Draft Code of Manufacturing Practice: Natural Health Products

Draft Code of Manufacturing Practice

Natural Health Products

This document is available at health.govt.nz

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Contents

1Introduction

1.1The Natural Health Products Regulatory Regime

1.2Why a Code of Practice for Manufacture is needed

1.3Good manufacturing practice principles

1.4Basing the Code of Manufacturing Practice on GMP principles

1.5Sections of the Code

1.6Other legislation to read in conjunction with this Code

2Manufacturing practice requirements

2.1Introduction

2.2Personnel

2.3Premises

2.4Equipment

2.5Production

2.6Materials

2.7Quality control

2.8Supporting documentation

3Complaints and recalls

3.1Complaints

3.2Recalls

4Contract manufacture and analysis

4.1Introduction

4.2Contract – general considerations

4.3Contract giver obligations

4.4Contract acceptor obligations

5Starting material requirements

5.1Starting materials of herbal origin

5.2Starting materials of animal origin

6Dose form requirements

7Standards and guidelines

List of Figures

Figure 1:Natural Health Product Regulatory Scheme

Figure 2:Components of requirements for an NHP quality assurance system

Draft Code of Manufacturing Practice: Natural Health Products1

1 Introduction

1.1 The Natural Health Products Regulatory Regime

1.1.1 The Natural Health Products (NHP) regulatory regime is designed to address three main risks associated with natural health products:

the ingredients in the product could be unsafe
consumers could be diverted from appropriate health treatment
products could be manufactured in an unsafe way.
These risks are addressed by:
ingredients having to be selected from a large permitted ingredients list
controls on health claims, and labelling
setting robust manufacturing standards.

1.2 Why a Code of Practice for Manufacture is needed

1.2.1 The requirement for the Authority to establish a code of practice for the manufacture of NHPs (the Code) is set out in the Natural Health Products Bill (the Bill).

1.2.2 The Bill provides that the NHP Authority must issue a Code to come into force no later than one year after commencement of the legislation.

1.2.3 The full regulatory scheme will be phased in over three years after the legislation comes into force.

1.2.4 All product notifiers and manufacturers have a responsibility to ensure that their NHPs are manufactured in a way that ensures consumers are not put at undue risk due to a lack of quality control during manufacture, and that they meet the minimum standards of safety, as defined by the Bill.

1.2.5 To achieve this, the manufacturing facility must have a well-defined quality assurance system that incorporates the principles of good manufacturing practice (GMP), and the interrelated concepts of quality control and quality risk management. It should be fully documented and be monitored for effectiveness.

1.2.6 A quality assurance system incorporates wide-ranging concepts covering all matters that individually or collectively influence the quality of a NHP. The term quality control refers to all the procedures undertaken to ensure the quality and uniformity of manufacture of a particular NHP. In regard to manufacture, quality risk management can be described as the systematic process for the assessment, control, communication and review of risks to the quality of NHPs.

Figure 1: Natural Health Product Regulatory Scheme

Figure 1 demonstrates how the Code forms an integral part of the regulatory scheme, and together with the regulations and guidelines, will help to ensure the safety of natural health products for consumers.

1.3 Good manufacturing practice principles

1.3.1 GMP is the part of quality assurance that ensures products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the product notification or product specification. GMP is concerned with both production and quality control. Following are the basic requirements of GMP.

All manufacturing processes are clearly defined, systematically reviewed in the light of experience and shown to be capable of consistently manufacturing products of the required quality and complying with their specifications.
Critical steps of manufacturing processes and significant changes to the process are validated.
All necessary facilities for GMP are provided, including:

– appropriately qualified and trained personnel

– adequate premises and space

– suitable equipment and services

– correct materials, containers and labels

– approved procedures and instructions

– suitable storage and transport

– recording and investigation of any significant deviations

– comprehensible and accessible records of manufacture, including distribution, which enable the complete history of a batch to be traced

– distribution (wholesaling) methods that minimise any risk to product quality

– a system for the recall any batch of product, from sale or supply

– a system for investigating and resolving complaints about marketed products

– investigation of the causes of quality defects, appropriate measures taken in respect of the defective products and to prevent recurrence.

1.3.2 As further background to quality risk management and quality assurance, manufacturers may find the ISO 9001 series on quality management informative and useful.

1.4 Basing the Code of Manufacturing Practice on GMP principles

1.4.1 The Code includes provisions related to developing systems and procedures that fulfil the principles and that cover all the following areas:

personnel
premises and equipment
production
quality management and quality control
complaints and recalls.

Figure 2: Components of requirements for an NHP quality assurance system

Figure 2 shows the interconnecting relationship between the components of a quality assurance system for NHPs that covers all areas relevant to an effective GMP principle-based Code. All manufacturing facilities will be required to develop, maintain and hold documentation to demonstrate that they have an appropriate quality risk management system in place covering all areas as indicated.

1.5 Sections of the Code

1.5.1 The Code is split into the following sections.

Section 2 describes the detail of the manufacturing practice relevant to personnel, premises and equipment used, quality control measures in place, production and supporting documentation.
Section 3 describes the detail for the management of complaints and recalls.
Section 4 describes the detail for contract manufacture and analysis.
Section 5 describes the detail for the collection and identification of starting materials of herbal and animal origin.
Section 6 describes the detail for testing requirements to be included on specifications for particular dose forms.
Section 7 provides a list of the standards and guidelines from which this Code is drawn.
The Code should be read in conjunction with the Natural Health Products Code of Manufacturing Practice Guidelines (the Guidelines). The Guidelines will assist with interpretation and application of the Code. The Guidelines include:
a risk assessment matrix, which allows users to broadly assess the risks arising from the product and its manufacture; it is not designed to be a prescriptive tool providing a definitive ‘risk classification’
case studies, which describe a scenario and its key product and manufacturing attributes and a summary of some of the key considerations of application of the Code
information about audits
question and answer guidance.

1.6 Other legislation to read in conjunction with this Code

1.6.1 Other legislation that your products must comply with include, but are not limited to the:

Animal Products Act 1999
Food Act 2014 and its associated Standards
Fair Trading Act 1986
Hazardous Substances and New Organisms Act 1996
Medicines Act 1981 and the Medicines Regulation 1984
Misuse of Drugs Act 1975
Psychoactive Substances Act 2013 and the Psychoactive Substances Regulations 2014.

2 Manufacturing practice requirements

2.1 Introduction

2.1.1 This section outlines the outcomes to be achieved under the Code. It is the responsibility of the manufacturer to understand the requirements within the context of their manufacturing circumstances.

The requirements that all manufacturers must achieve are stipulated as outcomes and are highlighted in text boxes.

Each section has guidance which describes best practice for how the outcome can be achieved. Whether the best practice applies is dependent on the individual manufacturing circumstances.

2.2 Personnel

The manufacturer has an adequate number of personnel with the necessary qualifications and practical experience to ensure the quality of a product.

General

2.2.1 A good quality assurance system that ensures the consistent quality of manufacture of NHPs relies upon people.

2.2.2 There are sufficient qualified personnel to carry out all the tasks which are the responsibility of the manufacturer.

2.2.3 Individual responsibilities are clearly understood by the individuals and are written into the supporting documentation.

2.2.4 The manufacturer has an organisation chart.

2.2.5 The responsibilities placed on any one individual do not present any risk to quality.

2.2.6 People in responsible positions have specific duties recorded in written job descriptions and adequate authority to carry out their responsibilities. Their duties may be delegated to designated deputies of a satisfactory qualification level. There are no gaps or unexplained overlaps in the responsibilities of those personnel concerned with the application of the principles of GMP.

Key personnel

There is a clear separation between the quality and production responsibilities. Documentation defines the key production and quality responsibilities.

2.2.7 Key personnel and their responsibilities are documented. Documentation includes the person in charge of production, the person in charge of quality control, and the person in charge of releasing products for supply. Where practicable, these are different people, and key posts are occupied by full-time personnel.

2.2.8 In large organisations it may be necessary to delegate some of these functions. In small organisations it may be difficult to have separate personnel for these key roles, depending on the number of employees.

Production personnel

2.2.9 The person in charge of production generally has responsibility to:

ensure that products are manufactured and stored according to approved instructions
ensure production records are correct before they are sent to the quality control person
check that the appropriate validations (where required) are done
ensure that the required initial and ongoing training of the production department personnel is carried out and adapted according to need
check the maintenance of the department, premises and equipment.

Quality control personnel

2.2.10 The person in charge of the quality control aspect generally has responsibility to:

approve or reject starting materials, packaging materials, and intermediate, bulk and finished products
evaluate batch records
ensure that all necessary testing is carried out
approve specifications, sampling instructions, test methods and other quality control procedures
approve and monitor any contract analysts
check the maintenance of the department, premises and equipment
ensure that the appropriate validations (if necessary) are done
ensure that the required initial and ongoing training of the quality control department personnel is carried out and adapted according to need.
Other duties of the quality control function are summarised in section 2.7.

Additional responsibilities

2.2.12 The people in charge of production and quality control generally have some shared responsibilities relating to quality. These may include:

authorisation of written procedures and other documents, including amendments
monitoring and control of the manufacturing environment
hygiene of personnel, premises and equipment
process validation
training
approval and monitoring of suppliers of materials
approval and monitoring of contract manufacturers
designation and monitoring of storage conditions for materials and products
retention of records
monitoring of compliance with the principles of GMP
inspection, investigation and taking of samples, in order to monitor factors which may affect product quality.

Training

Training programmes are in place to ensure that staff activities and visitors or untrained personnel do not present a risk to the quality of a product.

2.2.13 Besides basic training on the theory and practice of GMP, newly recruited personnel receive training appropriate to their duties.

2.2.14 The manufacturer provides training for all the personnel whose duties take them into production areas or into control areas (including the technical, maintenance and cleaning personnel), and for other personnel whose activities could affect the quality of the product.

2.2.15 Ongoing training is given, and its practical effectiveness is periodically assessed. Training programmes are available, approved by either the person in charge of production or the person in charge of quality control, as appropriate.

2.2.16 Personnel working in areas where contamination is a hazard, such as clean areas or areas where highly active, toxic, infectious or sensitising materials are handled, are given specific training.

2.2.17 The concept of quality assurance and all the measures capable of improving understanding and implementation is fully discussed during the training.

2.2.18 Training records are kept.

2.2.19 It is preferable that visitors or untrained personnel are not taken into the production and quality control areas. If this is unavoidable, they are given information in advance, particularly about personal hygiene and appropriate protective clothing. They are closely supervised.

Personal hygiene

Hygiene programmes are in place. They include procedures relating to the health, hygiene practices and clothing of personnel.

2.2.20 These procedures are understood and followed by everyone with responsibilities in production and control areas.

2.2.21 Hygiene programmes are promoted by management and widely discussed during training sessions.

2.2.22 All personnel receive a medical examination upon recruitment, if appropriate. After this, medical examinations are be carried out when necessary for the work and personal health. Steps are taken to ensure as far as is practicable that no person affected by an infectious disease or having open lesions on the exposed surface of their body is engaged in the manufacture of NHPs. Staff and management are all responsible for ensuring that management is made aware when a staff member has a health condition that could affect the quality of products.

2.2.23 Every person entering the manufacturing area wears protective garments appropriate to the operations to be carried out.

2.2.24 Eating, drinking, chewing or smoking, or the storage of food, drink, smoking materials or personal medication, in the production and storage areas is not permitted.

2.2.25 Any unhygienic practice within the manufacturing areas or in any other area where the product might be adversely affected is not permitted.

2.2.26 Direct contact is avoided between the operator’s hands and the exposed product as well as with any part of the equipment that comes into contact with the products.

2.2.27 Personnel are instructed to use the hand-washing facilities.

2.3 Premises

Premises are located, designed, constructed, adapted and maintained to suit the operations to be carried out.

The layout and design of premises minimises the risk of errors, and permits effective cleaning and maintenance in order to avoid cross-contamination, build-up of dust or dirt and, in general, any adverse effect on the quality of a product.

General

2.3.1 Premises are situated in an environment which, when considered together with measures to protect the manufacture, presents minimal risk of causing contamination of materials or products. Premises are carefully maintained, ensuring that repair and maintenance operations do not present any hazard to the quality of products. They are cleaned and, if applicable, disinfected according to detailed written procedures.

2.3.2 Lighting, temperature, humidity and ventilation are appropriate and such that they do not adversely affect, directly or indirectly, the NHPs during their manufacture and storage, or the accurate functioning of equipment. Premises are designed and equipped so as to offer maximum protection against the entry of insects or other animals.

2.3.3 Steps are taken in order to prevent the entry of unauthorised people. Production, storage and quality control areas are not used as a right of way by personnel who do not work in them.

Manufacture of a range of products

2.3.4 If a facility manufactures a wide range of products (for example, both medicines and NHPs), certain additional products (such as certain hormones, cytotoxics, highly active substances and drugs) and health products that do not meet the definition of a NHP should not be produced in the NHP manufacturing facility.

2.3.5 The manufacture of technical poisons, such as pesticides and herbicides, should not be produced in the NHP manufacturing facility.

2.3.6 Different batches of the same product can be made in sequence (the principle of campaign working) in the same facilities provided that specific precautions are taken and the necessary validations are made between batches.

Production area

2.3.7 Premises are laid out to allow the production to take place in areas connected in a logical order corresponding to the sequence of the operations and to the requisite cleanliness levels.

2.3.8 The adequacy of the working and in-process storage space permit the orderly and logical positioning of equipment and materials so as to minimise the risk of confusion between different NHPs or their components, to avoid cross-contamination and to minimise the risk of omission or wrong application of any of the manufacturing or control steps.

2.3.9 Where starting and primary packaging materials, intermediate or bulk products are exposed to the environment, interior surfaces (walls, floors and ceilings) are smooth, free from cracks and open joints, and do not shed particulate matter and permit easy and effective cleaning and, if necessary, disinfection.

2.3.10 Pipe work, light fittings, ventilation points and other services are designed and sited to avoid the creation of recesses which are difficult to clean. As far as possible, for maintenance purposes, they are accessible from outside the manufacturing areas.

2.3.11 Drains are of adequate size, and have trapped gullies. Open channels are avoided where possible, but if necessary, they are shallow to facilitate cleaning.

2.3.12 Production areas are effectively ventilated, with air control facilities (including where necessary, temperature, humidity and filtration) appropriate to the products handled, to the operations undertaken within them and to the external environment.