Industry Perspective
Alison Sherwood
This presentation contains a summary
of the opinion and perspective from
GPhA member industry
representatives on the topic of QbD.
This presentation does not necessarily
represent the opinion of the presenter
nor Sandoz Inc.
Looking Back- 1 year agoFDA and Industry had a Common GOAL:
QbD by 2013
Where are we today?
FDA Survey of New ANDAS- most have QbD Elements
Revised QbR- pending
QbD tied to ANDA Acceptance- remains uncertain
QbD for Post Approval Changes- unclear expectations
Deficiencies May 2012- June 2013
• Result of Review Backlog / CR letter Delays?
• little to no shift to QbD reviews observed
• Majority of deficiencies still viewed as “traditional”
3 Batch Stability Requirement
• Can these demonstrate design space or process validation?
QbD
Extensive
knowledge
sharing for
solid oral
products
Other Dosage Forms:
less attention
expectations less clear
• Sterile Products
• Topical Products
• Oral Inhalation and Nasal
Products
Industry
Working
Groups
09/2011- QbR for Terminal Sterilization
09/2012- FDA presented an overview of
QbD and the Sterility Assurance QbR
05/2013- QbR for Aseptic Operations introduced
Industry Adoption of Sterility
Assurance QbR –admittedly
under-utilized
Q1/Q2- no formulation
development (?)
Sterilization process
Container/closure
In Use Studies / Labeling
Necessary with Q1/Q2 Formulations
Consideration For the Risk Assessment
• Suitability of excipient grade
• traditional api-excipient compatibility studies
(dry mixtures may not be applicable)
• Endotoxin as CMA
• Bioburden as CMA
• Alternate preservatives
• pH range- as design space?
Terminal Sterilization
• Extensive Prior Knowledge
• Known Design space of
Autoclave Process
(temperature, time, loads)
• Risk Consideration – impact on
chemical stability of product
• Risk Consideration – impact on
integrity of container/closure
• Risk Consideration- scale up
• Parametric release
facility,
component
sterilization
Aseptic Fill
• Extensive Prior Knowledge
• Known Design space of Filling
and Filtration process
• Risk Consideration- impact of
environment, in-house water
system
• Risk Consideration- scale up
• Media Fills representative of
process
• Tubing compatibility
Known
Design Space
Control
Strategy
Consideration
For Risk
Assessment
• stopper compatibility
• Drug delivery
• Sterilization process
• Extractable/leachables
• Co-packaged diluents/syringes
• Drug-device products
(injector pen)
• Product visibility vs light
protection
• Glass vial delamination
• Headspace % oxygen levels
Consideration For Risk Assessment
• QTPP
• Diluents
• Chemical stability of product
• Preservative effectiveness and challenge
organisms
• Needle sizes for intramuscular
Clinical Endpoint or PD
Efficacy Studies
In vitro Drug Release
/absorption
Microbiological Attributes
and Container/ Closure
Classification: Emulsion,
dispersion, or solution
• Little to no systemic
abosorption
• Clinical studies
Consideration
for Risk
Assessment
• Less sensitive than PK
• Expensive and lengthy
• More pressure for a
holistic approach :
equivalence of physical
and analytical properties
• In-Vitro Product
Performance Testing
(drug release)
Consideration For
Risk Assessment:
Microbiological
• Preservative Effectiveness
• Bioburden CMAs
• Bacteriostatic properties
Consideration for
Risk Assessment:
Container/closure
• Compatibility
• Oxygen permeability
• Tube uniformity
Consideration
For Risk
Assessment
• Product performance testing
• Product Quality testing (viscosity,
homogeneity within container
closure)
• API particle size, solubility,
polymorph and interaction
• Excipient Viscosity and lot to lot
variability
• Rheological properties and shear
• Phase separation
• Particle and Globule size
• Foaming characteristics
• Critical Process Parameters
Dose Uniformity
Local and systemic action
Particle Size Distribution
AND Spray Pattern
Container/ Closure and
Drug delivery device
Consideration
For Risk
Assessment
• Homogeneity of dry
powders or suspensions
• Raw Material particle
size and interaction
Consideration For Risk Assessment
• Spray pattern
• Size and Morphology of particles
• Propellant and formulation impact
Consideration For Risk Assessment
• Mechanical reliability, accuracy, robustness
• Compatibility with drug contact
components
• Shelf life or dose counter
• Knowledge sharing between drug applicant
and device applicant
• Protective properties
• Extractables/leachables
GPhA
Member
Companies
Contributors
• Marcy Macdonald
– Impax Labs
• Richard StecPerrigo
• Tony Amann-
Boehringer Ingelheim