Day 3 of CTD CCK Session Series 22 Sep 2019 (First half lecture before tea), Hotel Regent Plaza, Karachi

1. Pharmaceutical Regulatory Dossiers Compliant
with Modern Sciences
22 Sep 2019
Obaid Ali & Roohi B. Obaid
Day 3

3. FDA’s new pharmaceutical quality initiative:
Knowledge aided assessment & structured
applications
Reference
Lawrence Yu et al,
2019
It reflects the views &
understanding of presenter.
It may not be construed to
represent the views of referred
paper’s authors or policies of
organization or association to
which presenter has ties
Disclaimer

4. PAT, GMP of 21st Century
Quality by Design (QbD)
ICH, Operational Excellence

5. Summary based Review
Question based Review
Integrated Quality Assessment
KASA

6. 1
KASA is designed to
2 3 4

7. Capture & manage knowledge during the lifecycle
of a drug product
1
KASA is designed to
2 3 4

8. Establish rules & algorithms for
risk assessment, control & communication
1
KASA is designed to
2 3 4

9. Perform computer aided analysis of applications to compare
regulatory standards & quality risk across applications & facilities
1
KASA is designed to
2 3 4

10. Provide a structured assessment that minimize text based
narratives & summarization of provided information
1
KASA is designed to
2 3 4

11. KASA interface tabulates
for each critical product quality attribute
What
Inherent risk to quality

12. KASA interface tabulates
for each critical product quality attribute
What
Control approaches
Using a list of generalized structured
description related to pharmaceutical
design, development, control strategy
& facility implementation

13. KASA interface tabulates
for each critical product quality attribute
What
Concise summary
from the assessor detailing how the
generalized approaches are applied in
the regulatory applications

14. KASA interface tabulates
for each critical product quality attribute
What
Links
to supporting information from the
applications

17. Pillar 1
Assessment of Risk to Quality by Establishing
Rules & Algorithms

18. Pillar 1
Assessment of Risk to Quality by Establishing
Rules & Algorithms
Initial inherent product &
manufacturing risk
Failure Modes, Effect & Criticality
Analysis (FMECA) approach
Objectively & quantitatively assessed & rank risk associated
with failure modes of drug product design & manufacturing

19. Pillar 1
Assessment of Risk to Quality by Establishing
Rules & Algorithms
Product Risk
consider each critical drug product quality attribute
e.g. assay, potency, dissolution, purity, uniformity

20. Pillar 1
Assessment of Risk to Quality by Establishing
Rules & Algorithms
Manufacturing Risk
consider the impact of proposed material transformation steps on
the product quality attributes &
The potential risk involved with implementing the proposed
control strategy at the manufacturing site

23. Pillar 2
Risk Control by assessing Product
Design/Understanding and Quality Standards
Inherent Risk of Pillar 1 is controlled by
design of product and the use of patient focused
quality standards

24. Pillar 2
Risk Control by assessing Product
Design/Understanding and Quality Standards
Product Risk Control focuses
Drug substance characteristics & drug product design
understanding & control

25. Pillar 2
Risk Control by assessing Product
Design/Understanding and Quality Standards
DS Characteristics
Risk in therapeutic index, manufacturing complexity,
adequacy of control for identity, purity, stability &
quality

26. Pillar 2
Risk Control by assessing Product
Design/Understanding and Quality Standards
Product Risk Assessment
Product design, intended use, degree of product
understanding & product QC inherent to the CQAs

27. Pillar 2
Risk Control by assessing Product
Design/Understanding and Quality Standards
DP Design determines
Fit for intended use, meet patient needs & maintain its
performance through its proposed shelf life

28. Pillar 2
Risk Control by assessing Product
Design/Understanding and Quality Standards
Product understanding is the ability
to link input CMAs to output CQAs so that input
material attributes can be appropriately constrained to
control risk to the product quality (Yu et al., 2014)

29. Pillar 2
Risk Control by assessing Product
Design/Understanding and Quality Standards
KASA System
Capture knowledge and signals from noises across
application & facilities

30. Pillar 2
Risk Control by assessing Product
Design/Understanding and Quality Standards
Assessment to determine acceptability
Applicant specifications based on desired clinical
performance instead of process capability or
manufacturing process control

31. Pillar 2
Risk Control by assessing Product
Design/Understanding and Quality Standards
KASA System
Increase flexibility within pharmaceutical
manufacturing while continuing to maintain quality

34. Pillar 3
Risk Control by assessing Mfg/Facility &
Performing Approval Inspections
Manufacturing Risk Control focuses
Design & implementation of manufacturing process

35. Pillar 3
Risk Control by assessing Mfg/Facility &
Performing Approval Inspections
All critical sources of common cause variability are identified &
explained
Mfg process is generally considered well
understood & controlled when

36. Pillar 3
Risk Control by assessing Mfg/Facility &
Performing Approval Inspections
Variability is managed by the process at all scales through successful
implementation of the control strategy
Mfg process is generally considered well
understood & controlled when

37. Pillar 3
Risk Control by assessing Mfg/Facility &
Performing Approval Inspections
Process performance & product quality attributes can be adequately
& reliably monitored & controlled (Yu et al., 2014)
Mfg process is generally considered well
understood & controlled when

38. Pillar 3
Risk Control by assessing Mfg/Facility &
Performing Approval Inspections
Facility risk control, or the implementation element of manufacturing
risk, focuses on the
manufacturer’s GMP status & ability to support the control and
continued performance of the operations.

39. Pillar 3
Risk Control by assessing Mfg/Facility &
Performing Approval Inspections
Determination of risk control leverages the demonstrated capabilities
of the manufacturing or testing facilities (as it relates to the proposed
manufacturing process)

40. Pillar 3
Risk Control by assessing Mfg/Facility &
Performing Approval Inspections
Evaluation of facility’s recent manufacturing history, experience of
the facility within the unit operations included in the application &
relevant quality signal for any similar already marketed product etc.

41. Pillar 3
Risk Control by assessing Mfg/Facility &
Performing Approval Inspections
Remaining risk is assessed by preapproval inspection and post
approval inspection to see reliability, accuracy of the submitted data
and ability to reproduce.
Objective standards are used to identify the need of inspection.

42. Pillar 3
Risk Control by assessing Mfg/Facility &
Performing Approval Inspections
Structured format i.e. CTD and submitted via electronic mode

43. Pillar
3
Pillar
2
Pillar
1
Assuring patient focused quality standards and
the objectivity of regulatory actions through
knowledge management
KASA contributes

44. Pillar
3
Pillar
2
Pillar
1
Enhancing science and risk based regulatory
approaches through established rules and
algorithms
KASA contributes

45. Pillar
3
Pillar
2
Pillar
1 Enriching regulatory oversight through
lifecycle management of products & facilities
KASA contributes

46. Pharmaceutical Regulatory Dossiers Compliant
with Modern Sciences, Karachi, July – Sep 2019
Thank You