04_gmp conformity assessment of overseas manufacturing sites

7/29/2019 04_GMP Conformity Assessment of Overseas Manufacturing Sites

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GMP Conformity Assessment ofOverseas Manufacturing Sites

Deputy Director (Overseas Audit Unit) / Senior GMP AuditorGMP Audit BranchManufacturing & Quality Audit Division

Health products Regulation GroupHealth Sciences Authority


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TOPICS(A)Overview Overseas

GMP ConformityAssessment Scheme

(B) Filing of new facilitylocated in PIC/S membercountries, US or Japan

(C) Filing of new facilitylocated in countries other

than PIC/S membercountries, US & Japan

(D) Question & Answer

TOPICS


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Overview of Overseas GMPConformity Assessment Scheme

Quality Medicines Harmonisation Programme (QMHP)

(I) Pharmaceutical Data Review

A component of product evaluation to ensure all drugs

meet current international quality standards and areappropriate and safe for continued use.

(II) Bioequivalence (BE) Data Review

An essential component to ensure that generic productsare therapeutically equivalent to the innovator products,thereby serving as safe and effective alternatives toinnovator drugs.

(III) GMP Conformity Assessment of OverseasManufacturers (PIC/S accredited GMP audit system)

A vital and integral component of the drug approvalprocess. GMP is a quality system standard, which deals

with the building of quality into drugs at all stages ofmanufacture.


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Objective:To protect public health by ensuring medicinal

products supplied to Singapore are manufactured byoverseas manufacturing facilities that has been

certified to meet GMP compliance

GMP conformity assessment

Product Registration /

Marketing Authorisation

in support of


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Overview Overseas GMPConformity Assessment Scheme

GMP Conformity Assessment Scheme[fka Overseas Audit Programme (OAP)]

Implemented from 1 April 2004

(a) GMP Documentary Evidences Verification

route

(b) On-site GMP audits route


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Local Drug Manufacturers Overseas Drug Manufacturers

Existing Overseas Drug Manufacturers

Registered with HSA as at 1 April 2004(Pending Consideration of Implementation)

New Overseas Drug Manufacturers

(Already implemented with effectfrom 1 April 2004)

Certified by BA* Not Certified by BA*

Submit Quality SystemDossier (QSD) for

evaluation

Exempted from On-site GMP audit;

Subject to verificationof GMP Evidence

On Site GMP audit

*BA HSA BenchmarkAuthorities include US FDAand Japan PMDA & PIC/S

member authorities

Overview of GMP Conformity Assessment Scheme


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(a) GMP Documentary

Evidences Verification route


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Filing of new facility located in PIC/S

member countries, US or Japan

GMP Documentary Evidences

Verification route is applicable

The manufacturing site has been audited by

PIC/S Member Authority

US/FDA

Japan/PMDA (MHLW)

(Exception)


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An Update on New PIC/S

Participating Authorities Singapore becomes a PIC/S member on 1 Jan 2000

(Number 24th First in Asia)

Countries Accession Dates

25th Greece January 2002 26th Malaysia January 2002 27th Latvia January 2004

OAP 1 April 2004 28th Czech Republic (USKVBL) July 2005 29th Poland January 2006 30th Estonia January 2007 31st South Africa July 2007 32nd Argentina January 2008 33rd Malta January 2008 34th Cyprus July 2008


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Austria Malta Argentina Norway

Belgium Netherlands

Czech Republic Poland South Africa SwitzerlandCyprus Portugal

Denmark Romania Australia Iceland

Estonia Slovakia

Finland Spain Canada Lichtenstein

France Sweden

Germany United Kingdom

Greece Malaysia Singapore

Hungary

IrelandItaly

Latvia

To-date: PIC/S has 34 participatingauthorities (33 Countries)


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Work Flow of A GMP Evidence

Evaluation Application

Accepted and inform PBB

Submit productregistration / variation

application to PBB

Route application toMQA for verification

Evaluation / Request for

other evidence / seekclarification with issuing

competent authority

Rejected and inform PBB


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Type of valid GMP Evidence

could be accepted

GMP Certificate issued by a PUJ authority

CPP issued by a PUJ authority

ML for site located in PUJ country only

Other equivalent GMP Documentary Evidence

- Certificate of GMP Compliance (CoC)


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Type of GMP Evidence would notbe accepted

GMP Certificate issued by any Non-PUJ authorityCPP issued by any Non-PUJ authorityML issued by any Non-PUJ authorityOther

- US FDA Form 2656 (Annual Registration of Drug Establishment

Certificate from US FDA) I.e. factory Licence

- US FDA 482 and 483

- Annual Product Registration certificate issued US FDA

- Letter from US FDA stating that no Form 483 was issued- Others Quality System certificate (e.g. ISO Certificate)


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GMP Documentary

Evidence Evaluation Route

(1) Local Sponsor specific

(2) Manufacturing site specific

(3) Activity and Dosage Form Specific


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(b)On-site GMP audit route


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Filing of new facility not located in

PIC/S member countries, US or Japan

GMP Documentary Evidences Verificationroute is also applicable if themanufacturing site has been audited by

PIC/S Member Authority

US/FDA

Japan/PMDA (MHLW)


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Filing of new facility not located in

PIC/S member countries, US or Japan

GMP Documentary Evidences Verificationroute is NOT applicable if themanufacturing site has NOT been audited

by any PUJ authority.

ON-Site GMP audit route is applicable


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Work Flow of An On-site GMP

Audit Application

Accepted QSD and arrangefor on-site GMP audit

Submit product registration/ variation application and

QSD to PBB

Route application to MQA forprocessing after Acceptance

of application

Assign an audit teamEvaluation of QSD / Request

additional information



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Work Flow of An On-site GMP

Audit Application (continue)

Send post-audit letter

Evaluate response (one month)

Correspondence till list of NCsare satisfactory addressed

Send close out letter

Pre-audit activities Send Pre-audit Letter Air passage / Visa / Vaccination Accommodation

Opening meeting On-site audit Closing meeting (Issue NC Letter

Critical, Major and Minor)


On-site audit activities

Post-audit activities

Issue Certificate ofManufacturing Status (2 years validity)


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For more information

Visit HSAs website:GMP Conformity Assessment Of Overseas Manufacturers Of medicinalProducthttp://www.hsa.gov.sg/publish/hsaportal/en/health_products_

regulation/GMP/audit_icensing_manufacturers/conformity_assessment.html

Guidance Documents :http://www.hsa.gov.sg/publish/hsaportal/en/health_products_

regulation/GMP/audit_icensing_manufacturers/conformity_assessment/guidance_documents.html

Guidance Notes on GMP Conformity Assessment Of An OverseasManufacturer

Guidance Notes on Preparation of a Quality System Dossier (QSD)

PIC/S Guide To Good Manufacturing Practice (GMP) for Medicinalproducts


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For more information

Please feel free to contact:

Overseas Audit UnitManufacturing & Quality Audit Division

Health Products Regulation GroupHealth Sciences Authority

E-mail: [email protected]


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Q & A


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