Psychoactive Substances
Code of Manufacturing Practice
Citation: Ministry of Health. 2014. Psychoactive Substances: Code of Manufacturing Practice. Wellington: Ministry of Health.
First published in January 2014.
Updated in November 2014 by the Ministry of Health
PO Box 5013, Wellington 6145, New Zealand
ISBN 978-0-478-41586-5 (online)
HP 6073
This document is available at www.psychoactives.health.govt.nz
This work is licensed under the Creative Commons Attribution 4.0 International licence. In essence, you are free to: share ie, copy and redistribute the material in any medium or format; adapt ie, remix, transform and build upon the material. You must give appropriate credit, provide a link to the licence and indicate if changes were made.
Foreword
New Zealand is a world leader in the regulation of psychoactive substances. The importation, manufacture and supply of these substances are regulated through the Psychoactive Substances Act 2013.
The Act establishes the Psychoactive Substances Regulatory Authority with the aim to ensure that products meet adequate safety requirements before they can be distributed in New Zealand. Risk assessments focus on approving only those substances that pose no more than a low risk of harm to users.
The Psychoactive Substances Code of Manufacturing Practice (the Code) focuses on making sure all psychoactive products on the market in New Zealand are made to a consistently high standard in clean, controlled environments, and details the quality control requirements for manufacturers of psychoactive substances. The Introduction to the New Zealand Code of Good Manufacturing Practice for Manufacture and Distribution of Therapeutic Goods: Part 1: Manufacture of pharmaceutical products should be read in conjunction with the Code, as it provides valuable guidance that will assist with meeting the GMP requirements for psychoactive substances and products.
This is the second version of the Code and reflects the full regulatory requirements for manufacturing following the passage of the Psychoactive Substances Amendment Act 2014 on 8 May 2014 and commencement of the Psychoactive Substances Regulations 2014 on 3 November 2014.
The first version of the Code (17 January 2014) was structured into two documents: the technical requirements of the Code, as outlined in this document, and an Implementation Plan. The Implementation Plan was designed to manage the interim regime. It gave manufacturers with an interim licence sufficient time to develop the documentation that would allow them to move to a fully compliant Good Manufacturing Practice environment, as well as providing an assurance around the process used to manufacture those psychoactive products that were being sold on the local market during the interim transition period.
Under this second version of the Code, a manufacturing facility in which a psychoactive product is manufactured will need to demonstrate full compliance with the Code before a licence to manufacture is granted and a product can be approved.
Stewart Jessamine
Group Manager
Clinical Leadership, Protection & Regulation
acting as the Psychoactive Substances Regulatory Authority under a delegated authority from the Director-General of Health
Psychoactive Substances: Code of Manufacturing Practice iii
Psychoactive Substances: Code of Manufacturing Practice iii
Contents
Foreword iii
1 Introduction 1
1.1 Overview of the Psychoactive Substances Act 1
1.2 The quality risk management approach to the manufacture of psychoactive substances and products 2
1.3 Overview of the Code 3
1.4 What the Code is based on 4
1.5 What is required for compliance with the Code? 4
2 The Code of Manufacturing Practice 5
2.1 Quality control of psychoactive substances 5
2.2 Quality control of excipient(s) 7
2.3 Quality control of packaging materials 7
2.4 Quality control of delivery device(s) 8
2.5 Quality control of intermediate products 8
2.6 Manufacture of the psychoactive product 8
2.7 Quality control of the psychoactive product 9
2.8 Validation of analytical procedures 10
2.9 Stability testing of the psychoactive product 10
2.10 Good manufacturing practice 11
3 Further information 14
3.1 Auditing of manufacturing facilities 14
3.2 Accredited testing facilities 14
3.3 Standards and pharmacopoeia 14
3.4 Assistance preparing the documentation required 15
Appendix 1: Additional guidance 16
Good Manufacturing Practice 16
Ingredients of human or animal origin and TSE risk management 17
Colouring agents 18
DMFs and CEPs 18
Appendix 11: International guidelines 22
Establishing specifications and test procedures 22
Validation of analytical procedures 23
Impurities 23
Stability testing 25
Other references 27
List of Figures
Figure 1: Psychoactive Substances Regulatory Scheme 2
Psychoactive Substances: Code of Manufacturing Practice iii
1 Introduction
1.1 Overview of the Psychoactive Substances Act
1.1.1 Purpose of the Act
The Psychoactive Substances Act 2013 (the Act) came into force on 18 July 2013. The purpose of the Act is to regulate the availability of psychoactive substances in New Zealand to protect the health of, and minimise harm to, the individuals who use these substances. The Act sets up a system of pre-market approval for psychoactive products by requiring them to demonstrate that they pose no more than a low risk of harm to the individuals who use them, and by placing restrictions on how and to whom they can be sold.[1]
The Act establishes the Psychoactive Substances Regulatory Authority (the Authority) with the aim to ensure that products meet adequate safety requirements before they can be distributed in New Zealand. The Authority approves products and licenses importers, researchers, manufacturers, wholesalers and retailers. The Office of the Psychoactive Substances Regulatory Authority (the OPSRA) is responsible for administration of the Act and its associated regulations.
1.1.2 Psychoactive substances regulations and guidelines
The Psychoactive Substances Regulations 2014 (the Regulations) further define the full regulatory requirements for psychoactive substances.
Additional supporting detail relating to implementation of the regulatory scheme is set out in the Psychoactive Substances Regulatory Guidelines - Products (the Guidelines). Anyone seeking to have a product approved will be required to demonstrate that the product poses no more than a low risk of harm to individual consumers. Before the Authority can approve a psychoactive product, the degree of harm will be assessed on the basis of the evidence supplied and the advice of the Psychoactive Substances Regulatory Authority Expert Advisory Committee.
The Guidelines can be found at the Psychoactive Substances Regulatory Authority website: www.psychoactives.health.govt.nz
1.1.3 The Code of Manufacturing Practice
The Act defines the manufacture of psychoactive substances or products as the means to make up, prepare, produce, or process the substance or product for the purpose of sale. It also includes packaging the substance or product for the purpose of sale.
Section 29 of the Act specifies the requirement for the Authority to develop and maintain a code of manufacturing practice relating to the manufacture of psychoactive substances and products. The Code of Manufacturing Practice (the Code) covers the quality and consistency of the manufacturing process.
The Code sets out the OPSRA’s expectations to manufacturers to ensure that they consistently produce psychoactive substances to an accepted quality. The Code details the quality requirements necessary for manufacturers to demonstrate that they are able to produce psychoactive substances and products that:
· are manufactured in Good Manufacturing Practice (GMP) licensed facilities
· are manufactured to defined quality standards
· use ingredients that comply with internationally established standards
· comply with a set of specifications agreed by the OPSRA as part of the product approval.
Under section 17 of the Act, it is a compulsory condition of any licence to manufacture that the licence holder complies with the Code at all times.
Figure 1: Psychoactive Substances Regulatory Scheme
The Code forms an integral part of the quality control of psychoactive substances, and together with the regulations and other guidelines, will ensure psychoactive substances and products comply to safety standards that consumers and the Authority can rely on.
1.2 The quality risk management approach to the manufacture of psychoactive substances and products
Risk management principles are used in many areas of business and government, including finance, insurance, occupational safety, public health and pharmacovigilance, and by agencies regulating these industries. The importance of quality systems is recognised in these industries, and quality risk management is a valuable part of any effective quality system. In approaching the risk management of psychoactive substances, the OPSRA has drawn extensively on risk management experience in the pharmaceutical and chemical manufacturing sectors.
The manufacture and use of a psychoactive product involves a degree of risk. The quality of the product is just one component of the overall risk, and needs to be managed by developing appropriate quality risk management systems. In order to comply with the Code, manufacturers of psychoactive substances and products will need to develop and use quality risk management processes to assess, control, communicate and review the risks to the quality of their products, and reduce the potential harm due to its manufacture to an acceptably low level.
The Code details the outputs (in terms of the quality control of psychoactive products) that a systematic approach to quality risk management will deliver and sets out a framework for the risk management of psychoactive product manufacturing. It is a foundation document that is independent of, yet supports, international guidelines and codes (such as the International Committee on Harmonisation guidelines). It also complements existing quality practices, requirements, standards and guidelines used within the pharmaceutical industry and other regulatory environments.
The Code provides specific guidance on the principles and some of the tools of quality risk management that can enable more effective and consistent risk-based decisions, both by the OPSRA and by the psychoactive substances industry, regarding the quality of psychoactive substances and the facilities they are manufactured in. The information required as part of compliance with the Code provides assurance that a particular manufacturer can produce psychoactive substances or products in an environment that incorporates appropriate risk management systems.
As a result, the Code has been developed with a ‘product’ focused approach to quality risk management, with manufacturers required to provide product-based documentation to the OPSRA that demonstrate that they have the appropriate ‘quality systems’ in place in the manufacturing facility (ie, demonstration that a product is manufactured to a high quality necessitates the pre-development of quality systems, and supporting documentation).
The effectiveness of risk management systems for specific products will be assessed by the OPSRA through a review of both the facility and the product data generated by the manufacturer. The specific details of what data and information must be produced are detailed in section 2.
1.3 Overview of the Code
1.3.1 General approach to the information required
The Code describes the specific information required to demonstrate that a manufacturer can consistently produce quality psychoactive products by using:
· a controlled process
· ingredients that comply with internationally established standards
· detailed specifications
· defined quality standards.
1.3.2 Overview of specific requirements
For each psychoactive substance or product manufactured in the facility
The OPSRA requires:
· information on the source, quantity and quality of the psychoactive substance in any psychoactive product, presented as certificates of analysis[2]
· information to demonstrate the full characterisation of the psychoactive substance, including full details of the chemistry, the manufacture and the controls placed on manufacture, and information on the stability of the psychoactive substance
· agreed specifications (quality tests) that any psychoactive substance and product manufactured must meet before it is released to be sold
· the quantitative formulation of the psychoactive product
· the dose form of the psychoactive product (eg, tablet, suspension, capsule)
· information on how the psychoactive product is made, and proof that the process consistently produces a high-quality product
· proof that the manufacturing facility can test the quality of the psychoactive product accurately
· validation of the test methods used for the psychoactive substances used and the psychoactive products manufactured at the facility
· an outline of stability trials that will be conducted to show the psychoactive product does not degrade
· information to support the ongoing stability of the psychoactive product
· information on the controls on the quality of the excipients, packaging materials, delivery devices and intermediate products used.
For the manufacturing facility
The OPSRA also requires evidence of GMP compliance for all psychoactive substance and product manufacturing sites, with appropriate certification.
1.4 What the Code is based on
The Code is based on internationally established standards and criteria published by the International Conference on Harmonisation (ICH). Additional guidance on GMP, Ingredients of human or animal origin and TSE risk management, Colouring agents and DMFs and CEPs published by pharmaceutical regulators such as Medsafe and the European Medicines Agency is included in Appendix 1. A brief summary of the key points of the ICH guidelines relevant to the Code is included in Appendix 11.
1.5 What is required for compliance with the Code?
All psychoactive substances and products, and their manufacturers, will be assessed to the same requirements. However, the OPSRA does not test every product itself. The assessment by the OPSRA of compliance with the Code is based on the information supplied by the manufacturer on the quality of the specific products they manufacture, as well as by the OPSRA conducting regular inspections on manufacturing facilities to ensure they have the required systems and documentation in place.
A note on terminology
In this document, and the referenced guidance documents, the term ‘active ingredient’ or ‘drug substance’ is used to refer to the psychoactive substance in the final psychoactive product, which in turn is referred to as the ‘finished product’ or ‘drug product’. ‘Excipient’ refers to other ingredients that make up the psychoactive product but do not possess a psychoactive effect (eg, bulking or binding agents).
2 The Code of Manufacturing Practice
2.1 Quality control of psychoactive substances
2.1.1 Controls applied by the manufacturer of a bulk psychoactive substance
a. Details of each psychoactive substance manufacturing site must be provided, including the postal and physical addresses, as well as any distinction about the particular sub-site details (eg, building number).