experience

Refer to 21CFR 211, Subpart J – Records and Reports

Gowning ISO 8 Clean Room

Ms. Emily Stump; PDM Core Manufacturing Manager

Gowning ISO 7 & 5 Clean Rooms

CleaningDisinfectants

• Conflict• Vesephene• LpH

Fumigant • SporKlenz

RACAL Respirator Emily Stump Jessica Mierkey

Environmental MonitoringRodac Plate Surface Sampler - Tryptic Soy Agar (TSA)

Environmental MonitoringBiotest RCS Microbial Air Sampler

TSA StripsAPI Strips Biomerieux Inc.

Isolate IdentificationGenus:species

Environmental MonitoringMetone handheld Particle Counter

SterilizationISO 8 Clean Room

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– cGMP compliant– Licensed facility– Licensed product

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