Regulatory Affairs Archives - Regulatory Affairs & Quality Management Singapore

regulatory consultation meeting

The next step after performing a regulatory intelligence exercise would be followed by an arrangement for a consultation with the regulatory authority. This is common especially for IND application and NDA application in which there may be concerns regarding the documentation requirements or even addressing any critical CMC, pre-clinical and clinical study related questions. Today TRC shall share based on observation from the past on what’s the Dos and Don’ts during a formal regulatory consultation meeting in tabular format:

Note that this is just based on TRC’s suggestion of best practice and we do not advocate or represent any voices.

Dos	Don’ts
Present your best self by dressing appropriately and finding a quiet place to participate in the meeting. Switch on the camera during video call meeting.	Do not appear as an unkempt look or even join the meeting in a noisy place to create unpleasant “white noise” during the meeting. If you are unable to switch on the camera during the call, remember to inform during the meeting.
Ask questions that are within the meeting agenda provided.	Do not ask questions for the sake of asking questions if they are not necessary. In a regulatory meeting, there will be different department personnel joining in. But it would be best to limit those who are executing the work and have an influential decision on how to move the application forward to avoid any unnecessary question or awkward silence to have a need to ask question.
If the explanation is not clear or specific enough even though the time is running out, ask politely whether you could clear out this important issue so as not to leave it hanging.	Do not keep pressuring the regulators to double confirm the answers that they are providing. A written response would be provided at the end of the meeting. If there is anything that is not clear, you can write back again once the email is received.
Be respectful and transparent about the application that you are intending to submit. Give an overview of the application preparation and the objectives of what you intend to achieve within the meeting.	Do not have more than “one” voice interrupting the flow and “ over talking” about the application that you are intending to submit during the meeting to avoid any confusion or misunderstanding which will not provide you with the appropriate response that you are looking for.
Follow a systematic approach to start off the meeting which is by being punctual, following the agenda of the meeting strictly and avoid any over discussion so as to not waste any precious time allocated.	Do not trail off the main questions during discussion and allow the regulator to provide the guidance and ask the next question in sequence unless the question that you have in mind is extremely critical or related to the response that you are hearing.
At the end of the meeting, it’s good to pre-empt or suggest a follow up “informal” call by a designated representative should there be any concern that is not well understood from the formal responses provided.	Consolidate all the queries that you have in mind after reviewing the responses provided by the regulators and avoid bombarding them with calls from different people. They are not your answering machines.

If you think that the above article is useful for you , feel free to share it with your peers and we are also looking forward to hearing some of your experience during consultation meeting. If you require assistance to arrange and support any formal meeting with the local authority, get in touch!

What are Regulatory Affairs Subscription Plans

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.

Common Technical Dossier

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:

To initiate the regulatory submission flow, TRC would request Client to provide a secured link for us to access the dossier.
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.
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.
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.
Once the gaps are addressed, we would proceed to perform online submission including the application form filling and uploading of documents.
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.
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.
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.

This is a rather short article to share about the definition and published list of borderline medical device that might be supportive for your regulatory intelligence exercise.

A borderline medical device might have some features of a medical device which is to diagnose ,treat or prevent a symptoms or diseases and possibly contain agent or even mode of action which achieve its intended function via pharmacological, immunological or metabolic means. A common product would be that of a wart product which is to get rid of warts through cryotherapy. The mode of action of the wart product could put it at risk of being a drug product rather than a medical device if it contains a caustic agent that destroy warts by chemical coagulation of protein . Hence it is useful for us to know the rule defined by the authority in order for us to classify the product appropriately as medical device.

Definition of medical device in accordance to ASEAN Medical Device Directive:

A “medical device” shall mean any instrument, apparatus, implement, machine, appliance, implant, in vitro reagent and calibrator, software, material or other similar or related article: (i) intended by the product owner to be used, alone or in combination, for human beings for one or more of the specific purpose(s) of: (a) diagnosis, prevention, monitoring, treatment or alleviation of disease; (b) diagnosis, monitoring, treatment, alleviation of or compensation for an injury; (c) investigation, replacement, modification, or support of the anatomy or of a physiological process; (d) supporting or sustaining life; (e) control of conception; (f) disinfection of medical devices; and (g) providing information for medical or diagnostic purposes by means of invitro examination of specimens derived from the human body; which does not achieve its primary intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its intended function by such means.

Definition of borderline medical device as agreed by the ASEAN Medical Device Committee (AMDC):

In accordance to published guidance document by Medical Device Authority of Malaysia,

Borderline medical devices are devices that are difficult to distinguish from a medical device, for example products that might be medicines, cosmetics, food supplements, biocidal products or personal protective equipment. These products are called borderline products until their status of medical device or non-medical device .

The list of borderline medical devices is updated yearly based on decision by the ASEAN Medical Device Committee (AMDC).

Useful references for you to check:

If your product does is not listed within the list, you can always write in to us to get a confirmatory response regarding the classification with local authority.

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:

Labels of product to be sold including including inner label, outer carton and package insert
Photograph of the product’s contents.
Labels of product sold/supplied in country of manufacture including inner label, outer carton and package insert
Manufacturer’s Licence or certificate
Good Manufacturing Practice (GMP) certificate if any
Product registration certificate (if applicable)
Free sale certificate of equivalent from country of manufacture
Test results of toxic heavy metals and microbial contamination
Storage condition/containers
Quality parameters for CPM products
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
Information on legal classifications of product in countries of sales
Website undertaking – for products with website stated on label(s)
TSE undertaking – for products containing materials (including those used for making capsule shells) derived from ruminants (e.g. cattle, buffalo, sheep, goat, deer, antelope)
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

Ensure that the CPM does not contain any substances from the Poison Act and its schedule.
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.
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.
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”

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

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.

cell gene therapy product registration in singapore

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.

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:

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.

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:

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.

Cosmetics are required to be notified before they can be sold in the market unless in the few circumstances below:

Supplied solely as a sample in connection with any advertising, sponsorship or promotional activity
Supplied solely for testing or trial use in connection with any research or development of that product
Manufactured by or in accordance with the specifications of a medical practitioner, and supplied solely by that medical practitioner for the use of patients under his care

Before supplying cosmetic in Singapore, we need to perform the following steps:

We need to determine whether the cosmetic product meets the definition of Cosmetic in the local context . As shared in my previous article: https://theregconsultants.com/regulatory-classification-of-medical-products/ ,

A “cosmetic product” is defined as any substance or preparation that is intended to be placed in contact with the various external parts of the human body or with the teeth or the mucous membranes of the oral cavity with a view exclusively or mainly to:

Cleaning
Perfuming
Changing appearance
Correcting body odours
Protecting
Keeping in good condition

Example of products that are not cosmetics: oral supplements for beauty purposes, injections/injectable products, massage and essential oil, aesthetic/beauty devices, lubricants, insect repellents, sanitary pads, hand sanitizers, cream for treatment of acne/eczema/psoriasis, toothbrush, dental floss, detergent, temporary tattoo fake eye lashes, nail stickers and LED light used in dental kit (whitening gel is a cosmetic).

In terms of product safety, we need to consider the main components such as the composition, labelling , claims , whether the product manufactured meets the specifications set and whether appropriate testing has been performed to ensure that the product is safe and function as it is claimed.

We need to ensure that the cosmetic products does not contain ingredients that are in the negative list based on ANNEXES OF THE ASEAN COSMETIC DIRECTIVE.

Labelling of cosmetics should contains the key information below:

Name of the cosmetic product
Function of the cosmetic product
Instructions for use
Full ingredients listing
Country of manufacture
Contents (weight/volume)
Batch number
Manufacturing/ expiry date (expiry date is only required for products with less than 30 months durability)
Name and address in Singapore of company responsible for placing the product in the market
Special precautions, if any (especially those listed in Annex III, VI, VII in the ASEAN Cosmetic Directive)

Cosmetic claims should be appropriate assigned based on the key ingredient function, target site of application and physiological effects of cosmetics. Some examples of claims that can be accepted accordance to ASEAN Cosmetic Claims Guide are presented below:

Product Type	Claims
Hair care product	Eliminates dandruff permanently Restores hair cells Hair loss can be arrested or reversed Stimulates hair growth
Skin products	Prevents, reduces or reverses the physiological changes and degeneration conditions brought about by aging Removes scars Numbing effect Prevents, heals, treats or stops acne Treatment of cellulite Lose centimetres Reduces/controls swelling/oedema Removes/burns fat Fungicidal action Virucidal action
Oral or dental hygiene products	Treatment or prevention of dental abscess, gumboils, inflammation, mouth ulcers, periodontitis, pyorrhoea, periodontal disease, stomatitis, thrush or any oral diseases or infections Whitens tetracycline-induced stains

Quality of the product- In order to ensure that the product manufacturer meets with international requirements, it would be appropriate to ensure that the manufacturing facilities have relevant certification that complies with GMP or ISO standard 22716:2007 ,perform local testing if required to check for heavy metals and microbiological content, as well as for common adulterants.

Examples of appropriate testing on products are provided below:

Product Type	Claims
Teeth whitening products	To test the concentration of hydrogen peroxide. Hydrogen peroxide, when in high concentrations, is corrosive and may cause irritation to the eyes, mucous membranes and skin. Only products with hydrogen peroxide of concentration up to 0.1% can be allowed for supply to consumers directly.
Skin Whitening creams	To test for the presence of adulterants e.g. Hydroquinone, tretinoin and mercury. Hydroquinone and tretinoin are potent ingredients that are not suitable for use in in skincare cosmetic products. The inappropriate use of hydroquinone could result in changes in skin colour and hypersensitivity reactions such as rashes, redness, tingling and burning of skin. Tretinoin could lead to redness and peeling of the skin and should only be used under medical supervision.

Cosmetic notification should be performed by appointed companies that are intending to import or sell the cosmetic products in the market. As cosmetic products are not evaluated by the authority, it is important for importers to be responsible for the safety and quality of the product. There are 3 main things that should be maintained on site for the importer namely:

Product Information File which contains all the quality and safety records of the cosmetics to comply to the relevant standards. It should be kept to update in accordance to what is happening over at the manufacturing end that could have an impact on your product.
Records of cosmetic supply to the market- It should be maintained for 2 years in accordance to the Guidelines on the Control of Cosmetics. The record should contain the name and notification number of the product, name and address of company supplied, and the batch number, date and quantity of product supplied.
Monitor and report any product defect / adverse events to the authority and perform a prompt recall for the product. The reporting timeline is 7 days for adverse events that result in death or life threatening and 15 days for adverse events that results in hospitalisation or any persistent or significant disability or incapacity.

To end off the article, we are sharing some useful links for you to kick start the process:

If you need any support to confirm that your cosmetic product is meeting the local requirements, feel free to be in touch or share it with your peers who might need them.

health supplement registration in Singapore

At the current moment, Health Supplements are not subjected to registration prior to importation. Notification is on a voluntary basis. There may be advantage for you to execute the notification of the health supplements from a commercial perspective and it is always to be pro-active to adapt to the existing regulations rather than to rush frantically to submit when announcement is made officially.

We share some key points to note for importing health supplements:

We need to be sure that your product falls under the category of health supplement. In order to fulfill the definition of Health Supplement in the local context , assess the below question :
Is your product used to supplement a diet, maintain, enhance and improve the healthy functions of the human body?
Does your product contain one or more of the following or combination of the ingredients:
Vitamins, minerals, amino acid, fatty acids, enzymes, probiotics, and other bioactive substances;
Substances derived from natural sources, including animal, mineral and botanical materials in the forms of extracts, isolates, concentrates; and

Synthetic sources of ingredients mentioned in (i) and (ii).

Your product dosage form should not be an injectable or eye drop.

From safety and quality perspective, we need to ensure that the health supplement does not contain negative list of substances and meet the limits allowable for vitamins and minerals, heavy toxic metal, and microbial limits. The product is manufactured to a consistent quality meeting release requirements for specific dosage form and is stable throughout the proposed shelf life. Please refer to below table for quick reference on the links for your compliance exercise :

Checklist	Links:
Check for negative list of substances	ASEAN-Guiding-Principles-for-Negative-List-HS-V4.0
Heavy metal limits	Arsenic 5 parts per million Cadmium 0.3ppm Lead 10ppm Mercury 0.5ppm
Microbial limits	ASEAN Guidelines on Limits of Contaminants for Health Supplements
TSE checklist	ASEAN Guidelines for Minimising the Risk of Transmission of Transmissible Spongiform Encephalopathies in Health Supplements
Vitamins and Mineral Limits	ASEAN General Principles for Establishing Maximum Levels of Vitamins and Minerals in Health Supplements
Quality Standards	Physical test parameters based on dosage forms Testing requirements Manufacturing standards
Labelling Standards	Guideline for labelling standards
Stability and Shelf Life	ASEAN Guidelines on Stability and Shelf-Life of Health Supplements

Health supplement claims must not be labelled , advertised or promoted for treatment or prevention of any disease or related conditions. There are some general principles which we can follow:

We need to ensure that the claim is truthful and is simple to understand.
We need to ensure the claim is well substantiated from good-quality scientific evidence from human studies.
There should not be testimonials from health professionals .
Testimonials from individual must be genuine and validated with real person information.
The claims cannot exploit fear or discourage from medical advice.
There should be no reference to performance in studies ,anti-aging, sexual function and relationships , consumption, hormonal levels, blood sugar levels, claims of safety.
Refrain from using scientific data that the public cannot comprehend to exaggerate the efficacy of the product.
The advertising of the product should comply with Singapore Code of Advertising Practice (SCAP).

Below are references to consider before affixing claims to your health supplement:

We hope the above has been useful for you for importation of health supplements into Singapore. Share it with your peers who might need them!

regulatory classifica

Registration of a medical product starts with an official classification which will determine the documentary requirements, timelines, and fees. Today we are going to share a few misconceptions and the approach to classify a product correctly.

Misconception

We assume that the classification in the country of origin will be the classification in the country to be exported . E.g A product that is a classified as an OTC product in the country of origin might be deemed as a medical device in the country where it is exported to.
We did not check the definition of a specific category of the product based on local regulations. We assume the definition based on what we understand in common regarding a specific category of product. E.g a medical device should only treat, diagnose, and prevent a medical condition through “mechanical action” but not by immunochemical or pharmacological means.
Marketing claims which might not be suited for the specific category of the product such as health supplement that might overclaim its function without referencing to established pharmacopeia or proven efficacy through human studies such as a clinical trial.

Approach to classification of a product

Active ingredient- Is this a Poison or controlled substance under the Pharmaceutical Act? What is the strength or allowable limit of a substance that might put it at risk of being categorized as a higher risk product?
Mode of action- Does the principle of action qualify it as more” therapeutic” in a pharmaceutical way or relieving or replacement of a physiological process like a medical device?
Indications- Are the indications backed by clinical studies or literature papers? Does the indications allow you to classify as a lower category then what it actually is?
Matching the definition in regulatory guidelines – Considering the above elements, do a check against the definition to see whether it meets the classification that you think your medical product would fit.

Common definitions based on Health Product Act that might be useful for classification of a product:

Medical Device : any instrument, apparatus, implement, machine, appliance, implant, reagent for in‑vitro use, software, material or other similar or related article that is intended by its manufacturer to be used, whether alone or in combination, for humans for one or more of the specific purposes of

diagnosis, prevention, monitoring, treatment or alleviation of disease
diagnosis, monitoring, treatment or alleviation of, or compensation for, an injury
investigation, replacement, modification or support of the anatomy or of a physiological process, mainly for medical purposes;
supporting or sustaining life;
control of conception
disinfection of medical devices
providing information by means of in‑vitro examination of specimens derived from the human body, for medical or diagnostic purposes

Therapeutic product means any substance that is intended for use by and in humans for a therapeutic, preventive, palliative or diagnostic purpose, including any of the following purposes: for preventing, diagnosing, monitoring, treating, curing or alleviating any disease, disorder, ailment, injury, handicap or abnormal physical or mental state, or any symptom thereof;

for investigating, modifying or replacing any physiological process;
for influencing, controlling or preventing conception
for inducing anaesthesia;

has as a constituent any of the following active ingredients:

(i)any chemical or botanical element, naturally‑occurring chemical or botanical material, or chemical product obtained by chemical change or synthesis;

(ii) any metabolite from a micro‑organism;

(iii)any macromolecule extracted from an organism;

(iv)any substance derived from a biological system, including any of the following:

a whole cell or micro‑organism, such as a whole virus or bacterium used as a vaccine;
a part of a micro‑organism, such as a sub‑unit vaccine;
a plasma‑derived product;
a biotechnology‑derived substance, such as a protein or polypeptide, or a recombinant vaccine for a preventive purpose;

exerts an inherent effect either pharmacologically, chemically or by other physiological means, leading to its use for a therapeutic, preventive, palliative or diagnostic purpose.

Cosmetic product means any substance or preparation that is intended by its manufacturer to be placed in contact with the various external parts of the human body or with the teeth or the mucous membranes of the oral cavity, with a view exclusively or mainly to

a)cleaning them;

(b)perfuming them;

(c)changing their appearance;

(d)correcting body odours;

(e)protecting them; or

(f)keeping them in good condition.

Health Supplement is used to supplement a diet and to support or maintain, enhance and improve the healthy functions of the human body. It cannot be an injectable or a preparation that needs to be sterile, such as injections and eyedrops. It cannot be an item of a meal or diet.

Chinese proprietary medicine means any medicinal product used in the system of therapeutics according to the traditional Chinese method, that is to say, any medicinal product —

which has been manufactured into a finished product;
which contains one or more active substances derived wholly from any plant, animal or mineral, or any combination thereof;
which is, or all of the active substances of which are, described in the current edition of “A Dictionary of Chinese Pharmacy” «中药大辞典» or “The Chinese Herbal Medicine Materia Medica” «本草纲目»;
which does not contain as an active substance any chemically‑defined isolated constituent of any plant, animal or mineral, or any combination thereof; and
which is not intended to be administered by injection into a human body;

Homoeopathic medicine means any substance used in the system of therapeutics in which a disease is treated by the use of minute amounts of one or more substances which, in their undiluted forms, are capable of producing in healthy humans symptoms similar to those of the disease being treated;

Quasi‑medicinal product means:

any anti‑dandruff preparation;
any medicated cosmetic product for the treatment of pimples or acne, except any preparation containing etretinate or 13‑cis‑retinoic acid;
any medicated soap;
any sweet for relieving coughs or throat irritations;
any medicated plaster;
any sunscreen or suntan preparation;
any medicated beverage;
any vitamin or nutritional preparation from any natural source; or
any medicated toothpaste;

We hope that the above article has been useful for you. If you do have a borderline product that might require a second opinion to justify your classification. Feel free to engage with us. Best of luck, share this with peers who might need them.

What is a biosimilar?

A biosimilar product is a biological therapeutic product demonstrated to be similar, in physicochemical characteristics, biological activity, safety and efficacy to an existing registered biological product. The development of a biosimilar product places emphasis on the characterization of the reference’s Quality Target Product Profile and performing comparability and safety studies to demonstrate safety, quality and efficacy.

Pre-requisites of qualifying for registration of biosimilar in Singapore

Singapore Reference Biological Product (SRBP) must be currently registered in Singapore and has the same manufacturing source. If the manufacturing source differs, bridging study is required to be performed which might include data from analytical studies (e.g. structural and functional data) that compare the proposed biosimilar product, the SRBP and the reference product used in the comparability studies, and may also include clinical PK and/or PD bridging studies data for all three products.
Product must be approved in: EU EMA, Australia TGA, UK MHRA, US FDA and Health Canada.
Where there is more than one indication, the efficacy and safety of the biosimilar product must be justified, or demonstrated separately for each of the claimed indications

Quick registration checklist

Registration category

NDA-2 :For the first strength of a biosimilar product with the same dosage form, route of administration and presentation as the Singapore reference biological product (SRBP)
NDA-3 for subsequent strength of the biosimilar product.

Evaluation route:

Abridged route: Approved by at least one drug regulatory agency defined by WHO
Verification route: Approved by at least two reference drug regulatory agencies with similar indication, dosing regimen, patient group, or directions for use.

Administrative requirements:

A valid CPP ,GMP certificate for both DS and DP issued from PIC/s member countries, Proposed Labelling, Patent Declaration, World wide registration status, Declaration of rejection, withdrawal, and deferral .
Assessment by reference agencies and Official letter declaring that all aspects of the product’s quality intended for sale in Singapore are identical to that currently approved by the primary reference drug regulatory agency.

CMC requirements:

Complete 3.2.S and 3.2.P including comparability studies . Comparability studies should include: series of physicochemical tests, along or in combination with such biological tests as in vitro and in vivo bioassays, and receptor binding studies based on QTP established on SBRP with focus on molecular characteristics and quality attributes.

Non-clinical documents: Complete non-clinical module including comparability studies that covers in vitro studies- to establish comparability in reactivity and likely causative factor and animal studies -investigate PD activities relevant to the clinical application and non-clinical toxicity.
Clinical documents: Complete clinical module including comparability studies.

The comparability studies should begin with PK and PD studies . PK studies focus on key PK parameters and for PD Studies- PD markers should be selected based on their clinical relevance.
For comparative clinical studies, clinical comparability margins should be prespecified and adequately justified. The most sensitive clinical model should be used to detect potential differences between the biosimilar product and the SRBP.

Risk Management Plan

If you require any pre-analysis for your biosimilar product, please feel free to get in touch or check out other relevant articles for a quick read:

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-selection-of-medical-products-to-enter-singapore/

https://theregconsultants.com/whatisaaseanctd/

Regulatory Affairs & Quality Management Singapore | The Reg Consultants (TRC)

Dos and Don’ts in a regulatory consultation meeting