Good Manufacturing Practice (GMP) evidence for overseas drug substance (DS) manufacturers

Overseas drug substance manufacturers will need to provide evidence of GMP compliance to support product registrations or variations in Singapore

Overview

This guidance outlines the requirements for evidence of GMP compliance for Drug Substance (DS) manufacturers of therapeutic products to support  a product registration or variation application in Singapore.  

Evidence of GMP Compliance for DS Manufacturing Sites

GMP compliance evidence must be specific to the DS to which the application relates. The types of acceptable GMP compliance evidence are listed below. Companies may submit either (a), (b), (c), or (d) to support their applications:

(a) A valid GMP certificate issued by a PIC/S 1  authority with the DS of interest stated. If the DS of interest is not specified on the GMP certificate, it must be accompanied by a Written Confirmation 2  for the DS of interest from the PIC/S authority which issued the GMP certificate.

(b) A valid GMP inspection report issued by a PIC/S authority stating that the DS of interest is within its scope and accompanied by the close-out letter where there are inspection findings. 

(c) A valid Active Pharmaceutical Ingredient (API) Registration Certificate covering the DS of interest listed on EudraGMDP. 

(d) A valid Certificate of Pharmaceutical Product (CPP) – Active Pharmaceutical Ingredient (API) covering the DS of interest issued by US FDA.
 

Other evidence such as a valid manufacturing licence issued by a PIC/S authority may be submitted if the aforesaid evidence adequately covered the DS of interest and the site has been demonstrated to meet PIC/S GMP standard.

For applications supported by a valid CEP for the DS of interest, HSA adopts a reliance approach to leverage the GMP compliance assessment under the EDQM Inspection Program for the sites specified in the CEP. For such applications, submission of proof of GMP compliance for the drug substance manufacturer is optional. 

1. Pharmaceutical Inspection Co-operation Scheme (PIC/S)
2. Written Confirmation using the European Union (EU) template or any other official document from the PIC/S authority is acceptable 

Eligibility criteria for GMP Inspection for DS manufacturing sites

In exceptional circumstances, companies may request HSA to conduct a GMP inspection for overseas DS manufacturing site where the site is not supported by the required evidence of GMP compliance at the point of submission of a registration application for a New Chemical / Biologic Entity (NCE / NBE). Such requests will be considered if the product meets the following criteria:

(a) The product falls within one of the national priority therapeutic areas:
i. Oncology
ii. Cardiovascular
iii. Ophthalmology
iv. Infectious diseases
v. Mental health
vi. Metabolic / endocrine disorders
vii. Neurology

AND must satisfy at least one of (b), (c), or (d) listed below:

(b) The product demonstrates potential to address a local unmet medical need, where:

i.  There is currently no available treatment option for the disease condition; OR

ii. The product represents a significant improvement compared to currently available therapies, as evidenced by either:

  • Demonstrated increased efficacy in treatment or prevention of the disease condition; OR
  • Substantial reduction of a treatment-limiting drug reaction.
(c) The product represents a significant therapeutic advancement, as demonstrated by:

i.  A new or innovative method of treating disease that differs significantly from existing treatments through a new mechanism of action or an innovative delivery method; OR
ii. A technological invention that enables treatment of previously untreatable conditions or offers transformative improvements over existing approaches.

(d) The product demonstrates potential to improve sustainable healthcare access as evidenced by alignment with Singapore’s National Medicines Policy objectives (click here for the National Medicines Policy).

Priority consideration

Priority will be given to companies with pharmaceutical manufacturing facilities or clinical research and development activities in Singapore.

Important information

Any request for HSA to conduct GMP inspection of DS manufacturing sites is subject to the following:

(a) Each GMP inspection is specific to only one DS and one manufacturing site. No more than one EOI for the same DS is permitted.

(b) Each GMP inspection is treated as a separate chargeable activity.

(c) The GMP inspection is only conducted to support a product registration application in Singapore. No certificate will be issued.

How to apply

To request for HSA GMP inspection of overseas DS manufacturing sites, the company must submit an Expression of Interest (EOI). HSA will issue the outcome of the EOI within 3 months. Companies may submit the therapeutic product registration application only after receiving the EOI outcome. Click here for submission of EOI.