May 2016
GMP CONFORMITY ASSESSMENT OF AN
OVERSEAS MANUFACTURER
GMP CONFORMITY ASSESSMENT OF AN OVERSEAS MANUFACTURER
1.
May 2016
Introduction
Under the Medicines Act/Health Product 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
PIC/S
FDA
MHLW
WHO
GMP
SOP
SMF
QSD
-
Health Sciences Authority, Singapore
Pharmaceutical Inspection Co-operation Scheme
Food and Drug Administration, United States
Ministry of Health, Labour and Welfare, Japan
World Health Organization
Good Manufacturing Practice
Standard Operating Procedure
Site Master File
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/content/hsa/en/Health_Products_Regulation/Manufacturing_Imp
ortation_Distribution/Overview/Guidance_Documents_for_Industry_and_Applicants.html
3
Purpose
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.
HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP
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GUIDE-MQA-020-012
GMP CONFORMITY ASSESSMENT OF AN OVERSEAS MANUFACTURER
May 2016
3.2
This Guidance Notes also sets out the requirements and arrangements for an onsite 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:
1. PIC/S member authorities:
Listing of PIC/S Members is available on:
http://www.picscheme.org
2. ASEAN member states listed on the ASEAN Inspection Services:
Malaysia/NPCB
Indonesia/BPOM
Thailand/FDA
5.2
5.3
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).
•
Establishment Inspection Report (EIR) and covering letter issued by US/FDA
stating the acceptable status of manufacturer (this is only applicable for
manufacturers that has been audited by US/FDA).
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 or certified true copy of the certificate/documents shall be submitted,
whenever possible.
HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP
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GUIDE-MQA-020-012
GMP CONFORMITY ASSESSMENT OF AN OVERSEAS MANUFACTURER
5.4
May 2016
•
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 or
established by the certificate issuance authority, the GMP evidence shall be
considered to remain valid for 3 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.
The application form to request for GMP evidence evaluation is available at the
HSA website:
http://www.hsa.gov.sg/content/hsa/en/Health_Products_Regulation/Manufacturin
g_Importation_Distribution/Application_and_Registration/e-services_Forms.html
5.5
The following information should be provided in the GMP evidence and/or
additional supporting documents issued by the relevant authority:
•
•
•
•
•
•
5.6
HSA DOES NOT regard the following documents as an acceptable GMP
evidence although they may be useful supporting documentation:
•
•
•
•
•
5.7
The name of the manufacturer of the medicinal products.
The address of the manufacturing site.
The date of issue and/or expiry of the document.
The approved medicinal product(s) or approved type(s) of medicinal
products, dosage form(s)
The approved steps of manufacture at the site (if applicable).
The standard of manufacture with which the manufacturer of the product
complies.
Annual product registration certificate from FDA
Annual Registration of Drug Establishment Certificate from FDA
FDA Form 482 and 483;
Letter from FDA stating that no Form 483 was issued;
Other quality system certificate (e.g. ISO Certificate)
A service charge shall be payable upfront upon submission of request for the
GMP evidence evaluation. The details of the service charges are available as
Schedule of Service Charges For GMP Conformity Assessment Of An Overseas
Manufacturer at the HSA website:
http://www.hsa.gov.sg/content/hsa/en/Health_Products_Regulation/Manufacturing_
Importation_Distribution/Overview/Audit_and_Licensing_of_Manufacturers/GMP_C
onformity_Assessment/Service_Charges.html
HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP
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Payment may be made in cheque (made payable to Health Sciences Authority) or
GIRO and this service charge is non-refundable.
6
What shall I do if I do not have acceptable GMP evidence?
6.1
Where acceptable GMP evidence of manufacture is not available, or where the
certificate/document submitted is insufficient to demonstrate equivalent GMP
standard, HSA may be requested to carry out an audit of the overseas
manufacturer.
6.2
General requirements on application for an audit of the overseas manufacturer:
•
•
•
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 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 Guidance
Notes: Preparation Of A Quality System Dossier for detailed requirements.
The firm/company must provide an undertaking that it is agreeable to the onsite audit, the service charges of QSD evaluation (one-off) and periodic on-site
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 are available as Schedule Of Service Charges For GMP
Conformity Assessment Of An Overseas Manufacturer at the HSA website:
http://www.hsa.gov.sg/content/hsa/en/Health_Products_Regulation/Manufacturi
ng_Importation_Distribution/Overview/Audit_and_Licensing_of_Manufacturers/
GMP_Conformity_Assessment/Service_Charges.html
Payment maybe made by 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
communication and documentation.
The application form to request for an overseas site audit is available at:
http://www.hsa.gov.sg/content/hsa/en/Health_Products_Regulation/Manufactur
ing_Importation_Distribution/Application_and_Registration/eservices_Forms.html
6.3
The GMP conformance established after the on-site audit will be valid for 3 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
HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP
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GUIDE-MQA-020-012
GMP CONFORMITY ASSESSMENT OF AN OVERSEAS MANUFACTURER
May 2016
evaluation. The Guidance Notes On Preparation Of A Site Master File is available
at:
http://www.hsa.gov.sg/content/hsa/en/Health_Products_Regulation/Manufacturin
g_Importation_Distribution/Overview/Guidance_Documents_for_Industry_and_Ap
plicants.html
7.
Other Information
7.1
HSA reserves the rights to remove the endorsement of GMP compliance given to
the overseas manufacturer where evidence exists or has reasons to believe it
exists that the manufacturer does not meet an acceptable standard.
7.2
Enquiries relating to GMP conformity assessment may be directed to the
following contact:
Audits and Licensing Division
Health Products Regulation Group
Health Sciences Authority
150 Cantonment Rd
Cantonment Centre
Blk A, #01-02
Singapore 089762
Tel : (65)-68663510
Fax : (65)-64789068
7.3
The GMP conformity assessment of overseas manufacturers will be implemented
with effect from 1 April 2004.
8.
End of Document
HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP
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GUIDE-MQA-020-012
Contact Officer:
Boon Meow Hoe
Overseas Audit Unit
Audits and Licensing 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
Ms Mai Ong
Overseas Audit Unit
Audits and Licensing Division
Health Products Regulation Group
Health Sciences Authority
150 Cantonment Road, Cantonment Centre,
Block A #01-02 Singapore 089762
www.hsa.gov.sg
T: 68663513
F: 64789068