quality risk management - welcome to the pqg >€¦ · slide 2 i thrussell, mhra 13 ... • need...

©

Safeguarding public health

Quality Risk ManagementChallenges and opportunities

Ian ThrussellStrategy and Development TeamGMP Inspection, I&S Division

[email protected]

March 2008I Thrussell, MHRA

PQG QP Meeting

©

Presentation overview

• Current regulatory and external environment

• QRM fundamentals• system relationships, definition, primary principles,

Q9 model process, application

• Regulatory changes• EU and UK

• Challenges and opportunities

• Summary


PQG QP Meeting

©

Current regulatory and external environment

• Fundamental issue is patient safety – availability of products of appropriate quality

• Perceptions:- Regulatory processes inflexible - Innovation and improvement stifled- Risk averse compliance focus with non-science or non

risk-based regulations and guidance- Toleration of the status quo


PQG QP Meeting

©


Issues still occur despite regulations, guidance, standards, training, communication, inspection and enforcement:

- Serious manufacturing issues: Chiron influenza vaccine contamination

- Serious control issues: recent Foot and Mouth Disease- Cross contamination issues – glycerol, heparin, mix

ups- Unexpected events: TGN1412 (Northwick Park incident)- Criminal activities: counterfeiting

• Lessons being learnt!


PQG QP Meeting

©


• EU position- GMP for medicinal products for human use based on

Directive 2003/94/EC- An effective QMS is already mandated by EU GMPs and

most of the accepted common elements of an effective QS are already required by EU GMP.

- Risk management is implicit in the current guide.- Inspections conducted into company QSs for many years

but looking at QRM processes is newer.


PQG QP Meeting

©


• EU position:- “Risk” concept not new: mentioned 90 times and in 20

different documents in EU GMP legislation and guidance- “Unless otherwise justified” concept frequently used in

both GMP and Quality guidelines- Risk management use in other areas

· Medical devices: since early ’90s, e.g. ISO 14971 ‘Application of risk management to medical devices’

· Pharmacovigilance: risk management plans – 3 to 153 pages, used to extend knowledge on safety or change warnings/dosage/excipients, withdraw from market

· inspection of source plasma sites for blood products


PQG QP Meeting

©


• Pressure on cost pressures for industry and regulators- Margins / resources reduced- Drive for improved efficiency and effectiveness- Supply chains changing, more global and complex

• Recent initiatives:- ICH Q8, Q8R, Q9, Q10- Better and risk-based regulation:

· EU· Other regions and countries


PQG QP Meeting

©

QRM fundamentals – system relationships

Existing GMP

The Regulatorysystem

Quality system Q10

GMP

Quality Risk Management

Q9

Pharmaceutical

Development

Q8


PQG QP Meeting

©

QRM fundamentals – definition

‘A systematic process for the assessment,

control, communication and review of risks to

the quality of the drug (medicinal) product

across the product lifecycle.’


PQG QP Meeting

©

QRM fundamentals - primary principles

The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient

The level of effort, formality and documentation of the quality risk management process should be commensurate with the level of risk


PQG QP Meeting

©

Risk Review

Risk

Com

mu n

i cat

i on

Risk Assessment

Risk Evaluationunacceptable

Risk Control

Risk Analysis

Risk Reduction

Risk Identification

Review Events

Risk Acceptance

InitiateQuality Risk Management Process

Output / Result of theQuality Risk Management Process

RiskM

anage mentt ools

QRM fundamentals – Q9 model processDefine problem, assemble information, team and timeline

Choice of internal procedure or risk management tool - Q9 process (shown), FMEA, HACCP etc

Link to company’s QS


PQG QP Meeting

©

QRM fundamentals – application

• A structured, scientific decision-making process about risks to patients and therefore implicitly to product quality

• Across all stages of product lifecycle

• However …. formality is not always necessary:- Practical knowledge and internal procedures (e.g. SOPs)

will be appropriate- Define level where formal (QRM) or other processes apply- “Horses for courses”


PQG QP Meeting

©

QRM fundamentals – industry application areas

• Current use is largely reactive:

- on sites when there are significant problems

- use structure and formality to get to root cause(s)

- provides guide to rank issues

• Evaluating a company’s response when things go wrong is a major diagnostic indicator of the robustness of the organisation’s systems and culture


PQG QP Meeting

©

QRM fundamentals – industry application areas

• Proactive use during:- development:

- IMP/commercial: protection product / environment; choice of facility/equipment type; depth of validation of facilities/equipment, process, cleaning, IT; location / method / extent of EM; supply chain evaluation; training; change management systems; quality incidents systems

selection of product / process, studies to conduct, data to be submitted in CTA / MAA, specifications in PSF


PQG QP Meeting

©

QRM fundamentals – Competent Authority application areas

• European Commission: - Better Regulation launch in 2002- simplify and improve regulatory environment- impact assessments, consultations

• Changes to Compilation of Community Procedures - facilitate approaches to regulatory inspections - proposes baseline inspection time on different sites- aim is to establish common ground- no conflict with QRM/Better Regulation

• Updates to the EU GMP Guide – Chapter 1 and Annex 20


PQG QP Meeting

©

Regulatory changes – EU: Variations Regulations

• “Better regulation of pharmaceuticals: towards a simpler, clearer and more flexible framework on variations”- focus on the changes having a genuine impact on quality

and further reduce the overall number of variations- regulatory action classified according to relative risk- applies to Community and National Licences- design space optional but encouraged- continuous improvement encouraged- Type 1A - do and tell procedures: annual reporting or

immediate notification (admin procedures)- Type 1B by default


PQG QP Meeting

©

Regulatory changes – UK: Hampton Report

• ‘Reducing administrative burdens: effective inspection and enforcement’, March 2005

• Executive summary:

“Risk assessment should be comprehensive, and should be the basis for all regulators’ enforcement programmes. Proper analysis of risk directs regulators’efforts at areas where it is most needed, and should enable them to reduce the administrative burden of regulation, while maintaining or even improving regulatory outcomes.”


PQG QP Meeting

©

Regulatory changes – UK: Hampton Report

• Principles:- allow & encourage economic progress, intervene only

when there is a clear case for protection- comprehensive risk assessment to focus resources- no inspection without a reason - provide authoritative, accessible advice- businesses not have to give unnecessary information- quickly identify businesses that persistently break

regulations, face proportionate and meaningful sanctions- regulators accountable for their efficiency and

effectiveness, remain independent in decisions taken


PQG QP Meeting

©

Regulatory changes – UK: Better Regulation

• Not ‘no’ regulation!• Wide range of UK regulators in scope• Statutory Code of Practice: the Regulators' Compliance Code • Legal enabler for the Hampton Principles• BRE/NAO ‘reviews’ of the Principles are in progress

- 6 key areas:· Focus on outcomes Design of regulation· Advice and guidance Data requests· Risk based inspections Sanctions

• MHRA to be ‘reviewed’ during 2008


PQG QP Meeting

©

Regulatory changes – UK: MHRA business plan

• One of seven Strategic Agency Objectives:“Minimise the burden of regulation so far as is compatible with our public health role”

• Supported by Key Target 10 to ‘progress the Better Regulation agenda’- develop and implement risk assessments for all inspection

types- pursue the actions in the DH Simplification Plan - take forward Better Regulation of Medicines Initiative

(BROMI)


PQG QP Meeting

©

Regulatory changes – UK: MLX 345 on ‘risk-based inspection programme for good practice inspections’

• Public consultation closed 15 Jan 08- provides background and general approaches- starter questions invite responses- link to introduction of daily fees (MLX 344, <9 Jan 08)

• Process not event:- phased implementation- ‘risk appetite’ in pharmaceuticals is different to many other

regulated areas [FSA - ‘the level of harm or failure which one is prepared to accept’]

- consequences will directly affect the health of large number of individuals


PQG QP Meeting

©

Regulatory changes – UK: MLX 345 on ‘risk-based

inspection programme for good practice inspections’

• Learning from blood component regulation- blood banks not routinely inspected- desk assessment of annual compliance reports- inspect non-compliant sites

• For the more compliant companies - less frequent inspections and of less scope and depth ….

…. and vice versa!

• Current risk assessment focuses on high risk sites and inspection frequency


PQG QP Meeting

©

Regulatory changes – UK: MLX 345Model for risk assessment and inspection planning

Knowledge,Intelligence aboutsite, personnel etc.

INSPECTION

Self AssessmentReport

Post InspectionLetter Intelligence

Previous InspectionHistory

Corporate GovernanceCorporate Compliance

Statements

Risk ProfilePro-forma

Risk ManagementReview Board

ComplianceLetter to

Company ChiefExecutive

InspectorRisk Assessment

Inspection PlanningFrequency, Duration,

Scope Depth andBreadth

Regulatory Actions


PQG QP Meeting

©

Challenges and opportunities

• Trust and culture change:- Clear understanding of stakeholders needs and

options- Trust and openness in working and learning together- Culture change:

· Overcome internal conservatism and ‘silo’ thinking· Organisational change management – resistance

to change, new competencies needed


PQG QP Meeting

©


• Regulatory duty to take into account all kind of companies (global companies. medium and small size, generics etc)

• Must be no disadvantage to those with new approaches, especially first movers, or Small and Medium Enterprises

• Need to clarify and share definitions and understandings to facilitate effective implementation

• Degree of industry comfort with the life cycle approach?e.g. inspectors may go into Development more often


PQG QP Meeting

©


• Responses currently undergoing analysis - 145 responses were received.

• General agreement that agreed that regulatory inspection requirements should be based on risk to public health and that non compliant organisations should carry a greater inspection burden.

• Further guidance is being developed and will be issued on the risk assessment process and how its three key elements of compliance history and inspection intelligence, corporate compliance statement and self-assessment reports will be performed.


PQG QP Meeting

©


• The MHRA intends to work with the Industry to evaluate these processes.

• A pilot of is planned to commence in the 2nd Quarter of 2008.

• A dialogue will be maintained with stakeholders through seminars, consultative committees, stakeholder meetings, and individual meetings with targeted groups.


PQG QP Meeting

©

Conclusion

MHRA:

• Committed to safeguarding public health but with an appropriate level of flexibility.

• Successful implementation requires:- effective and robust QRM underpinned by an effective QS- trust and culture change

• Committed to fostering innovation: new products, new ways of working, product availability

• Pleased to be consulted and to support initiatives• Regulators also have finite resources - not possible to go

further or faster without them!


PQG QP Meeting

©

Abbreviations

• QRM: Quality Risk Management• Q8: ICH draft guideline - Pharmaceutical Development,

Quality by Design• Q9 ICH draft guideline - QRM• Q10 ICH draft guideline - pharmaceutical quality system• QS Quality Systems• CAPA Corrective and preventive action• EM Environmental monitoring• IMP Investigational Medicinal Product• PSF Product Specification File• CTA Clinical Trial Authorisation• MAA Marketing Authorisation Application


PQG QP Meeting

©

Crown copyright 2007

The materials featured within this MHRA presentation are subject to Crown copyright protection. Any other copy or use of Crown copyright materials featured in this presentation, in any form or medium, is subject to prior approval of the MHRA which has Delegated Authority from Her Majesty's Stationery Office (HMSO) to administer Crown copyright for MHRA originated material. Applications should be in writing, clearly stating the proposed use/reuse of the information, and should be sent to the MHRA at the following address: Conference and Education Function, 16th Floor, MHRA, 1 Nine Elms Lane, London SW8 5NQ. Fax 020 7084 3522 or e-mail [email protected]. You may not sell or resell any information reproduced to any third party without prior agreement. The permission to reproduce Crown copyright protected material does not extend to any material in this pack which is subject to a separate licence or is the copyright of a third party. Authorisation to reproduce such material must be obtained from the copyright holders concerned.

quality risk management - welcome to the pqg >€¦ · slide 2 i thrussell, mhra 13 ... • need...

Documents