Making sense of human cell and tissue products regulation

In brief

The Therapeutic Goods Administration has released guidance on recent changes to the regulation of human cell and tissue products. Special Counsel Ric Morgan and Senior Associate Tracy Lu dissect the complex regulatory framework, particularly in relation to advertising.

Background

The Therapeutic Goods Administration (the TGA) has published guidance notes relating to changes to the regulations regarding human cell and tissue (HCT) products that came into effect on 1 July 2018.

What does it mean?

It is very important to understand what the relevant HCT product is, and how it is processed and used, so that it can be correctly classified. The classification determines the level of regulation, and the differences between the various levels of regulation are significant.

Further, given the distinction in regulatory treatment of services and products, it is also important to consider any advertisement relating to HCT in context (eg whether it is referring to stem cell 'products', or stem cell 'treatments', 'therapies', 'processes' or 'procedures'), for the purpose of determining whether it contravenes any relevant prohibition.

First … the terminologies

HCT products are products that comprise, contain or are derived from human cells and tissues.

Autologous HCT products are products where the human cells and tissues are extracted from and applied to the same person.

HCT products include some that are commonly used in 'stem cell' treatments. The human body is comprised of many types of specialised cells, which perform specific functions. Stem cells are unspecialised cells, which can be induced to become specialised cells.

Stem cell treatments are still largely considered to be experimental, although developments continue to be made.

Now … the distinction between services and products

The changes prohibit advertising where it may have been possible to advertise HCT products in the past. (We explain this below.)

Any prohibition on the advertising of an HCT product will extend to any advertisement (including any testimonial) in relation to a service or procedure that specifies the use of an HCT product (including by reference to its brand name, abbreviation, acronym, or a colloquial term such as 'stem cells').

However, the advertising of such services or procedures without reference to HCT products is not prohibited.

Which level of regulation is applicable?

The TGA imposes four levels of regulation on the supply of HCT products. Separate regulation, such as the regulation of medical practitioners, would also apply to the conduct of procedures involving the use of HCT products.

1. Excluded goods

The TGA does not regulate supply of excluded goods. These are HCT products that are:

1. fresh viable human organs, or parts of human organs, for direct donor-to-host transplantation, and that are used in accordance with applicable laws and standards;
2. fresh viable human haematopoietic progenitor cells (previously known as bone marrow cells) for direct donor-to-host transplantation for the purpose of haematopoietic reconstitution;
3. reproductive tissue for use in assisted reproductive therapy; or
4. therapeutic goods that:
   1. comprise, contain or are derived from human cells or human tissues collected from a patient who is under the clinical care of a medical or dental practitioner;
   2. are manufactured by, or under the professional supervision of, a registered practitioner in a hospital for that patient who must be a patient of that hospital; and
   3. are not advertised directly to consumers.

(See Item 4 of the Therapeutic Goods (Human Cells, Tissues and Organs) Determination 2018.)

Importantly, the 'no advertisement' requirement was introduced as a result of the amendments made to the Therapeutic Goods (Excluded Goods) Order No.1 of 2011, combined with the new Therapeutic Goods (Human Cells, Tissues and Organs) Determination 2018, with effect from 1 July 2018.

2. Medicines

The TGA regulates the following as medicines:

1. blood, meaning whole blood collected from a single human donor, and processed either for transfusion or further manufacturing;
2. blood components, meaning therapeutic components of blood (red cells, white cells, platelets, plasma and platelet-rich plasma or PrP) that can be prepared by centrifugation, filtration and freezing, but not including haematopoietic progenitor cells; and
3. haematopoietic progenitor cells, meaning self-renewing or multi-potent stem cells, or both, capable of maturation into haematopoietic lineages, lineage-restricted pluripotent progenitor cells, or committed progenitor cells,

unless they are 'excluded goods'. This is the case regardless of whether the product is an autologous HCT or not. (See Therapeutic Goods (Manufacturing Principles) Determination 2018.)

All medicines are subject to the usual general advertising restrictions. Eg under sections 42DL (1) and (7) of the Therapeutic Goods Act 1989 (Cth), an advertisement for a medicine cannot, without prior approval, refer to a list of diseases as set out in Table 1, Appendix 6 of the Therapeutic Goods Advertising Code, which includes:

• cardiovascular diseases;
• diseases of joint, bone, collagen and rheumatic disease;
• haematological diseases;
• immunological disorders;
• musculo-skeletal diseases; and
• nervous system diseases.

3. Biologicals

The TGA regulates HCT products that are not excluded goods or medicines as biologicals. As for medicines, this is the case regardless of whether the product is an autologous HCT or not. This only applies where the HCT product is represented in any way to be, or is (whether because of the way in which it is presented or for any other reason) likely to be taken to be:

1. for use in the treatment or prevention of a disease, ailment, defect or injury affecting persons;
2. for use in making a medical diagnosis of the condition of a person;
3. for use in influencing, inhibiting or modifying a physiological process in persons;
4. for use in testing the susceptibility of persons to a disease or ailment; or
5. for use in the replacement or modification of parts of the anatomy in persons.

Examples of biologicals include conditioned serum, stromal vascular fraction derived from processed adipose tissue used for anti-inflammatory purposes, and prepared placenta products.

All advertising of biologicals is prohibited. (See sections 42DL (2) and (11) of the Therapeutic Goods Act 1989 (Cth).)

4. Exempt

In certain circumstances, HCT products that are medicines or biologicals are exempt.

The exempt status only reduces certain types of regulation. This means that for an exempt HCT product, there is no requirement to:

• include it on the Australian Register of Therapeutic Goods (the ARTG); or
• hold evidence of satisfaction of good manufacturing practice (GMP)  requirements.

(See Schedules 5 and 7 of the Therapeutic Goods Regulations 1990 (Cth).)

However, the relevant advertising restrictions for medicines or biologicals still apply. Similarly, it must also still comply with all standards applicable to medicines or biologicals.

To be exempt, the HCT product must meet all of the following requirements:

1. the goods are collected from a patient who is under the clinical care of a medical or dental practitioner;
2. the goods, after collection, are manufactured (in the sense that manufacture includes processing) by, or under the professional supervision of, the practitioner;
3. the single indication of the goods is homologous use:
   1. on that patient; and
   2. in a single clinical procedure; and
   3. by, or under the professional supervision of, that practitioner;
4. the goods have been subjected to only minimal manipulation; and
5. the practitioner is registered in a state or internal territory,

Where:

• homologous use' means use of the goods to repair, reconstruct, replace or supplement the cells or tissues of a person (the recipient), if the goods will perform the same basic function or functions in the recipient as the original cells or tissues performed in the person from whom they were collected (the donor), whether or not the use is autologous.
• 'minimal manipulation' means that any process or processes to which the goods have been subjected have not altered any of the biological characteristics, physiological functions or structural properties of the original cells or tissues that are relevant to the purpose for which the manufacturer of the goods intends the goods to be used.
  
  Examples of processes that are considered to be minimal manipulation include:
  
  • centrifugation;
  • refrigeration;
  • freezing; and
  • freeze drying.

  Examples of processes that are not considered to be minimal manipulation include:

  • cell culture;
  • in vitro differentiation of cells or tissues; and
  • genetic modification.