Advanced Therapy Products Amendment - Hong Kong Pharmacy and Poisons (Amendment) Ordinance 2020

The Amendment Ordinance is not yet in force and will come into operation on a day appointed by the Secretary for Food and Health by a notice published in the Gazette, which is anticipated to be in approximately one year’s time. The Amendment Ordinance is the culmination of several years of debate and public comments on the proposed regulatory framework for ATPs, beginning with a public consultation that ran from April to June 2018. Due to the complicated nature of ATPs, and the currently limited knowledge around both their effectiveness and risk profiles, the aim of the Amendment Ordinance is to help safeguard public health by ensuring that the Pharmacy and Poisons Ordinance (Cap. 138) ("PPO") and associated regulations are able to effectively regulate the research and therapeutic use of these products.

What are ATPs?

ATPs are specialised medical products and are different to chemical pharmaceutical products in that they are based on genes, cells and tissues. While they are different to chemical pharmaceutical products, these ATPs will form a specific subset of pharmaceutical products under the PPO, meaning that the PPO and other relevant ordinances/regulations will apply to ATPs. The Amendment Ordinance inserts into the PPO a definition of ATPs that defines three specific product types: gene therapy products, somatic cell therapy products and tissue engineered products. These product types are then also defined in the PPO for the purposes of clarity:

Gene therapy products (NB – these do not include vaccines):

• Products that contain 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 relates directly to the recombinant nucleic acid sequence or the product of genetic expression of that sequence.

Somatic cell therapy products:

• Products that contain or consist of cells or tissues:
  - that have been substantially manipulated so that their biological characteristics, physiological functions or structural properties relevant for their intended clinical use have been altered.
  - that are not intended to have the same function in the recipient as they do in the donor.
  
  
• The product treats, prevents or diagnoses a disease, or restores, corrects or modifies physiological functions through the pharmacologic, immunologic or metabolic action of those cells or tissues.

Tissue engineered products:

• Products that contain or consist of cells or tissues:
  - that have been substantially manipulated so that their biological characteristics, physiological functions or structural properties relevant for their intended regeneration, repair or replacement have been altered.
  - that are not intended to have the same function in the recipient as they do in the donor.

What is required for ATPs under the Amendment Ordinance?

The Amendment Ordinance places specific regulatory requirements on ATPs and these have been included as amendments to the Pharmacy and Poisons Regulations (Cap. 138A) ("PPR"). To create alignment with other global regulatory frameworks, the new regulatory requirements in HK have been based on the EU regulatory framework for similar ATPs. In recognition of the potential risk associated with ATPs, the new regulations place special requirements for manufacturing, labelling and record keeping, in addition to the already existing general requirements for pharmaceutical products.

On the manufacturing side, as with all pharmaceutical manufacturing under the PPR, all facilities that manufacture ATPs must obtain a license. Under the Amendment Ordinance, the manufacturer of the ATP will only be required to keep photographs, for one year following expiry date of the product, of the standard particulars required for pharmaceutical manufacturing (Regulation 31(1)) e.g. what the product is made from, where the product is made, batch number, expiry date etc.

For labelling, licensed manufacturers must include the product code and the unique donation identifier assigned in accordance with the code of practice issued by the Pharmacy and Poisons Board (the "Board"). If the product is for autologous use, then the labelling must include the unique identifier assigned in accordance with the codes of practice issued by the Board and also the statement "For autologous use only" (or the Chinese characters).

The record keeping requirements require specific discussion, as some are potentially burdensome on licensed manufacturers or licensed wholesale dealers of ATPs. One relatively simple requirement for both of these parties is that they must keep a record of the name and address of any registered medical practitioner or registered dentist supplied with an ATP. A more onerous requirement for both licensed manufacturers and licensed wholesale dealers, however, is that "all books, records and documents" are required to be kept or retained for a period of 30 years after the expiry date of the product. Should the entity cease to exist or function, the records must be transferred to the Board within certain time periods.

Draft Guidance Documents

As stated, while the Amendment Ordinance has been passed by the HK government, its provisions will not come into force for approximately one year. In the intervening period, the HK Drug Office ("DO") has released a number of draft guidance documents that aim to assist in the understanding of the new regulatory requirements for ATPs. The period for public comment on these guidance documents will run until 31 December 2020.

In total there are eight draft guidance documents:

For industry:

1. Guidance on Application of Certificate of Drug/ Product Registration – Advanced Therapy Products
   
   
2. Guidance on Application of Certificate for Clinical Trial – Advanced Therapy Products
   
   
3. Guidance on Application of Import and Export Licences – Advanced Therapy Products
   
   
4. Guidance for Pharmaceutical Industry – Adverse Drug Reaction Reporting Requirements

For healthcare professionals ("HCPs"):

1. Guidance on Record Keeping for Medical Practitioners, Dentists and Institutions Providing Advanced Therapy Product Treatment
   
   
2. Guidance for Healthcare Professionals – Adverse Drug Reaction Reporting Clinical Trial
   
   
3. Guidance on Application of Certificate for Clinical Trial – Advanced Therapy Products
   
   
4. Guidance on Application of Import and Export Licences – Advanced Therapy Products (NB – this is for the treatment of a particular patient)

There is also a related draft guidance document, "Guidance for Cell and Tissue Products (Those not classified as Advanced Therapy Products)", to assist with product classification issues.

While there is not the scope to discuss all of the Guidance Documents in detail, the draft "Guidance on Application of Certificate of Drug/ Product Registration – Advanced Therapy Products" outlines a number of points to be aware of when categorising a product for the purposes of the ATP regulatory requirements. Firstly, blood transfusions, corneal transplants and bone marrow transplants are not considered to meet the definition of an ATP. Secondly, if the ATP for which you seek Marketing Authorisation ("MA") meets the definition of 'organ' and has been subjected to 'processing' as defined in the Human Organ Transplant Ordinance (Cap. 465) ("HOTO"), then the product will be considered a 'regulated product' under HOTO. As per the draft guidance, it is possible to apply for an exemption from the regulated product requirements under HOTO, but if it is not granted, the product would then be subject to all statutory requirements of both the HOTO and the Amendment Ordinances. Secondly, for products that may meet the definition of more than one ATP class, the following will apply:

1. A product falling within the definition of both somatic cell therapy product and tissue engineered product should be considered as a tissue engineered product; and
   
   
2. A product falling within the definition of both somatic cell therapy product, or tissue engineered product, and gene therapy product, should be considered as a gene therapy product.

Summary

The Amendment Ordinance introducing formal regulatory requirements for ATPs into the existing PPO and PPR has been several years in the drafting. The Amendment Ordinance provides clear regulatory requirements for these products that will be given more substantive effect through the guidance documents produced by the DO, although these are currently only in draft form for comment. Given the nature of ATPs, and their currently relatively unknown effectiveness and risk profiles, the new regulations are a logical step in safeguarding the general public.