Sannie Chong SF (Ph.D.) Pre-Marketing Health Products Regulatory Group Health Sciences Authority Singapore

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Introduction

The need to enhance

Enhancing Quality – Work in progress

Remarks

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A Statutory Board of the Ministry of Health, The Singapore Public Service

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Vigilance

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Vigilance, Compliance & Enforcement

Pre-Marketing

Policy, Legislation & Operations

International Collaboration

Horizon Scanning, Service Management, Quality Assurance

Pre-market Post-market

Audit & Licensing

Medical Devices

Therapeutic Products

Clinical Trials

Complementary Health Products

Advanced Therapies

Enforcement Compliance

Tobacco Regulation

Audit Licensing & Certificate

HPRG

Review of Drug-Device Products

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• Complexity of products

- Chemicals, Biologics, Biosimilars, ...

• Ever increasing number of marketing applications

• Rapid emergence of new technologies

• Challenges associated with globalisation

• Limited resources

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More difficult to characterize ◦ Variability and complexity of biological molecules

(cell substrate, size, structure, source, etc)

◦ Post-translational modifications

◦ Limitations of analytical methods

Products are process specific ◦ Different from the well-controlled chemical synthesis

◦ Labile and sensitive to changes in manufacturing processes and conditions

◦ Process is prone to contamination

◦ End product not likely to be fully characterised – Quality should therefore be built-into the manufacturing processes.

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a) The approach for the evaluation of combination products, e.g. chemical-biologic (e.g.: toxin-mAb), drug-device?

b) ….

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• Complexity of products

- Chemicals, Biologics, Biosimilars, ...

• Rapid emergence of new technologies

• Challenges associated with globalisation

• Ever increasing number of marketing applications

• Limited resources

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• Products marketed meet appropriate standards of safety, efficacy and quality

Legal provision: Medicine Act (Chapter 176)

• Majority of the products have prior approval – should minimise delay in access to those in need

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Total land area: 710 sq km

Population size: > 5 million

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Full Dossier

Full Dossier

No prior approval by

drug regulatory agency

Full quality, non-clinical & clinical

Timeline: 270 working days#

Abridged Dossier

Timeline: 180 working days#

Approved by ≥ one drug regulatory

agency

Full quality & abridged clinical

# excluding stop clock

# Excluding stop clock

Verification Dossier

Approved by ≥ one reference agencies *

Reference agency assessment report

Timeline: 60/120 working

days#

Evaluation Routes for Biologics

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Life-cycle management:

• Pharmaco-vigilance

• Quality surveillance by testing

• GMP audits

• Field alerts response

Enhancing Quality ≠ Heightening Standards

Quality enhancement goals have been built in current systems of:

- Registration routes

- Registration process

So as to achieve balanced approach in the course of protecting and advancing national health and safety

Plan and work in progress – build on the current system, and to focus on:

- Lean approach

- International collaboration

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Regulatory Guidelines Predictability

(consistency)

Quality System

Lean Sigma Timeliness (eliminate redundancy)

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Transparency

Build close collaboration network with like-minded regulatory authorities e.g. Heads of Agencies Consortium

The Consortium consists of health regulatory agencies from:

The Therapeutic Goods Administration (TGA) of Australia;

The Health Products and Food Branch (HPFB) of Health Canada;

Swissmedic, Swiss Agency for Therapeutic Products, of Switzerland; and

Health Sciences Authority (HSA) of Singapore.

Established in 2007 as a means to promote regulatory convergence and foster synergy to address scientific and regulatory issues.

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The Consortium’s work focuses on concrete regulatory work sharing initiatives including but not limited to:

Good Manufacturing Practices (GMPs);

Good Review Practices (GRPs);

Post-market medicines safety and surveillance;

Assessment reports for pharmaceuticals including generic drugs and new chemical entities; and

Coordination of involvement of technical experts in the International Conference on Harmonisation (ICH) working groups, and the collaboration on the Information Technology (IT)-architecture.

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Priority: Generics review as a priority area for collaboration

Facilitate greater availability of generics through the convergence of regulatory requirements, promoting more efficient use of available resources, reducing regulatory burden and duplication of effort

Approach:

◦ The sharing of reviews

◦ Staff exchange

◦ Identify opportunities for convergence

Aim: Serve as a “proof of concept”

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Build strong evaluation team via national collaboration e.g. participate as WHO Expert in WHO (generic) evaluation together with colleagues from e.g. Europe, Canada

Active participation in relevant initiates e.g. Good Review Practice initiative by APEC for Quality system together with colleagues from US FDA, Australia, Canada, Japan, China, etc

On the regional front, publish guidelines e.g. ASEAN Process Validation including QbD to communicate the regional regulatory requirements

APEC: Asia-Pacific Economic Cooperation

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ACCSQ ASEAN Consultative

Committee on Standards and Quality

Established in 1992 by the ASEAN Economic Ministers

Comprises the national standards and conformance bodies

Main objective to reduce technical barriers to trade in order to support economic integration in ASEAN

PPWG

Pharmaceutical Product Working

Group

ACCSQ initiated harmonisation of ASEAN pharmaceutical technical requirements

The 13th ACCSQ meeting held in March 1999 in Manila, Philippines agreed that PPWG be set up

Formation of ACCSQ-PPWG in1999 with Malaysia as the lead

Objective is to develop harmonization schemes of pharmaceuticals' regulations of the ASEAN member countries to complement and facilitate the objective of ASEAN Free Trade Area (AFTA), particularly, the elimination of technical barriers to trade posed by these regulations, without compromising on drug quality, safety and efficacy.

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PPWG Chair: Malaysia

Co-Chair: Thailand

ASEAN Common Technical Requirement (ACTR)

Quality : Indonesia,

Safety: Philippines

Efficacy: Thailand

ACTR Guidelines Analytical Validation: Thailand

Variation: Malaysia and Singapore

Process Validation: Singapore

Stability Studies: Indonesia

ASEAN Common Technical Document (ACTD) Quality: Indonesia

Non-Clinical: Philippines

Clinical/Efficacy: Thailand

Implementation Working Group (IWG) Chair: Singapore

Co-Chair: Indonesia

Mutual Recognition Arrangement - GMP Singapore and Malaysia

MRA - BA/BE Indonesia and Malaysia

Post-Marketing Alert System Singapore and Malaysia

Biologics Technical Working Group (since 2011) Indonesia and Singapore

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Established by the PPWG at the 17th ACCSQ PPWG Meeting TWG with

Indonesia and Singapore taking the lead.

Terms of reference (TOR) of the Biologics TWG adopted in 19th ASEAN

PPWG held in Bangkok, Thailand, 3-6 July 2012

The focus:

o Harmonization of standards and technical requirements

o Capacity building

Priority Area:

oVaccines, biosimilars and blood products

Action plan for the coming years

o Development of technical guidelines for biologics

o Modifying ACTD for biologics

o Guidelines for Vaccines – stability, safety & efficacy, quality

o Survey of country’s requirements

o Post marketing alert system

o Capacity building – quality management system, evaluation, training &

information sharing.

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Health Canada

Mr Sia Chong Hock, Manufacturing and Audit Division

Mrs Marie Tham, International Collaboration

Dr Dinesh Khokal, Dr Ding Fung Toh and

Dr Zhang Wei, Therapeutic Products Branch

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