Introduction & Background Medicines and Healthcare Products Regulatory Agency

25 June 2013 – ANVISA, Brasilia Mark Birse, Group Manager Inspections (GMP/GDP)

We protect and improve the health of millions of people

every day through the effective regulation of medicines and

medical devices, underpinned by science and research

Our Mission

Clinical Practice Research Datalink

A New Perspective

To maximise the health gain that can be achieved through the

use of anonymised linked NHS data in research studies and

help improve the way clinical trials of innovative medicines

can be undertaken.

National Institute for Biological Standards and Control

A New Perspective

• World leader in

international

standardisation and

control of biologics

• Responsible developing

and supplying >95%

WHO global

measurement standards

Regulation of

Medicines

Clinical Trials Authorisations

Marketing Authorisations

Post Marketing Safety Monitoring

Licensing of manufacturers and wholesale dealers

Inspections

Enforcement and Prosecution

Regulation of

medical devices

Overseeing Notified Bodies

Post Market Surveillance/inspection

Enforcement and prosecution

Blood Safety and

quality Adverse Event reports

Inspections

A New Perspective

Regulatory Functions

The Agency’s Structure Agency Board

Chair - Sir Gordon Duff

+ 8 non-executive directors

Chief Executive

Sir Kent Woods

Licensing

Ian Hudson

Devices

John Wilkinson

Inspection,

Enforcement &

Standards

Gerald Heddell

Information

Management

Alison Davis

Human

Resources

Geoff LeFevre

Operations

& Finance

Peter Commins

Policy

Jonathan Mogford

Communications

Rachel Bosworth

Vigilance & Risk

Management of

Medicines

June Raine

Corporate Executive Team

CPRD

John Parkinson

NIBSC

Stephen Inglis

NIBSC

Stephen Inglis

Risk Based Inspection Programmes:

Regulators Mark Birse, Group Manager Inspections (GMP/GDP)

Agenda

Risk Based Inspections: Regulators

• Inspection planning

– PIC/S model

– Inspection duration and focus

– Regulatory convergence

– New MHRA RBI model – Feb 2013

• Compliance other than inspection

• Innovation

A RECOMMENDED MODEL FOR RISK-BASED INSPECTION

PLANNING IN THE GMP ENVIRONMENT

PI 037-1

1 Jan 2012

PIC/S Recommendation PI 037-1

• Simple and flexible Quality Risk Management tool that rates

manufacturing sites on the estimated risk that they may pose

• For Inspectorates when planning the frequency and scope of GMP

inspections

• Applied following the completion of a first full inspection

• Allows inspectorate to assign a relative risk rating to manufacturers

• Note: a recommendation only

PIC/S

PIC/S

PIC/S

PIC/S

PIC/S

Frequency and length of inspections

At MHRA standard length of inspection is based on:

Licence type(s) v Site size

(Where multiple licenses are held time on site may be

increased as assessed by the Inspector)

Safeguarding public health

Frequency and length of inspections

Frequency and length of inspections

Regulatory Convergence

• Waiver programmes

• EUDRA GMDP

• EUDRA 3rd Country planning

• PIC/S inspection plans shared - make joint

• TGA model

• EDQM plans shared

New MHRA RBI system – Feb 2013

Objectives of new system:

• To improve the quality of medicines on the UK market

• To improve compliance through self regulation

• To change company behaviours

• To reduce regulatory burden whilst maintaining regulatory compliance

• To optimise the use of inspection resource

New MHRA RBI system – Feb 2013

MHRA has developed new IT functionality in partnership with:

Accenture (RICF)

• Allows risk-related information to be stored in a single location – the Risk

Information Case Folder (RICF)

• Adopts a company hierarchy allowing data to be assessed at site and/or

company and/or company group level as well as viewing information across

the range of GXPs

Oracle Health Sciences (Empirica Risk)

• Empirica Risk uses a sophisticated statistical algorithm (using three

interlocking sub-models: multivariate normal, negative binomial and logistic

regression) to analyse risk signals and suggest whether current planned

inspection dates should be altered in response to signals.

New MHRA RBI system – Feb 2013

The new system could allow greater levels of information sharing across

inspectorates and risk based decisions to be made on wider data sets

and globally across different Competent Authorities.

• MHRA is putting interested Inspectorates in contact with Oracle.

Intelligence and risk information currently being collected and held at

other Competent Authorities could be used to strengthen the MHRA

system. The sites within the MHRA system supply wider than just the

UK or even EU.

• MHRA is considering ways to widen it’s intelligence gathering and

allow this data to be supplied to us.

Compliance challenges across the product lifecycle

Research

Preclinical

Phase Clinical

Phases

Launch

Manufacturing

& Distribution

Innovation

GDP, GPvP GLP GMP, GCP

Regulations

regulators Engagement Engagement

Innovation

Innovation Office

MHRA Innovation Office launched March 2013:

• Part of the UK government’s industrial strategy for life sciences

launched in December 2011 which is designed to help overcome

barriers and create incentives for the promotion of healthcare

innovation.

• To support research and ensure that regulation does not stifle

innovation.

• Covers novel medicines, medical devices and processes used to

manufacture these products.

• Simple form and dedicated contact point

– innovationoffice@mhra.gsi.gov.uk

– 20 day response time

MHRA Compliance Improvement Programme

Anticipation of supply chain and compliance risk indicators as RBI inputs

• Gathering of information to identify potential supply chain vulnerability for those

products considered 'essential'

Risk based escalation of companies demonstrating poor compliance

• Escalation prior to reaching the threshold for considering regulatory action

• ‘Warning letter' type approach to senior management to alert to compliance concerns,

and clearly outlining the consequences of continues non-compliance.

• Close monitoring through inspection and non-inspection measures

• Aim: to encourage and focus company attention on returning to a state of compliance

• Referral for regulatory action is still possible. Information gathered during the 'closer

monitoring' phase may be used as evidence to support a recommendation for action

Improving compliance-related communication with stakeholders

• Review of the way we trend and publish inspection metrics

• Widening scope of compliance-related communication with stakeholders

Thank you for your attention

About copyright All material created by the Medicines and Healthcare products Regulatory Agency, including materials featured within these MHRA presentation notes and delegate pack, is subject to Crown copyright protection. We control the copyright to our work (which includes all information, database rights, logos and visual images), under a delegation of authority from the Controller of Her Majesty’s Stationery Office (HMSO). The MHRA authorises you to make one free copy, by downloading to printer or to electronic, magnetic or optical storage media, of these presentations for the purposes of private research, study and reference. Any other copy or use of Crown copyright materials featured on this site, in any form or medium is subject to the prior approval of the MHRA. Further information, including an application form for requests to reproduce our material can be found at www.mhra.gov.uk/crowncopyright Material from other organisations 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.

© Crown Copyright 2013