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.

1. 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.

2. 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.

3. 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.

4. 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.

5. 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/

 

 

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:

1. GMP Certificate: Issued by PIC/S (Pharmaceutical Inspection Co-operation Scheme) member authorities for the specific drug substance.
2. 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.
3. API Registration Certificate: This certificate confirms that the Active Pharmaceutical Ingredient (API) is listed on EudraGMDP (European Database on Good Manufacturing Practices).
4. Certificate of a Pharmaceutical Product (CPP): This must be issued by the US FDA for the API.
5. 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

 2. Quality of the CMC documents- Drug Product

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/

 

 

 

All overseas manufacturing sites are subjected to GMP conformity assessment by the local authority. GMP conformity assessment is in support a therapeutic product registration. Only local registered entity in Singapore can support the GMP conformity assessment application. The cost and timeline is dependent on the pathway in accordance to the pathway.

 

What is GMP conformity assessment?
GMP conformity assessment or Overseas Audit Program Assessment refers to evaluation of a new overseas manufacturing site in compliance to established GMP guidelines. Singapore being part of PIC/S scheme member countries adopt the PIC/s standard for Good Manufacturing Practices for Medicinal Products.

 

1st pathway : GMP Documentary Evidence Verification (DEVA)
This pathway is only feasible for proof of GMP compliance that are issued by PIC/S member authority. Acceptable proof of GMP compliance includes manufacturing license, GMP certificate and CPP issued in WHO format.
Applicant would need to ensure that the submission of the proof of GMP compliance is in English language, original scanned colour copy and indicates the basic information of the manufacturing site including name and address, dosage form, authorized activity and GMP standards of which the manufacturer complies with.
The fee is SGD$630 per manufacturing site per dosage form. There is no specific timeline involved as this is evaluated in conjunction with the submission of a product registration. Once the site is registered, there will not be a need to go through a similar conformity assessment for a similar dosage form.

 

2nd pathway Overseas On-site Audit 
Manufacturers would be subjected to this pathway due to the following conditions such as unavailability of acceptable GMP evidence, inadequate GMP evidence to demonstrate compliance, regulatory concern regarding GMP compliance of manufacture or product alert related to product defect or recall associated with the site concerned.
For this pathway, application would need to prepare a Quality System Dossier in accordance to Preparation of a Quality System Dossier (GUIDE-MQA-019) with a list of supporting documents to the authority for evaluation. Once the application is accepted for evaluation, an overseas inspection will take place based on the schedule of inspectors and availability of the manufacturing site that is to be audited.

 

The fees are presented below:
QSD evaluation- $4,770
On site audit located in ASEAN country- $18,400
On site audit located in ASEAN- $20,400
On-site audit located outside of Asia- $24,400

 

Post inspection, the authority will issue a letter to summarize the inspection including any potential observations or deficiencies that are required to be addressed. Applicant will be given about a month time to provide CAPA.
Upon successful close out of the post inspection findings, the applicant will be informed of the outcome.

 

We hope the above information is supportive for your product registration in Singapore If you need help to evaluate your GMP documents , please get in touch or if not feel free to share with your peers.

 

Useful references:
1. https://www.hsa.gov.sg/therapeutic-products/register/gmp-conformity-assessment
2. PIC/S Guide to GMP for Medicinal Products.

 

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 :

1. 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.
2. 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;
3. c) products manufactured in a PIC/S-GMP compliant site

Process in brief

1. Participating National Regulatory Authority(NRA) publish on their website in the form of a Notice : Notices of Invitation to Express Interest.
2. Applicant can submit their interest by filling up the appropriate application form to the authority.
3. Lead NRA seeks concurrence of participating NRAs for accepting Expression of Interest
4. Lead NRA requests applicant to submit required documentation to participating NRAs.
5. Assessment work is then carried out together by all participating NRAs and a joint assessment report is prepared
6. 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:

1. the technical application dossier must include the same technical information as that submitted to reference NRA or WHO-PQP;
2. 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;
3. c) administrative part of dossier specific to each participating NRA requirements will be submitted directly to each participating authority;
4. 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:

1. List of Priority Products
2. Processing timelines
3. ASEAN-JA-Procedure-for-Pharmaceutical-Products-Information-for-Applicants

 

As a country facing an ageing population and a growing incidence of chronic diseases, it is unsurprising that various pharmaceutical businesses seek to make their products available in Singapore to meet the increasing demand for advanced medical treatments.

However, the selling of new pharmaceutical products is heavily regulated in Singapore and is only permitted after a valid product license has been obtained through registration with the Health Sciences Authority (HSA). Such stringent regulations are in place to ensure the product is safe for consumption by the public.

For pharmaceutical companies planning to introduce their pharmaceutical products into Singapore’s market, navigating the regulatory landscape seamlessly and ensuring compliance with the HSA’s requirements are paramount. Fortunately, the entire process need not be complicated. Let us share six essential tips to ensure a smooth and successful pharma registration in Singapore.

Tip #1: Familiarise Yourself with the Regulatory Requirements for Pharmaceutical Product Registration

When you fail to plan, you plan to fail. Without adequate knowledge of the pharmaceutical product registration process and an intimate understanding of the HSA’s regulatory requirements, you are only setting yourself up for failure.

So, thoroughly study the HSA’s guidelines pertaining to pharmaceutical product registration beforehand, encompassing everything from product safety to manufacturing processes. Familiarising yourself with the regulations provides a robust foundation, allowing you to tailor your submission to meet all requirements, thus ensuring a successful registration.

Tip #2: Compile a Comprehensive Pharmaceutical Product Registration Dossier

Your registration dossier serves as the foundation of your application to the HSA. Every information contained within the dossier will be scrutinised to ensure your product complies with existing regulations. Any omission of relevant data could compromise your entire pharma registration effort. So, ensure your submission is complete with all relevant information about your pharmaceutical product, including its composition, efficacy data, manufacturing processes, and safety profiles.

Tip #3: Engage the help of a local regulatory consultant

Navigating the medical regulatory landscape can be complex even for a pharmaceutical company based in Singapore, let alone foreign businesses from a different market. If you are unsure where to begin, leveraging the expertise of a consultant with experience in the local regulatory scene can prove invaluable.

A reliable pharmaceutical regulatory consulting firm can provide helpful insights and guide you through the various intricacies of the administrative process, ensuring your application aligns seamlessly with the HSA’s guidelines, thus boosting your chances of success.

Tip #4: Understand your product classification

Pharmaceutical products in Singapore are classified into several categories based on their intended use, risk level, and mode of action. The HSA’s classification system is as below:

• Complimentary Health Product (CPM) “Health supplements”
• Therapeutic Products covering chemical drugs, biotechnology products, blood products, biosimilars
• Medical devices (Risk Class A, B,C and D)
• Chinese Proprietary Medicine (CPM)
• Cell Gene Therapy Product (Class 1 or Class 2)

 

Each class is governed by distinct regulatory requirements. So, understanding this classification system and which category your pharmaceutical product belongs to is paramount. Accurate classification ensures you follow the appropriate guidelines, streamlining the pharma registration process and preventing your application from being dismissed on a technicality.

Learn More: Misconception of regulatory classification of medical products

Tip #5: Clinical trials

HSA often requires robust clinical evidence to support registration applications. Overseas clinical trial data are accepted for registration which saves the hassle of conducting local trials. Also, engaging the help of a local regulatory consultancy firm to analyse the clinical documentation could cement your compliance to the local requirements pertaining to the safety and efficacy of your pharmaceutical product. This ensures compliance with HSA guidelines.

Tip #6: Ensure compliance and good practice

The HSA governs more than just the safety and manufacturing process of a pharmaceutical product. The labelling and packaging must also comply with the HSA’s good manufacturing practice (GMP) standards and quality control. Compliance with these standards is crucial for the successful registration of pharmaceutical products in Singapore.

So, prepare detailed documentation and evidence, such as inspection reports, certificates, and quality control processes, showcasing adherence to the GMP standards. This diligence can help expedite the pharma registration process and establish a foundation for long-term compliance.

Ultimately, a thorough and well-executed registration strategy requires meticulous planning, strict adherence to regulatory guidelines, and a keen understanding of the local regulatory landscape. With these elements in place, you can set the stage for a successful market entry and ensure sustained success in Singapore.

If you require assistance with your product registration, look no further than The Reg Consultants for your pharmaceutical regulatory consulting needs. With a wealth of experience in assisting pharmaceutical and medical companies, both local and overseas, we can aid your business in streamlining the product registration process and securing the necessary approvals for marketing and distribution within the ASEAN region. Contact us today to learn how we can help.