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.
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 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) .
Brazil pharmaceutical companies offer a diverse and innovative portfolio of products. However, due to geographical distance, most companies focus on developing their market within Brazil and the U.S. There are many compelling reasons for Brazilian companies to consider expanding into Singapore and other ASEAN countries, where they can leverage strategic regulatory advantages and market opportunities that support efficient entry and growth.
Regulatory Synergies: Singapore and Brazil
One of the key regulatory advantages for Brazilian companies looking to enter the ASEAN market is that Brazil’s health regulatory authority, ANVISA, is a member of the Pharmaceutical Inspection Co-operation Scheme (PIC/S). Many ASEAN countries, including Singapore, require PIC/S GMP compliance, allowing Brazilian companies to bypass additional inspections during the registration process. This waiver can significantly reduce lead times in regulatory approval, giving Brazilian companies a quicker route to market.
Climate Compatibility: Shared Zone IVb Stability Requirements
A unique advantage Brazil holds is its geographic location in Zone IVb, which aligns with ASEAN’s required climatic stability conditions for pharmaceutical products. This means that Brazilian companies can use existing stability studies, avoiding the need for additional testing specific to the ASEAN region. This shared climatic zone can result in considerable cost savings on stability studies and compliance, giving Brazilian products a competitive edge in terms of time and expense.
Comparing Regulatory Processes: Brazil vs. Singapore for Generic and New Drug Registration
While there are similarities, it’s essential for Brazilian companies to understand the regulatory differences between Brazil and Singapore, especially regarding generic and new drug registration. Below are key considerations that companies should factor into their ASEAN market expansion strategy.
- Registration Pathways
In both Brazil and Singapore, the registration pathway differs significantly for new drugs versus generics. For instance:
New Drugs: In Singapore, Health Sciences Authority (HSA) offers a structured pathway for innovative and new drugs, which may include priority review if the drug is deemed essential and lacks alternatives. In contrast, ANVISA in Brazil also has a pathway for new drugs, though companies may face longer timelines due to a multi-stage evaluation process.
Generics: The process for registering generics tends to be faster in both Brazil and Singapore, but while ANVISA requires proof of bioequivalence and local testing, HSA may accept certain international data, reducing redundancy and potentially expediting registration for companies with existing global dossiers.
- Evaluation Timelines
Evaluation timelines vary widely:
In Brazil, ANVISA’s timelines can range from six months to two years depending on factors such as product type and completeness of the initial submission. Backlogs can also affect timelines, particularly for new drug applications.
HSA is known for shorter timelines, often ranging from nine to eighteen months for both new drugs and generics, especially for applications that meet international standards and are well-documented. Singapore also offers prioritized processing for essential medications, which may benefit companies with innovative therapies.
- Documentary Requirements: Common Technical Document (CTD)
Both Singapore and Brazil use the CTD format, but specific requirements within the document vary, particularly for Modules 2-5:
Module 2 (Quality Summary): In Singapore, HSA requires a comprehensive QoS which may differ from ANVISA’s requirements.
Modules 3 to 5: For new drugs, Brazil and Singapore both demand comprehensive preclinical and clinical data, but Singapore may accept foreign clinical trial data if it’s from recognized health authorities, whereas ANVISA may require supplementary data to align with Brazilian standards.
- Stability and Climatic Zone Requirements
Given the shared Zone IVb classification between Brazil and ASEAN countries, Brazilian companies can often use existing stability studies for Singapore, eliminating the need for additional stability testing. This alignment is particularly advantageous for generics, as it simplifies compliance with local stability requirements in Singapore.
- Labeling and Language Requirements
Singapore mandates labeling in English, and specific products may require simplified language for consumer understanding. Brazil similarly requires Portuguese labeling for domestic sales.
Making Expansion Decisions Easier: A Simple Regulatory Checklist
For Brazilian companies considering expansion into the ASEAN market, the following checklist can support a preliminary regulatory assessment, helping to identify both potential hurdles and advantages:
- Registration Pathway: Assess whether the registration pathway aligns with your product type, as requirements may differ significantly between new drugs and generics.
- Evaluation Timeline: Consider the estimated evaluation timeline for product approval, which can vary based on the specific ASEAN regulatory authority’s processes and the complexity of the product type.
- Technical Dossier Requirements (M2-M5): Review the dossier sections required for submission in ASEAN, particularly Modules 2 to 5 of the Common Technical Document (CTD). This assessment should take into account if the product is a new drug or a generic, as requirements may differ.
- Labeling Requirements: Ensure compliance with ASEAN-specific labeling requirements, which often include language adaptations and specific formatting to meet local standards.
By considering these key points, companies can conduct initial regulatory intelligence to streamline the expansion process. If your company is ready to enter the ASEAN market, The Reg Consultants (TRC) is available to provide expert regulatory support, helping you navigate these requirements with ease.
Feel free to check out other relevant articles:
https://theregconsultants.com/overcoming-the-challenges-of-registration-of-a-generic-drug-in-singapore/
https://theregconsultants.com/why-is-regulatory-intelligence-exercise-crucial-for-pharma-companies-looking-to-expand-into-new-territories/
https://theregconsultants.com/why-is-regulatory-intelligence-exercise-crucial-for-pharma-companies-looking-to-expand-into-new-territories/
https://theregconsultants.com/5-self-check-questions-for-pharma-market-access-in-singapore/
In recent times, we’ve received numerous inquiries about the possibility of rebranding complementary health and cosmetic products in Singapore, particularly due to geopolitical factors. Many companies are looking to facilitate export to their home countries, and understanding how to rebrand products as “Made in Singapore” can be a strategic advantage. In this article, we’ll explore what constitutes a product as “Made in Singapore,” the pathway to achieve this , and the certifications available from Singapore Customs , Singapore Manufacturing Federation, as well as the Singapore International Chamber of Commerce, that can facilitate export.
What is Considered a “Made in Singapore” Product?
A “Made in Singapore” product refers to goods that are substantially manufactured or processed within Singapore, in line with regulatory criteria established by local authorities. To earn this designation, a significant portion of the production costs—including labor and materials—must be incurred locally, ensuring considerable local value addition. Furthermore, products must comply with Singapore’s safety, health, and environmental standards to meet quality expectations.
It’s essential to note that if a product is manufactured outside of Singapore and only undergoes labeling or assembly here, it may be labeled as “Packed in Singapore” or “Secondary assembled by ABC Pte Ltd in Singapore.” However, it cannot be marketed as “Made in Singapore,” as this designation necessitates significant manufacturing or processing within the country.
Importance of Free Sale Certificate (FSC) and Certificate of Origin (COO)
When exporting goods, obtaining a Free Sale Certificate (FSC) and a Certificate of Origin (COO) can significantly streamline the process and enhance market acceptance in your destination country.
- Free Sale Certificate (FSC): Issued by Singapore Customs, the FSC confirms that the products are sold locally in Singapore and are compliant with local regulations. It serves as a testament to the product’s quality and safety, making it easier for foreign authorities to accept the product without extensive scrutiny.
- Certificate of Origin (COO): This document attests to the origin of the goods and is essential for international trade. Many countries require proof of origin to determine applicable tariffs and compliance with trade agreements. There are two types of COOs:
- Ordinary COO (Non-Preferential): Identifies the origin of the good but does not allow overseas buyers to claim preferential tariff treatment, as it is not issued under any Free Trade Agreement.
- Preferential COO: Enables your buyer to benefit from lower or no customs duty when exporting under a Free Trade Agreement or Schemes of Preferences.
Steps to Brand Your Complementary Health Products or Cosmetics as “Made in Singapore”
- Set Up a Manufacturing Facility: Establish a manufacturing facility that adheres to Good Manufacturing Practice (GMP) requirements to produce your product, or partner with a licensed contract manufacturing facility that specializes in complementary health products. Ensure that your facility is registered with relevant authorities to facilitate inspections and audits.
- Ensure Regulatory Compliance: Comply with the relevant regulatory controls for your type of health product. Prepare comprehensive documentation to establish the quality, safety, and efficacy of your product. This documentation should include:
- Product specifications
- Safety data sheets
- Clinical studies (if applicable)
- Quality assurance protocols
Seek the appropriate approvals before marketing and distributing it locally. This may involve obtaining licenses to import and distribute if necessary.
- Obtain Necessary Certifications: Once you receive approval from the regulatory authority, you can apply for a Free Sale Certificate from Singapore Customs or a Certificate of Origin from the Singapore Manufacturing Federation and the Singapore International Chamber of Commerce to facilitate exportation, depending on the domestic procedures of your destination country.
- Free Sale Certificate: To apply for the FSC, submit your application along with supporting documents that demonstrate your product’s compliance with local regulations. The certificate will detail the product’s description, registration numbers, and the local regulatory authority’s confirmation.
- Certificate of Origin: To obtain a COO, you will need to provide documentation that supports the origin of your goods. This may include:
- Invoices
- Shipping documents
- Manufacturing process details
COs are issued by the Singapore International Chamber of Commerce and the Singapore Manufacturing Federation. Ensure that you are familiar with the requirements of the importing country to facilitate a smooth export process.
For further information, please refer to the following resources:
We hope this information proves useful to you. Be sure to check out our other related blogs that may interest you:
Previously, drug substance manufacturers submitting applications for new drugs, generic drugs, or minor variations involving the introduction or change of a drug substance (DS) manufacturer were not required to provide GMP evidence. However, starting from October 1st, it is essential to note that GMP compliance evidence will be mandatory for these submissions in Singapore. This regulatory change aligns the quality requirements for drug substance manufacturers with those for drug product manufacturers, ensuring a consistent standard of quality across the industry.
Required Evidence for GMP Compliance
To comply with the updated regulations, drug substance manufacturers must submit the following acceptable forms of GMP compliance evidence:
- GMP Certificate: Issued by PIC/S (Pharmaceutical Inspection Co-operation Scheme) member authorities for the specific drug substance.
- GMP Inspection Report: This report must detail the GMP inspection, including the drug substance of interest, along with a close-out letter from PIC/S authorities that do not issue certificates.
- API Registration Certificate: This certificate confirms that the Active Pharmaceutical Ingredient (API) is listed on EudraGMDP (European Database on Good Manufacturing Practices).
- Certificate of a Pharmaceutical Product (CPP): This must be issued by the US FDA for the API.
- Manufacturing License: A license from a PIC/S authority covering the drug substance of interest.
Implications of the New Requirement
As these new regulations take effect, there will be several implications for products already registered in Singapore or those planning to submit applications:
- For new drug and new generic drug applications scheduled for submission in Q3-Q4, manufacturers will need to reassess their compliance with the new requirements.
- Existing products that involve a change of manufacturing site will require a reassessment of the supplier’s conformity to the GMP standards mandated in Singapore, which may impact the overall product lifecycle.
Important points to note:
- Products that were approved or submitted before October 1st will not be affected by this new requirement.
- DS manufacturer who has a valid CEP issued for their DS complying to the monograph of European Pharmacopeia , the submission of the GMP evidence is optional.
Ensuring GMP compliance is more than just a regulatory obligation; it represents a commitment to quality and patient safety. By preparing the necessary documentation and adhering to GMP standards, manufacturers can streamline their approval processes and enhance their credibility within the industry.
If you require assistance in evaluating your dossier prior to submission or have any questions regarding GMP compliance, please don’t hesitate to reach out. We are here to help you navigate these requirements effectively.
Entering a new market like Singapore can indeed be a strategic move for Chinese pharmaceutical companies expanding into Southeast Asia. Today TRC would like to highlight 6 key areas from a regulatory perspective:
1. Quality of the CMC documents- Drug Substance
a) GMP Compliance: Starting from October 2024, compliance with Good Manufacturing Practice (GMP) regulations will be necessary for drug substance manufacturers in Singapore. This requires either a valid GMP certificate issued by the Pharmaceutical Inspection Co-operation Scheme (PIC/S) authority or a Certificate of Suitability and valid Active Pharmaceutical Ingredient (API) registration certificate covering the drug substance of interest listed on the European Union Drug Regulatory Authorities (EURDRA) GMP. Without these documents, product registration in Singapore will not be possible.
b) Specifications: Specifications and limits for the drug substance must be established in accordance to validated analytical methodology and based on understanding of the manufacturing process and data collected from the course of stability studies, stress testing and process validation . Reference to ICHQ2 and Q6A will be appropriate. The drug product manufacturer should have final control over the quality of the drug substance incorporated into the final formulation. Therefore, the drug product manufacturer should maintain a final controlled version of the drug substance specifications.
c) Process Validation: Process validation data should be submitted in accordance with the requirements outlined in the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) M4Q guidelines.
d) Stability Studies: Stability data from at least three primary batches, two pilot batches, or one small-scale batch should be submitted from the drug substance manufacturer based on ICH Q1 requirements. If the drug substance is sourced from multiple sites, stability data from each site should be provided. Additionally, stress testing data should be submitted to assess the stability of the drug substance under various conditions.
2. Quality of the CMC documents- Drug Product
a) Certificate of Pharmaceutical Product (CPP) –Proof of approval should be in World Health Organization (WHO) format and issued from the country of origin or the country where the product owner/manufacturer is based. If the CPP indicates that the product is not marketed, it will not be accepted.
c) Specifications of the Drug Product – Specifications and limits for the drug product should be established and conducted based on validated analytical procedures in accordance with ICH Q2 and ICH Q6A guidelines. These specifications govern the release and stability of the drug product which impacts on the safety and quality of the drug product.
d) Process Validation – Process validation data requirements depend on the type of dosage form, including solid oral drug products, aseptically processed drug products, and terminally sterilized drug products. Submission should include data from three consecutive manufactured batches according to the proposed manufacturing process and batch size.
e) Stability- Stability studies should cover data specified for Zone IVb (30°C/75%RH) and include data from three primary batches of 12 months for critical dosage form such as injectables and two primary batches of 6 months for conventional dosage form such as tablets and capsules . Studies should be conducted according to the proposed batch size, strength, and container closure system intended for marketing in Singapore.
3. Clinical efficacy
a) Acceptance of Foreign Clinical Trial Data –Most ASEAN countries, including Singapore, accept foreign clinical trial data. This means that data generated from clinical trials conducted outside of Singapore can be used to support product registration in these countries as long as they are conducted in accordance to GCP guidelines and relevant ICH guidelines.
b)Phase III Confirmatory Trials –To support each requested indication and dosing regimen for the product being registered, data from Phase III trials, which are confirmatory, randomized, controlled pivotal trials, compliance with Good Clinical Practice (GCP) guidelines is required.
c) Bridging Studies/Comparative Studies –In the case of biosimilars and generics, bridging studies or comparative studies may be required. These studies aim to demonstrate that the biosimilar or generic product is comparable to the reference product in terms of pharmacokinetic (PK) and pharmacodynamic (PD) parameters. The goal is to show that there are no significant differences between the test product and the reference product in terms of safety and efficacy.
5.Language Barrier- Dossier written in simplified Mandarin should be translated and verified in a way that the content reflects what is written in the original language and official documentation such as Proof of GMP, approval letters should be authenticated by the foreign embassy or consulate of the country of origin.
6. Marketing Authorization Requirements–In Singapore, only a local registered entity can hold the marketing authorization for pharmaceutical products. This means that companies seeking to market their products in Singapore must either establish their own legal entity in Singapore or engage a consultant who operates locally.
The MAH is responsible for ensuring compliance with regulatory requirements throughout the lifecycle of the product. This includes responsibilities such as product registration, pharmacovigilance, labeling and advertising compliance, and maintaining a quality management system.
To learn more about the responsibilities of a MAH, please visit: https://theregconsultants.com/responsibilities-of-a-marketing-authorization-holder-mah/
With that we have concluded key areas to evaluate prior to entering the Singapore market, if you need help and support to evaluate your dossier for registration in Singapore, please feel free to get in touch: https://theregconsultants.com/contact-us/
The ASEAN Joint Assessment Procedure is a procedure in which the same marketing authorization application is simultaneously submitted to all participating ASEAN National Medicines Regulatory Authorities (NRAs).
ASEAN National Medicines Regulatory Authorities (NRAs) includes:
- Health Sciences Authority (HSA)- Singapore
- National Pharmaceutical Regulatory Agency (NPRA)- Malaysia
- Thai Food and Drug Administration (Thai FDA)
- Food and Drug Administration (Philippines FDA)
- Badan Pengawas Obat dan Makanan (BPOM),Indonesia
- Drug Administration of Vietnam (DAV)
- Ministry of Health, Brunei (MoH, Brunei)
- Department of Drugs and Food (DDF), Cambodia
- Food and Drug Administration Myanmar
- Food and Drug Department (FFD) , Laos
The join assessment procedure is initiated with minimum of 3 NRAs.
At the moment , it covers only :
- a) medicines for treatment of priority diseases in ASEAN region such as but not limited to: treatment for specific cancers such as breast , lung, Hepatitis C, treatment of AIDS/HIV, Tuberculosis, Treatment-Resistant Depression.
- b) products already approved by a reference National Regulatory Authority(NRA) ,prequalified by WHO-PQP, or assessed through special regulatory pathways such as EU Article 58 or US-FDA tentative approval;
- c) products manufactured in a PIC/S-GMP compliant site
Process in brief
- Participating National Regulatory Authority(NRA) publish on their website in the form of a Notice : Notices of Invitation to Express Interest.
- Applicant can submit their interest by filling up the appropriate application form to the authority.
- Lead NRA seeks concurrence of participating NRAs for accepting Expression of Interest
- Lead NRA requests applicant to submit required documentation to participating NRAs.
- Assessment work is then carried out together by all participating NRAs and a joint assessment report is prepared
- At the end of the process, the final decision on the application is then taken, within established time lines, by each individual NRA through their normal decision-making process based on the joint report and, where applicable, nationally-relevant considerations.
Applications must comply to the following:
- the technical application dossier must include the same technical information as that submitted to reference NRA or WHO-PQP;
- b) the technical part of the dossier in ACTD or ICH-CTD format shall be provided in electronic form to be uploaded to a dedicated, secure web site set up by WHO; only participating NRAs will be able to access and download the dossiers;
- c) administrative part of dossier specific to each participating NRA requirements will be submitted directly to each participating authority;
- d) fees as required by each participating NRA will be paid according to normal national procedures.
Processing timeline: 180 working days for assessment procedure
If you have a product that may fall into the therapeutic area mentioned and need support for submission, please feel free to get in touch with TRC.
Useful references:
- List of Priority Products
- Processing timelines
- ASEAN-JA-Procedure-for-Pharmaceutical-Products-Information-for-Applicants
