Scientific Considerations for Microneedle Drug Products: Product Development, Manufacturing, and Quality Control 1 Caroline Strasinger, PhD Office of New Drug Products (ONDP) Chair of the FDA Transdermal Working Group James J. Norman, PhD Office of Process and Facilities (OPF)
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Scientific Considerations for Microneedle Drug Products Considerations for Microneedle Drug Products: Product Development, Manufacturing, and Quality Control 1 Caroline Strasinger,
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Scientific Considerations for Microneedle Drug Products: Product Development, Manufacturing, and Quality Control
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Caroline Strasinger, PhD Office of New Drug Products (ONDP) Chair of the FDA Transdermal Working Group
James J. Norman, PhD Office of Process and Facilities (OPF)
Disclaimers The contents of this presentation are ours and do not necessarily reflect the view and/or policies of the United States Food and Drug Administration or its staff. The United States Food and Drug Administration will not be bound by any comments or information contained in this presentation. Use of Images Our use of images as examples does not represent FDA preference for specific products, processes, or manufacturers. None of the images were taken from FDA submissions. Conflict of Interest Statement James is a co-author on patent applications related to microneedles. He has waived his rights to any royalties from these patent applications.
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Poking its way into the Regulated Industry?
Build
Innovate
3 Communicate
Resources for Communicating with FDA • IND Guidance Documents
– Formal meetings between the FDA and Sponsors or Applicants – IND Meetings for human drugs and biologics – Exploratory IND studies – INDs for Phase 2 and Phase 3 Studies:
Chemistry, Manufacturing, and Controls Information – Best Practices for Communication Between IND Sponsors and FDA
During Drug Development • Request for Designation:
Human factors are reviewed by multiple offices in multiple centers
QTPP: Sterility / Bioburden Control • Do microneedles need to be sterile?
– Target tissue and depth of penetration – Duration of application – Intended patient population (immunocompromised, young, elderly)
• Approaches to sterile manufacturing – Aseptic manufacturing: combination of previously sterilized components – Terminal sterilization – novel approaches can be validated
• Justifying a non-sterile product – Scientific rationale for why the product does not increase infection risk – Examples: clinical trial experience, animal data, in vitro experiments
• Manufacturing limitations – If sterile manufacturing is not possible, low bioburden manufacturing with
documented controls and release criteria may be acceptable – The need for a sterile product should be evaluated early in development
– Formulation migration – consider the worst-case product orientation – Continued testing of mechanical attributes – Desiccant performance
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Process Reliability and Robustness
Example Microneedle Processes
Pre-Filling Hollow Microneedle Devices
“Poke and Patch” Topical Formulations
Extrusion for Solid Dose Injection
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Example Microneedle Processes
Dip Coating Spray Coating
Drawing Lithography
Micromolding
Gas-Jet Drying
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Hot Melt
Dip Coating Processes
Potential High Risk Quality Attributes
Example Dip-Coating Processes Micro-Reservoir
Rolling Drum
• Content uniformity • Sterility, if applicable • Mechanical attributes
Wider in every dimension? (x +∆x)3 relationship?
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Dip Coating – Control Strategies • Raw Material Controls
– Rheological properties – Surface tension of the
formulation – Needle orientation and
array flatness – Needle roughness and
surface energy
• Environmental Conditions – Humidity and temperature – Air flow
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• Process Parameters – Relative needle velocity – Coating depth
• Vision Systems and Other Process Analytical Technology (PAT) – Acceptance Criteria – Method Validation – Refer to 2004 Guidance on Process
Analytical Technology (PAT)
Other Coating Processes
Example Considerations • Distinguishing drug on the base from the “deliverable dose” during development • Demonstrating robustness against air and surface contamination in critical areas • Conducting worst-case process simulations/media fills (required for aseptic processes)
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Micromolding – Example Processes
• Solution casting – Convection/vacuum drying
– UV curing
– Microwave curing
• Melt casting – Vacuum filling
– Microparticle melting
• Other – Ultrasonic welding
Considerations for Silicone Micromolds •Mold Creation
– Establishing a type of silicone and curing system – Master structures: maintenance and qualification – Laser ablation: parameter justification, cleaning – Leachables assessment – Mold qualification: Durometer and geometry post-sterilization
•Mold Cleaning – Cleaning validation – Consider permeability of silicones to cleaning solvents (ex: isopropanol)
•Mold Replacement – Silicones are subject to both physical and chemical degradation – Assessment of mold lifetime
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Concluding Remarks • Early communication with OPQ is recommended to create a more
fluid and predictable review process.
• Expectations for microneedle quality scale with the phase of development.
• ICH guidelines provide a framework for adopting a Quality by Design (QbD) approach for designing and manufacturing microneedles.
• Microneedle manufacturing has unique control strategy considerations. 23
References – Organized by Slide Number 8. http://medcitynews.com/2013/05/its-smaller-than-a-fingernai l-but-this-needle-free-nanopatch-could-be-the-future-of-