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/

 

 

Have you ever wondered what the difference between the terms “biosimilar” and “generic drugs” is? In the pharmaceutical industry, the distinctions between biosimilar and generic drugs play an important role in affecting healthcare accessibility and affordability, particularly in the context of pharmaceutical product registration. This guide explores the contrasting regulatory frameworks for biosimilars and generics, their development and approval processes, and their impact on the healthcare industry.

Biosimilar drugs are highly similar to biologic drugs, which are derived from living organisms. While they are not identical to the original biologics, they are designed to match the reference product in terms of quality, safety, and efficacy. Due to the complexity of biologics, biosimilars require rigorous testing and regulatory approval. The difference between biosimilar and generic drugs lies in the nature of the original products—biologics versus chemically synthesised drugs.

Generic drugs are chemically equivalent to brand-name drugs and contain the same active ingredients, dosage, and efficacy. They are generally more affordable as they do not require the same extensive testing as the original branded drug, focusing instead on proving bioequivalence. The difference between biosimilar and generic drugs lies in the fact that generic drugs are simpler, chemically synthesised versions of brand-name pharmaceuticals, whereas biosimilars are derived from biological sources.

Definition and Development

At first glance, biosimilars and generics seem similar as both provide affordable alternatives to established medications. However, a major difference between biosimilar and generic drugs lies in their origin and the regulations governing their development.

Generic drugs are exact copies of small-molecule brand-name drugs, where the manufacturing process can be precisely replicated. These drugs contain identical active ingredients, dosages, and formulations, allowing them to be approved through a more straightforward regulatory process, focused on proving bioequivalence. This means that the generic drug delivers the same amount of active ingredient into the bloodstream as the original, ensuring similar therapeutic effects.

Biosimilar drugs, on the other hand, are biologics derived from living sources, such as plant or animal cells, making their structures more complex and less defined. Because of their biological nature, creating an exact copy of a biologic is impossible. As a result, biosimilars require a more rigorous approval process that involves comparative studies to demonstrate that they have no clinically meaningful differences in safety, efficacy, and biological activity from the reference product. The difference between biosimilar and generic drugs is primarily based on their complexity and the necessity for comprehensive comparability studies in biosimilars.

Approval Process

The governing regulatory authority in Singapore for health products is the Health Sciences Authority (HSA), which plays a vital role in verifying the safety and efficacy of both biosimilars and generics. Nevertheless, the registration process for each category differs due to the difference between biosimilar and generic drugs.

Generic drugs typically follow a well-established pathway that focuses on demonstrating bioequivalence, meaning the drug delivers the same active ingredient to the body as the original. In contrast, biosimilars undergo a more rigorous assessment to establish a high level of similarity to the reference product (the original biologic) in terms of quality, safety, efficacy, and biological activity. This often involves extensive analytical studies and clinical trials, reflecting the more complex nature of biologics.

Efficacy and Safety

In regulatory assessments, both biosimilars and generics must demonstrate efficacy and safety. However, the difference between biosimilar and generic drugs lies in their approval process. While generics must prove bioequivalence to a brand-name drug, biosimilars must establish their similarity to the biologic reference product by matching its safety and efficacy profile through comprehensive testing.

Market Access and Affordability

The introduction of both biosimilars and generics has had a significant impact on the pharmaceutical market. The difference between biosimilar and generic drugs is primarily their origin—biosimilars are derived from biologics, while generics are chemically synthesised versions of brand-name drugs. Both types of drugs offer substantial cost savings, and have greatly improved access to affordable healthcare.

Physician and Patient Considerations

While both biosimilar and generic drugs offer significant benefits, healthcare providers must carefully consider their interchangeability. The difference between biosimilar and generic drugs becomes crucial when deciding on treatments, as biosimilars may not always be substituted for the original biologic, unlike generics, which can often replace brand-name drugs without complications. The decision should be made in consultation with a qualified healthcare professional who can evaluate the patient’s specific needs and medical history.

Understanding the difference between biosimilar and generic drugs helps healthcare providers and regulatory stakeholders navigate the approval processes. Recognising the distinct pathways for both categories ensures safe and effective medication options for patients.

For expert guidance on navigating the complexities of pharmaceutical registration in Singapore, consider partnering with a reputable consultancy firm like The Reg Consultants. Our team of regulatory specialists offers comprehensive pharma regulatory services and possesses in-depth knowledge of the local landscape for biosimilars and generics. We can guide you through the intricate approval process, ensuring your products meet all regulatory requirements.

Understanding the difference between biosimilar and generic drugs is crucial to positioning your product accurately in the market. Contact The Reg Consultants today to leverage our expertise and ensure a seamless regulatory journey tailored to your specific needs.

Frequently Asked Questions

1. What is the difference between biosimilars and generic drugs?

The primary difference is that biosimilars are derived from biologic drugs, while generics are chemically identical to brand-name drugs. Biosimilars require more rigorous testing to prove similarity to biologics.

2. What is crucial for a biosimilar application in Singapore?

It is important to find out what is the Singapore Biological Reference Product so as to build comparative quality, PK and PD profile for registration.

3. What is the registration process for biosimilars in Singapore?

In Singapore, the registration process for biosimilars involves submitting a comprehensive application to the Health Sciences Authority (HSA) via the NDA-2 route and obtaining prior approval from reference agencies such as EMA, FDA, TGA. The application process typically takes about 230 working days.

4. Are clinical trials required for biosimilar registration in Singapore?

Yes, clinical trials may be required as part of the registration process for biosimilars in Singapore. The extent of required trials depends on the degree of similarity established through analytical studies and the specific characteristics of the biosimilar.

5. What documentation is needed for biosimilar registration?

The documentation needed for biosimilar registration typically includes a detailed dossier containing information on the manufacturing process, quality control measures, preclinical and clinical study results, and any other relevant information to support the application.

Please link to my articles that I have written previously:

Generic: https://theregconsultants.com/overcoming-the-challenges-of-registration-of-a-generic-drug-in-singapore/ 

Biosimilar; https://theregconsultants.com/quick-overview-of-biosimilar-registration-in-singapore/ 

Get in touch with us today to find out how we can tailor our services to fit your needs.

 

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.

 

As a regulatory service provider aka consultant, each regulatory consultant has their own unique way of execution of regulatory task especially for regulatory submission.  However it would not differ too much from what we are going to share with you.

TRC would like to share with potential prospects of how we usually manage regulatory submission.  Please refer to the steps below:

1. To initiate the regulatory submission flow, TRC would request Client to provide a secured link for us to access the dossier.
2. When dossier is downloaded , TRC would first begin to verify that all sections of the CTD is provided and also verify the file size . For file size exceeding the uploading size onto submission platform, a request would be sent to the Client to split the pdf into smaller size and re-send it to us.
3. TRC would execute minor formatting such as renaming of modules if not named appropriately as an example. However, TRC do not do any publishing or formatting of CTD to e-CTD.
4. A gap analysis exercise is conducted to identify the points to be addressed prior to submission accordance to classification of the product and evaluation pathway. The gap analysis report will be sent to the prospect to work on the gaps for our review. This would usually take about minimum of 3 round and not exceeding 5 rounds.
5. Once the gaps are addressed, we would proceed to perform online submission including the application form filling and uploading of documents.
6. Once submission is completed, TRC would furnish the entire set of dossier and a copy of the submission form to the prospect for their reference. TRC also perform our due diligence to keep track of the timelines to receive 1^st set of screening queries and between stages throughout the evaluation process to ensure that the submission is on track.
7. During the evaluation process, TRC lends their support by facilitating and reviewing the responses provided by the prospect to answer to the queries raised by the evaluator. Similarly, TRC would take the initiative to clear any doubts with regards to the query letter raised to support the prospect to provide the required responses. This is to ensure that each round of evaluation process would be well answered and to avoid duplication of questions from both ends.
8. Once approval is received via email, TRC will notify the prospect and remind the prospect to take note of the post-licensing condition imposed in the notification email.

We hope that above  has been useful for you if you are contemplating to engage us to support your regulatory submission in Singapore. Do reach out or explore TRC’s new and articles to navigate through article that are useful to you.

Chinese Proprietary Medicines(中成药产品)  refers to finished medicinal  product, such as a capsule or tablet, and contains one or more active ingredients from any plant, animal or mineral, or any combination of sources. All the active ingredients must be documented for use in traditional Chinese medicine.

Prior to importation and distribution of CPM in Singapore, CPM must undergo a product listing approval process.

A brief outline of the registration requirements, processing timeline and fees are presented below:

Documentary requirements for imported products are listed below:

1. Labels of product to be sold including including inner label, outer carton and package insert
2. Photograph of the product’s contents.
3. Labels of product sold/supplied in country of manufacture including inner label, outer carton and package insert
4. Manufacturer’s Licence or certificate
5. Good Manufacturing Practice (GMP) certificate if any
6. Product registration certificate (if applicable)
7. Free sale certificate of equivalent from country of manufacture
8. Test results of toxic heavy metals and microbial contamination
9. Storage condition/containers
10. Quality parameters for CPM products
11. Endorsement of product formula (including all active and inactive ingredients) by overseas manufacturer and undertaking by overseas manufacturer that product does not contain any Western drugs or active synthetic substance
12. Information on legal classifications of product in countries of sales
13. Website undertaking – for products with website stated on label(s)
14. TSE undertaking – for products containing materials (including those used for making capsule shells) derived from ruminants (e.g. cattle, buffalo, sheep, goat, deer, antelope)
15. Info for Fermented Substance – for products containing fermented substance(s) (e.g. Cordyceps, Red Yeast Rice)

Processing timeline and fees

The listing  process takes about 60 working days and there are no fees associated with listing.

Key pointers before registration

1. Ensure that the CPM does not contain any substances from the Poison Act and its schedule.
2. If the CPM contains substances listed under the Endangered Species (Import & Export) Act, dealers should contact the Wildlife Management Group of the NParks to obtain the necessary Convention on the International Trade in Endangered Species of Wild Fauna and Flora (CITES) import and export permits.
3. The labels cannot reference to certain diseases or conditions such as : blindness, cancer, cataract, drug addiction, deafness, diabetes, epilepsy , hypertension, insanity, kidney disease, leprosy, menstrual disorders, paralysis, tuberculosis, sexual function, infertility, impotency , frigidity, conception, and pregnancy.
4. Test report:

• The date of analysis stated on the test report must be within 2 years from the date of evaluation on the CPM product listing.
• The product’s batch number must be stated on the test report, and it must be in accordance with the batch numbering system declared in the online application form.
• If the test result is “not detected/ND”, the limit of detection must be stated on the test report
• The test result cannot be stated as “less than legal limit”

5. Quality parameters for CPM should include

• Storage condition
• Physical characteristics of the product such as colour, taste, smell, shape, size of capsule, and can be included in the product’s Certificate of Analysis (COA) or as a separate document.
• Physical specifications as per dosage form

6. Note that physical samples of the product and testing might be required by the authority upon request. Testing should be conducted based on laboratories with accredited methods.

Useful Reference:

Guidelines on CPM Product Listing  English version and Chinese version

Feel free to share this with your peers who has plans to import Traditional Chinese medicine in Singapore or contact us if you need local expertise to support your listing process.

 

Cell, tissue, gene therapy product (CTGTP) are health products intended for use in humans for a therapeutic, preventive, palliative or diagnostic purpose. CTGTP can contain any of the following and achieves its primary intended action by pharmacological, immunological, physiological, metabolic or physical means.

CTGTP products are divided into 2 classes namely:

Class 1 CTGTP product is deemed as lower risk product that 

1. is the result of only minimal manipulation of human cell or tissue;
2. is intended for homologous use;
3. is not combined or used with a therapeutic product and medical device
4. is assigned by the Authority as a Class 1 CTGT product due to a lower health risk to a user of the product

Examples: Bone grafts for orthopedic indications ,Scleral patch graft for ocular surgery

Class 2 CTGTP is deemed as a higher risk product which includes human cells or tissue that has been subject to more than minimal manipulation; or is intended for a non-homologous use; or is combined with a therapeutic product or a medical device.

Examples: gene modified cells, cells grown on scaffold , culture expanded cells and vectors with therapeutic gene.

Class 1 product registration requirements

Class 1 CTGTP are exempted from product registration. However, prior to supply, there is a need to notify the authority through an online application form. The processing timeline is about 14 working days and it costs $90 per application.

Requirements include:

• Application form
• Table of contents
• Cover letter
• Certified true copy of a valid certificate of accreditation (e.g. American Association of Blood Banks [AABB], American Association of Tissue Banks [AATB], Foundation for the Accreditation of Cellular Therapy [FACT], the College of American Pathologists [CAP])
• Evidence demonstrating that the establishment is registered with local regulatory agency (e.g. US FDA establishment registration and listing for HCT/Ps [human cells, tissues, and cellular and tissue-based products], Health Canada Cells, Tissues or Organs registration certificate, UK Human Tissue Authority)
• Product release specifications or Certificate of Analysis
• Package insert
• Product label
• Product shelf-life and container closure (packaging) information
• List of Class 1 CTGTP checklist

Class 2 product registration requirements

Class 2 CTGTP needs to registered with the authority  before it can be supplied. The processing timeline will takes about 230-320 working days depending on the evaluation route. It costs about $30,000 per application inclusion of overseas GCP inspection. The requirements are briefly presented below:

Application type:

There are three application types and two evaluation pathway illustrated below:

1. NDA-1 : For the first strength of a product containing a new CTGTP.
2. NDA-2 : For the first strength of a product containing: New combination of registered CTGTP in either of the following:

• New dosage form, such as capsules and injectables.
• New presentation, such as single-dose vials, multi-dose vials and pre-filled syringes.
• New formulation, such as preservative-free.
• Registered CTGTP for use by a new route of administration.

3. NDA-3 : For subsequent strengths of a product that has been registered or has been submitted as a NDA-1 or NDA-2.

Evaluation route:

• Full route: Applies to any new product that has not been approved by any comparable overseas regulator at the time of application submission to HSA.
• Abridged route: Applies to any new product that has been approved by at least one of our comparable overseas regulators.

#Comparable overseas regulators: TGA, Health Canada, FDA, EMA and MHRA.

Documentary requirements:

• CMC requirements: Module 3.2.S to Module 3.2.P .Detailed requirements are as per Appendix 8.
• Non-clinical requirements: Comply with ICH CTD Guidelines M4S (Safety) technical guidelines
• Clinical requirement: Comply with ICH CTD Guideline M4E (Efficacy) technical guidelines, in particular the ICH E3 guidance document on Structure and Contents of Clinical Study Reports

References:

1. Health Products (Cell, Tissue and Gene Therapy Products) Regulations 2021
2. Chemistry, Manufacturing and Controls requirements for Cell, Tissue or Gene Therapy Product for Clinical Trials and Product Registration
3. Guidance on Cell Tissue and Gene Therapy Products Registration in Singapore
4. Guideline on Notification Process for Class 1 Cell, Tissue or Gene Therapy Product

We hope this article is useful to provide you a brief insight into how cell gene therapy products are regulated in Singapore. Feel free to share with your peers . If  you need help or support to evaluate the readiness of your dossier please feel free to contact us.

As pharmaceutical companies worldwide continue to expand their global reach, navigating the intricate landscape of international markets becomes an increasingly complex endeavour. In this era of heightened regulatory scrutiny, pharma companies must be well-versed in the multifaceted world of regulatory affairs in order to successfully expand their operations beyond borders. We’ll explore the indispensable role of regulatory affairs management in helping pharma companies achieve seamless international expansion while ensuring public health and safety. 

Learn More: The Importance of Regulatory Affairs Management in the Healthcare Industry

1. Market Entry Strategy

Regulatory affairs management plays a pivotal role in formulating a robust market entry strategy for pharmaceutical companies. Regulatory affairs professionals diligently assess the regulatory landscape in target countries, identify potential barriers, challenges, and opportunities, to provide informed guidance to the company. This enables them to make strategic decisions about which markets to pursue and which pathways to take during pharma registration for successful regulatory approval in the country. Tailoring market entry approaches to each country’s unique requirements can help enhance the chances of successful product launches, minimising delays and potential roadblocks.

2. Regulatory Intelligence

Staying well-informed about the ever-changing regulatory environment is a fundamental aspect of pharma registration. It helps businesses to remain in compliance with several guidelines. In execution of regulatory intelligence exercise , regulatory affairs professionals meticulously monitor and analyse regulatory changes, guidelines, and requirements in the target markets. The information is then presented to them to help them adapt swiftly to any emerging challenges. This safeguards the integrity of their products and helps the company to maintain a competitive edge in new markets. 

3. Regulatory Submissions

Regulatory affairs management involves preparing and submitting comprehensive dossiers and applications during the pharma registration process, which is a key step to take towards obtaining regulatory approvals or licences. This is important if the company wishes to market its products in foreign jurisdictions. Regulatory affairs professionals make sure that submissions meet local regulatory requirements in each target market to help expedite the approval process and facilitate timely product launches. 

4. Compliance and Quality Assurance 

The success of pharmaceutical companies depends heavily on their ability to comply with international standards and regulations as well. In order to adhere to these guidelines, regulatory affairs professionals work closely with quality assurance teams to establish and maintain robust quality management systems. They also facilitate regulatory inspections and audits, ensuring that manufacturing facilities and processes meet the highest standards of quality, safety, and efficacy. 

5. Post-Market Compliance

Regulatory affairs management extends beyond the initial product launch. They play a crucial role even in post-market compliance, where companies need to report adverse events, product complaints, and provide safety updates to regulatory authorities. Regulatory affairs professionals diligently manage the timely submission of regulatory reports and fulfil any post-marketing commitments or obligations to help businesses foster trust and credibility in new markets.

For pharma companies looking to penetrate a new market, the early stages of setting up a regulatory team can be time-consuming and resource intensive. During this critical phase, engaging the assistance of regulatory affairs professionals can help the company to progress and launch products while setting up their own team.

The Reg Consultants (TRC) is a regulatory consulting firm in the pharma industry with years of experience helping pharmaceutical and medical  companies and achieve regulatory approval. Find out how we can help your business here.