General Information
Classification of ATPs
Registration of ATPs
Clinical Trial of ATPs
Preparation and Provision of ATPs
Adverse Drug Reaction Reporting
Others
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General Information |
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Q.1 What is advanced therapy product (ATP)?
A.1 According to Section 2 of the Pharmacy and Poisons Ordinance (Cap. 138) (“PPO”), “pharmaceutical product” –
(a) means a substance or combination of substances that –
(i) is presented as having properties for treating or preventing disease in human beings or animals; or
(ii) may be used in or administered to human beings or animals with a view to –
(A) restoring, correcting or modifying physiological functions by exerting a pharmacological,
immunological or metabolic action; or
(B) making a medical diagnosis; and
(b) includes an ATP.
ATP is included in the definition of “pharmaceutical product” and means any of the following products that is for human use –
(a) a gene therapy product;
(b) a somatic cell therapy product;
(c) a tissue engineered product.
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Q.2 What is a gene therapy product?
A.2 According to Section 2 of the PPO, gene therapy product –
(a) means a product –
(i) that contains an active substance containing or consisting of a recombinant nucleic acid that may be used in or administered to human beings with a view to regulating, repairing, replacing, adding or deleting a genetic sequence; and
(ii) the therapeutic, prophylactic or diagnostic effect of which relates directly to –
(A) the recombinant nucleic acid sequence it contains; or
(B) the product of genetic expression of that sequence; but
(b) does not include a vaccine against an infectious disease.
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Q.3 What is a somatic cell therapy product?
A.3 According to Section 2 of the PPO, somatic cell therapy product means a product that –
(a) contains or consists of any of the following cells or tissues –
(i) cells or tissues that have been subject to substantial manipulation so that their biological characteristics, physiological functions or structural properties relevant for the intended clinical use have been altered;
(ii) cells or tissues that are not intended to be used for the same essential functions in their recipient as in their donor; and
(b) is presented as having properties for, or may be used in or administered to human beings with a view to –
(i) treating, preventing or diagnosing a disease; or
(ii) restoring, correcting or modifying physiological functions,
through the pharmacological, immunological or metabolic action of those cells or tissues.
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Q.4 What is a tissue engineered product?
A.4 According to Section 2 of the PPO, tissue engineered product –
(a) means a product that –
(i) contains or consists of any of the following cells or tissues –
(A) cells or tissues that have been subject to substantial manipulation so that their biological characteristics, physiological functions or structural properties relevant for the intended regeneration, repair or replacement have been altered;
(B) cells or tissues that are not intended to be used for the same essential functions in their recipient as in their donor; and
(ii) is presented as having properties for, or may be used in or administered to human beings with a view to, regenerating, repairing or replacing a human tissue; but
(b) does not include a product that –
(i) contains or consists of exclusively non-viable human or animal cells or tissues; and
(ii) does not act principally by pharmacological, immunological or metabolic actions.
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Q.5 In the definitions of somatic cell therapy product and tissue engineered product, “substantial manipulation” is mentioned. What is “substantial manipulation?
A.5
Regarding cells and tissues, substantial manipulation refers to a product preparation process that would alter the biological characteristics, physiological function or structural properties of the cells or tissues that the product contains or consists of.
According to the Schedule to the PPO, the following processes are NOT substantial manipulations:
- Cutting
- Grinding
- Shaping
- Centrifugation
- Soaking in antibiotic or antimicrobial solutions
- Sterilization
- Irradiation
- Cell separation, concentration or purification
- Filtering
- Lyophilization
- Freezing
- Cyropreservation
- Vitrification
Apart from the above, other preparation processes are generally considered as substantial manipulation.
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Q.6 What Ordinances in Hong Kong are (or may be) relevant to ATPs?
A.6 The following Laws of Hong Kong may provide regulation to ATPs:
- Pharmacy and Poisons Ordinance (Cap. 138)
- Import and Export Ordinance (Cap. 60)
- Prevention and Control of Disease Regulation (Cap. 599A)
- Undesirable Medical Advertisements Ordinance (Cap. 231)
- Trade Descriptions Ordinance (Cap. 362)
- Human Organ Transplant Ordinance (Cap. 465)
- Human Reproductive Technology Ordinance (Cap. 561)
- Private Healthcare Facilities Ordinance (Cap. 633)
Pharmacy and Poisons Ordinance (Cap. 138)
As stated in A1, ATP falls within the definition of pharmaceutical product. Under the Pharmacy and Poisons Ordinance (Cap. 138), an ATP must be registered with the Pharmacy and Poisons Board before it can be supplied in Hong Kong. Registered ATP should be labelled with the Hong Kong registration number, in the form of "HK-XXXXX", on its container. Suppliers and manufacturers of ATPs must also apply for relevant licences, i.e. Wholesale Dealer Licence and Licence for Manufacturer of Pharmaceutical Products respectively. Currently, all licensed manufacturers of pharmaceutical products must fully comply with the Good Manufacturing Practice (GMP) of the Pharmaceutical Inspection Co-operation Scheme (PIC/S).
In addition, according to Regulation 36B of the Pharmacy and Poisons Regulations (Cap. 138A), a person must not conduct a clinical trial on human beings, or cause or permit such a trial to be conducted except in accordance with a clinical trial certificate issued to the person.
Moreover, the Pharmacy and Poisons Regulations (Cap. 138A) stipulates the labelling and record keeping requirements specific to ATPs in order to enhance their traceability.
Import and Export Ordinance (Cap. 60)
The import and export of ATPs are regulated under the Import and Export Ordinance, which provides that all importation and exportation of an ATP into or out of Hong Kong must be under the authority of a valid licence.
Prevention and Control of Disease Regulation (Cap. 599A)
If a person imports biological material into Hong Kong and he / she has reason to suspect that the material contains an infectious agent, he / she shall obtain a permit from the Director of Health. Application details for import of biological materials are available at
https://www.dh.gov.hk/english/useful/useful_forms/useful_forms_qpd.html.
Undesirable Medical Advertisements Ordinance (Cap. 231)
The Undesirable Medical Advertisements Ordinance prohibits advertisements of medicine, surgical appliance or treatment to claim curative or preventive effects on any diseases or conditions in human beings as specified in the Schedules to the Ordinance.
Trade Descriptions Ordinance (Cap. 362)
The Trade Descriptions Ordinance aims at protecting consumers by prohibiting the application of false trade descriptions to goods or services in the course of trade or operation of business and the supply or offering to supply any goods or services to which false trade description is applied. It also prohibits specified unfair trade practices, including misleading omissions, aggressive commercial practices, bait advertising, bait-and-switch and wrongly accepting payment, deployed by traders against consumers.
Human Organ Transplant Ordinance (Cap. 465)
The Human Organ Transplant Ordinance prohibits commercial dealings in human organs intended for transplanting, and restricts the transplanting of human organs between living persons and the transplanting of imported human organs. A person is guilty of an offence if he makes or receives any payment for the supply of, or for an offer to supply an organ which is removed from a dead or living person and is intended to be transplanted into another person. More information on the regulation of human organ transplant in Hong Kong is available at the webpage of the Department of Health (http://www.dh.gov.hk/english/links/links_hot.html).
Human Reproductive Technology Ordinance (Cap. 561)
The Human Reproductive Technology Ordinance is to regulate reproductive technology procedures, and the use, for research and other purposes, of embryos and gametes. It also confines the provision of reproductive technology procedures to infertile couples subject to any express provision to the contrary in any code.
Private Healthcare Facilities Ordinance (Cap. 633)
Procedures involving the transplant of cell- or tissue-containing ATPs to patients (including autologous transplant) are Scheduled Medical Procedures under the Private Healthcare Facilities Ordinance and should only be performed in hospitals or day procedures centres with relevant licence in force. For further details, please refer to the website of the Office for Regulation of Private Healthcare Facilities, Department of Health (https://www.orphf.gov.hk).
The above list of Ordinance and Regulation is not exhaustive and healthcare providers should seek legal advice on the legality of their use of ATPs. For the contents of the relevant legislation, please refer to the website of Hong Kong e-Legislation at https://www.elegislation.gov.hk.
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Classification of ATPs |
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Q.7 How do I know whether my product is an ATP?
A.7 As stated in A1, the Pharmacy and Poisons Ordinance (Cap. 138) stipulates the definition of ATP. If your product falls within the definition of ATP, it will be classified as ATP (and thus a pharmaceutical product) and subject to the regulatory control under the relevant ordinances.
In determining whether a product falls within the definition of ATP, you should thoroughly assess all the available product information which includes:
(a) the active ingredient of the product;
(b) the preparation process of the active ingredient of the product;
(c) the use and mode of action of the product; and
(d) the presentation of the product.
All the information should be taken into account as a whole in the classification assessment. For further details, please refer to “Guidance on Classification of Advanced Therapy Products” issued by the Pharmacy and Poisons Board, available at https://www.ppbhk.org.hk/eng/regulation_of_atp.html.
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Q.8 Are products containing cells and tissues from animal source included for consideration as ATPs?
A.8 Yes. A product containing or consisting of cells or tissues from human and/or animal origin that falls within the definition of ATP will be considered as an ATP.
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Q.9 Are bone or tissue grafting products that are derived from human or animal origin and are intended for regenerating a human tissue considered as ATPs?
A.9
If a bone grafting product (e.g. bone graft, bone powder and bone paste) or tissue grafting product (e.g. membrane derived from pericardium or dermis) contains or consists of exclusively non-viable human or animal cells or tissues and does not act principally by pharmacological, immunological or metabolic action (e.g. providing structural support or physical barrier), it generally does not fall within the definition of ATP.
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Registration of ATPs |
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Q.10 Are ATPs sold in Hong Kong registered?
A.10
As stated in A6, the regulatory requirements for pharmaceutical products apply to ATPs. As stipulated under Regulation 36(1) of the Pharmacy and Poisons Regulations (Cap. 138A) , pharmaceutical products must be registered before they can be sold, offered for sale, distributed or possessed for the purposes of sales, distribution or other uses in Hong Kong.
The Hong Kong registration number for a registered ATP should be labelled on the container in the form of "HK-XXXXX”. Information of registered ATPs are available on the website of the Drug Office as follows:
Sale of unregistered pharmaceutical products is an offence under the Pharmacy and Poisons Ordinance (Cap. 138). The maximum penalty is a fine at level 6 of Criminal Procedure Ordinance (Cap. 221) ($100,000) and two year’s imprisonment.
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Q.11 What is the legal requirement for import of an unregistered ATP for treatment of a particular patient?
A.11
As stated in A1, ATP is included in the definition of pharmaceutical product under the PPO. According to Regulation 36(1) of the Pharmacy and Poisons Regulations (Cap. 138A), pharmaceutical products (and thus ATPs) must be registered before they can be sold, offered for sale or distribute or possessed for the purposes of sale, distribution or other use in Hong Kong.
The above requirement is not applicable in the case of possession or use where the ATP is possessed or is to be used for the purpose of treatment by a registered medical practitioner/dentist of a particular patient in accordance with Regulation 36(1A)(ab) of the Pharmacy and Poisons Regulations.
Under the Import and Export Ordinance (Cap. 60), all imports of pharmaceutical products must be covered by an Import Licence. For every single importation, the importer needs to apply for an Import Licence from the Drug Evaluation and Import/Export Control Division of Department of Health. The applicant for Import Licence for an unregistered ATP should be a licensed wholesale dealer on behalf of a registered medical practitioner or dentist.
Application for import licence for importation of unregistered ATP for the treatment of a particular patient will be considered on a case by case basis. For further information, please refer to the “Guidance on Application of Import and Export Licences – Advanced Therapy Products” available at the webpage of our office (https://www.drugoffice.gov.hk/eps/do/en/doc/atp_guidance/DO_Guidance_IE_ATP-EN.pdf).
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Clinical Trial of ATPs |
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Q.12 What should I do if I want to conduct a clinical trial of ATP in Hong Kong?
A.12
You need to apply for a clinical trial certificate in order to conduct any clinical trial on human beings in Hong Kong. The applicant could be—
- sponsor of the clinical trial or a local company that holds relevant licence(s) (e.g. wholesale dealer licence) and that can handle ATPs
- sponsor-investigator who initiates and conducts a clinical trial
- principal investigator who conducts the clinical trial
For details about the application, please refer to the “Guidance on Application of Certificate for Clinical Trial – Advanced Therapy Products” issued by the Pharmacy and Poisons Board, available at https://www.ppbhk.org.hk/eng/regulation_of_atp.html.
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Q.13 What documents are required for the application for the clinical trial certificate of an ATP?
A.13 To apply for a clinical trial certificate of an ATP, you should submit the completed application form, checklist and the relevant documents as specified in the “Guidance on Application of Certificate for Clinical Trial – Advanced Therapy Products” (as mentioned in A12). Due to the complicated nature of ATPs, you should take note of the requirements on traceability, risk minimisation measures, long-term follow-up, etc. relevant to ATPs when devising the proposed protocol, investigator’s brochure and patient consent form. Please refer to Appendix 3 of the guidance document for further details.
The application for clinical trial certificate should be submitted to the Drug Evaluation and Import/Export Control Division of our office by email (ct@dh.gov.hk) or mail (Suites 2002-05, 20/F, AIA Kowloon Tower, Landmark East, 100 How Ming Street, Kwun Tong, Kowloon).
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Preparation and Provision of ATPs |
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Q.14 Do I need to obtain a licence for processing a cell-based therapy product at my clinic?
A.14
If the processing of a cell-based therapy product is part of the manufacturing processes* (e.g. expanding cells in culture, activating immune cells, transforming stem cells to another cell type) of pharmaceutical products under the Pharmacy and Poisons Ordinance (Cap. 138), you are required to obtain relevant licence for the premises under the Ordinance and the processing could only be conducted at specified premises. You are also required to comply with specified guidelines and code of practice for obtaining the licence. For more information relating to licensing of pharmaceutical manufacturer, please refer to the webpage of our office at https://www.drugoffice.gov.hk/eps/do/en/pharmaceutical_trade/guidelines_forms/useful_guidelines_forms.html.
Please note that private healthcare facilities are under the regulatory control of Private Healthcare Facilities Ordinance (Cap. 633). As mentioned in A6, a relevant licence issued under the Private Healthcare Facilities Ordinance is required for hospitals or day procedure centres where Scheduled Medical Procedures under the Private Healthcare Facilities Ordinance are performed. For more information, please refer to the website of Office for Regulation of Private Healthcare Facilities at https://www.orphf.gov.hk.
* The definition of “manufacture” is stipulated in Section 2 of the Pharmacy and Poisons Ordinance (Cap. 138).
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Q.15 What record should I keep if I supply ATPs to my patients for the purpose of medical treatment?
A.15
Under Section 28 of the PPO, for a medicine supplied by a registered medical practitioner or a registered dentist for the purpose of treatment, particulars relating to the supply should be entered in the record of treatment or other document. Particulars include –
(a) the date on which the medicine was supplied;
(b) the name and address of any person to whom or on whose behalf it was supplied; and
(c) the ingredients of the medicine and the quantity, dosage and duration of supply.
In addition to the above legal requirements, an ‘ATP Record’ (e.g. a register) should also be maintained to enable the identification of patient who received a particular batch of an ATP and the treatment details for traceability purpose. The ATP Record should contain the following information–
(a) date of supply/treatment;
(b) identifier of the patient;
(c) details of the ATP applied –
(1) name;
(2) batch number;
(3) the ISBT 128 code or Single European Code, if any; and
(4) supplier name, and manufacturer name if different from supplier;
(d) medical practitioner or dentist responsible for the use of product if the record is kept by an institution.
For information relating to record keeping of ATP and a sample of the ATP Record, please refer to the “Guidance on Record Keeping for Medical Practitioners, Dentists and Institutions Providing Advanced Therapy Product Treatment” available at the webpage of our office
(https://www.drugoffice.gov.hk/eps/do/en/doc/atp_guidance/DO_Guidance_Record_HCP_ATP-EN.pdf).
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Adverse Drug Reaction Reporting |
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Q.16 What is an adverse drug reaction (ADR)?
A.16
An ADR is a response, which is noxious and unintended, to a pharmaceutical product.
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Q.17 What kind of ADRs should I report to your office?
A.17
Healthcare professionals are encouraged to report the following adverse drug reaction cases:
- All suspected serious adverse drug reaction, even if the reaction is well known;
- Suspected drug interactions including drug-drug and drug-herb interactions;
- Non-serious adverse drug reactions but the reactions are deemed medically significant by the healthcare professional (e.g. increased frequency or unusual presentation of a known adverse drug reaction);
- Unexpected adverse drug reactions, i.e. the reactions are not found in the product information or labelling (e.g. an unknown side effect in a new drug).
Due to their novelty, complexity and technical specificity, ATPs may raise some new and unexplored risks and safety concerns which required special attention. For more information relating to the potential ADRs of concern for ATPs, please refer to the “Guidance for Healthcare Professionals – Adverse Drug Reaction Reporting” available at the webpage of our office https://www.drugoffice.gov.hk/eps/do/en/healthcare_providers/adr_reporting/index.html.
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Q.18 How can I report an ADR?
A.18
You can report through the following channels:
(a) Report online by completing the online report form at https://www.drugoffice.gov.hk/adr.html; or
(b) Download the report form (available at https://www.drugoffice.gov.hk/adr.html) and return the completed report by
- email to adr@dh.gov.hk;
- fax to (852) 2319 6319; or
- mail or delivery to the Adverse Drug Reaction and Adverse Event Following Immunization Unit, Drug Office, Department of Health, at Room 1856, 18/F, Wu Chung House, 213 Queen’s Road East, Wan Chai, Hong Kong.
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Others |
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1 August 2021 |
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Regulation of Advanced Therapy Products
