Key Takeaways
- A compliant Product Information File (PIF) is mandatory for all cosmetic product notifications in Singapore.
- The PIF demonstrates safety, quality, and compliance with Health Sciences Authority (HSA) and ASEAN Cosmetic Directive (ACD) requirements.
- Common pitfalls include unsubstantiated claims, use of banned ingredients, and incomplete safety assessments.
- The Reg Consultants (TRC) supports cosmetic companies by reviewing and maintaining PIFs to meet ACD requirements and avoid enforcement issues with HSA.
Why PIF Compliance Matters in Singapore’s Cosmetic Industry
Cosmetic product notification isn’t just a simple formality. The Product Information File (PIF) is a comprehensive safety dossier that establishes your product safety and quality standards. Without a compliant PIF, your brand risks import refusals, product seizures, market withdrawals, or unannounced audits — all of which can severely affect timelines and reputation.
Recent HSA recalls of cosmetic products containing undeclared restricted substances underscore the importance of having a fully compliant PIF. Working with a regulatory affairs consultant ensures your PIF is robust before market entry.
What is a PIF and Who Needs It?
The PIF is mandatory for every cosmetic product notification in Singapore. It must be kept readily accessible, whether physically or digitally, for inspection at any time by the HSA. For overseas brands, this responsibility is usually handled by a local cosmetic notification holder r or appointed partner.The product owner is reposnible to provide the local appointed holder with PIF and need to take proactive steps to ensure that a compliant PIF is in place before their products enter the Singapore market.
Key Components of a Compliant PIF
A compliant Product Information File (PIF) is a complete dossier that demonstrates your product meets Singapore’s cosmetic regulations and ASEAN Cosmetic Directive (ACD) standards. Core elements include:
a) The qualitative and quantitative composition of the product, in case of perfume compositions, the name and code number of the composition and the identity of the supplier;
b) Specifications of the raw materials and finished product;
c) The method of manufacture complying with the good manufacturing practice as laid down in the ASEAN Guidelines
d) Assessment of the safety for human health of the finished product, its ingredients, their chemical structure and level of exposure;
e) Existing data on undesirable effects on human health resulting from use of the cosmetic product; and
f) Supporting data for claimed benefits of cosmetic products should be made available; to justify the nature of its effect;
They should be organized into Part I(Administrative documents and Product Summary ), Part II (Quality data of raw materials), Part III (Quality data of Finished Product) and Part IV( Safety and Efficacy Data) as per a dossier.
Together, these components form the backbone of cosmetic compliance, supporting a smooth HSA notification and protecting your brand from enforcement actions.
Common Pitfalls We See
Recurring issues that delay approval or trigger enforcement include:
- Unsubstantiated product claims: Terms like “whitening” and “anti-ageing” require supporting evidence such as clinical trial summaries, published data, or in vitro studies.
- Use of banned or restricted ingredients: Outdated formulations or poor ingredient verification often result in the accidental inclusion of substances restricted under the ACD. This not only causes rejection but can raise red flags for future submissions.
- Incomplete or weak stability and shelf-life data: HSA expects evidence to demonstrate that a product maintains its safety and quality until its expiry. Submitting generic data or failing to provide in-market product samples can delay approval.
- Safety assessments from unqualified assessors: A cosmetic safety dossier must be signed off by a qualified safety assessor recognised under EU/ASEAN standards. Using assessors without the proper credentials may undermine the validity of your PIF.
- Inconsistent or non-compliant labelling: Issues such as missing mandatory warnings, incorrect font sizes, or formatting errors are frequently overlooked but can trigger corrective action or product recalls.
- PIF file is not available or established for the product placed on market.
- PIF file is not updated with the latest quality and safety information supporting safe usage.
Each of these pitfalls can result in costly delays or enforcement actions that damage your brand’s credibility.
How TRC Can Help
At The Reg Consultants (TRC), we provide end-to-end pharma regulatory services to help companies manage the complex requirements of cosmetic product notification. With expertise in regulatory affairs, TRC offers:
- Comprehensive PIF reviews and support during audit by the authority
- Ingredient screening against the ACD and HSA’s database.
- Labelling and claims review
- Acting as a local cosmetic notification holder
- Ongoing annual updates and file maintenance to ensure that your PIF remains inspection-ready and avoids unpleasant surprises.
As experienced regulatory affairs consultants in Singapore, we understand both the technical requirements of PIF compilation and the practical challenges companies face during cosmetic product notification.
Stay Audit- and Market-Ready with TRC
A compliant PIF is both a defensive shield against enforcement actions and a strategic asset that supports smooth market entry. For companies going through the cosmetic product notification process in Singapore, keeping a PIF inspection-ready is non-negotiable.
With TRC by your side, you can rest assured that your PIF is always audit-ready and aligned with HSA expectations. More than a compliance check, we become a trusted partner, helping you safeguard timelines, protect brand reputation, and enter the Singapore market with confidence.
Contact us to safeguard your brand today.
We’re back for our weekly deep dive into the fascinating world of regulatory affairs! This week, I want to tackle a topic that comes up surprisingly often in my conversations with clients, especially those looking to bring life-saving products like vaccines to new markets: How do you leverage a WHO Prequalified (PQ) dossier for registration in Singapore?
Many assume a WHO PQ means a straight shot, but as we as seasoned regulatory people know, it’s rarely that simple. While WHO Prequalification is an incredible achievement and a powerful foundation, there are always those crucial local nuances that need expert navigation.
What Exactly is a WHO Prequalified Dossier?
The World Health Organization (WHO) Prequalification program is a global initiative designed to ensure that key health products meet international standards of quality, safety, and efficacy. Think of it as a stamp of global assurance. WHO conducts a rigorous assessment, scrutinizing everything from the product’s quality data to the manufacturing site’s Good Manufacturing Practice (GMP) compliance. It’s a comprehensive review aimed at facilitating access to essential, quality-assured medical products, particularly for procurement by UN agencies and other international bodies.
What Kinds of Products Fall Under WHO PQ?
Initially, the program focused heavily on medicines for HIV/AIDS, TB, and malaria. Over time, it has expanded significantly. Today, WHO Prequalification covers a broad spectrum of products vital for global health, including:
- Medicines (Finished Pharmaceutical Products and Active Pharmaceutical Ingredients): Especially generics and essential medicines.
- Vaccines: This is a huge one! Ensuring vaccine quality and efficacy for global immunization programs is a cornerstone of WHO PQ.
- In Vitro Diagnostics (IVDs): Products used for detecting diseases.
- Immunization Devices: Like syringes and safety boxes.
- Vector Control Products: Tools to fight vector-borne diseases.
Based on experiences and inquiries, vaccines are often the first product that comes to mind when leveraging WHO PQ. The principles, however, apply broadly across these categories.
Advantages of a WHO PQ Dossier
The advantages are:
- A Global Seal of Quality: A WHO PQ product has already undergone a thorough evaluation by a globally respected authority. This immediately instills confidence in national regulatory agencies (NRAs) about the product’s quality, safety, and efficacy profile.
- Streamlined Initial Review: For many NRAs, especially those with limited resources, a WHO PQ can significantly streamline their initial assessment, as much of the heavy lifting on the core scientific data has already been done.
- Market Access and Procurement: For many manufacturers, WHO PQ is a prerequisite for supplying products to major international procurement bodies, opening up vast markets.
- Robust Scientific and Quality Foundation: The WHO Prequalified dossier provides a comprehensive, pre-vetted scientific and quality package (often in CTD format). This means the core technical data, which is typically the most time-consuming to generate and compile, is largely established, significantly reducing the burden of its “major overhaul” when preparing for national submissions.
Bridging the Gap for Singapore Submission
Here are the key gaps we typically need to bridge:
- Local Administrative & Legal Requirements (Module 1): The WHO PQ dossier, while often following the CTD structure, will have a WHO-specific Module 1. HSA, like any national authority, has its own unique Module 1 requirements. This includes specific application forms, declarations, appointment of a local company/agent (which, surprise, surprise, is a must!), and adherence to local legal frameworks.
- Singapore-Specific Labelling & Package Inserts: Even if the core data is accepted, the product information (labels, package inserts, patient information leaflets) must be fully compliant with HSA’s detailed requirements for language, content, and format. This isn’t just a translation job; it’s a regulatory art form!
- Good Manufacturing Practice (GMP) Conformity: While WHO conducts GMP inspections for PQ, HSA recognizes PIC/S GMP as the standard. Based on recognition agreements and internal evaluation, manufacturing sites can either be subjected to a GMP DEVA assessment or an overseas inspection.
- Risk Management Plan (RMP): HSA requires a comprehensive Risk Management Plan, along with a Singapore-Specific Annex (SSA), to be submitted as part of the registration application for therapeutic products, including vaccines.
- Vaccine-Specific Lot Release: This is a crucial point for vaccines! Even after registration, all imported registered vaccines require a notification to HSA on lot release information before they can be supplied in Singapore. This is a critical post-registration compliance step.
- Dossier Format Alignment (ICH CTD/ACTD): While WHO PQ is increasingly aligned with CTD, HSA accepts both ICH CTD and ASEAN Common Technical Dossier (ACTD) formats. There can be subtle but important differences in how information is presented or what specific details are required within certain sections, especially if the ACTD format is chosen or if there are specific HSA guidance documents that refine the CTD expectations.
Essentially, a WHO PQ dossier gives you a solid scientific and quality foundation in which “a major overhaul” is essentially avoided when preparing for local submission.
How TRC Can Support Your Journey
TRC specializes in taking WHO Prequalified dossier and meticulously transforming it into a complete, compliant submission for HSA.
We don’t just translate documents; we understand the intent behind HSA’s guidelines and the specific nuances of what they’re looking for. From managing the intricate Module 1 administrative requirements, ensuring all labelling is compliant, to advising on GMP assessments and navigating the vaccine-specific lot release process – we cover all the bases.
Our “on-the-ground” practical experience in Singapore regulatory affairs means we can foresee potential roadblocks and proactively address them, streamlining your path to market. We work like an extension of your own team, guiding you through every step, ensuring that your life-saving vaccines, or any other WHO Prequalified product, reach the patients who need them, right here in Singapore.
Ready to make your WHO PQ a launchpad for Singapore market access? Let’s talk!
Amongst the ever-emerging trend of new generation drugs, there is a group that is not widely discussed yet still remains the gold standard of treatment — or even serves as the pharmacophore on which many modern drugs are built. Examples of grandfather products include aspirin, morphine, diphenhydramine, and propranolol — all introduced decades ago and still widely used today. Their pharmacophore structures have inspired the development of many modern drugs, demonstrating the enduring value of these legacy products. This term is exchanged quite regularly during conversations here and there but is often neglected when strategizing market entry. Today, we are here to touch on this group of special products.
What are Grandfather or Legacy Products?
In regulatory terms, grandfather products (also called legacy products) refer to products that were introduced to the market before modern regulatory frameworks were established. For chemical entity drugs, this usually means they were first approved decades ago under older requirements and have remained on the market with minimal updates to their dossiers.
Where do grandfather products often originate from?
Most grandfather or legacy products originate from established pharmaceutical markets such as the United States, Europe, and Japan, where products were approved under national regulations before harmonized ICH guidelines existed. Additionally, some products from regional manufacturers in ASEAN or other Asia-Pacific countries also fall into this category if they were registered locally before CTD implementation.
Such products may:
- Lack comprehensive ICH CTD-format dossiers, making it difficult to directly submit to regulatory authorities that require standardised formats
- Be registered under older country-specific formats with missing modules (e.g. no full Module 3 CMC data and incomplete Module 5 clinical data), resulting in significant rework before submission
- Have undergone manufacturing or formulation changes over time not fully captured in the current registration file, raising concerns on data consistency, bridging justifications, and regulatory acceptability
Common Issues with Legacy Product Dossiers
From my experience, clients often face these challenges with grandfather chemical entity products:
- Missing Module 3 data :Older products may only have a brief manufacturing summary without detailed process validation, impurity profiles, or stability data as per current ICH/ASEAN requirements. This leads to delays in submission preparation as sourcing and compiling such data can take months or require additional manufacturer support.
- Non-compliance with current guidelines:
Specifications, analytical methods, and validation reports may not align with updated pharmacopeial or ICH standards. This could result in deficiency queries or rejection if no bridging justification is provided. – Specifications, analytical methods, and validation reports may not align with updated pharmacopeia or ICH standards.
- Outdated safety or clinical information : For most well-established grandfather products, additional clinical data is generally not required if the product retains its original formulation, indication, and dosage form, and has a long history of safe use. However, dossiers may still lack current risk management plans or pharmacovigilance documentation, which are standard expectations under modern regulatory frameworks. In some cases, if a product is being introduced in a new dosage form or combined with a novel formulation, regulators may request bridging data or justification to confirm its safety and efficacy in the proposed context.
How TRC Can Help
At TRC, we support clients to resolve these gaps for market entry or re-registration in Singapore. Here are realistic examples of solutions we have provided:
Case 1: CMC Gap Analysis and Strategic Planning
A client approached us to register a 1980s-origin chemical entity analgesic in Singapore. The original dossier had:
Our approach:
- Conducted a Module 3 gap analysis against HSA’s current requirements
- Identified critical missing data and advised on the feasibility of sourcing them from the manufacturer or via new testing
- Developed a regulatory strategy to allow the client to decide whether to proceed with registration or prioritise alternative products in their portfolio
Case 2: Regulatory Intelligence Assessment for antibiotic
A Southeast Asian client aimed to bring in a legacy antibiotic product registered regionally before ASEAN CTD implementation.
Our approach:
- Conducted a regulatory intelligence assessment to clarify HSA expectations for legacy products
- Identified potential data requirements (e.g. stability data under ASEAN climatic zone IVb conditions, updated impurity profile data)
- Prepared a clear requirements list for the client to initiate discussions with their manufacturer efficiently and to plan next steps for dossier preparation
Case 3: Specification and Analytical Review Support for CNS Product
A European manufacturer sought to register a CNS (central nervous system) drug but its finished product specifications were outdated.
- Reviewed the current USP/EP standards for the active ingredient and finished product
- Provided recommendations to align the specifications with current standards to mitigate the risk of questions being raised during screening and evaluation
- Guided the client in preparing bridging justification documents to support acceptance of older analytical methods with supplementary validation where needed
Legacy or grandfather products hold strong market value, but their outdated dossiers often pose barriers to registration under modern frameworks.
Performing a regulatory intelligence exercise early — to understand current requirements and feasible pathways — is critical. Starting a gap analysis as the first step ensures that data gaps can be proactively addressed, reducing time to market entry.
At TRC, we specialise in guiding clients through these complexities to achieve successful registration outcomes in Singapore. Contact us if you need support in revitalising your legacy products for new market opportunities.
We often get leads from prospects telling us:
“My product is FDA/EMA approved, so there shouldn’t be any issue for local submission. Efforts on your end should be minimal – can we reduce costs?”
I’m sure those who know the reality are quietly laughing behind their screens as I say this.
Why Do We Still Need Local Preparation?
When preparing a regulatory submission, having reference agency approval:
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Supports your application, as the dossier has been reviewed by a stringent authority
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Provides assessment reports that local health authorities can leverage to evaluate safety, quality, and efficacy
But here is the reality: reference agency dossiers are not fully representative of local requirements. Regulations are built upon international standards and incorporate specific national requirements, dossier formats, and administrative expectations that local marketing authorization holders should adhere to.
Critical Gaps We Often See
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Generics: Local bioequivalence (BE) requirements, acceptance of foreign BE studies, and strict reference product criteria can differ greatly from those in the US or EU.
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Biosimilars: Local authorities may request additional analytical data or bridging studies when the reference biologic is sourced differently.
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NCEs: While clinical data may be robust globally, gaps can occur if local clinical pharmacology factors—such as food effects, drug interactions, or special population data—are insufficient or missing.
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Stability studies not performed in accordance with Zone IVb requirements.
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Process validation performed but lacking validation data for all commercial-scale batches (only pilot scale provided), absence of hold time validation data for in-process materials or bulk product, or no justification for process parameter ranges or their linkage to critical quality attributes (CQAs).
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Manufacturing controls not clearly demonstrating the linkage between drug substance and finished product manufacturer.
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GMP standards adopted not aligned with PIC/S requirements.
Other Common Issues We Encounter
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Dossiers submitted not in the required ASEAN CTD or ICH CTD format
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Outdated Quality Overall Summary (QOS) that does not reflect current drug substance (DS) and drug product (DP) changes
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“‘Grandfather” products registered based on old regulations or legacy processes may still be accepted in reference countries but often fail to meet evolving local regulatory requirements leading to challenges in registration.
What Should You Do?
If you want to register your product locally, it is essential to:
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Conduct regulatory intelligence to understand local requirements and assess your dossier gaps before submission.
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Engage an external local expert to perform a targeted gap analysis to de-risk your registration process.
How TRC Can Support You
We can help by:
If you need a local regulatory expert or another pair of eyes to help you, we are just a click away!
Biologics submissions are often more complex than small molecule applications, not just due to the science but because of the higher regulatory scrutiny involved. In Singapore, HSA’s review of biologics focuses heavily on product quality, clinical safety, and manufacturing consistency.
At TRC, we’ve supported multiple clients preparing or refining their Common Technical Document (CTD) dossiers for biologic products. Here are some of the most common issues we’ve encountered — either flagged during internal quality checks or in regulatory feedback from HSA:
1. Incomplete Viral Safety Data
Biologics derived from cell lines or involving human/animal raw materials must include robust viral clearance studies and testing for adventitious agents. Missing or insufficient viral validation summaries can delay review significantly. Applicants should ensure that viral reduction steps are well justified and validated.
2. Gaps in Comparability Data
When there are changes in manufacturing processes, comparability studies are essential to show that the pre- and post-change product remains equivalent in quality and efficacy. This is a frequent sticking point, especially for companies with foreign data relying on prior regulatory approvals. HSA expects a clear and data-driven comparability package — not just a reference to EMA or FDA acceptance.
3. Inadequate Characterization of Cell Banks
Master Cell Bank (MCB) and Working Cell Bank (WCB) characterization should be detailed and compliant with ICH Q5D/Q5B. Some applicants overlook genetic stability data or omit full sterility and purity test reports — items that HSA considers critical.
4. Lack of Clear Endotoxin and Sterility Validation
For injectable biologics, sterility and endotoxin testing methods must be fully validated and described in Module 3. In some cases, clients assume that referencing a compendial method is enough — but validation under actual product conditions (matrix effect, interference) must still be demonstrated.
5. Container Closure Integrity Not Adequately Demonstrated
Especially for prefilled syringes or vials, HSA may request evidence of container closure integrity (CCI) testing, particularly under worst-case shipping or storage conditions. CCI studies should be product-specific and reflect real-world usage, not just generic studies.
Biologics submissions are resource-intensive — but a strong CTD package reduces review time and prevents unnecessary back-and-forth with the authority. At TRC, we support clients in spotting and addressing these issues early, so they don’t become stumbling blocks down the road.
If your team is preparing a biologics application for the Singapore market and would like a second pair of eyes on your dossier, feel free to reach out.
When making post-approval changes to chemical drugs registered in Singapore, understanding which MIV-2 changes require a Notification vs Do-and-Tell under HSA’s guidance is crucial for smooth regulatory compliance.
This distinction is explained in Annex 13B (MIV-2 Notification) and Annex 13C (MIV-2 Do and Tell) of the guidelines.
What is an MIV-2 Change?
MIV-2 refers to minor variations— lower-risk changes that require less stringent regulatory oversight.
Quick summary of MIV-2 type, implementation and examples
| MIV-2 Notification (Annex 13B) |
MIV-2 Do-and-Tell (Annex 13C) |
| Changes that requires prior notification to HSA and can be implemented after 40 working days if no objection is raised. |
Changes that can be implemented immediately but must be notified to HSA within 6 months. They can be bundled. |
| Implementation can proceed after 40 working days from application submission if there are no queries from the authority. |
No prior approval needed; just notify after implementation |
| Examples: minor change of manufacturing processing of drug product , change of batch size of non-sterile drug product, change of primary packaging material of non-sterile Drug substance or drug product |
Examples: change of product owner , change of specification of drug substance to comply with latest compendium, revision of CEP |
Tips to Note Prior to MIV-2 Submission
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Assign the change to the correct MIV-2 category by carefully assessing the conditions listed under each type (Notification or Do-and-Tell).
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Do-and-Tell changes may be submitted as standalone MIV-2 applications, or bundled with other related MIV-2 changes — provided they were implemented within the preceding 6 months.
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Prepare documents according to the checklist for each category. For example, if a letter of justification has specific required content, please follow it exactly and do not modify the template.
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Only one MIV-2 submission can be submitted at any one time for a single product. Please plan your changes in advance to avoid delays.
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There is no application fee for MIV-2 submissions. The processing timeline is typically 40 working days, provided there are no queries from HSA.
Good luck, and reach out anytime if you need support with your MIV-2 submissions.
When companies prepare to register biologic products in Singapore, there’s a common assumption that all biologics must go through the NDA-1 route. But that’s not always the case.
Understanding Singapore’s NDA-1, NDA-2, and NDA-3 categories — and which applies to your product — is key to smooth regulatory submissions and avoiding unexpected delays.
NDA-1: New Biological Active Substance
Under HSA’s framework, NDA-1 applies when the product contains a new chemical or biological active substance that has never been registered in Singapore. This typically includes:
These applications require full safety, efficacy, and quality data, and undergo a thorough scientific review, often with longer evaluation timelines.
NDA-2: New Dosage Form, Strength, Route, or Formulation
NDA-2 covers new dosage forms, strengths, administration routes, or formulations of an already-registered active substance. Examples include:
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A subcutaneous version of an approved IV monoclonal antibody
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A prefilled syringe instead of a vial
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A biosimilar referencing a biologic already registered in Singapore
Many biosimilars fall under NDA-2 when referencing a Singapore-registered originator. This means no new active substance is introduced, but bridging and comparative studies (analytical, PK/PD, sometimes clinical) are required. If the reference product isn’t registered locally, the biosimilar may be up-classified to NDA-1.
NDA-3: Subsequent Strength(s) of Registered Product
NDA-3 applies to additional strengths of products already registered or submitted as NDA-1 or NDA-2. The new strength must have the same product name, active ingredient, dosage form, presentation, indication, dosing regimen, and patient population as the original.
Examples include introducing a 50 mg vial after registering a 25 mg vial of the same biologic. Data requirements are usually limited to bridging information.
Why is this important?
Misclassifying your NDA category can cause delays, extra data requests, or even rejection at screening. Knowing the right NDA pathway helps you plan better and work smoothly with HSA.
Navigating Singapore’s regulatory pathways takes experience and understanding of local requirements. Whether you’re registering an innovative biologic, a biosimilar, or new strengths and formulations, it’s important to:
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Accurately classify your NDA category
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Understand HSA’s data and documentation expectations
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Strategically plan your submission for efficiency
As a regulatory consultant, I work closely with clients to simplify these complexities and help prepare submissions that meet HSA requirements. Feel free to reach out if you need support. Wishing you all the best in your regulatory journey!
1. Drug Substance: More Than Just Chemistry (Module 3.2.S)
Biologics are made using living systems, which means the drug substance section (Module 3.2.S) is much more complex than in small molecule applications. HSA expects:
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Detailed information on cell bank systems, including Master and Working Cell Banks (MCB/WCB)
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Description of the expression system and host cell line
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Clear flowcharts of the manufacturing process with critical control points identified
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Robust validation of viral clearance steps
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Risk assessment of raw materials, especially if animal- or human-derived
A well-structured CMC package here is essential for a smooth review.
2. Comparability and Characterisation: Not Optional
One of the most common causes of regulatory delays in biologics submissions is insufficient comparability data. This applies to both innovator biologics (post-change) and biosimilars.
HSA will look closely at:
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Physicochemical characterisation: including glycosylation profiles, size variants, aggregates
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Biological activity assays: to demonstrate that the biosimilar or updated product maintains expected functionality
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Comparative studies across Modules 3, 4, and 5 — not just one section in isolation
If you’re referencing a non-local comparator product, a strong scientific and regulatory justification is critical.
3.Stability Studies: Real-Time, Real-World
Biologics are temperature-sensitive and prone to degradation, making stability studies a critical part of the dossier. Although biologics are excluded from the ASEAN Stability Guidelines and not required to be tested under Zone IVb conditions (30°C/75% RH), HSA still expects robust stability data under ICH-recommended conditions.
For Module 3.2.P.8, HSA typically expects:
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Real-time, real-temperature stability data under the proposed storage conditions (e.g., 2–8°C), using ICH Q5C guidance as reference
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Data from multiple commercial-scale batches to support consistency in shelf-life across manufacturing lots
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Shipping validation studies, including stress testing or temperature excursion data, to ensure product integrity during transport
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A well-justified shelf-life, based on real-time data, not solely on extrapolation from accelerated studies
Even though Zone IVb is not applicable to biologics, your stability strategy must still demonstrate that the product remains safe, pure, and potent throughout its lifecycle — including under real-world transport and storage conditions.
Incomplete stability data is one of the most common flags at the screening stage.
4.Clinical and Nonclinical Data: Focus on Immunogenicity
In Modules 4 and 5, HSA’s review focuses on whether the clinical and nonclinical data:
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Clearly support the biologic’s safety, efficacy, and immunogenicity profile
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Include bridging data or scientific justification if the biosimilar comparator is not registered in Singapore
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Are derived from ICH-compliant studies, even if conducted overseas, as local Singapore data is not required by default
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Include robust immunogenicity assessments, especially for biologics intended for chronic use or repeated dosing
While HSA does not require studies in Singaporean patients, it expects that the clinical data be applicable to the intended population, and any major differences in demographics or clinical practice should be addressed through scientific justification.
Even for rare diseases or products supported by limited clinical data, a well-reasoned explanation is still expected.
5. Quality Overall Summary (QOS): More Than a Summary
The QOS (Module 2.3) in Singapore plays a central role in the reviewer’s assessment. It’s not just a summary — it’s a narrative of your product’s journey, from manufacturing to safety to clinical utility.
A good QOS should:
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Clearly connect CMC, nonclinical, and clinical data
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Provide justifications for control strategies and batch selection
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Reference tables and annexes logically
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Be tailored to HSA’s review style — concise, structured, and scientific
Cut-and-paste summaries from EU or US applications often don’t work well in Singapore.
6.Regulatory Strategy: Think Local Early
While HSA accepts ICH-aligned submissions, it expects sponsors to demonstrate a clear understanding of the local regulatory context.
Key points to consider:
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Reference product: If a biosimilar comparator is not registered in Singapore, provide bridging data or a scientific justification referencing global approvals and literature
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Post-approval commitments: Be prepared for ongoing requirements, such as continued stability studies or local pharmacovigilance plans, especially for newly marketed biologics
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Clear comparability strategy: HSA places importance on how changes to manufacturing or biosimilarity are justified. Submissions should include a transparent, risk-based comparability plan that aligns with ICH Q5E principles
Even for biologics already approved by major agencies (e.g., FDA, EMA), you may need to bridge data or adapt your justifications to address specific HSA queries or the Singapore healthcare context.
7. Common Pitfalls to Avoid
Based on experience supporting biologics submissions in Singapore, here are common areas that often lead to screening queries or delays during HSA review:
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Quality Overall Summary (QOS) not clearly presenting key quality attributes or addressing issues HSA typically prioritizes (e.g., comparability, control strategy, or stability justification)
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Comparability data that is insufficient, unclear, or does not adequately support product consistency or biosimilarity
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Stability protocols that overlook ICH Q5C guidance or fail to provide adequate real-time, real-temperature data — biologics are not subject to ASEAN Zone IVb requirements, but must still demonstrate product integrity
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Reference product justification missing or weak for biosimilars, especially if the comparator is not registered in Singapore
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Analytical method validation or bridging justifications not sufficiently detailed in Module 3, particularly when methods are adapted across sites or jurisdictions
Addressing these areas early can help reduce avoidable screening issues and improve overall dossier quality.
Starting with a gap analysis is highly recommended if you’re adapting a dossier from another region.
How TRC Can Support You
At TRC, we help companies prepare and localise their biologics submissions for the Singapore market. Our services include:
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CTD format and content gap analysis tailored to HSA expectations
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Submission preparation and planning, including guidance on required documents and formatting
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Support with regulatory strategy, such as identifying reference product considerations or bridging needs
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End-to-end coordination through the evaluation process, including screening query management and communication with HSA
We work closely with clients and their technical teams to ensure submissions are well-aligned with Singapore’s regulatory requirements — without duplicating scientific or manufacturing work already in place.
Biologics are powerful therapies, but the regulatory path in Singapore is not straightforward. Each module of the CTD needs careful attention — not just to meet international standards, but to reflect what HSA expects locally.
Whether you’re a small biotech or an established pharma company, having a clear local regulatory strategy can significantly shorten your path to approval.
Feel free to reach out if you’d like to discuss your biologics submission plans. We are happy to support.
Disclaimer: This blog is written based on the author’s current understanding, regulatory experience, and publicly available information. It is intended for general informational purposes only and does not constitute regulatory advice. For official requirements, please refer to the latest guidelines issued by the Health Sciences Authority (HSA) .
Are you considering bringing your Chinese medicine products to Singapore? With a clear regulatory framework, zero registration fees, and swift evaluation timelines, Singapore presents an exciting opportunity for Chinese companies aiming to expand into Southeast Asia. Let’s explore the key differences in regulations between China and Singapore—and how The Reg Consultants (TRC) can guide your seamless entry into this promising market.
China vs. Singapore: A Quick Regulatory Comparison on How Chinese Medicine is Regulated
China: National Medical Products Administration (NMPA) oversees Chinese medicine, which is mainly classified as traditional Chinese patent medicine. The regulatory process is rigorous, requiring extensive safety and efficacy data. Products with therapeutic claims must undergo clinical trials and detailed documentation reviews.
Singapore: Health Sciences Authority (HSA) regulates Chinese medicine under the Chinese Proprietary Medicine (CPM) category. This includes oral, topical, or inhaled products based on traditional principles. Unlike China, no clinical trials are needed, offering a streamlined and efficient process that maintains high safety and quality standards.
Registration Pathways and Timelines
China: For therapeutic products, the regulatory process spans multiple steps—clinical trials, lab testing, and safety assessments. Timelines often stretch from 2 to 5 years, making market entry a lengthy commitment.
Singapore: The evaluation process for CPM products is notably faster—approximately 60 working days. Better yet, there are no registration fees, making Singapore a cost-effective and accessible market for expansion.
Documentation requirements:
China: Extensive clinical, safety and GMP data
Singapore: Leverage on country of origin clinical and safety data. Data are more focused on CMC perspective.
Why Singapore is Your Gateway to Southeast Asia
1. Simplified and Cost-Effective Registration
Singapore offers a straightforward regulatory pathway with unparalleled advantages for Chinese manufacturers:
Evaluation in Just 60 Days: HSA expedites evaluations for CPM products without sacrificing quality or compliance.
Zero Registration Fees: By removing registration costs, Singapore reduces financial barriers for companies entering the market.
2. Practical Documentation Requirements
Singapore’s approach to documentation emphasizes practicality, minimizing administrative burdens for manufacturers:
Formulation and Ingredient Safety: Provide clear details about your product’s composition.
Manufacturing Standards: Submit quality control and safety protocols to meet GMP standards.
Ready to bring your Chinese medicine products to Singapore? Contact TRC today and let’s embark on this exciting journey together!
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Entering the pharmaceutical market in Singapore presents a complex web of regulations and requirements that companies must navigate. Market access refers to the process of making pharmaceutical products available to those who need them at the right price and time. The process involves various activities focused on ensuring patients receive the treatments they require. At its core, pharma market access revolves around two main elements: pricing and reimbursement. For any business looking to thrive in this competitive landscape, understanding the nuances of pharmaceutical market access is crucial. In this article, we’ll explore the essential factors that pharmaceutical companies should consider, from regulatory frameworks to effective pricing strategies.
Regulatory Landscape
The Singapore regulatory framework for pharmaceuticals is governed by several key authorities, with the Health Sciences Authority (HSA) playing a central role. This body is responsible for evaluating and approving medicines and medical devices, making sure they meet rigorous safety, quality, and efficacy standards. For companies looking to enter the market, preparing detailed documentation that aligns with the HSA’s strict requirements is crucial. Familiarity with these regulatory requirements is vital, as they can greatly influence both the timeline and the success of product approvals.
Reimbursement Policies
Understanding reimbursement policies is crucial for pharmaceutical companies seeking successful market access. Getting products listed on the national health authority’s drug formulary ensures they are available to patients. Achieving market access means that a product is approved for use and eligible for reimbursement by national healthcare systems or insurance providers. In Singapore, the Government and various healthcare institutions have set up specific mechanisms for reimbursing new medicines. Companies need to evaluate the cost-effectiveness of their products and how they fit with the country’s healthcare priorities. By navigating these reimbursement processes, businesses can develop strategies that enhance their market access efforts and increase their chances of success.
Here’s a list of key reimbursement policies in Singapore that can assist pharmaceutical companies, along with brief descriptions and information on how they can get their drugs listed:
1. Drug Formulary Listing
The Drug Formulary is a list maintained by the Health Sciences Authority (HSA) and the Ministry of Health (MOH) that includes medicines approved for use in Singapore’s public healthcare system. Listing on this formulary ensures that a drug is accessible to patients at subsidised rates.
Companies must submit comprehensive clinical and economic evidence demonstrating their product’s safety, efficacy, and cost-effectiveness. The Drug Advisory Committee evaluates this submission and makes recommendations to the MOH for listing approval.
2. Health Technology Assessment (HTA)
HTA evaluates the clinical effectiveness and cost-effectiveness of new health technologies, including drugs, to inform reimbursement decisions. This process helps determine the value a drug provides relative to existing treatments.
Companies should prepare data from well-designed clinical trials and economic evaluations. Engaging with the Health Technology Assessment (HTA) agency early in the process can provide guidance on the required data and submission format.
3. Medisave and MediShield Life
Medisave is a national savings scheme that allows Singaporeans to set aside part of their income for medical expenses. MediShield Life is a basic health insurance plan that helps cover large hospital bills and certain outpatient treatments.
A drug must meet specific clinical criteria to be covered under Medisave or MediShield Life. Companies must demonstrate how their product aligns with existing treatment protocols and patient needs and submit the necessary documentation to the MOH for evaluation.
4. Clinical Practice Guidelines (CPGs)
CPGs are evidence-based recommendations developed by expert panels to guide healthcare professionals in the treatment of specific conditions. Drugs that are included in CPGs may receive better visibility for reimbursement consideration.
Pharmaceutical companies can collaborate with medical associations and healthcare professionals to ensure their drug is included in relevant CPGs. Providing clinical evidence supporting the drug’s use in accordance with these guidelines can enhance its chances for inclusion.
5. Specialist Drug Programme (SDP)
The SDP is designed to facilitate access to innovative therapies that may not yet have been formally approved or listed but show promise in treating serious conditions. This programme allows for early access under specific conditions to include their drug in the SDP by presenting compelling clinical data and justifying the need for early access. A review process evaluates the product’s potential benefits against risks.
Pricing Strategies
Singapore is largely a tender-based market with a pricing strategy that is stratified between meeting tender and private needs. Companies may need to conduct their own on-the-ground study with the support of local distributors, engage a market access specialist, or obtain IMS data pertaining to the relevant therapeutic area on which they are going to benchmark their pricing. While it is always good to be able to obtain a B2B price, at times, this can be challenging, which makes it much easier to get a consumer price and work out the base cost. Knowing how to position products effectively in terms of pricing not only impacts market entry but also affects long-term sustainability in this dynamic market.
Market Entry Barriers
Apart from regulatory challenges, It’s crucial to study the local gold standard treatment for a particular indication culture of the people here to appropriately select the type of products to enter Singapore. Some companies are focused on introducing new drugs into Singapore rather than generic drugs due to the lack of profit margin or volume to meet the country of origin’s volume. Recognising these barriers early on is crucial for developing effective market access strategies. Engaging pharma regulatory services can help companies navigate these complexities more effectively. Proactively tackling these challenges allows the companies to facilitate a smoother entry into the market and better position themselves for success in the competitive pharmaceutical landscape.
Market Access Strategies
Companies must adopt robust market access strategies to achieve and sustain pharmaceutical market access in Singapore. This includes engaging with stakeholders such as KOLs, holding symposiums, participating in congresses, and collaborating closely with procurement agencies such as the Ministry of Health or the Group Procurement Office. By understanding the complexities of the local market and implementing tailored strategies, businesses can significantly improve their chances of successful product registration and establish a lasting presence in the market.
In conclusion, navigating Singapore’s pharmaceutical market access landscape requires thorough knowledge of the regulatory environment, reimbursement policies, pricing strategies, and potential entry barriers. Leveraging expertise in regulatory affairs and implementing effective market access strategies can significantly enhance a company’s chances of success.
If you’re ready to tackle the complexities of pharmaceutical market access with confidence, reach out to The Reg Consultants today. Our team is here to offer tailored regulatory affairs services and insights to help you thrive in the Singaporean market.
