A Practical Approach to Implementing ICH Q10 Pharmaceutical Quality Systems

A Practical Approach to

Implementing ICH Q10

Pharmaceutical Quality Systems

Chris Masterson

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A Practical Approach to Implementing

ICH Q10 Pharmaceutical Quality Systems

Table of Contents:

Foundation

“Simple” Process

Quality Manual and Quality Policy

GMP Lifecycle Policy

Quality Objectives / KPIs

Continual Improvement Plan/Report

Management Review

Conclusion

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The Foundation

The Foundation: Have procedures! (21CFR 211.100 (a))

Follow them! (21CFR 211.100 (b))

What is a “Pharmaceutical Quality System” (PQS)? A comprehensive model of an effective quality “system”, including

ISO concepts and GMP regs using a product life cycle approach to enhance the quality of medicine.

ICH Q10 Objectives: Section 1.5 Establish, Implement and Maintain PQS

Monitor and Control PQS

Continually Improve PQS

(Note: Time doesn’t permit hitting everything in ICHQ10.)

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Foundation Toolbox: “HOW” You Do It

Moral “Compass”

Tenacious/Fearless

Continuous Improvement

Candor

Discovery

Big Picture View

Wisdom/Knowledge (Culture shock)

Place the tools in your toolbox…and let’s go.

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“Simple” Process

Slide format will describe:

ICH Q10 Section Reference

Brief description (simplified from ICH Q10)

Interpretation / Advice

Example(s)

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Quality Manual and Policy (1.8; 2.2)

Section 1.8: Quality Manual

(a) Quality Policy (Refer to Section 2.2)

(b) Scope

(c) Processes, including linkages and interdependencies

(d) Management Responsibilities

Section 2.2: Quality Policy

(a) Sr Mgt to establish Quality Policy to provide direction

(b) Comply with reg. reqs. and continually improve PQS

(c) Communicate to all; all should understand.

(d) Review periodically for continued

effectiveness.

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Quality Manual and Policy

Interpretation / Advice

Quality Manual: NMT 10 pages long

Embed Quality Policy in Quality Manual

Simple and easy-to-read

Very high level

Endorsed / Signed by QMRC

“Example” Quality Manual can be shared individually.

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Quality Policy Example

The Quality mission is to assure that COMPANY X commercial and clinical products are manufactured, tested and released to meet the highest standards for quality, safety, identity, strength and purity, while facilitating innovation and improvement and adding value to COMPANY X.

We are committed to successful collaboration with internal and external customers to ensure our customers are educated on COMPANY X Quality expectations, assuring GXP regulations are met or exceeded, best practices are incorporated and robust and efficient Quality processes are developed, followed and continuously improved.

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Quality Manual and Policy

Quality System Processes

The Quality System is comprised of the following

systems. Documented policies/procedures shall be

established, maintained and continuously improved.

Written Procedures

Written procedures will be generated and followed to control and

maintain documentation. The magnitude of control is dependent on

the type of document ranging from level 1 (least specificity) through

level 4 (greatest specificity) as follows:

Level 1: Quality Manual

Level 2: Policy Documents

Level 3: Procedural Documents

Level 4: Detailed Instructional Documents/Records

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Quality Manual and Policy

ID/include Quality Systems needed.

Document System

Deviation, Investigation

CAPA, Change Control

Customer Complaint, Recall

Quality (Technical) Agreement, Product Discontinuation

Product Disposition, Annual Product Quality Review

Out of Spec (OOS), Risk Management, Self Inspections

External Audits, Nonconforming Product Control,

Inspection, Sampling and Testing

Etc.

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GMP Lifecycle Policy (1.3, 1.7(b), 3.1)

1.3: The regional GMPs do not explicitly address all product lifecycle stages. This guideline encourages the use of science and risk based approaches at each lifecycle stage, promoting continuous improvement.

1.7(b): Elements should be applied in a manner that is appropriate and proportionate to the lifecycle stage, recognizing the goals and knowledge of each stage.

3.1Lifecycle Stage Goals: 3.1.1 Development (Preclinical, Ph 1, Ph 2, Ph 3): “Design” a product and process to meet

intended performance and meet customer needs. Refer to ICH Q8.

3.1.2 Technology Transfer: Transfer product and process knowledge between development and manufacturing and within/between manufacturing sites. Forms basis for the Mfg process, control strategy, PV approach and continuous improvement.

3.1.3 Commercial Mfg: Achieve product realization, establish and maintain a state of control and continuously improve.

3.1.4 Discontinuation: Planned approach to ending the product life. (E.g. Stability tests, complaints, doc retention, sample retention, etc.)

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GMP Lifecycle Policy

Interpretation / Advice: Create a “GMP Lifecycle Policy” to provide direction to

company. (Resource: PDA)

Define in “SOP” the hand-off from Development to Mfg. (E.g. PD handles Ph 1/2; Mfg handles Ph 3 and Comm.

Define in “SOP” the hand-off from Analytical Development to QC. (E.g. AD handles Ph 1/2; Mfg handles Ph 3 and Comm.

Quality Unit GMP oversight is required for all product intended for human use.

Discontinuation “SOP” needed. (low priority until unprepared)

“Example” GMP Lifecycle Policy can be shared individually.

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Product Lifecycle

Discontinuation

Commercialization

Development

Tech Transfer

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Product Lifecycle from ICH Q10

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Quality Objectives (2.3)

2.3 Quality Planning 2.3(a) Sr Mgt should ensure Quality Objectives are defined and

communicated.

2.3(b) Quality Objectives are supported by all levels.

2.3(c) Quality Objectives should align with company strategy and be consistent with quality policy.

2.3(d) Mgt should provide appropriate resources and training to meet quality objectives.

2.3(e) Performance Indicators that measure progress against Quality Objectives should be established, monitored, communicated regularly and acted upon. (See “Management Review”)

Interpretation / Advice Communicate QOs to Sr Mgt, with industry news. (E.g. Quarterly update

from Quality Head to CEO and staff on KPI’s and 1 page “newsletter” with links.)

Bump up One Goal to HIGHEST Level

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Quality Objectives / KPIs

Advice:

Develop 4-6 that will help show “Company GMP Compliance”. (Measuring compliance, not Quality group)

Focus on areas of “opportunity” or “pain points”

If you could improve only a few areas, what would they be?

A. Define “As Is”. Where you are.

B. Define “To Be”. Where you want to be at year end.

Define how to get from A to B. Build “Road Map”.

Define what to measure, formulae and process / people to measure them.

Must be SMART: Specific, Measurable, Achievable, Relevant and Time-bound.

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EXAMPLE of Quality Objectives: KPIs

Target January February March April May June July August September October November December YTD YTD

Cumul. Total

1 On time closure of Quality Systems

1a Deviations (Internal)> 80% 50% 14% 45% 100% 54% 37 QS

1b CAPAs> 80% 25% 50% 80% 80% 63% 16 QS

1c Complaints> 80% 100% 100% 100% 100% 100% 69 QS

1d OOSs (Internal Laboratory Investigations)> 80% N/A N/A 100% 100% 100% 3 QC

2012 Quality Objectives: Tier 1 by Month - All Departments

KEY PERFORMANCE INDICATOR (KPI)Presenter NOTES

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Continual Improvement (1.5.3; 2.4)

1.5.3 Facilitate continual improvement by identifying and implementing product quality improvements. Use Quality risk Mgt.

2.4 Management should determine and provide resources (people, cash, fac/equip, materials) to implement, maintain and continually improve the PQS.

4.2 Monitor regs, guidance and industry trends.

Interpretation / Advice: Tie to Corporate/Department GOALS! Cultural.

Brainstorm Systems’ Gaps

Do you have all Quality Systems (SOPs, Policies, etc)?

Document System, Deviation, Investigation, CAPA, Change Control, Customer Complaint, Recall, Quality (Technical) Agreement, Product Discontinuation, Product Disposition, Technology Transfer, Annual Product Quality Review, Out of Spec (OOS), Risk Management, Self Inspections, External Audits, Nonconforming Product Control, Inspection, Sampling and Testing

Prioritize Gaps (E.g. Ranking)

Fill Gaps (E.g. Use tool such as CI Plan/Report)

Speak up if a group lacks resources; Quality’s responsibility to ID resource needs.

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Continual Improvement

Examples

Continuous Improvement Plan: Q1

Continuous Improvement Report: Q1 of next year

Quality intranet site; Monthly Quality Newsletter

“Example” Continuous Improvement Plan and Report can

be shared individually. Keep Simple and SMART!

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Management Review (2.1; 2.4; 2.6; 3.2.4;

4.1; 4.3) Section 2.1: Management Commitment

(a) Senior Mgt must assure a PQS is in place to achieve “Quality Objectives” which are communicated to all.

(b) Mgt assists in PQS design and implementation and visibly/strongly supports efforts. Assures quality issues are escalated. Assures “independent” Quality authority is communicated to all. Performs “Management Reviews”. Advocates “Continuous Improvement”. Commits resources.

2.4 Resource Management: Management should determine and provide resources (people, cash, fac/equip, materials) to implement, maintain and continually improve the PQS.

2.5: Internal Communication: Management should assure communication processes are established, used and include escalation of issues and broad communication throughout org.

2.6: Management review

(a) Senior Mgt must be responsible for PQS governance through Management Review to assure continued PQS suitability and effectiveness.

(b) Mgt must assess conclusions of periodic reviews of process performance and product quality of the PQS.

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Management Review 3.2.4: Management Review of Process Performance and

Product Quality: Management review should assure process performance and product quality are managed over the lifecycle. How you set up reviews depends on org. complexity. Management should assure communication processes are established, are timely, are used and include escalation of issues to Sr Mgt. for review. Include: (1) Reg. Authority inspections and commitments, audit findings and

other org. assessments.

(2) Periodic Quality reviews that may can include: Complaints and Recalls

Process performance and product quality monitoring conclusions

CAPA effectiveness for process and product changes

(3) Previous Management Review follow-up actions

Identify:

(1) Improvements to Mfg. processes and products

(2) Provision, training and realignment of resources

(3) Capture and dissemination of knowledge

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Management Review

4.1 Management review of the PQS: Mgt. should have a

formal review process for the PQS periodically, to

include:

Quality System Objectives and KPIs (e.g. Complaint, CAPA,

Dev, Change control, CMO activities, internal audits,

trending, risk assessments, reg inspections and customer

audits

4.3 Outcomes can include:

Improvement of PS and related processes.

Resource (re)allocation and training

Revisions to Quality Policy or Quality Objectives; Escalate

results to Sr Mgt

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Management Review

Interpretation / Advice:

Quality reporting structure is important! Independence needed (E.g. Report/Dotted line to CEO)

Quality Unit Approval/Rejection responsibility/authority shall not be questioned. (21CFR 211.22(a))

Develop a Quality Council or Quality “Management Review” Committee (QMRC) who is responsible for fulfilling the “Management Review” role. Choose senior managers, but those who are engaged in the business (recommend at the Director level). Depending on the company size, a corporate QMRC may be formed, with local Quality Councils. Regardless, a group must perform this function which fits into your org structure.

Develop a Quality Specifications Committee to review and approve test specifications and testing standards. Likely a separate team with analytical testing experts. In young companies, may want to merge with QMRC.

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Management Review Example(s)

Management Review : (Embed in Quality Manual) Management review of the Pharmaceutical Quality System will be

ongoing via the QMRC

Quality Management Review Committee (QMRC) Senior management will review the suitability and effectiveness of the Cubist

Quality Systems periodically to ensure Quality Objectives are met. This Quality Management Review Committee (QMRC) will have a charter defining its responsibilities.

Quality Specifications Committee (QSC) Specifications will be approved and endorsed by a Quality Specifications

Committee (QSC). The QSC meets to review proposed new and revised quality policies, procedures, specifications and standards. Meeting minutes from all QSC meetings are required to be recorded and are maintained in Quality department files.

“Example” QMRC and QSC Meeting Charters can be shared individually.

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Conclusion:

Read ICH Q10!

Write a Quality Policy

Write a Quality Manual

Educate colleagues to create “Quality Culture”

Start/Maintain “Management Review” meetings

Define SMART “Quality Objectives”

Write a “GMP Lifecycle” Policy

Create a “Continuous Improvement” culture Write a CI Plan in Q1

Write a CI Report in Q1 of following year

Keep it Simple.

(Catch me afterward if you’d like specific questions answered.) Available for review: 2012 Q. Obj; Q. Manual; 2011 CI Plan and Report; 2012

Goals; QSC Charter; QMRC Charter

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Backup Slide

Network with colleagues; share best practices

Use the concept of continual improvement; “Rome wasn’t

built in a day”.

Use Operational Excellence (Lean) tools to assist (E.g.

Brainstorming, Narrowing, Selection, Ranking and

Prioritization)

Use corporate tools (e.g. OLEx)

Don’t restrain yourself; look outside pharma

Partner Education / Build Relationships

Industry should Lead (develop Quality Principles)

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