On this page: Terminology for quality management | Change management | Senior management responsibilities for GMP and quality management | Quality manual development | Product distribution expectations | Product Quality Reviews (PQRs) | Quality risk management
Terminology for quality management
Pharmaceutical Quality System (PQS)
In the latest PIC/S Guide to GMP, 'Pharmaceutical Quality System' (PQS) has replaced the term 'Quality Management System'. This is in line with ICH Q10 global harmonisation efforts, PIC/S harmonisation efforts and to align the GMP guide with contemporary principles of quality systems management. The new terminology better reflects the specific design elements and requirements for a quality system used to manage the manufacture of medicinal products.
The PQS approach described is applicable to the manufacture of all therapeutic goods to which the PE009-13 applies.
Manufacturing authorisation
The term 'manufacturing authorisation', generally refers to the licence to manufacture therapeutic goods issued by TGA to domestic manufacturers. For manufacturers located overseas, this would refer to the certificate of GMP compliance issued following an inspection.
Marketing authorisation
A 'marketing authorisation' is the approval given to supply a therapeutic good in Australia and involves entry on the Australian Register of Therapeutic Goods (ARTG).
The marketing authorisation includes the details of the product in the Australian Register of Therapeutic Goods (ARTG), as well as all other matters in relation to product registration, listing or inclusion agreed in writing between TGA and the sponsor, and any other requirements imposed by a relevant Delegate of the Secretary upon ARTG entry.
Examples of regulatory requirements include, but are not limited to:
- compliance with standards and registered formulations
- special storage and transportation conditions
- shelf life
- packaging and labelling
- batch release testing requirements
The manufacturer is responsible for ensuring their PQS is designed and operated to ensure all relevant requirements of the marketing authorisation are observed during the manufacture of medicines.
Holder of the marketing authorisation
The holder of the marketing authorisation is the product sponsor.
Change management
Regulated changes
Manufacturing changes that affect the product's listed or registered details are termed 'regulated changes' and require an application to vary the marketing authorisation. Please refer to Australian Regulatory Guidelines for Sunscreens.
These requirements are mandatory and are in addition to the requirements of the PIC/S Guide to GMP (PE009-13).
The requirements within the PIC/S Guide to GMP (PE009-13) in relation to change control and risk assessment apply to both regulated and other changes.
Change control applies to all GMP-related activities
The expectation that change control does not just apply to validation activities, but to all GMP-related activities undertaken by a manufacturer has been clarified (clause 1.4 xii, xiii).
Any changes to existing processes, systems, facilities, equipment, products, documents, etc. should be evaluated through a change control process. The effort and extent of change control processes should be commensurate with the nature of the change and based on risk management principles.
All changes implemented should be verified for their effectiveness following implementation.
Managing deviations
There are no changes to the expectations for managing deviations and other similar events (Clause 1.4 xiv). However, PE009-13 now provides clarity regarding the expectations for the investigation of deviations, including adequate root-cause-analysis and identification of corrective and preventative actions.
Release for supply
For more information on release for supply, refer to:
Senior management responsibilities for GMP and quality management
Particular emphasis is placed on the roles and responsibilities of senior management who have ultimate control over manufacturing facilities and activities (new clauses in PE009-13 (including clause 1.5)). Senior management hold the responsibility to make sure that adequate resources are available (human, financial and physical) in order to ensure that the manufacturing activity is managed appropriately.
It is expected that senior management ensure that an effective PQS is implemented and undertake an active role in the support, development and implementation of the PQS. Under the new PE009-13, senior management are ultimately responsible and accountable for the effectiveness of the PQS.
Management reviews
Management reviews (clause 1.6) are a basic quality system element designed to collate, evaluate and communicate details of the effectiveness of the PQS to the management group. Management reviews are particularly important in escalating concerns and enabling senior management support with the aim of resolving issues and managing risks. TGA's basic expectations, based on ICH Q10 principles, are that the management review system should include:
- results and findings of regulatory inspections, , audits and other assessments, and commitments made to regulatory authorities
- periodic reviews of management quality, which can include:
- measures of customer satisfaction such as product quality complaints and recalls
- conclusions of process performance and product quality monitoring
- the effectiveness of process and product changes including those arising from corrective action and preventive actions
- follow-up actions from previous management reviews
The management review system should identify appropriate actions, such as:
- improvements to manufacturing processes and products
- provision, training and/or realignment of resources
- capture and dissemination of knowledge
Management Review of the Pharmaceutical Quality System
Management should have a formal process for reviewing the PQS on a periodic basis. The review should include:
- measurement of achievement of PQS objectives
- assessment of performance indicators that can be used to monitor the effectiveness of processes within the PQS, such as:
- complaint, deviation, corrective and preventative actions (CAPA) and change management processes
- feedback on outsourced activities
- self-assessment processes including risk assessments, trending, and audits
- external assessments such as regulatory inspections and findings, and customer audits
Monitoring by managers of internal and external factors impacting the PQS can include:
- emerging regulations, guidance and quality issues that can impact the PQS
- innovations that might enhance the PQS
- changes in business environment and objectives
- changes in product ownership
Frequency of management reviews
TGA inspectors would generally expect reviews to be conducted at least annually (clause 1.6). However, management reviews may be performed more frequently for new operations, sites that have not previously performed management reviews and sites where the initial management review identifies a number of issues that require rectification.
More frequent reviews may be required for sites with larger and more diverse manufacturing operations.
Quality manual development
A Quality Manual (or equivalent document) is required to be written and maintained (clause 1.7 in PE009-13).
Your quality manual or equivalent should be established and contain the description of the PQS including:
- the quality policy
- the scope of the PQS
- identification of the PQS processes, as well as their sequences, linkages and interdependencies. Process maps and flow charts can be useful tools to facilitate depicting PQS processes in a visual manner
- management responsibilities within the PQS
Product distribution expectations
When products are distributed, minimise any risk to product quality and take account of 'good distribution practice' (GDP) (clause 1.8 (ix)).
TGA does not currently inspect the wholesale distribution of therapeutic goods that have been released for supply.
For sunscreens, sponsors and manufacturers hold shared responsibility for ensuring that products are stored, distributed and subsequently handled so that quality is maintained throughout their shelf life. Quality or technical agreements should clearly identify the responsibilities of manufacturers and Australian sponsor, where they are separate entities.
TGA inspections do include an evaluation of the transport conditions for starting materials, bulk and packed medicines between sites of manufacture and clause 1.8 (ix) would apply in these circumstances.
GDP in the case of Australia would be limited to the application of transport requirements specified in Annex 15 of the PIC/S guide to GMP and not necessarily any other official GDP guideline.
Product Quality Reviews (PQRs)
Manufacturers of sunscreens are expected to generate PQRs in accordance with GMP requirements (clause 1.10).
For more information see our guidance on Product Quality Reviews, because the guidance for listed and complementary medicines also applies to sunscreens.
All authorised products require PQRs
'All authorised products' in clause 1.10 refers to all products manufactured, within the reviewed time period, under a manufacturing authorisation. This implies that domestic manufacturers are expected to conduct PQRs for all medicinal products manufactured under the manufacturing licence and overseas manufacturers are expected to conduct PQRs for all medicinal products for which a GMP clearance is granted.
Export-only medicine PQRs
The PQR requirements for export only products are the same as the PQR requirements for all authorised products.
Supply chain traceability for active substances in PQRs
As part of your PQR, manufacturers of finished sunscreens should have a clear understanding of the approved suppliers of active substances, and each entity and their responsibility in the supply chain between the site of manufacture and receipt (clause 1.10(i)).
For guidance on the evaluation of supply chains for active materials used in sunscreens see Supplier assessment, approval and qualification.
Frequency of PQRs
It is important that you perform a review of all relevant elements of clause 1.10 on at least a yearly basis; however, where very few batches of one product are manufactured in one year, or no manufacturing takes place, it may also be acceptable to perform a full PQR on a two yearly basis providing a rationale is documented and scientifically justified.
Manufacturers and sponsors are expected to maintain vigilance over elements of clause 1.10 that do not directly relate to manufacturing activities, e.g. results of ongoing stability, returns, recalls and complaints that may provide information regarding products available in the market, for periods where very few batches of one product are manufactured in one year, or no manufacturing takes place.
Grouping of products for PQR
Grouping of products is when one PQR is prepared for a group of products. Grouping for the preparation of PQRs is acceptable for sunscreen products and should take consideration of the following:
- a similar base formulation
- the same dosage form
- the same active ingredients
- a similar SPF rating
- been manufactured using similar equipment
Shared responsibility for PQRs between manufacturers and the sponsor
Preparation of PQRs is a shared responsibility between the sponsor and the manufacturer(s) of a product. Manufacturers and sponsors should design and implement effective systems to ensure that PQR reports and relevant data are supplied, compiled and reviewed.
Responsibilities in relation to PQRs should be clearly defined within quality or technical agreements between parties.
Each manufacturer in the supply chain is expected to generate and hold PQRs relevant to the specific manufacturing step they are undertaking. These are expected to be supplied to the sponsor and available for review during inspections of manufacturing sites.
The full PQR containing all relevant sections from all manufacturers should be held and reviewed by authorised persons performing the release for supply step. Sponsors are also expected to have access to the PQRs, to ensure product compliance with the marketing authorisation.
Quality risk management
Quality risk management is mandatory
It is a mandatory requirement for you to have an operational quality risk management system in place to ensure that the evaluation of a risk to product quality is based on a sound, scientific basis and that risk assessments are appropriately documented (clauses 1.12 and 1.13).
Annex 20 is voluntary and provides guidance only on Quality Risk Management tools that may be applied by a manufacturer when assessing the risk to product quality.