The Future of Pharmaceutical Analytical Methods Regularity Path … · 2019-04-25 · The Future of Pharmaceutical Analytical Methods Regularity Path to Method Lifecycle Management

©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

[email protected]


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”

http://blogs.fda.gov/fdavoice/index.php/2016/02/modernizing-pharmaceutical-manufacturing-to-improve-drug-quality-ensuring-a-safe-and-adequate-supply-of-drugs/


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 ?


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


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


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


“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.


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?


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


Key Opinion Leaders (KOLs) Leading with MLCM

Contract Pharma Services Provider


KOLs Leading with MLCM

CDMO & Generics


“…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.”


“…we have higher confidence

in the data quality.”

Innovator



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>


MLCM Promotes

Safety, Quality & Standardization

2600+ monographs

in need of updating

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjOzO6q8IHgAhUSnOAKHap7CeYQjRx6BAgBEAU&url=https://qualitymatters.usp.org/strengthening-global-medicines-quality-usp-s-new-role-harmonization&psig=AOvVaw0f42IeP3u2uB9hjeMDziqB&ust=1548263106865786

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwju5tHz84HgAhXyUd8KHQuYAT4QjRx6BAgBEAU&url=https://www.purpleculture.net/pharmacopoeia-of-the-peoples-republic-of-china-2015-english-edition-vol-3-p-26223/&psig=AOvVaw3MjH6E5RebKGytFNcv-lY-&ust=1548264224540472

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjzpIKj9IHgAhWIVN8KHSIRBEgQjRx6BAgBEAU&url=https://www.emaze.com/@AIRRCQCI&psig=AOvVaw2IZiVreKAxwKiNgswKsBL7&ust=1548264316458484


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


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:


GO

METHODS!

The Future of Pharmaceutical Analytical Methods Regularity Path … · 2019-04-25 · The Future of Pharmaceutical Analytical Methods Regularity Path to Method Lifecycle Management

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