In vitro fertilisation (IVF) solutions

• Device name(s)
• Classification

• Contact person and title
• Telephone number and fax number

• Device description - schematic diagrams, photographs, and drawing in addition to a written description
• Device specification - identification of components and materials used as well as rationale for use
• Patient-contacting status including whether contact is with donor during oocyte removal, gamete, embryo or recipient
• Intended use - clear and device specific statement
• Indication(s) for use - including safety requirements

• Required

• Required

• Required

• Should identify each potential hazard to the patient (or the gamete/embryo), the cause of the hazard, the level of concern, and the steps taken to address the hazard
• Include risks of individual components, particularly in relation to chemicals and ingredients of biological origin

• Should be clearly identified. In detail, their sources and specifications / characteristics should be clearly identified
• Medicinal component:
  • ARTG number, if it has been approved in Australia;
  • Drug Master File (DMF);
  • assessment reports prepared by the approved agency, if it has been approved in overseas; or
  • a Certificate of Suitability with supporting information described in Appendix 11 of the Australian regulatory guidelines for prescription medicines (ARGPM)

• Justification (e.g. donor screening and testing) is needed to minimise risks for transmission of pathogens.
• Animal origin - following information is required:
  • Sources (e.g. derivations if applicable, country of origin)
  • Specification / characterisation (compliance with Conformity Assessment Standards Order No. 2 if applicable)
  • TSE / Viral safety evidence
• Human materials - TGA inspection of the manufacturing facility may be required. For HSA, reference to a Plasma Master File (PMF) and/or Drug Master File (DMF) held by TGA.
  • human materials/tissues (except blood) - audit of facility according to cGMP Human blood and tissues may be required
  • human blood/derivatives - requires:
    1. third party audit (for overseas manufacturers), and
    2. Master File (MF) (PMF and/or DMF as relevant) to be evaluated according to the appropriate drug evaluation guideline

BP Water for Injections or USP Water for Injection

BP Water, highly purified

• Required

• Required

• MEA is used for toxicity (embryotoxicity) and functionality of reproductive media. The MEA should correspond, as closely as possible, to the procedures used for human IVF, such as the acquisition, maintenance, culture, transfer and cryopreservation of embryos

• Manufacturer should provide clear information about how the assay was performed (one-cell or two-cell MEA) and the assay results in the labelling (see labelling below)

• Required
• For IVF solutions that are not introduced into sterile sites in the body and are intended for multiple use, evidence of adequate preservative efficacy is required to support the shelf life, to satisfy the requirements of 8.1 (1) (b).
• Expectation is that IVF solutions introduced into sterile sites in the body (e.g. used to flush the follicle during oocyte removal) should be for use in one patient only during a single procedure.

• Expectation is that solutions are intended to be sterile.
• Where possible, solutions should be sterilized in their final sealed container (terminal sterilization) and a sterility assurance level (SAL) of 10^-6 is expected. Validation of these processes can be performed in accordance with Medical Device Standards Order No. 3, Schedule 1, 1tem 1 and other items as applicable.
• When the solution cannot be terminally sterilized, the solution may be aseptically processed. When aseptic processing is used:
  • an appropriate sterility assurance level (SAL) is expected as demonstrated by media fill validations. The aim of any process simulation shall be to achieve zero contaminated units. Validation of aseptic processes can be performed in accordance with Medical Device Standards Order No. 3, Schedule 1, Items 2 and 9.
  • presterilization of solution container/closure, product parts and/or components and all equipment coming into direct contact with the aseptically processed solution is required. Validation of the processes used to sterilise containers etc can be performed in accordance with Medical Device Standards Order No. 3, Schedule 1 Item 1 and other items as applicable.
• Sterility testing of the finished product is required as a batch release test for all aseptically prepared products. Sterility testing of terminally sterilised products is also required unless approval for parametric release has been granted.

• Required

• Required

• Tests for bacterial endotoxins and material-associated pyrogens are both required, and test methods are not limited to USP.

• Manufacturer should provide clear information about how the assay was performed and qualified, provide a justification for the specification, and the assay results (should be included) in the labelling.

• Results of biocompatibility testing including the raw data and reports as well as summaries performed on the finished device (for testing, refer ISO 10993-1¹), or certification that identical materials are used in a legally marketed device with a similar intended use, are needed
• For maternal safety, the following test is needed:
  • cytotoxicity test
• For the safety concerns with gamete/embryos including their development, the following tests need to be considered²:
  • genotoxicity test -
    1. bacterial gene reverse mutation assay, if this test is not successful then the following two tests to be considered:
    2. in vitro mammalian cell chromosomal aberration assay (or In vitro mouse lymphoma tk assay), and
    3. in vivo rodent bone marrow micronucleus assay
• embryotoxicity/sperm toxicity assay, to include
  • mouse embryo assay (if applicable) or
  • sperm mortality assay (if applicable)

• Clinical data are needed to satisfy the requirements in DR4 or Australian Regulatory Guidelines for Medical Devices (ARGMD) as applicable, such as:
  • Efficacy
  • Safety of the product

• Labelling should meet requirements in the Australian Regulatory Guidelines for Medical Devices (ARGMD).
• Specifically:
  • labelling is to clearly identify the intended use, indication(s) for use, contraindications, precautions, warnings and instructions for use
  • labelling is to include the word 'sterile' and information on the method that was used to sterilise the device (for symbols, refer to ISO 15223-1³)
• Labelling should indicate whether the product has been tested for reproductive or developmental toxicity