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LifeCycle Management of Drug Products: Industry

Perspective

Dawn Culp

VP, Global Regulatory Affairs Policy, Mylan

The views presented here today are those of

the presenter and do not necessarily reflect

those of Mylan or the GPhA.

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• Q12 is a continuation of the Q8, Q9, Q10, and Q11 set of ICH

Quality Guidelines and will apply to pharmaceutical products

(chemical and biological)

• This lifecycle management guidance will provide clarity around

regulatory commitments in the dossier and how manufacturers can

more efficiently implement post-approval manufacturing changes

• It will provide a framework to facilitate the management of post-

approval CMC changes in a more predictable manner

Q9

Quality Risk

Management

Q8

Pharmaceutical

Development

Q11

Development and

Manufacture of

Drug Substances

Q10

Pharmaceutical

Quality System

Q12

Pharmaceutical

Lifecycle

Management

ICH Q12 – What?

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• There is no harmonized approach on technical and regulatory considerations

for lifecycle management

• While Q8 – Q11 provide opportunities for a more science and risk-based

approach for assessing changes, several gaps exist which limit the full

realization of the intended benefits

• Post-approval “operational flexibility” envisioned by Q8 – Q11 has not been

achieved

• Inconsistent utilization of post-approval change management plans and

comparability protocols

• To date, ICH has focused on the early stages of the product lifecycle

(development to launch). A similar focus is needed for the commercial

manufacturing phase to fill the gaps and fully realize the opportunities

promised by ICH Q8 – Q11

• Industry, regulators and patients will benefit from a reliable supply of high

quality products

ICH Q12 – Why?

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• Develop a harmonized approach to “regulatory commitments”

• Delineate the appropriate level of detail and information

necessary for regulatory assessment and inspection in the dossier

• Establish criteria for a harmonized risk-based change

management system

• Establish criteria for post-approval change management protocols

for proactively defined post-approval changes

ICH Q12 – How?

Expert Working Group

Rapporteur: Moheb Nasr (GSK)

Co-Rapporteur: Ashley Boam (FDA)

Industry

PhRMA

Regulators

FDA EFPIA

IGPA

BIO

EMA

PMDA Canada JPMA

EFCG Switzerland Taiwan

Singapore

ICH Q12 – Who?

USA (Perrigo)

USA / India (Dr. Reddy’s Labs)

EU (Mylan)

Japan (Towa Pharmaceuticals)

Small internal

working group

Switzerland

ICH Q12 – When & Where? ICH Q12 – When & Where?

Adoption of topic by approval of ICH Steering Committee to develop

concept paper

Agreement of concept paper and business plan by IQDG

June 2014:

Adoption of concept paper and business plan by Steering Committee

1st EWG Meeting (Lisbon, Portugal)

2nd EWG Meeting (Japan)

3rd EWG Meeting (USA)

Adoption of Step 2 Document

Adoption of Step 4 Document

July 2014:

Nov 2014:

June 2015:

Nov 2015:

Q2 2016:

Q2 2017:

Sept 2014:

Future:

Past:

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Since the first meeting:

• The EWG has broken out into 3 regional working groups to address

unique regional issues

• The EWG has also broken out into 4 drafting teams to work on

writing the 4 sections of the guideline

ICH Q12 – Progress to Date

North America Europe Asia

Regulatory Commitments

Change Management

Post-Approval Change Management Plan (PACMP)

Knowledge Management

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• Regulatory commitments define the binding information

concerning the manufacture and control of a pharmaceutical

product

• They are proposed by the manufacturer and approved by the

health authority

• They can provide the basis for applying appropriate regulatory

mechanisms for management of changes to a product and its

associated manufacture and control through the lifecycle

• The definition of these commitments will enable the

determination of the level of regulatory submission/notification, if

any, for post-approval changes; and the supportive information to

be included in the regulatory dossier to facilitate assessment and

inspection without increasing requirements

Drafting Team #1 - Regulatory Commitments

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• The foundation of managing products is the management of the

knowledge acquired throughout the lifecycle of the product

• Will focus on the utilization of knowledge, within a firm’s PQS, to

enhance clarity and to enhance communication within firms and

transparency with regulators (both assessors and inspectors)

• Knowledge management is defined in ICH Q10 as a systematic

approach to acquiring, analyzing, storing, and disseminating

information; however, from a practical standpoint, ICH Q12 will

build upon this definition so that the knowledge gained over the

product lifecycle can be effectively used within the industry and

communicated to the regulators

Drafting Team #2 – Knowledge Management

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• Quality risk management should be utilized to evaluate

proposed changes; and the level of effort and formality

of the evaluation should be commensurate with the level

of risk

• Take the principles from ICH Q9 and Q10 to provide a

framework for an adaptive/risk-based approach to

change, where adaptive means proportional to the

“criticality” of the change

Drafting Team #3 – Change Management

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• A PACMP is a regulatory submission or a section of a

submission that facilitates manufacturers’ ability to

implement manufacturing changes and improvements

without further regulatory submission; and enhances the

regulators’ understanding of the manufacturers’ change

management and quality processes

• The integration of the PACMP into the development of

an overall lifecycle management plan will be further

discussed by the ICH Q12 EWG

Drafting Team #4 – Post-Approval Change

Management Plan (PACMP)

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• Quality is not a department, it is a

state of mind (culture)

• ICH Q12 is not about making things

“easier” for us, it’s about doing

things right; and should facilitate the

opportunities for a risk-based

approach with responsibility and

accountability on the manufacturers

(“own the process”)

Product Lifecycle Management – Industry

Perspective

Quality

Idea

Development

Filing

Tech Transfer

Validation

Launch

Ongoing Manufacturing

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• The health authorities don’t set the bar, they set the floor

• Technology, globalization and consumerism are

constantly changing and the regulatory environment

needs to keep up

• It’s not what you know, it’s what you do with what you

know when you know it

Product Lifecycle Management – Industry

Perspective

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ICH Q12 – Generic Industry Position

Decreased burden on regulators and

a better understanding of company

Pharmaceutical Quality System (PQS)

for management of post-approval

CMC changes (increased confidence)

Greater opportunities for

innovation and continued

improvement

Increased industry responsibility

for quality and a reliable supply

of product

Goals

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• How?

(1) Regulatory Commitments

a) Focus on factors that are directly related to product performance

i. API and FP Specifications

ii. Control Strategy (as opposed to tactics)

iii. Commitments that ensure continued quality in the face of change (greater reliance on quality systems)

iv. Goal is to establish process-independent quality standards

(2) Broad Post-Approval Change Management Plans (PACMP’s)

a) Reflect back to Regulatory Commitments

i. Changes that don’t impact regulatory commitments don’t need PACMP’s

b) Limited value to using PACMP’s for individual changes

i. For Industry

» Requires 2 steps (PAS + 2nd submission)

» Requires separate PACMP’s for each change event

ii. For Regulators

» Additional workload (due to 2-step process)

» Requires review of separate PACMP’s for multiple changes

ICH Q12 – Generic Industry Position (continued)

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• Final Concept Paper Q12: Technical and Regulatory Considerations

for Pharmaceutical Product Lifecycle Management dated 28 July

2014. Endorsed by the ICH Steering Committee on 9 September

2014.

• Final Business Plan Q12: Technical and Regulatory Considerations

for Pharmaceutical Product Lifecycle Management dated 28 July

2014. Endorsed by the ICH Steering Committee on 9 September

2014.

ICH Q12 – References

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