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Scheduling delegate's interim decisions and invitation for further comment: ACCS/ACMS, March 2017

Scheduling medicines and poisons

17 May 2017

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2.2 In Vitro Diagnostic and Analytical Preparations

2. Joint meeting of the Advisory Committee on Chemicals and Medicines Scheduling (ACCS/ACMS #15)

2.2 In Vitro Diagnostic and Analytical Preparations

Referred scheduling proposal

An application was submitted for consideration by the delegate to seek advice from the Joint Advisory Committees on Chemicals and Medicines Scheduling (ACCS-ACMS) on a proposal to amend 'Part 5, Appendix A General Exemptions of the Poisons Standard' to include Schedule 9 poisons at 0.001 per cent or less as exemptions for in vitro diagnostic and analytical preparations.

Current scheduling statu

In Australia, poisons in Schedules 1 to 8 at concentrations of up to 0.001 per cent in in vitro diagnostic and analytical preparations are included in Appendix A as follows:

Appendix A - General Exemptions

IN VITRO DIAGNOSTIC AND ANALYTICAL PREPARATIONS containing 0.001 per cent or less of a poison included in Schedules 1 to 8.

Scheduling history

In 1987, the Drugs and Poisons Scheduling Committee (DPSC) rejected a proposal that a general exemption for all scheduled substances when incorporated into an in vitro diagnostic test kit be included in the Poisons standard. The Committee felt that each case needs to be considered on its merits so that substances contained in these kits can be properly assessed and the correct labelling, storage and clinical advice given.

Scheduling application

This is a general application. The applicant's proposed amendment to the Poisons Standard is as follows:

Appendix A - Amend Entry

IN VITRO DIAGNOSTIC AND ANALYTICAL PREPARATIONS containing 0.001 per cent or less of a poison included in Schedules 1 to 89.

The applicant's reasons for the request are:

  • This amendment is requested to allow in vitro diagnostic medical device (IVD) companies to legally import, store and supply IVDs containing very small amounts of substances included in Schedule 9.
  • These IVDs items are positive controls used for screening clinical specimens for the detection of drugs of abuse. The amount of drugs included in the controls is very small (≤ 300 ng/mL) well below the amount specified in the standard. The range of drugs which are screened for varies but the most common drugs are MDMA, LSD, phencyclidine (PCP) and methaqualone.
Australian regulatory information

In Australia, all in vitro diagnostic medical devices (IVD medical devices or IVDs) that are intended to be used for a therapeutic purpose are subject to regulation under the Therapeutic Goods Act 1989. A new regulatory framework for IVDs was implemented on 1 July 2010, following amendments made to the Therapeutic Goods (Medical Devices) Regulations 2002 (the Regulations) to include IVDs as a subset of medical devices.

The changes made to the legislation apply to all IVDs, and require that all manufacturers of IVDs certify that their products are safe, perform appropriately for their intended purpose, and are manufactured to a high standard of quality by complying with a set of Essential Principles (EPs) to identify performance levels required, hazards to be addressed, or issues to be considered. The EPs for safety and performance form the basis of the IVD regulatory framework and are set out in Schedule 1 of the Regulations.

In vitro diagnostic medical devices (IVDs) are defined as:

  1. a reagent, calibrator, control material, kit, specimen receptacle, software, instrument, apparatus, equipment or system, whether used alone or in combination with another diagnostic product for in vitro use; and
  2. intended by the manufacturer to be used in vitro for the examination of a specimen derived from the human body, solely or principally for:
    1. giving information about a physiological or pathological state or a congenital abnormality; or
    2. determining safety and compatibility with a potential recipient; or
    3. monitoring therapeutic measures; and
  3. not a product that is:
    1. intended for general laboratory use; and
    2. not manufactured, sold or presented for use as an IVD medical device.
International regulations
New Zealand

In New Zealand, in IVDs are currently exempt from mandatory notification to WAND (web assisted notification of devices) database but must still comply with the requirements of the Medicines Act 1981 and its Regulations.[38]

USA

An overview of IVD Regulation is available on the FDA website.[39]

  • 21 CFR 864.4010(a) is applied to general purpose reagents (GPRs). A GPR is a chemical reagent that has general laboratory application, is used to collect, prepare, and examine specimens from the human body for diagnostic purposes, and is not labelled or otherwise intended for a specific diagnostic application. GPRs do not include laboratory machinery, automated or powered systems).
  • 21 CFR 864.4020(a) is used to classify analyte specific reagents (ASRs). ASRs are antibodies, both polyclonal and monoclonal, specific receptor proteins, ligands, nucleic acid sequences, and similar reagents which, through specific binding or chemical reaction with substances in a specimen, are intended for use in a diagnostic application for identification and quantification of an individual chemical substance or ligand in biological specimens) used in IVDs.

Also on the FDA website is a review on Drugs of Abuse Tests.[40]

Canada

In Canada,[41] reagents, instruments, apparatus, equipment or systems not manufactured, sold or represented by manufacturers for use in in vitro diagnostic applications are not considered to be in vitro diagnostic devices (IVDDs). This includes products used in general laboratory applications, even if they are used by laboratories to develop their own diagnostic assays for the laboratory's own use.

IVDDs labelled "For Research Use Only" (not otherwise labelled or otherwise represented by a manufacturer for a specific diagnostic application, or labelled with specific performance characteristics, or a bibliography listing articles referring to the use of the marker for a specific application) are exempt from the Medical Devices Regulations.

In accordance with subparagraph 3(2) of the Regulations, all in vitro diagnostic products that are a drug or contain a drug listed in Schedule E or F to the Food and Drugs Act, in the Schedule to Part G or Part J of the Food and Drug Regulations, in the Schedules to the Controlled Drugs and Substances Act, or in the Schedule to the Narcotic Control Regulations, are not subject to the Medical Devices Regulations. The following is a short description of these schedules.

Section 15 of the Act prohibits the sale of a drug mentioned in Schedule F. Therefore, if an in vitro diagnostic product was a drug or contained a drug listed on Schedule F to the Act, its sale would be prohibited. In the case of in vitro diagnostic products that was a drug or contained a drug listed on Schedule E to the Act, it would be subject to the provisions of the Food and Drug Regulations.

In vitro diagnostic products listed on the Schedule to Part G or the Schedule to Part J of the Food and Drug Regulations are subject to the provisions of the Controlled Drugs and Substances Act (CDSA) and the Food and Drug Regulations. The Schedule to Part G lists controlled drugs, such as barbiturates and anabolic steroids. The Schedule to Part J lists restricted drugs, such as some amphetamines and lysergic acid diethylamide. All drugs listed in Schedules G and J of the F&D Regulations are also listed on the Schedules to the CDSA.

In addition to the products listed on Schedules G and J of the Food and Drug Regulations and on the Schedule to the Narcotic Controlled Regulations, there are other products listed on the schedules to the CDSA that are also not subject to the Medical Devices Regulations.

In vitro diagnostic products listed on the Schedule to the Narcotic Controlled Regulations are subject to the provisions of the CDSA (also listed in its schedules) and of the Narcotic Controlled Regulations.

Europe

There is guidance document regarding IVD and medical devices in the EU.[42] In the EU, devices intended to be used only in the course of law enforcement or other non-medical purposes, for example paternity tests or tests for detecting drugs of abuse/alcohol, are not IVD's. If however, the in vitro examination of human specimens with a medical purpose is one of the intended uses of a specific product, the IVD Directive will apply.[43] A list of substances used in IVDs in the EU is given in the IDV directive and includes Drugs of Abuse/Toxicology such as amphetamines, barbiturates, benzodiazepines, cannabinoids THC, cocaine, codeine, morphines and other.

Examples of test kits are available at the following websites:

Substance summary

An in vitro diagnostic medical device (IVD):

  • is any medical device which is a reagent, calibrator, control material, kit, specimen receptacle, software, instrument, apparatus, equipment or system, whether used alone or in combination (with other diagnostic goods for in vitro use); and
  • intended by the manufacturer to be used in vitro for the examination of specimens derived from the human body, solely or principally for the purpose of giving information about a physiological or pathological state, a congenital abnormality or to determine safety and compatibility with a potential recipient or to monitor therapeutic measures.

The range of drugs tested varies but currently the most common are MDMA, LSD, phencyclidine (PCP) and methaqualone. In vitro diagnostic preparations for the screening of drugs of abuse are not therapeutic goods and therefore do not require approval by the TGA. However, the controls and calibrators for the IVDs are therapeutic goods and do require TGA approval. Therefore, the products related to this application are all evaluated and approved by the TGA before supply.

The products involved are controls or calibrators, i.e. urine or serum samples, that contain specified amounts of a range of commonly used drugs of abuse. The products are used exclusively in pathology laboratories, which are secure premises from which diversion is unlikely. Also the amount of drug present in the products is very small (≤ 300 ng /mL) and therefore the risk of diversion or abuse is considered to be low.

Pre-meeting public submissions

No submissions were received.

Summary of ACCS-ACMS advice to the delegate

On the basis of the information contained in the application, the committee recommended that the current inclusion in Appendix A (General Exemptions) of 'IN VITRO DIAGNOSTIC AND ANALYTICAL PREPARATIONS containing 0.001 per cent or less of a poison included in Schedules 1 to 8' remains appropriate.

The committee suggested that additional information may be available regarding the scope of use from IVD Australia, MTAA and workplace testing facilities, and requested the Secretariat to engage with these bodies to gain further information to support reconsideration by the committee/delegate.

Members agreed that the relevant matters under Section 52E(1) of the Therapeutic Goods Act 1989 included: (a) risks and benefits of the use of a substance (b) the purpose for which a substance is to be used and the extent of use; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; (e) the potential for abuse of a substance; and (f) any other matters that the Secretary considers necessary to protect public health.

The reasons for the advice comprised the following:

  • Consideration of Schedule 9 substances proposed for inclusion in Appendix A should be considered on a case-by-case basis.
  • Some Schedule 9 poisons are very potent and the potential diversion of small amounts of specific chemicals may be problematic.
  • The toxicity of the Schedule 9 poisons varies according to the class of substance (opioid, hallucinogen, stimulant) and is dose related. Schedule 9 poisons can lead to serious health risks if diverted due to their toxicity and potency.
  • The committee noted the risk of diversion from an IVD is low from authorised diagnostic laboratories however external to these, the risks outweighed the benefit.
  • The potential for abuse of in vitro diagnostic substances would be significantly increased when provided in analytical solutions, however is likely to be very minimal if limited to the well-plate of IVD kits when supplied to NATA accredited laboratories and hospitals, and given the very small quantities (less than or equal to 500 nanograms per mL) in test kits regulated under the Therapeutic Goods (Medical Devices) Regulations 2002, and the matrix in which the Schedule 9 poisons exist (i.e. urine).
  • There is a growing area of workplace testing, as well as testing that is undertaken in laboratories and universities, and limiting supply to forensic laboratories, hospitals and workplaces is an important consideration.
  • An exemption under Appendix A for Schedule 9 poisons at a concentration of 0.001 per cent or less for in vitro diagnostic and analytical preparations may not automatically apply in all jurisdictions.
Delegate's considerations

The delegate considered the following in regards to this proposal:

  • Scheduling proposal
  • ACCS-ACMS advice
  • Public submissions received
  • Section 52E of the Therapeutic Goods Act 1989
  • Scheduling Policy Framework (SPF 2015)
  • Other relevant information
Delegate's interim decision

The delegate's interim decision is that the current inclusion in appendix a (general exemptions) of 'in vitro diagnostic and analytical preparations containing 0.001 per cent or less of a poison included in schedules 1 to 8' remains appropriate.

The delegate considered the relevant matters under section 52E (1) of the Therapeutic Goods Act 1989: (a) the risks and benefits of the use of a substance; (b) the purposes for which a substance is to be used and the extent of use of a substance; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; (e) the potential for abuse of a substance; and (f) any other matters that the Secretary considers necessary to protect public health.

The reasons for the interim decision are the following:

  • The delegate acknowledges the committee's advice.
  • Consideration of Schedule 9 substances proposed for inclusion in Appendix A should be considered on a case-by-case basis.
  • Some Schedule 9 poisons are very potent and the potential diversion of small amounts of specific chemicals may be problematic.
  • The toxicity of the Schedule 9 poisons varies according to the class of substance (opioid, hallucinogen, stimulant) and is dose related. Schedule 9 poisons can lead to serious health risks if diverted due to their toxicity and potency.
  • The committee noted the risk of diversion from an IVD is low from authorised diagnostic laboratories however external to these, the risks outweighed the benefit.
  • The potential for abuse of in vitro diagnostic substances would be significantly increased when provided in analytical solutions, however is likely to be very minimal if limited to the well-plate of IVD kits when supplied to NATA accredited laboratories and hospitals, and given the very small quantities (less than or equal to 500 nanograms per mL) in test kits regulated under the Therapeutic Goods (Medical Devices) Regulations 2002, and the matrix in which the Schedule 9 poisons exist (i.e. urine).
  • There is a growing area of workplace testing, as well as testing that is undertaken in laboratories and universities, and limiting supply to forensic laboratories, hospitals and workplaces is an important consideration.
  • An exemption under Appendix A for Schedule 9 poisons at a concentration of 0.001 per cent or less for in vitro diagnostic and analytical preparations may not automatically apply in all jurisdictions.
  • The current entry remains appropriate, but further information may be available, and will be sought from the applicant, IVD Australia, MTAA and workplace testing facilities to assist reconsideration by the committee/delegate.

Footnotes

  1. NZ: Medical Devices: In-Vitro Diagnostic (IVD) Devices
  2. USA, IVD Regulation: Overview of IVD Regulation
  3. USA, review on Drugs of Abuse Tests
  4. Canada: Guidance Document: Guidance for the Risk-based Classification System for In Vitro Diagnostic Devices (IVDDs)
  5. EU, IVD medical devices review: MEDDEV. 2.14/1 rev. 1 Guidelines on Medical Devices: IVD Guidances: Borderline issues - A Guide for Manufacturers and Notified Bodies (pdf,94kb)
  6. IVD directive: In Vitro Diagnostic Product Classification - Revision 5 (pdf,141kb)

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