GUIDE-MQA-020-009 (GMP Conformity Assessment of an Overseas Manufacturer)

DECEMBER 2008

GMP CONFORMITY ASSESSMENT OF AN OVERSEAS MANUFACTURER

PREPARATION OF A SMF FOR A MANUFACTURER OF COSMETIC PRODUCTS DECEMBER 2008

HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP of 7 GUIDE-MQA-020-009

1. Introduction

Under the Medicines Act of Singapore, the standard of manufacture and quality control of a medicinal product shall be taken into consideration by the Health Sciences Authority (HSA). Manufacturers located within Singapore are subjected to licensing and periodic GMP audits by HSA. Manufacturers of medicinal products for export to Singapore are subjected to GMP conformity assessment, whereby the manufacturer are required to periodically provide acceptable evidence that the overseas manufacturing facility conforms to GMP standard, failing which HSA shall assess the GMP conformance of the facility through site audit. The current PIC/S Guide to GMP for Medicinal Products is the standard used by HSA to assess the GMP conformity of the manufacturer.

2 Definitions/Abbreviations

HSA - Health Sciences Authority, Singapore PIC/S - Pharmaceutical Inspection Co-operation Scheme FDA - Food and Drug Administration, United States

MHLW - Ministry of Health, Labour and Welfare, Japan WHO - World Health Organization GMP - Good Manufacturing Practice SOP - Standard Operating Procedure

SMF - Site Master File QSD - Quality System Dossier

Overseas Audit: Encompasses evaluation of QSD/SMF and on-site audit of a

manufacturer located outside of Singapore. Deficiency: “Deficiency” has the same meaning as “Non-Conformity”. A deficiency is a non-conformance to 1 or more provisions of the PIC/S Guide to GMP for Medicinal Products. Quality System Dossier (QSD): Documents submitted which is intended to demonstrate that the manufacturer has in place a quality system that can potentially meet the PIC/S GMP standard. The QSD is required to be submitted only in the case of a manufacturer located outside of Singapore, which has not been previously audited and certified by a PIC/S member authority, US FDA or Japan MHLW. For details, please refer to the current Guidance Notes on Preparation of a QSD (GUIDE-MQA-19), at: http://www.hsa.gov.sg/publish/hsaportal/en/health_products_regulation/GMP/guidelines.html

3 Purpose

3.1 This set of Guidance Notes is intended to provide information on the types of GMP evidence acceptable to HSA, and how the acceptable



GMP evidence can be submitted to HSA to support the registration of the medicinal product.

3.2 This Guidance Notes also sets out the requirements and arrangements for an on-

site audit of the overseas manufacturing facility when the GMP evidence of the facility is not acceptable or available.

4 Scope

This Guidance Notes applies to all manufacturers of medicinal products located outside of Singapore whose products are registered or subjected to registration in Singapore.

5 What Is The Acceptable GMP Evidence? 5.1 HSA will only accept documentary evidence of GMP conformance from overseas

competent authorities where HSA is satisfied with the system of GMP audit, which shall be equivalent to the standard adopted by Singapore. The following competent authorities/regulatory agencies are deemed to have equivalent GMP audit systems:

Country Authority/Regulatory Agencies PIC/S Members available on: http://www.picscheme.org

Others United States of America Food & Drug Administration Japan Ministry Of Health, Labour And Welfare 5.2 The acceptable GMP evidence issued by a competent authority listed under

paragraph 5.1 may be in the form of:

• GMP Certificate (Certificate of GMP Compliance), or

• WHO Certificate of a Pharmaceutical Product; or

• Manufacturer’s License or Manufacturing Authorization incorporating the specific medicinal product(s)/dosage form(s).

5.3 General requirements on application for GMP evidence evaluation:

• The application should be made by a Singapore registered firm/company and the firm/company should authorize a responsible person (e.g. Managing Director, Regulatory Manager) to make the application.

• Original certificate/documents shall be submitted, whenever possible.



tp://www.hsa.gov.sg/publish/hsaportal/en/health_products_regulation/GMP/audit_i

• All certificates/documents shall be in the English language. Where certificates/documents are not in the English language, an accurate translation shall be provided.

• HSA shall consider the GMP evidence to remain current until the date of expiry of the GMP evidence. In cases where no expiry date is stated, the GMP evidence shall be considered to remain valid for 2 years from the date of issue. Expired certificates/documents shall not be accepted.

• The manufacturer shall refurnish new GMP evidence before the expiry date of the submitted documentary evidence of GMP conformance. The new GMP evidence shall be submitted via filing new application.

5.4 The application form to request for GMP evidence evaluation is available at the HSA

website: htcensing_manufacturers/conformity_assessment/eServices_Forms.html

5.5 The following information should be provided in the GMP evidence and/or additional

• The name of the manufacturer of the medicinal products.

cument. d type(s) of medicinal products,

ps of manufacture at the site (if applicable). e product complies.

5.6 HSA S NOT regard the following documents as an acceptable GMP evidence

• Annual product registration certificate from FDA cate from FDA

at no Form 483 was issued;

5.7 A service charge shall be payable upfront upon submission of request for the GMP

.hsa.gov.sg/publish/hsaportal/en/health_products_regulation/GMP/guideli

supporting documents issued by the relevant authority:

• The address of the manufacturing site. • The date of issue and/or expiry of the do• The approved medicinal product(s) or approve

dosage form(s) • The approved ste• The standard of manufacture with which the manufacturer of th

DOE

although they may be useful supporting documentation:

• Annual Registration of Drug Establishment Certifi• FDA Form 482 and 483; • Letter from FDA stating th• Other quality system certificate (e.g. ISO Certificate)

evidence evaluation. The details of the service charges is available as Schedule of Service Charges For GMP Conformity Assessment Of An Overseas Manufacturer at the HSA website:

http://wwwnes.html

ay be made in cheque (made payable to Health Sciences Authority) or IRO and this service charge is non-refundable.

Payment mG

http://www.hsa.gov.sg/html/business/00000000000000001522.html




What Shall I Do If I Do Not Have Acceptable GMP Evidence?

le, or where the fficient to demonstrate equivalent GMP

6.2 General requirements on application for an audit of the overseas manufacturer:

nd the firm/company should authorize a responsible person (e.g. Managing

uidance

site

6

6.1 Where acceptable GMP evidence of manufacture is not availabcertificate/document submitted is insustandard, HSA may be requested to carry out an audit of the overseas manufacturer.

• The application should be made by a Singapore registered firm/company a

Director, Regulatory Manager) to request for an overseas GMP audit. • The firm/company is required to submit Quality System Dossier together with

the completed application form. Please refer to Guide-MQA-019 GNotes: Preparation Of A Quality System Dossier for detailed requirements.

• The firm/company must provide an undertaking that it is agreeable to the on-site audit, the service charges of QSD evaluation (one-off) and periodic on-audit, which are inclusive of the associated travel and accommodation costs. The service charge for QSD evaluation shall be payable upfront at the point of submission of the application. The service charges for overseas GMP audit shall be payable upon receiving notification from HSA. The details of the service charges is available as Schedule Of Service Charges For GMP Conformity Assessment Of An Overseas Manufacturer at the HSA website: http://www.hsa.gov.sg/publish/hsaportal/en/health_products_regulation/GMP/guidelines.html . Payment maybe made in cheque (made payable to Health Sciences Authority) or GIRO and the service charge is non-refundable.

• The company is also required to arrange for a translator to be available during the on-site audit at the company’s cost if English is not the language used in

6.3 an overseas site audit is available at ttp://www.hsa.gov.sg/publish/hsaportal/en/health_products_regulation/GMP/audit

communication and documentation. The application form to request for h_icensing_manufacturers/conformity_assessment/eServices_Forms.html

6.4 The GMP conformance established after the on-site audit will be valid for 2 years.

For the purpose of continuing the product registration, the company is required to file in a new application to request for an overseas site audit together with an updated SMF (see Guidance Notes on Preparation Of A Site Master File, at the website listed below) or to file a new application to request for GMP evidence evaluation. The Guidance Notes on Preparation Of A Site Master File is available at: http://www.hsa.gov.sg/publish/hsaportal/en/health_products_regulation/GMP/guidelines.html

7 PRISM






7.1 Alternatively, the applicant may use the application forms in the PRISM system to

• To request for GMP evidence evaluation

hall be made via PSI or GIRO system

8.1 HSA reserves the rights to remove the endorsement of GMP compliance given to the rer where evidence exists or has reasons to believe it exists that

the manufacturer does not meet an acceptable standard.

8.2

oducts Regulation Group Health Sciences Authority

8.3 assessment of overseas manufacturers will be implemented with

04.

• To request for an overseas GMP audit and to submit the QSD

7.2 Payment for the associated service charges sthrough the PRISM system.

8. Other Information

overseas manufactu

Enquiries relating to GMP conformity assessment may be directed to the following contact:

Manufacturing and Quality Audit Division Health Pr

11 Biopolis Way #11-03, Helios, Singapore 138667 Tel : (65)-68663510 Fax : (65)-64789068

The GMP conformity effect from 1 April 20

9. End of Document

Contact Officer: Boon Meow Hoe Overseas Audit Unit Manufacturing & Quality Audit Division Health Products Regulation Group Health Sciences Authority 150 Cantonment Road, Cantonment Centre, Block A #01-02 Singapore 089762 www.hsa.gov.sg T: 68663507 F: 64789068 Ng Liong Thiam Overseas Audit Unit Manufacturing & Quality Audit Division Health Products Regulation Group Health Sciences Authority 150 Cantonment Road, Cantonment Centre, Block A #01-02 Singapore 089762 www.hsa.gov.sg T: 68663523 F: 64789068

http://www.hsa.gov.sg/

http://www.hsa.gov.sg/

GUIDE-MQA-020-009 (GMP Conformity Assessment of an Overseas Manufacturer)

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