In the world of healthcare, regulatory compliance is the foundation upon which patient safety and industry integrity are built. That is why when it comes to introducing a medical device to the Singaporean market, there are stringent demands of regulatory compliance to ensure utmost safety, reliability and efficacy.
In this blog, we delve into the medical device registration process in Singapore, ensuring you adhere to the necessary regulations and providing essential insights for a successful registration.
Understanding the Medical Device Registration Regulatory Framework in Singapore
The Health Sciences Authority (HSA) in Singapore plays a pivotal role in the evaluation and approval of medical devices. Companies must secure a dealer’s license prior to engaging in the manufacturing, import, or distribution of medical devices. It is a prerequisite that all medical devices undergo registration with HSA before they can be legally distributed in Singapore.
The evaluation route for your medical device depends on several factors, including the risk classification, prior approvals, and the duration of safe marketing history. The risk classification categorises devices as A (low risk), B (low to moderate risk), C (moderate to high risk), and D (high risk). Determining your device’s classification is a crucial first step, and HSA offers a tool to simplify the process.
However, Class A low-risk medical devices are exempt from the product registration requirement. While Class A medical devices are excluded from product registration, it is important to include the Class A Exemption List within your dealer’s license application through the MEDICS platform.
During the evaluation process, HSA will review the information presented in MEDICS and also the CDST that is shared. It is key to be prompt and comprehensive in your responses, as any delay in furnishing the necessary information may result in a longer medical device registration process.
Furthermore, the Priority Review Scheme expedites the registration and market entry process for medical devices, providing a faster route for approval. This scheme is applicable exclusively to Class B, C, and full evaluation route for Class D devices. Take note that Class D devices with a registrable drug in a secondary role are excluded from this scheme. Under the Priority Review Scheme, the turnaround time (TAT) is significantly shorter, with a 25% reduction compared to the TAT associated with the standard full route.
In certain circumstances, the HSA may grant approval for the import and distribution of unregistered medical devices through the utilisation of Special Access Routes. These situations encompass scenarios such as the import of re-export unregistered devices, unregistered devices intended for non-clinical purposes, custom-made medical devices, and various other specific cases.
Tips for a Successful Medical Device Registration
Here are some valuable tips and insights to ensure your journey towards medical device registration in Singapore is not only smooth but also successful.
It is highly advisable to seek assistance from local experts or consultants well-versed in the regulatory landscape of Singapore. Their experience and understanding of the system can help you to navigate the complexities of the medical device registration process with ease, ensuring compliance and efficiency.
At The Reg Consultants, we provide expert guidance and support throughout the entire registration process ensuring compliance with local GN regulations.
Make sure all required documentation is not only complete but also accurate. Attention to detail is critical as any discrepancies or omissions can lead to delays or even rejection of your registration.
Understand Risk Classification
Familiarise yourself with the risk classification system in Singapore. Knowing the category your device falls under is a major factor as it determines the evaluation route and registration requirements.
Compliance with Standards
Your medical device must meet the relevant safety and quality standards. This includes having ISO 13485 certification for medical devices, which is often a fundamental requirement for registration.
Simplifying Compliance at The Reg Consultants
Our mission is clear: to simplify compliance and empower your business to thrive in the complex landscape of medical device registration. With our support, you can navigate compliance with confidence.
Part of our routine activity in regulatory affairs is to stay in touch with the latest updates and happenings with our local authority so that we can interpret the new changes, assess the impact it has on our existing product licenses and implement a strategic plan to incorporate the changes. Today TRC would like to share the key steps in a typical internal regulatory assessment of new regulations changes:
- Understand the regulations thoroughly
Ensure that you obtain the latest draft or correct version of the new regulations and read the context in dept. Compare it with the current regulations and make notes on the differences that could be important for you to bridge the gaps.
When the draft guidelines are issued for consultation, ask all the questions that you have in mind to align your own understanding and to clear any doubts regarding the new changes.
If there are training sessions conducted by the authority prior to the implementation, it will be good to participate so as to refresh your memory and to enhance the understanding and learn about any new concerns during the Q and A session from other participants.
- Perform an internal assessment
Determine the BU (business unit) and product line that will be affected by the new regulations. Obtain the status of the marketing authorization and a brief understanding of the commercial status of the product in the territory involved.
Perform a gap analysis and document the gaps in order to bridge and incorporate the new change. This should be documented as concise and to the critical point as possible. Share the internal assessment document with the appropriate business unit to obtain feedback so that you can align the findings that you have identified during the gap analysis.
- Determine the steps to incorporate the change
Using the internal assessment as a guideline, prioritize changes in terms of criticality, the commercial impact on the product line and the resources available to support the implementation. Draw up a plan to strategize the implementation and align with local stakeholders and business unit on the requirements and timeline.
Monitor the process of implementation and review post implementation for areas of improvement and effectiveness as well as to capture any areas that were missed out during the initial phase of implementation.
Although the above steps are simple , there may be a risk of miscommunication and lack of internal resources when simultaneous of such regulatory changes are implemented, it could be useful to consider an additional experienced local support . If you think that TRC could be of help to you , please get in touch or learn more about how TRC subscription plan can facilitate the 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
- is the result of only minimal manipulation of human cell or tissue;
- is intended for homologous use;
- is not combined or used with a therapeutic product and medical device
- 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.
- 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:
There are three application types and two evaluation pathway illustrated below:
- NDA-1 : For the first strength of a product containing a new CTGTP.
- 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.
- NDA-3 : For subsequent strengths of a product that has been registered or has been submitted as a NDA-1 or NDA-2.
- 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.
- 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
- Health Products (Cell, Tissue and Gene Therapy Products) Regulations 2021
- Chemistry, Manufacturing and Controls requirements for Cell, Tissue or Gene Therapy Product for Clinical Trials and Product Registration
- Guidance on Cell Tissue and Gene Therapy Products Registration in Singapore
- 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.
License transfer has been a rising tacky issue for many manufacturers seeking independent license holding. Managing a successful therapeutic product license transfer consists of 3 steps: Seeking inform consent with Distributor , Selection of an independent license holder and Transfer operation. These steps must be followed closely in order to execute a seamless flow.
Please note certain terms that might be used interchangeably in this article content:
Manufacturer =Product Owner
Marketing authorization holder/Distributor/ Partner= Registrant
Seeking inform consent with Distributor
Having been through this phase myself in distributor’s shoes, the impact can be tremendous to a company’s balance sheet. The business framework of most distributors depends on a big single supply of their product portfolio and several other sources consisting of medical devices and supplements. Hence, a timely inform to the respective partner/distributor is essential to allow the distributor /partner to work out an alternative solution for themselves and to divert relevant internal resources to manage this flow. The appropriate timeframe recommended according to most distribution agreement is relatively short of about a few months but what is most practical would be an early year of notification.
During this process, it would be appropriate to discuss the following issues:
- Be honest and upfront about the company’s decision to end this business relationship. Extend your gratitude to your partner for their contribution in building your brand in this market and that it is a hard decision for your company to take internally to progress with this stage.
- Understand about the current state of the regulatory status of all licence taking into account whether there are any pending approvals for variations and upcoming renewal. This is a critical requirement prior to execution of a licence transfer. It is also appropriate to request distributor/partner to transfer the latest regulatory files related to each licence to the designated partner (whether it is internal or an independent licence holder) a month before the actual transfer so that there is time for the designated partner or internally to check upon any missing items. A casual meeting of a 1.5 hours face to face would be appropriate between Manufacturer, designated partner and current partner.
- Set the date of transfer. A final date should be set and agreed mutually between all parties involved to execute the licence transfer.
You can send in enquiry to TRC to check with us on our prior experience first hand so that we can support you in this negotiation as well.
Selection of an independent licence holder
If you do have a regional office locally with regulatory capacity, you might proceed directly with Step 1 and Step 3 mentioned in this article. However if you do not have a local office, you will have to reach out to source for competent and trustable licence holder such as a consultancy partner or another distributor to take on the licences for which the following factors must be considered:
- Assessment of the competency of the next designated party to take on the licences based on past experience, reputation in local market as well as the chemistry between both parties. In any business relationship, we do have to agree that we need to choose a party that can communicate well with you and have the same frequency of mindset to take on this role. They are crucial to your business going forward.
- Establishing clear expectations of the role and responsibilities of the next marketing authorization holder so as to ensure that they will comply with what is required locally to maintain the licence so that the company can continue to function.
- Discussion internally based objectively not just on costs for the selection. Ultimately, we cannot disagree on the fact that the complexity of this situation will only increase when this operation is repeated many times due to a commercial reason tied to volume demand from the manufacturer’s end or from choosing a partner just based on cost. It is appropriate to assume that there should be an increase in number of orders per year as per forecast provided however we need to note that there is always a trend for each market and each product due to situations that cannot be controlled such as losing of tender, prescription pattern of clinics and hospitals and influx of overseas patients (especially true for oncology patients).
Check out TRC’s list of services to see whether it fits your bill to be considered as an independent license holder.
The license transfer operation will require some preparation from Product Owner , current marketing authorization holder ( Existing Registrant) and new current marketing authorization holder (new Registrant) which will be highlighted below:
- Product Owner needs to prepare 2 documents:
- New letter of authorization to appoint the new registrant in which the content should include all the name of therapeutic product licenses and license number: SINXXXXXP , name and address of the new registrant and effective date of the transfer.
- Written confirmation that arrangement has been made between the existing registrant and the new registrant for the hand-over of the relevant product registration file.
- Existing Registrant ( Current Marketing authorization holder) needs to have the following information about the new appointed Registrant:
- UEN (Unique Entity Number) of the new registrant
- Client code of the new registrant
- Email address of the authorized person acting on behalf of the new registrant
- Registration number and name of the therapeutic product(s) for which the registration will be transferred to the new registrant
- New Registrant will need to have the following document and details from the Product owner as per below:
- Letter of Authorization from the Product Owner
- Written confirmation that arrangement has been made between the existing registrant and the new registrant for the hand-over of the relevant product registration file
Once the above is completed and a final confirmation from existing registrant that there is no pending renewal nor variations tied to the licences to be transferred, the existing registrant can log on to the online system known as: PRISM to execute the transfer inputting the details provided by Product Owner. Once the initiation of the transfer is performed, the new registrant will receive an email notification to log on to the system to accept the transfer to upload all the relevant documents and details provided by Product Owner. The process takes about 14 working days and both the new registrant and existing registrant will be notified of the outcome. There is currently no cost tied to this operation officially.
For further information, do check out the link to : Change of Registrant of registered therapeutic product.
The key success factor to seamless licence transfer is to maintain an effective communication between all parties, setting upon a date and performing internal regulatory check on the status of all therapeutic products. Wishing all good luck and success to take forward this operation. If you think TRC can be of help to you, please feel free to get in touch .
Steps to get ready for an overseas on-site GMP inspection for pharmaceutical products in Singapore
With the Covid-19 outbreak, many countries have implemented travel restrictions which have delayed inspections and business trips. Although business has slowed down, it’s a good time for us to review and realign our market strategy to the current situation. If you are currently an overseas company having plans to get your manufacturing site to be Pharmaceutical Cooperation Inspection Scheme (PIC/S) certified, Singapore is one of the best choices due to its stable socio-political situation and it has one of the most structured, organized and clear guidelines to get you started. I will take this opportunity to share with you briefly the 5 steps.
- For manufacturers who have existing Site Master File(SMF) and Quality Management System Documentation (QMS), it is good to start to align them according to PIC/S guideline for the Site Master File and to look into preparing Quality System Dossier (QSD) according to local regulations. A Quality System Dossier comprises of SMF, related QMS Documentation which includes SOPs, records, diagrams, workflows etc of the pharmaceutical manufacturing operations to provide an overview of the manufacturing site and its quality system so as to facilitate assessment of the manufacturer’s audit readiness.
- Conduct an internal audit to ensure that process workflow , documents and records are maintained as per Standard Operating Procedures and in compliance with Quality Management System set forth by the company.
- File for a product registration via a local agent or distributor to trigger the GMP inspection. An audit date will only be assigned should the documentation passed the desktop audit by the regulators. Any critical deficiencies will disqualify the manufacturing site from getting audited .
- Once the manufacturer has passed the desktop audit, a date will be assigned for an on-site audit.
- During the on-site audit, a list of observations, non-conformities and good practices will be presented during the closing meeting . The manufacturer will need to provide their Corrective and Preventive Actions (CAPA) 30 days from the date of the audit.
- If the responses provided are satisfactory, GMP certificate will be issued to the manufacturer within 10 working days calculated from the close-out date.
TRC offer the service of writing a QSD dossier for you. If you are keen, please feel free to get in touch.