Responsibilities of manufacturers of medicines and biologicals
Regulatory requirements, principles, standards and record keeping apply to manufacturers of medicines and biologicals.
Manufacturers of medicines, Active Pharmaceutical Ingredients (APIs), biologicals (excluding class 1 biologicals), blood and blood components and haematopoietic progenitor cells have responsibilities in relation to:
- During manufacture
- Informing the TGA
- Licence-specific responsibilities
- GMP inspections
- Post-inspection responsibilities
For Australian manufacturers with licences, many of these responsibilities are legal requirements in the Therapeutic Goods Act 1989 and the Therapeutic Goods Regulations 1990. Section 40 of the Therapeutic Goods Act 1989 and Regulations 19 and 20 contain conditions for licence holders.
For overseas manufacturers the same responsibilities and expectations apply, unless otherwise specified.
This is not an exhaustive list of responsibilities.
We have emphasised responsibilities that are in Australian therapeutic goods legislation.
When you manufacture medicines, APIs and biologicals:
Complying with principles, standards and conditions
As a manufacturer, there are GMP requirements (i.e. manufacturing principles), as well as other legislated requirements:
- Observe the applicable manufacturing principles in carrying out the steps in the manufacture [Section 40(4)(a)(ii) of the Therapeutic Goods Act 1989]
- Ensure that goods manufactured conform to any applicable standards (TGOs, pharmacopoeia, marketing authorisation conditions) [Section 40(4)(a)(i) of the Therapeutic Goods Act 1989]
- Observe any conditions, restrictions and authorisations of the licence or certification and do not undertake manufacture contrary to these limitations
- Ensure that the persons nominated as having control of the production of the therapeutic goods and of the quality control measures that are to be employed in the manufacture of the therapeutic goods maintain that control [Regulation 20(iv)]
- Implement any corrective and preventative action plans to rectify deficiencies, as communicated to and agreed to by the TGA
An important part of GMP is keeping records.
There are also legislated record-keeping requirements for Australian manufacturers [Regulation 20(i)], who need to keep records showing:
- the materials used in the manufacture of the goods, the supplier and quantities of the materials used and details of the tests performed on those materials
- the procedures and controls employed in the manufacture of the goods, including the results of tests carried out during the processing of the goods
- details of the tests performed on the goods and the results of those tests
- the stability studies (if any) that validate the recommended shelf life and appropriate storage conditions of the goods
We would expect overseas manufacturers to keep these records too.
Retain these records at the premises for at least 12 months after the expiry date of the goods to which they relate or, if there is no expiry date, for not less than 6 years after completion of manufacture of the goods [Regulation 20(iii)]. However, please check the code of GMP to see if the record keeping requirements are longer than this.
If the goods are produced in identifiable batches [Regulation 20(ii)]:
- assign a batch number to each batch of the goods
- if it is not unreasonable in the circumstances-retain at those premises, for not less than 12 months after the expiry date of the goods or, if there is no expiry date, for not less than 6 years after completion of manufacture of the goods, a sample of each batch of the finished goods
Informing the TGA
Notify the TGA of any significant changes to the business that may impact on the operational activities of the site, including if you cease some of your operations:
Information relating to quality, safety or efficacy
Manufacturers are responsible for informing the TGA [Section 40(5) and 40(4)(ab), Therapeutic Goods Act 1989] of:
- any information that indicates that the use of the goods in accordance with the recommendations for their use:
- may have an unintended harmful effect
- may not be as effective as was suggested by the application for registration or listing of the medicine or inclusion of the biological
- information that indicates that the quality, safety or efficacy of the goods is unacceptable
When contacting us, consider the nature and implications of the information and do one of the following:
- Contact Recalls (if there is a potential issue in relation to safety, efficacy, presentation or quality)
- Report a medicine or vaccine defect
- Report a problem with biologicals
- Contact the Manufacturing Quality Branch
Exceptional release of a biological
When a biologicals manufacturer is also the sponsor, you must notify us of exceptional release [Regulation 33B(2) and Regulation 33C].
Licence holders must:
- display publicly at the premises specified in the licence, a copy of the licence and of any document issued by the Secretary imposing or amending the conditions applicable to that licence [Regulation 20(a)]
- pay an annual charge
- return a licence when a licence is superseded or revoked
Changes to manufacturer or manufacturing processes
If you are changing manufacturing steps or the schedule of conditions, do not implement the change until you have submitted a variation application and the TGA has approved the variation.
Notify us of:
- the name, qualifications and experience of the person nominated as having control of the production of goods or the quality control measures, when there is a change in the nominated person as soon as practicable [Regulation 21]: submit a variation application
- the transfer of a manufacturing licence within 3 months [Regulation 22]: see guidance on licence transfer
When annual charge is due
For licence holders, if we ask at the time of annual charge payment, you are required [Regulation 19] to tell us:
- details of therapeutic goods manufactured by or on behalf of the licence holder during the period of 12 months immediately preceding the date on which the payment of the charge is due
- the name, qualifications and details of the relevant experience of any person nominated by the licence holder as having control of:
- the production of the goods
- the quality control measures that are to be employed in the manufacture of the goods
Manufacturers are responsible to:
- make personnel, records and facilities available for inspection by the TGA
- provide TGA inspectors with access to premises, facilities and records at any reasonable time for the conduct of inspections
Manufacturers are responsible for allowing inspectors from the TGA (who are authorised persons/officers) during normal operating hours [Section 40(4)(b), Therapeutic Goods Act 1989 and Regulation 24(1)] to:
- enter premises on which therapeutic goods are manufactured, tested and stored, for the purpose of exercising the powers and performing the duties of an inspector
- inspect the place at which those goods are manufactured, tested and stored
- take samples of those goods
- ask the owner of therapeutic goods, or the person apparently in charge of those goods, for information relevant to the manufacture, testing and storage of those goods
When an inspector takes a sample of therapeutic goods, the inspector (Regulation 26(1)]:
- must notify the person from whom the sample was taken that the inspector is going to send the sample to a laboratory operated by the TGA for analysis
- must give the person from whom the sample was taken a notice setting out details of the goods taken and, if the person from whom the sample was taken was not the sponsor of the goods, send a copy of that notice to the sponsor of the goods
- must forward the whole or part of the sample to the relevant laboratory
An inspector must ensure [Regulation 26(2)] that any sample of goods taken:
- appropriately packaged, fastened and sealed
- stored and transported in accordance with the instructions (if any) specified on the label of the goods
Responsibilities during inspections
During inspections, manufacturers have a number of responsibilities to enable the inspectors to meet their objectives.
Access for inspectors
Ensure that all inspectors are aware of health and safety requirements and any other requirements relating to the inspected premises. Provide the inspectors with any necessary personal protective equipment.
Permit or obtain free and unrestricted access for the inspection team to:
- premises referred to in your application, licence or certification
- documents and records
Your staff play an important role in the inspection:
- Appoint responsible members of your staff to accompany inspection personnel during the course of an inspection
- For overseas manufacturers, where necessary, provide a guide who can act as an English translator
- Ensure that key personnel, who have the appropriate knowledge of manufacturing operations are available during the inspection
- Inform your staff involved in the inspection about the scope and type of inspections that we may conduct
Please ensure that the translator can translate technical language. The translator needs to be able to translate a technical question asked by the inspector in English into your language, as well as translate technical information into English.
During the inspection:
- Provide all information relating to your manufacturing operations as requested by the inspector during preparation for the inspection
- Provide all necessary resources at the manufacturing site to assist the inspectors in conducting an efficient and effective inspection
- Cooperate with the inspectors to ensure the inspection objectives are achieved to the maximum extent possible
- Answer any questions honestly and openly, and provide accurate and truthful information in response to requests for information by an inspector
- Not mislead, omit or fail to disclose information to an inspector following a request
- Comply promptly with directions and requests for information relating to any manufacturing activities conducted at the site
Collection of information
Allow collection of information during the inspection through:
- interviews with personnel at all levels within the organisation
- observing manufacturing activities
- review and evaluation of systems and procedures for compliance and effectiveness
- photographs and copies of documents
Maintaining compliance with the manufacturing principles
Licence holders are required to maintain an effective quality system and observe the principles of Good Manufacturing Practice in the manufacture of therapeutic goods. It is critical that the quality system and resources are appropriate for the specific manufacturing operations performed.
Effectively implement corrective and preventative actions as agreed
Licence holders are required to implement all corrective and preventative actions as agreed with the TGA. If you are unable to meet a specific commitment or deadline, you should tell us by emailing the Lead Inspector.
|Version||Description of change||Author||Effective date|
|V1.0||Original publication following consultation with industry in January 2017||Manufacturing Quality Branch||August 2017|