©2019 Waters Corporation 1COMPANY CONFIDENTIAL
The Future of Pharmaceutical Analytical Methods
Regularity Path to Method Lifecycle Management
Jonathan E. Turner
Sr. Product Manager
Waters Corporation
©2019 Waters Corporation 2COMPANY CONFIDENTIAL
Quality Issues
Exponential Growth of Recalls
“When manufacturing problems arise in drug
manufacturing facilities, drug shortages may follow...”
“65 % of all drug shortages are caused by manufacturing
and quality issues”
©2019 Waters Corporation 3COMPANY CONFIDENTIAL
Regulatory Timeline
2002
FDA Initiative
Pharmaceutical
Quality for the 21st
Century
2018
ICH Q12- 5th quality
guideline, product & process
development Lifecycle
ICH Q2(R2) - Validation
2010
Nethercote, et al:
Three Stage FDA
Lifecycle Approach
for process
validation applies
to methods
2011
FDA updates 1987
guidance: Process
Validation: General
Principles &
Practices
2004
FDA publishes
Pharmaceutical
cGMPs for the 21st
Century –A Risk-
Based Approach
2017
USP Chapter <1220>:
The Analytical Procedure
Lifecycle in review
2015
FDA Analytical Procedures
and Methods Validation for
Drugs and Biologics
Guidance for Industry
Method Lifecycle included
2019
ICH Q14
Analytical Procedure
Development
Final Concept Paper
2005 – 2012
ICH Q8, Q9, Q10, Q11
Modernizes pharma’s
approach to Quality
2014
USP 621 Allowable
Adjustments for Isocratic
Methods
2019
USP 621 Allowable
Adjustments for Gradient
Methods ?
©2019 Waters Corporation 4COMPANY CONFIDENTIAL
Regulatory Guidelines related to MLCM
Process Development:
Q8, Q9, Q10, Q11 - Control strategies &
QbD for process repeatability
In Review:
ICH Q12 - Chapter on applying risk based
approaches to support (post approval) CMC
changes across the product lifecycle
ICH Q14 – Analytical Procedure Development
• To improve regulatory flexibility on post
approval method changes
• To facilitate more efficient, sound scientific
and risk based method approvals and post
approval changes
©2019 Waters Corporation 5COMPANY CONFIDENTIAL
Regulatory Guidelines related to MLCM
General Chapters:
Transfer of Analytical Procedures <1224>
Validation of Compendial Procedures <1225>
Verification of Compendial Procedures <1226>
Proposed Chapter:
USP <1220> The Analytical Procedure Lifecycle
©2019 Waters Corporation 6COMPANY CONFIDENTIAL
June 2018 (FDA Voices)
Emphasizing the importance of safety across
a drug’s lifecycle – Safety remains a key
component of our new plans.
We will work to establish a unified post-market
safety surveillance framework to monitor the
benefits and risks of drugs across their lifecycles,
both before and after approval.
Quality: A Major Area of Focus for the FDA:
FDA Proposes Process Modernization to Support New
Drug Development
©2019 Waters Corporation 7COMPANY CONFIDENTIAL
“Patients expect and deserve high-quality drugs
– this means consistently safe and effective
medicines, free of defects and contamination”.
July 2018: Formal initiation of two programs:
– the Quality Metrics Feedback Program and
– the Quality Metrics Site Visit Program
Quality: A Major Area of Focus for the FDA:
FDA Announces Two Initiatives to Modernize Drug
Quality Programs
The programs will help drug manufacturers to gain a better understanding of how
quality metrics are a common feature of quality culture, and support
improvements in product and process quality.
©2019 Waters Corporation 8COMPANY CONFIDENTIAL
Current regulatory guidelines do not provide
a framework that encourages users to
reliably understand, control, and
potentially reduce sources of variability
Drawback of Current Regulatory Guidelines Related to
Methods
What‘s the variability?
How much
variablity is
acceptable?
What‘s causing the variability?
Can we control
the variability?
Can we reduce
the variability?
©2019 Waters Corporation 9COMPANY CONFIDENTIAL
MLCM promotes identification of variabilities and implementation of control
strategies to minimize risks and increase method performance
MLCM leads to robust methods that are less susceptible to failures and is
potentially flexible to regulatory changes
Quality methods Quality Data Quality Products
Method Lifecycle Management (MLCM)
Approach
©2019 Waters Corporation 10COMPANY CONFIDENTIAL
Key Opinion Leaders (KOLs) Leading with MLCM
Contract Pharma Services Provider
©2019 Waters Corporation 11COMPANY CONFIDENTIAL
KOLs Leading with MLCM
CDMO & Generics
©2019 Waters Corporation 12COMPANY CONFIDENTIAL
“…the consensus is that in the long run,
this approach will afford more robust
methods, we’ll have less failure, and there
is potentially some regulatory flexibility.”
KOLs Leading with MLCM
“…we have higher confidence
in the data quality.”
Innovator
©2019 Waters Corporation 13COMPANY CONFIDENTIAL
KOLs Leading with MLCM
Chair: USP Validation & Verification Expert Panel
“The reasons behind USP proposed
Chapter<1220> The Analytical Procedure
Lifecycle is to decrease the frequency that
we see Out-Of-Specification (OOS) and Out
of Trend (OOT) results and to facilitate
smooth transfer of methods across
laboratories.”
General Chapters:
Transfer of Analytical Procedures <1224>
Validation of Compendial Procedures <1225>
Verification of Compendial Procedures <1226>
Proposed Chapter:
The Analytical Procedure Lifecycle <1220>
©2019 Waters Corporation 14COMPANY CONFIDENTIAL
MLCM Promotes
Safety, Quality & Standardization
2600+ monographs
in need of updating
©2019 Waters Corporation 15COMPANY CONFIDENTIAL
Waters Can Help!
Regulatory Audit (483 Observations)
MLCM can minimize OOS & OOT
Waters is uniquely suited to help!
-Greg Martin, Complectors Consulting & Chair USP Validation & Verification Expert Panel
0%
5%
10%
15%
20%
25%
30%
35%
Written Procedures SpecificationDetermination
Change ControlProcess
Investiagation(OOS) &
documentation
Cleaning Related Calibration records& Procedures
Stability protocol,statistical data
Method Validation Traininingrequirements
Laboratory ControlsInvestigation, (OOS)
Documentation
Training
Requirements
Trend Reporting, MVM,
Traceable Data and more…
Professional ServicesCert Vials & Method Validation Kits LC Portfolio
©2019 Waters Corporation 16COMPANY CONFIDENTIAL
Is a more holistic approach to method management
Promotes identification of parameters which contribute
significantly to method variability
Uses control strategies to minimize risks and increase
method performance
Leads to robust methods that are less susceptible to failures
and provides potential flexibility to regulatory changes
Improves transparency
Leads to better quality methods, and in return, better quality
products
Method Lifecycle Management
A New Approach to Understand & Mitigate Risk
Methods Lifecycle Management:
©2019 Waters Corporation 17COMPANY CONFIDENTIAL
GO
METHODS!