The document summarizes a presentation on the pharmaceutical regulatory science landscape in 2015. It discusses:
1) Changes and emerging trends in regulatory sciences, including increased globalization and harmonization efforts.
2) Quality metrics and using data to understand industry performance and identify issues.
3) Shifting business models, including more outsourcing and the need for continuous quality improvements.
4) Ensuring data integrity and addressing challenges like lack of integrity raising doubts about safety.
2. Obaid Ali & Roohi B. Obaid,
Pharmaceutical & Biological Regulatory Sciences Forum 26 Dec 2015, Karachi
Dash Board of 2015
Pharmaceutical Regulatory Science’s Review
4. Not the view of DRAP
Current judgment of speaker
No obligation on DRAP
Regulatory experience
It has nothing to do
with any specific
commercial
product
It is just a
knowledge sharing
exercise nothing
more than that
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5. Background Review of
Regulatory Sciences
Changes & Emerging shape of
Regulatory Sciences
Discussion, Case Studies &
Explanation
25. Quality Metrics
(Russell Wesdyk, Acting Director for the Office of Surveillance, OPQ, CDER, FDA
How is industry performing?
Who & what is out there?
Do we understand our industry?
What should Regulatory Authority do when they show up at the site?
Can we sum up what we have with data & transfer that data into knowledge?
26. Quality Metrics
(Russell Wesdyk, Acting Director for the Office of Surveillance, OPQ, CDER, FDA
More information is better
than less information
27. Business Model Shifting
(Monika Cahilli, Green Mountain Quality Assurance)
Increased Outsourcing
Paper Tiger does not always work
Management needs to be fully engaged in Quality Agreements
Feedback mechanism for Control Strategy
Continuous review of electronic data
28. How many data points are involved to
support the release of one product?
Learn to embrace in perfection in order to
accept residual risk
Business Model Shifting
(Monika Cahilli, Green Mountain Quality Assurance)
29. Data Integrity
(Douglas Starn, Director Enforcement & Import Operations, FDA)
Integrity & Fraud are mostly close
Lack of integrity at one area raise question about others
Ability to assure safety & efficacy is doubtful
Data accountability is the only tool
30. Data integrity issues are not always easy to
see and thus difficult to remediate
It is better to be safe than sorry…proper
control can prevent and limit data integrity
issues
Data Integrity
(Douglas Starn, Director Enforcement & Import Operations, FDA)
31. Quality & Innovations are linked
(Lisa Zboril, Vice President Regulatory Affairs, Pfizer)
Product lifecycle … what occurs in manufacturing & how
reflected in submission
Quality submission is planning, control & continuous
improvement
Early planning to target product profile and label requirement
Regular communication of uncertainties
32. Continuous improvements include
regulatory intelligence, deficiency tracking,
lessons learned & scientific rigor of data
In generic world, the key to success is being
efficient, timely and accurate
Quality & Innovations are linked
(Lisa Zboril, Vice President Regulatory Affairs, Pfizer)
33. Make the reviewer excited that they
are getting an application from you
Quality & Innovations are linked
(Ted Sherwood, Acting Director, Office of Regulatory Operations, FDA)
34. Background Review of
Regulatory Sciences
Changes & Emerging shape of
Regulatory Sciences
Discussion, Case Studies &
Explanation
35. Proposed Product Manufacturing Classification System
Right
particle
Best
process
Difficult
API
Good
API
Ref:
Lilly, GSK ……….
36. Highly Soluble &
Highly Permeable
Highly Soluble &
Less Permeable
Low Soluble &
Highly Permeable
Less Soluble &
Less Permeable
BCS
43. Breakthrough
Life saving therapy is being coming
Hepat
itis C
Cholesterol
lowering
agents
Cance
r
drugs
Rare disease
therapies
2014
41 new drugs
10 biologics
44. 2015
1st Bio-similar approval in US
Zarxio from Sandoz
Over 50 applications are in pipeline
Quick response on Ebola
A beautiful collaborative demonstration of different
organizations & countries to combat deadly virus
45. Quality remains a Challenge
Predictable & timely approval
Reduced inspection burden
Quality Metrics on way
Smart &
Progressive
vision
Able to
detect
quality
problems
before they
occur
46. Changes Evolved
• CMC from pre-clinical/clinical through review to post
approval changes & generic drug development
Changes in Review
• Continue to oversee innovators and biosimilars
Biotechnological
Products
• Quality aspect during development & approvalNew drug product
• Post-marketing changes & generic drug developmentLifecycle
• Manufacturing operation, microbiology review &
preapproval inspection
Collaborative Oversight
47. Adoption of a Risk based Model
Target oversight
where quality
failures are most
likely to harm
patients
Product
Facilities
Process
48. Footprints of knowledge is in your backyard to navigate you …
Example
Elemental impurities
Ref: Pharmaceutical Technology,
March 2015, Andrew Teasdale et al.
51. Excipients
1. Mind
(Talc)
2. Metal catalysts
(Mannitol)
3. Plant origin
(cellulose)
4. Animal origin
(lactulose)
5. Without metal
catalysts (colloidal
SiO2)
Footprints of knowledge is in your backyard to navigate you …
52. Limited solubility in DP
& limited interaction but
High metal content in
packaging
Highest risk (high conc. of
metal in packaging; high
degree of interaction b/w
packaging & DP)
Lowest risk (low conc. of
metal in packaging;
limited interaction b/w
packaging & DP)
Good solubility in DP,
intimate contact, but low
metal content in packaging
From
Packaging
MetalContentinPackaging
Metal solubility in product
R
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K
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K
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Footprints of knowledge is in your backyard to navigate you …
53. Security of internal supply chain
Control of vendor elemental impurity specifications & elemental impurity
reporting on ingredient COA
Security of external supply chain + a quality history for each vendor
Audit history Level of complaints Recall etc.
PRIOR KNOWLEDGE IS THE WAY TO MOVE FORWARD
Footprints of knowledge is in your backyard to navigate you …
55. Industry & Regulatory Agencies on Global Watch
Lifecycle data
management &
Quality System
Innovative
strategies to meet
timeframes
Global framework
& collaborations to
secure supply chain
Drug development
& Drug Pricing
battle
Controversy on
strategies &
Science Scale
Modernization in
Manufacturing &
Quality Initiatives
Efficient generic
drug review
regulatory
framework
Policies to enhance
drug safety &
security
Reference
Jill Wechsler, 2015
56. Lifecycle data management & Quality System
Alteration in
System,
Formulation &
Test Method
Variation
submission
Costly & time
consuming
Regulatory &
Post approval
changes
Developing
International
Quality Standards
Integrations
Review,
Inspection &
Surveillance
57. Innovative strategies to meet timeframes
Expedite
development &
approval of
innovative drug
Quick results of
reviews
Innovative risk
mitigation
strategies
Less stability data
at submission
Accepting
amendment during
the review process
Increased post-
marketing
commitment
Early decision for
dosage form
Early decision for
method validation
strategies before
time
58. Global Framework & Collaborations to secure supply
Storm of counterfeit &
adulterated drugs
Over 2000 incidences
of pharmaceutical
crime reported in 2014
Theft, counterfeiting,
diversions, illegal drug
websites
Aggressive &
collaborative actions
June 2015 operation
Pangea VIII by
Interpole
Poor quality
medicines
SSFFC (Substandard,
Spurious, Falsely
Labeled, Falsified &
Counterfeit)
59. Drug Development & Drug Pricing battle
Costing
Therapeutic
value
Free
economy
Innovation
Fee Liability Profit
60. Controversy on Strategies & Science Scale
Quality Metrics Overworking Increased burden
Reduced
inspection
Reduced
regulatory burden
on post approval
Slow move
61. Modernization in Manufacturing & Quality Initiatives
More powers of
inspection
Recall power
New Inspection
approach
Unannounced
inspection
Tougher
inspections
Disregarding the
delaying, denying,
limiting or refusing
of inspections
62. Efficient Generic Drug Review Regulatory Framework
API focus Inspections
Quality &
Complaints
63. Policies to enhance Drug Safety & Security
Meningitis
outbreak
IV
Compounding
Contamination
Microbial Penicillin Standardization
65. Aseptic processing proven safe but not sterile
IncreasedseparationofPersonnel
Increased confidence in Sterility Assurance
Manual aseptic fill
Conventional aseptic fill
Barrier System
Open RABS
Closed RABS
Open Gloved Isolator
Closed Glove Isolator
Glove-less Isolator
67. Inhalation of a non-sterile product (Ribavirin powder for
solution) with microbial contamination ….
What is harm?
68. Inhalation of a non-sterile product (Ribavirin powder for
solution) with microbial contamination ….
What is harm?
Increase risk of respiratory infection
Patients are usually immuno-compromised and more
susceptible to infection
69. Inhalation of a non-sterile product (Ribavirin powder for
solution) with microbial contamination ….
What is harm?
Increase risk of respiratory infection
Patients are usually immuno-compromised and more
susceptible to infection
RECALL (Virazole Expiry date: Oct 2018)
Valeant Pharmaceuticals, USA
70. If you want to go fast, go alone
If you want to go far, go together