4. Supply of Ingredients

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4. Supply of Ingredients

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Ingredients Regulation Overview for Ingredient Manufacturers
Singapore

This section provides information on any notification, registration, or importation requirements for the ingredient categories in scope.

4.1 As Drug Substances for Drug Manufacture (B2B)

4.1.1 Registration requirements

Whilst there are no registration requirements for active ingredients for drug product manufacture, the new Health Product (Active Ingredients) Regulations 2023 stipulates the licensing requirements for dealings with active ingredients. All license holders must be a Singaporean business entity.

4.1.2 Importation

4.1.2.1 Overview of Process

To import active ingredients into Singapore for manufacture of health products for local clinical use, the importer must hold an importer’s license for active ingredients. The company must comply with the Good Distribution Practice (GDP) Standard before a license can be granted. A Responsible Person must be named to implement the GDP quality management system, which must be a registered pharmacist.

An import declaration must be completed by the importer using the applicable HSA Product Codes and furnished with the relevant licence and/or approval information. Import permit applications are made through the Singapore Customs online system TradeNet. Each TradeNet permit application typically costs around S$3 with includes statutory, processing and messaging fees.

4.1.2.2 Documents Required from the Ingredient Supplier

Commercial invoice
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 the information detailed in Section 3.1.1 when it is supplied. This would likely be covered by an MSDS.

4.1.3 Change Notification

A change to the API trade name would have no regulatory implications.

4.2 In Pharmaceutical Products Produced by Singaporean Manufacturers (B2C)

4.2.1 Registration of Drug Product

4.2.1.1 Registration requirements

A therapeutic product must be registered before it can be supplied in Singapore. The applicant must be a business entity registered in Singapore. The company must be authorized by a responsible person in the company that owns the therapeutic product before it can apply for the product registration in Singapore.

4.2.1.2 Registration Procedure

Application comprises two key steps- i) online submission of the application form via the HSA’s online system PRISM and ii) submission of the technical dossier. The dossier must be submitted within two working days of the PRISM application submission.

Following the submission, the application is screened for correctness of application type/evaluation route and for completeness of the dossier. The screening also includes the DMF/CEP if submitted as part of the application.

Once the application is accepted, the evaluation stage begins according to the relevant route. The DMF/CEP is evaluated together with the application.

For registration of all new therapeutic products, there are four possible evaluation routes.

Full route: Applies to any new product that has not been approved by any drug regulatory agency at the time of application submission to HSA.
Abridged route: Applies to any new or generic product that has been evaluated and approved by at least one drug regulatory agency.
Verification route: Applies to any new or generic product that has been evaluated and approved by HSA’s reference drug regulatory agencies, which are EMA (for products approved via centralized procedure), US FDA, Health Canada, TGA and UK MHRA (for products approved via national procedure, or where MHRA acted as the Reference Member State for the Mutual Recognition Procedure or Decentralized Procedure prior to January 2020 when the UK formally left the European Union).
Verification-CECA route: Applies to any generic product manufactured in India which has been evaluated and approved by HSA’s reference drug regulatory agencies, which include EMA, US FDA, Health Canada, TGA and UK MHRA.

Evaluation route is selected by the applicant at the time of submission, but if the application does not meet the eligibility criteria for the route selected, applicants will be informed by an Input Request.

A regulatory decision is made at the end of the evaluation process.

4.2.1.3 Documents to be Provided by Ingredient Supplier

For APIs

DMF submissions:

Online DMF submission form (https://form.gov.sg/642ce72fda710f0012822899)
Cover letter stating Response ID from Online DMF submission form
Color scanned copy of Letter of Access
Complete DMF (open and closed parts)

The documents of the open and closed parts of the DMF are submitted by the ingredient supplier on CD/DVD directly to the HSA.

A new system also allows for the DMF to be submitted in eCTD format to the HSA, as long as the ingredient supplier has created a Corppass account (https://www.corppass.gov.sg/corppass/registration/nonuen/nonsingpass/registrationdetails;UI_SESSIONID=FCF5BE8917F7B0D65526B5051AB91F87). Documentation required for account creation are the business registration details and personal details of a nominated person to act as the appointed Corppass admin.

CEP submissions:

Duly authorized CEP with completed Declaration of Access section listing
1. Name of Product owner or local applicant
2. Name of product to be registered
3. Signature of CEP holder
4. Date of authorization
If the Ph. Eur. is claimed for the drug substance, the following CTD sections should be submitted:
1. S.2.1
2. S.4.1 and S.4.4 from both the drug substance and drug product manufacturers. Batch analysis data should be from the same drug substance batches if available. Analytical results should be provided from a minimum of two batches from the drug substance manufacturer and should be sufficient to support the specification as well as to demonstrate consistency in manufacturing. Batches submitted should preferably be of production scale or at least pilot scale.
3. S.6 and S.7 if the re-test period/shelf-life is not stated on the CEP. At the time of submission, the minimum stability data is at least 12 months of long term data and 6 months of accelerated data from at least three primary batches of the drug substance. Batches should be at least pilot scale and manufactured by a method that simulated the final commercial process.
If other standards are claimed for the drug substance, the following CTD sections should be submitted:
1. S.2.1
2. S.4.1 to S.4.5 from both drug substance and drug product manufacturers
3. S.6 and S.7 if the re-test period/shelf-life is not stated on the CEP

The HSA reserves the right to request any additional information about the CEP-certified drug substance if it is deemed appropriate.

For Excipients

CoAs can be supplied and submitted by the applicant in lieu of the excipient specifications.
If the formula for a proprietary ingredient is confidential, only the total quantity of the ingredient is included in the technical dossier but the formula is provided by the ingredient supplier directly to the HSA via email.

4.2.1.4 Cost and Timelines

Cost and timelines depend on the application type (New Drug Application/Generic Drug Application) and evaluation route.

Application Type	Screening time (working days	Screening fee	Evaluation time (working days)	Evaluation fee
New Drug				NDA-1	NDA-2	NDA-3
Verification evaluation	50	$580	60	$16,900	$16,900	$5,830
Abridged evaluation	50	$580	180	$11,400	$11,400	$5,830
Full evaluation	50	$2,910	270	$82,900	$82,900	$82,900
Generic				GDA-1	GDA-2
Verification evaluation	50	$580	120	$10,400	$5,300
Verification-CECA evaluation	50	$580	90	$10,400	$5,300
Abridged evaluation	50	$580	240	$4,080	$2,330

Note: Fees in Singapore dollars (1 SGD = approx. 0.69 EUR/0.73 USD)

4.2.1.5 Renewal Frequency and Cost

There is an annual retention fee of $318 to maintain registration of the therapeutic product.

4.2.2 Importation

Not applicable to locally manufactured products.

4.2.3 Change Notification Relating to API Trade Name Change

A change to the API trade name is not specified under any of the minor variation (MIV-1, MIV-2 Notification or MIV-2 Do and Tell) checklists, therefore it does not require any regulatory action.

4.3 As Active Substances for Health Supplements (B2B)

4.3.1 Registration Requirements

Active substances for health supplements are not subject to licensing and approval by the HSA. It is the responsibility of dealers (importers, manufacturers, wholesale dealers) and sellers to ensure their products are safe and that they conform with applicable safety and quality standards.

4.3.2 Importation

4.3.2.1 Overview of Process

Importation of ingredients for health supplements is not subject to control by the HSA and therefore need not be declared using HSA Product Codes. A customs declaration is still made by the importer using the product code “MISC”, upon confirmation that the goods are not controlled by any Competent Authority (CA).

4.3.2.2 Documents Required from the Ingredient Supplier

1) Commercial Invoice

4.3.3 Change Notification

A change to the active substance trade name would have no regulatory impact.

4.4 In Health Supplements Produced by Singaporean Manufacturers (B2C)

4.4.1 Registration of Health Supplement

4.4.1.1 Registration Requirements

Health supplements are not subject to licensing and approval by the HSA, but dealers may voluntarily notify HSA of their health supplements supplied in Singapore if the product contains ingredients from the dropdown list. A dealer must be a locally registered company in Singapore.

4.4.1.2 Registration Procedure

If a product is eligible for notification, the process is via online submission of the notification form and submission of the required documents by email.

4.4.1.3 Registration Documents to be Provided by Ingredient Supplier

No documents are required from the ingredient supplier to support health supplement notification.

4.4.1.4 Cost and Timelines

There are no fees for notification. Turn-around time is 60 working days.

4.4.1.5 Renewal Frequency and Cost

Not applicable.

4.4.2 Importation

Not applicable to locally manufactured products.

4.4.3 Change Notification

A change to the active substance trade name would have no regulatory impact.

4.5 As Ingredients for Veterinary Products (B2B)

There are no regulatory requirements for veterinary ingredients unless they are classified as a Poison or veterinary biologic. Vitamins and carotenoids would not be considered either of these.

4.6 In Veterinary Product Produced by Singaporean Manufacturers (B2C)

There are no pre-market requirements for approval of veterinary medicines in Singapore. It is the manufacturer’s responsibility to ensure the safety and efficacy of their products.