Understanding requirements for prescription medicines produced by genetic manipulation

Medicines produced by genetic manipulation can be divided into two broad categories:

• medicines derived or produced from GMOs (biological medicines)
• GMOs that are intended for use as medicinal agents (GMO medicines).

In Australia, dealings with GMOs, including research, manufacture, propagation and importation, are prohibited unless explicitly authorised under the Gene Technology Act 2000 in order to protect human health and safety, and the environment.

This includes all dealings with live, viable GMOs, including those intended for use as, or in the manufacturing or testing of medicines.

The Office of the Gene Technology Regulator (OGTR) - external site administers the Gene Technology Act 2000 and maintains a publicly accessible record of all dealings in Australia that involve GMOs or GM products (the Record).

The Record includes information on all GM products that are approved for supply in Australia under a number of Acts, including therapeutic goods containing GM products that are approved for supply under the Therapeutic Goods Act 1989.

The TGA is required to inform the Office of Gene Technology Regulator about applications for the supply of therapeutic goods that contain GMOs.

Applications for a GMO/biological medicine

Sponsors intending to submit applications to the TGA for a GMO as a medicine or biological medicine (including use in a clinical trial) must:

• consult the OGTR - external site to determine any obligations under the Gene Technology Act 2000
• indicate whether an application has been lodged with the OGTR to have the information required for the Record declared to be confidential commercial information.

Biological medicines are therapeutic goods that are derived from biological sources (including GMOs and GM products) and are regulated as registered prescription medicines. Examples include:

• vaccines
• antivenoms
• bacteria derived toxins
• Immunoglobulins
• monoclonal antibodies
• allergens
• blood products and clotting factors
• hormones such as insulin, growth hormone,
• enzymes such as pancreatins
• heparins.

These medicines are not biologicals (as defined in the Therapeutic Goods Act 1989 and its amendments) and are therefore not regulated under the Biologicals Regulatory Framework.

Guidance on quality issues for recombinant or biotechnological medicines is provided in European Union guidelines.

These include:

• production and quality control of medicinal products derived by recombinant DNA technology (pp. 205-216 of Rules 1998 (3A)-3AB1a)
• production and quality control of cytokine products derived by biotechnological processes (pp. 223-235 of Rules 1998 (3A)-3AB3a)
• use of transgenic animals in the manufacture of biological medicinal products for human use (pp. 287-294 of Rules 1998 (3A)-3AB7a)
• position statement on the use of tumourigenic cells of human origin for the production of biological and biotechnological medicinal products (CPMP/BWP/1143/00)
• note for guidance on quality of biotechnological products: viral safety evaluation of biotechnology products derived from cell lines of human or animal origin (CPMP/ICH/295/95)
• quality of biotechnological products: analysis of the expression construct in cell lines used for production of rDNA derived protein products (pp. 217-222 of Rules 1998 (3A)-3AB2a)
• quality of biotechnological products: stability testing of biotechnological/biological products (pp. 263-273 of Rules 1998 (3A)-3AB5a)
• development pharmaceutics for biotechnological and biological products (annex to Note for guidance on development pharmaceutics) (CPMP/BWP/328/99)
• note for guidance on quality of biotechnological products: derivation and characterisation of cell substrates used for production of biotechnological/biological products (CPMP/ICH/294/95)
• note for guidance on specifications: test procedures and acceptance criteria for biotechnological/biological products (CPMP/ICH/365/96).

GMO medicines may include:

• live attenuated vaccines (viral or bacterial)
• viral vectors
• modified somatic cells.

Sponsors who intend to use GMOs in gene therapy should refer to the relevant European Union guidelines including:

• note for guidance on the quality, preclinical and clinical aspects of gene transfer medicinal products (CPMP/BWP/3088/99)
• gene therapy product quality aspects in the production of vectors and genetically modified somatic cells (pp. 275–286 of Rules 1998 (3A)–3AB6a).

A number of biological medicines use GM cell lines to test the potency of the medicine (e.g. luciferase reporter cell lines). If the testing is done in Australia, sponsors require authorisation under the Gene Technology Act 2000 to use the GM cell line.

Small-scale dealings (less than 25 litres per vessel) with the majority of GM cell lines have been declared exempt from licensing under Schedule 2 of the Gene Technology Regulations 2001.

Sponsors must:

• assess whether the required testing would be exempt under the Gene Technology Act 2000, or would require further authorisation
• submit this assessment as part of any Category 1 application.

All biological medicines

Registration of biological medicines often includes a condition that information and samples of individual batches are to be provided to the TGA for analysis/assessment prior to supply to the market.

Note

Sponsors are responsible for the GMO import, and OGTR authorisation and should alert the TGA about the use of GM cell lines in testing of the medicine early in the evaluation phase by emailing biochemistry.testing@tga.gov.au.