Under the new regulatory framework for ATPs, from 1 August 2021, ATPs are regulated as a specific subset of pharmaceutical products. Accordingly, existing regulatory requirements relating to product registration, licensing of manufacturers and distributors, import and export, etc., apply to ATPs as they currently apply to other pharmaceutical products. In view of the complex nature and risks unique to ATPs, ATPs are also subject to additional licensing, product registration, labeling, record keeping and adverse drug reaction (ADR) reporting requirements under the Regulations. Industry players are advised to familiarize themselves with the new regulatory framework for ATPs, as well as the various guidance documents published by the Pharmacy and Poisons Board, to ensure full compliance with the new requirements relating to ATPs.
1. Definition and classification of ATPs
The scope of 'pharmaceutical products' regulated under the Ordinance has been broadened to include three types of ATPs for human use, namely: (i) gene therapy products; (ii) somatic cell therapy products; and (iii) tissue engineered products. Each type of ATP is defined with focus on substantial manipulation and non-homologous use (i.e., where the use of cells or tissues in the recipient is not for the same essential functions as that in the donor). Please refer to the following table for details.
The definition of ATP is modeled upon the definition adopted by the European Union (EU), which the Government notes is widely accepted internationally.
| Gene therapy product
- A 'gene therapy product' is a product:
- 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
- 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.
- The definition of 'gene therapy product' expressly excludes vaccines against infectious diseases.
- An example of a 'gene therapy product' would be genetically engineered immune cells for the treatment of certain types of cancer.
| Somatic cell therapy product
- A 'somatic cell therapy product' is defined as a product that:
- contains or consists of (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 clinical use 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
- 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.
- An example of a 'somatic cell therapy product' would be cultured stem cells from fat tissue for the treatment of chronic inflammation of the gut.
| Tissue-engineered product
- A 'tissue engineered product' is defined as a product that:
- contains or consists of (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
- 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.
- The definition of 'tissue engineered product' excludes products containing or consisting exclusively of nonviable human or animal cells or tissues, and which do not act principally by pharmacological, immunological or metabolic action.
- An example of a 'tissue engineered product' would be cultured corneal epithelial cells for the treatment of burns of the eyes.
Definition of 'substantial manipulation'
'Substantial manipulation' of cells or tissues means altering the biological characteristics, physiological functions or structural properties of the cells or tissues. However, the definition of 'substantial manipulation' expressly excludes 13 specific manipulation processes (which include, for example, cutting, grinding, irradiation, shaping and lyophilization) as set out in the Schedule to the Ordinance, as they are considered to be minimal manipulations only.
2. Regulatory requirements for ATPs
Other than existing regulatory requirements relating to product labeling, product registration, licensing of manufacturers and distributors, import and export, etc., that are applicable to general pharmaceutical products, notable requirements (with an emphasis to enhance traceability) applicable to ATPs are as follows.
All ATPs applying for registration in Hong Kong must produce official evidence of product registration in at least two of the specified countries (which include Japan, the US, many of the member states of the EU, and the UK).
- Licensing requirements for manufacturers
Individual dispensing of ATPs falls within the definition of 'manufacture' if the dispensing process involves substantial manipulation of cells or tissues. As such, hospitals and other specified institutions will need to obtain a manufacturer's license where their dispensing of ATPs would involve substantial manipulation of cells or tissues.
To allow tracing between donors and recipients, licensed manufacturers of ATPs are required to state on the product label the product code and the unique donation identifier of the ATP (the relevant guidance document issued by the Pharmacy and Poisons Board currently adopts the ISBT 128 standard and the Single European Code). Particular labeling requirements apply even for ATPs for autologous use only, i.e., where the donor and the recipient are the same person.
- Record keeping requirements
On top of the generally applicable record keeping requirements (e.g., date and nature of transaction, name of person supplied, etc.), licensed manufacturers and wholesale dealers must also record the name and address of registered medical practitioners or dentists supplied with ATPs.
If a licensed manufacturer prepares an ATP that contains cells or tissues, the manufacturer must also maintain records of the name and address of the person from whom such cells or tissues were obtained, and the relevant unique donation identifier.
Books, records and documents in relation to ATPs must be kept for at least 30 years after the expiry date of the product. This is substantially more onerous than the two-year period that applies to other pharmaceutical products, but is consistent with the practice in the EU.
- Retention of photographs instead of control samples
While a licensed manufacturer does not need to retain control samples for ATPs containing or consisting of cells or tissues (given the scarcity of the materials or finished products), it should keep photographs clearly showing the particulars on the product label of each batch of finished ATPs for at least one year after the expiry date of the products.
- ADR reporting requirements
In addition to reporting all serious ADR occurring in Hong Kong to the local authority, for ATPs, unexpected ADR must also be reported in view of their complex nature. An unexpected ADR is one whose nature, severity, specificity, or outcome is not consistent with the term or description used in the local product labeling.