It has come to the end of the year where budgeting and planning are in full force for 2024.  In regulatory, we do it via the RPA way which stands for Review, Plan and Act .

TRC shall share a short summary on what RPA means :

Review

  1. Start off with product annual review to check for gaps and alignment with global database.
  2. Align the schedule and activities with headquarters for the upcoming year so that you can roll out the relevant schedule and communication plan.
  3. Prepare communication plan or schedule of upcoming variations and new product registrations for each specific market and inform respective partners of the timeline and what to expect. This is an important exercise to also get input on any new regulatory requirements that might be happening within the local market.
  4. Identify key areas to work on internally as well as with respective local partners.

Plan

  1. Align the regulatory launch plan with commercial launch plan and obtain consensus on priorities of the variations and new product launches.
  2. Budget the amount required for respective expenditures to partners, authorities, operating expenses ,travel expenses, any pass-through costs involving translation work if applicable .
  3. Plan for face to face meeting and annual audit with respective partners as part of due diligence and to maintain the good rapport between yourself and them if applicable.
  4. Ensure that consensus on activities and budget are obtained and accurate till date.

Act

  1. Hold meeting with internal and external stakeholders to confirm the plan.
  2. Adjust the plan and schedule accordingly after meeting to ensure alignment to concerned parties’ inputs.
  3. Prepare the respective packages for each product that is specific to each market.
  4. Execute the plan accordingly to schedule and be ready to support when issues arise.

We hope the above short sharing is interesting for your read. If you need support for your regulatory activities in the coming year in Singapore, feel free to get in touch.

 

During the expansion of territory in the traditional  business model, there will be multiple distributors that manufacturers must deal with. Unlike big companies that have a dedicated staff looking after the region. Smaller companies  or companies that do not have a local office established in the territory will rely on their business manager who might not be as well versed in regulatory as a “project manager.”

regulatory project management

Sometimes it might lead to some miscommunication regarding the requirements since the meeting with the local companies would be limited hence it might be worth to consider having a regulatory project  manager to oversee the local regulatory experts  so to ensure alignment with regulatory goals and objectives set out by the headquarters.

 

Regulatory project management in TRC’s term is about managing data flow from the local experts to a centralized system where it is updated, accessible and reliable for the global headquarters to have visibility in terms of product licenses compliance.

 

Below are 5 tips to share on regulatory project management:

 

  1. Maintain and establish a good friendship with local regulatory experts.

This will play a big role when manufacturer would want to transfer the licenses back to their own name or switch distributor.  Based on observation, relationship tend to sour during the announcement and the local regulatory personnel will play a critical role to mediate the whole situation.

  1. Establish clear timelines and achievable expectation in terms of market feedback.

Headquarters  would roll out several variations decision consecutively expecting the local experts to provide an assessment on the risk, impact on the product line as well as the documentation requirements  in a short notice which would not be feasible. At times, the variation that are to be executed might not fall into any appropriate MIVs / Change notification category and local experts will need time to verify with the authority before providing a decision. It would be worth to consider establishing a schedule of upcoming variations/change notification and implementation timeline for each product line for each quarter to share with appropriate partners.

 

  1. Conduct regular reconciliation of regulatory information regarding the product licenses with individual partners to align with what is captured in the system.

To do this appropriately, it would be good to have a 1 hour focused call weekly if necessary to run through all the information and questions if not a bi-weekly catch up to just check for any new updates or situations or support that might be required from the local regulatory partners.

 

  1. Always be ready to support and facilitate any miscommunication or requirements from both ends.

The regulatory project manager must digest then interpret the requirements from both ends and align the understanding with the local experts and headquarters before going to either party to clear the air.

 

  1. Prioritize the most critical issues to be addressed instead of bugging the local experts repeatedly to answer a question.

In the situation where there are several critical issues e.g., site change, change of  supplier of excipients, minor update on labelling to reflect the new EC representative details, , the regulatory project manager will need to have visibility of each local market situation from both the regulatory and commercial front. This is to enable  the regulatory project manager to  strategize and rank the issues to be addressed first  in terms of the impact on sales, compliance, and implementation so  to advise the local regulatory partners appropriately.

 

Synergy in regulatory project management emphasizes heavily on being systematic, having clear understanding of the ground issues and maintain a good relationship with the local regulatory partners to ensure succession execution. TRC subscription plan would be able to facilitate this activity should you require support. Feel free to reach out if you need help or stay tuned for the next blog.

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:

  1. 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.

  1. 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.

  1. 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.

A regulatory subscription plan is a newly launched product created by TRC to support medical companies in need of regulatory assistance in a new territory where there is no local office established /when there are only requirement to support post-licensing activities / when additional or alternative support will come in handy when getting the right person on board proves to be difficult/ when you want to explore an alternative way of running your regulatory department /when there are certain conflict of interest between parent company and local company in which an independent party will be useful.

 

Regulatory Subscription Plan

The plan allows you to leverage upon a local expertise to perform the required daily regulatory tasks associated with a typical regulatory specialist and head of regulatory operations.  pertaining to the routine operational works on an adhoc basis, tie over peak periods, maternity cover for a short period of time relating to specific regulatory initiatives and  project management from a ASEAN perspective

We present a simple comparison chart of Regulatory Subscription Plan Vs Traditional Model.

Comparison parameters Regulatory Subscription Plan Traditional Model
Working Principle Flexible model of rendering regulatory expertise who is already experienced in the local market. Hiring a staff to manage the regulatory work based on requirements.
Cost It is a fixed cost for experienced personnel.

 

Can be more cost effective as opposed to having a regular staff if company is just planning on performing post licensing activities and ad-hoc new launched activities .

Can vary depending on the level of expertise from personnel engaged.

 

Can incur more cost in the long run and cause distress if company decided to downsize or retrench due to economic outlook.

Manpower Resource readily available with years of experience.

 

Dedicated serving regulatory personnel assigned ( no project manager and etc).

 

 

Need time and resources to train before work can be done.

 

Dedicated employee .

 

Resource allocation  and commitment No commitment basis for the plan.

 

 

 

Able to support various functions which can stretch to pre-product launch such as market research, mediation activities and even audit.

 

Commitment required for employment even on contractual basis. If not handled properly might have litigation issues.

“Safe mode” to follow

Fixed duties and function for employee – no flexibility to take on other tasks which is out of scope

 

Determining factor in choosing the right model Have no local office and need someone experienced to kick start the whole process of filing to minimize loss in lead time for product launches.

Limited budget with short time frame on deliverables

Have a non-committed alternative support for the regulatory work to cope with the temporary “lull” period while deciding on the next move for the company or even to support the team while there is internal restructuring which initiatives might still be required to go on.

Have a short trial on a possible operation model of the regulatory function which might be useful in the long run to deal with unexpected circumstances .

 

Established presence in the territories for years with good working relationship among partners and staff.

 “Expandable budget” to establish own team with a rather flexi timeline

A committed team is essential for the smooth  operations of the company.

 

 

 

 

Fail-safe mode model which worked for many years without resulting in any high turn-over, loss in time and resources to retrain for new employment.

 

If you have analyzed the chart above and think that it might be suitable to learn more or give it a try, consider to chat up with us using “Contact us” form or even head to the “e-shop” to learn more. We look forward to supporting your initiatives and thanks for your time in reading about this. Do share with your peers who might be in need of this and TRC would be pleased to offer a small token of appreciation for any successful sign-up.

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:

  1. ASEAN Medical Device Directives
  2. PRELIMINARY LIST OF BORDERLINE/ MD OR NON MD CLASIFICATION OF MEDICAL DEVICE
  3. List of Harmonized Classification of Devices
  4. HARMONISED BORDERLINE PRODUCTS IN ASEAN

 

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.

 

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

  1. Supplied solely as a sample in connection with any advertising, sponsorship or promotional activity
  2. Supplied solely for testing or trial use in connection with any research or development of that product
  3. 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:

    1. 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).

    1. 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.
    • Labelling of cosmetics should contains the key information below:
    1. Name of the cosmetic product
    2. Function of the cosmetic product
    3. Instructions for use
    4. Full ingredients listing
    5. Country of manufacture
    6. Contents (weight/volume)
    7. Batch number
    8. Manufacturing/ expiry date (expiry date is only required for products with less than 30 months durability)
    9. Name and address in Singapore of company responsible for placing the product in the market
    10. 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.

     

    1. 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:

    1. Guidelines on the Control of Cosmetic Products
    2. ASEAN Cosmetic Directive
    3. Overview on how the local authority regulates cosmetic  
    4. HEALTH PRODUCTS (COSMETIC PRODUCTS — ASEAN COSMETIC DIRECTIVE) REGULATIONS 2007

    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:

    1. 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 :
    2. Is your product used to supplement a diet, maintain, enhance and improve the healthy functions of the human body?
    3. Does your product contain one or more of the following or combination of the ingredients:
    4. Vitamins, minerals, amino acid, fatty acids, enzymes, probiotics, and other bioactive substances;
    5. 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).
    1. Your product dosage form should not be an injectable or eye drop.

     

    1. 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

     

    1. 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:

    1. List of Health Claims
    2. Claims substantiation Guidelines

     

    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

    1. 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.
    2. 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.
    3. 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

    1. 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?
    2. 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?
    3. 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?
    4. 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 invitro 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 invitro 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, naturallyoccurring chemical or botanical material, or chemical product obtained by chemical change or synthesis;

     (ii) any metabolite from a microorganism;

     (iii)any macromolecule extracted from an organism;

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

    • a whole cell or microorganism, such as a whole virus or bacterium used as a vaccine;
    • a part of a microorganism, such as a subunit vaccine;
    • a plasmaderived product;
    • a biotechnologyderived 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 —

    1. which has been manufactured into a finished product;
    2. which contains one or more active substances derived wholly from any plant, animal or mineral, or any combination thereof;
    3. 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»;
    4. which does not contain as an active substance any chemicallydefined isolated constituent of any plant, animal or mineral, or any combination thereof; and
    5. 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;

    Quasimedicinal product means:

    1. any antidandruff preparation;
    2. any medicated cosmetic product for the treatment of pimples or acne, except any preparation containing etretinate or 13cisretinoic acid;
    3. any medicated soap;
    4. any sweet for relieving coughs or throat irritations;
    5. any medicated plaster;
    6. any sunscreen or suntan preparation;
    7. any medicated beverage;
    8. any vitamin or nutritional preparation from any natural source; or
    9. 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.

     

    bi

    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

    1. 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.
    1. 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.
    1. 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.
    1. 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.
    1. 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.
    2. 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.
    1. 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/