3. Ingredient Requirements

Ingredients Regulation Overview for Ingredient Manufacturers
Singapore

This section provides the ingredient requirements for the product categories in scope.

3.1 Ingredients for Drug Products

3.1.1 Drug APIs

In accordance with the Health Products (Active Ingredients) Regulations 2023, a person who supplies an active ingredient must ensure the active ingredient is accompanied by all the following information, where applicable, when it is supplied:

1. the name of the active ingredient, being the appropriate non‑proprietary name and, where applicable, the proprietary name;
2. an appropriate identification number, including the control number, lot number, batch number or serial number;
3. the expiry or retest date (as the case may be) of the active ingredient in accordance with paragraph (3);
4. the conditions under which the active ingredient must be stored;
5. where any characteristic of the active ingredient requires any special measure or care to be taken in the handling, processing or storage of the active ingredient — an appropriate warning of that characteristic;
6. a precaution relating to the disposal of any unused active ingredient or any waste derived from the active ingredient (where appropriate) and any available collection system for the unused active ingredient or waste;
7. the name of the manufacturer of the active ingredient.

Drug substance manufacturers must comply with the requirement for Evidence of Good Manufacturing Practice Compliance of Chemical Drug Substance Manufacturers from 01 October 2024. Acceptable evidence of GMP compliance is:

1. Valid GMP certificate issued by any PIC/S authority (or GMP inspection report with closeout letter, or other evidence from the authority that that site complies with PIC/S GMP requirements; or
2. Valid API Registration Certificate covering the drug substance of interest listed on EUDRAGMP; or
3. A Valid Certificate of Suitability to the monographs of the European Pharmacopoeia (CEP) for the drug substance of interest issued by the EDQM.

3.1.2 Drug Excipients

The HSA has adopted the PIC/S PI 045-1 Guidelines on the Formalized Risk Assessment for Ascertaining the Appropriate Good Manufacturing Practice for Excipients of Medicinal Products for Human Use for control of excipients used in therapeutic products.

3.1.3 Premixes

Since Evidence of Good Manufacturing Practice Compliance of Chemical Drug Substance Manufacturers is required for therapeutic products, GMP evidence would need to be provided for the manufacture of an API pre-mix.

3.2 Ingredients for Health Supplements

3.2.1 Health Supplement Active Substances

According to the Guidelines for Establishing the Safety of Ingredients of Health Supplements and Traditional Medicines v3, it is the responsibility of dealers of health supplements (importers, manufacturers, wholesale dealers) and sellers to ensure that their products are safe through careful selection and safety substantiation of ingredients used.

For ingredients such as vitamins which have substantial documentation of safe use in humans, literature sources and authoritative references can be used as evidence of safety (e.g. pharmacopoeias, ingredients monographs or assessments from regulatory authorities or scientific bodies). 

3.2.2 Health Supplement Excipients

Additives and excipients should be of appropriate food or pharmaceutical grade quality and should at all times conform with the applicable Specifications of Identity and Purity recommended by the Codex Alimentarius Commission or the official pharmacopoeias or, in the absence of such specifications, with appropriate specifications developed by responsible national or international bodies. In terms of safety, food or pharmaceutical grade quality is achieved by conformance of additives and excipients to their specifications as a whole. They are prepared and handled in the same way as a health supplement active substance.

Additives and excipients permitted for use in health supplements must be listed in the Codex Alimentarius General Standard for Food Additives (GSFA) online database (http://www.fao.org/gsfaonline/additives/search.html).

Manufacturers of health supplements in Singapore are encouraged to request that suppliers of excipients provide a company statement attesting that the product is in compliance with the specification requirements of any one of the following references:

• Joint FAO/WHO Expert Committee on Food Additives (JECFA)
• Food Chemical Codex (FCC)
• Handbook of Pharmaceutical Excipients
• All official international/national pharmacopoeias or national food additive standards

3.2.3 Health Supplement Premixes

As per excipients and health supplement active ingredients.

3.3 Ingredients for Veterinary Products

Manufacturers are responsible for ensuring the safety of their products but there are no specifically defined requirements for veterinary drug ingredients.

3.4 References

1. Implementation of Good Manufacturing Practice Evidence for Drug Substance Manufacturers https://www.hsa.gov.sg/announcements/regulatory

updates/implementation-of-good-manufacturing-practice-(gmp)-evidence-for-drug-substance-(ds)-manufacturers

2. Health Products (Active Ingredients) Regulations 2023

https://sso.agc.gov.sg/SL/HPA2007-S831-2023?DocDate=20231214&WholeDoc=1

3. PIC/S PI 045-1 Guidelines on the Formalised Risk Assessment for Ascertaining the Appropriate Good Manufacturing Practice for Excipients of Medicinal Products for Human Use

https://picscheme.org/docview/2465

4. Guidelines for Manufacturing Standards of Health Supplements and Traditional Medicines

https://www.hsa.gov.sg/docs/default-source/hprg-tmhs/chpb-tmhs/tmhs_manufacturing_guidelines.pdf?sfvrsn=9f20855f_8

5. Guidelines for Establishing the Safety of Ingredients of Health Supplements and Traditional Medicines v3

https://www.hsa.gov.sg/docs/default-source/hprg-tmhs/chpb-tmhs/tmhs_ing_guidelines.pdf

6. FAQs about ASEAN Guiding Principles for the Use of Additives and Excipients in Health Supplements

https://www.hsa.gov.sg/docs/default-source/gdo/international-collaboration/guidance_faq_add_excp.pdf