This blog is intended as a current guide how to set about applying for a TGA GMP Manufacturing license for Medicinal Cannabis.
Process for applying for a TGA GMP Manufacturing Licence
Two Manufacturing Licences may be required for the manufacture of medicinal cannabis active pharmaceutical ingredients (API), for example, if:
- extracting or purify the cannabis plant, or finished dosage forms (FDF)
- manufacturing tablets, capsules, gummies flowers for inhalation, etc.
Depending on the dosage form that will be manufactured, a Manufacturing Licence may be required from the Office of Drug Control (ODC) under the Narcotic Drugs Act 1967.
A TGA Manufacturing Licence IS required to manufacture medicinal cannabis, API or FDF, for the supply in or export from Australia under the Therapeutic Goods Act 1989 and the Therapeutic Goods Regulations 1990.
To obtain a TGA Manufacturing Licence from the Office of Manufacturing Quality (OMQ), the following steps need to be completed:
1. Become a TGA Client
To apply for a TGA Manufacturing Licence, a manufacturer must be a TGA Client with access to the TGA e-business Portal, TGA Business Services. Refer to TGA Business services: getting started with the TGA.
- apply for a Client Identification Number (Client ID)
- complete and submit an Organisation details – Sponsor, Agent, and Manufacturer form to the TGA TBS helpdesk.
2. Apply for a TGA GMP Manufacturing Licence
The following activities are required to ensure that an inspection of a manufacturing site is included in the TGA schedule of planned inspections as soon as possible. Refer to: Australian manufacturing licences and overseas GMP Certification – a step-by-step guide.
The Application for an inspection of a manufacturing site should be made at least the 6 month stage (but no later than 3 months) prior to the site being ready for an inspection.
The Application should be submitted electronically via the eBS portal and should include:
- Full details (name and address) of the manufacturer.
- Types of products that will be manufactured at the site (Manufacturing Steps table):
- manufacturing type
- manufacturing class
- dosage form
- product code
- manufacturing steps
- The completed statutory declaration, Certificate 38(1)(g), that none of the circumstances stated in section 38(1)(g) of the Act apply to any person involved in the management of the manufacturer (Fit and Proper Person).
(Note that the Manufacturing Licence Application Tracking Number must be included on the declaration form. To obtain this number you must ‘Start, Save and Close’ a New Licence Application via the eBs portal. Refer to the Manufacturer Statutory Declarations Form.)
- The nominations of the persons responsible for Quality Control and Production. A Curriculum Vitae (CV) for each of the nominated persons is also required.
- A copy of the Site Master File (SMF).
- Payment of the Application fee
- A cover letter indicating the current status of the project
If only a draft SMF is available, the draft SMF must be attached and the cover letter should state that the SMF will be updated as information becomes available and that a final approved copy will be ready before the on-site TGA inspection.
If the Quality Control and Production nominee positions have not yet been filled, the cover letter should state this. A blank attachment with the following headings should be attached – ‘Production Nominee’, ‘Position still to be filled’ and ‘CV to be provided prior to the on-site inspection’
The online application will not validate if these documents are not attached.
3. Meet with the TGA
PharmOut and the TGA encourages manufacturers to contact the MQB to request a meeting and meet with inspectors once they have applied for a Manufacturing Licence. These meetings are not mandatory but PharmOut strongly recommends that manufacturers take up this offer. The meetings are usually held in either the TGA Sydney or Melbourne offices, as this is where the majority of inspectors are based, and typically last one hour. Our experience is that the TGA inspectors are incredible competent and helpful.
The meeting will usually be attended by at least two GMP inspectors. Personnel representing the manufacturer may include the Quality Assurance Manager, Production Manager, Consultants, etc.
The TGA will ask the manufacturer to provide an Agenda in advance of the meeting.
The agenda should include at a minimum:
- Discussion of the scope of the proposed Manufacturing Licence application and the on-site inspection.
- Proposed plans for manufacturing site – you should send them the site plan and all the plans that show room classifications, room pressure differentials, material, process, waste and personnel flows.
- Discussion of the inspection process – the TGA should explain the inspection and licencing process for example, the on-site inspection(s), no. of inspectors, no. of days (they may not know yet who the inspectors will be or for how long), report (post inspection letter (PIL) and final report), response/close out process, issue of Licence, etc.
- Discussion of critical timelines – on-site inspection, issue of licence, start manufacturing first batch, release of first batch.
The manufacturer will be expected to take the minutes from the meeting and then send them to the TGA.
The inspectors will discuss with the you the proposed plans and provide advice on the licencing and inspection process. The TGA does not act a Consultant and the inspectors at the meeting will not rubber stamp or give your plans the seal of approval. However, if the they ask you, ‘Have you considered x, y or z in your plans’ it is highly likely that they have noted something they are not happy with and you may want to consider reviewing your plans prior to the inspection.
4. Define TGA Timelines
The TGA have defined target time frames for the scheduling and close out of manufacturing inspections. The targets remain the same irrespective of the scope of the application.
|Time Period||Target Timeframe|
|Effective (1) application to inspection scheduling||≤ 2 months|
|Inspection scheduling to conducting inspection||≤ 1 month|
|Inspection to Post Inspection Letter (PIL)||≤ 4 weeks|
|Final report and inspection close out||Between 10 and 30 weeks (2)|
|Processing and issue of Manufacturing Licence||Approximately 2 weeks after inspection is closed|
- Time periods do not start until the application is “effective” i.e. application fees have been paid and all required documentation has been supplied.
- Depends on the inspection compliance rating. First inspections may require all major observations to be addressed before the license is issued. In addition, the close out process may include an on-site close out inspection.
Whilst the targets for the scheduling and conducting of inspections and the issuing of the Post Inspection Letter (PIL) can sometimes be negotiated with the TGA and Inspectors, the inspection close out is largely dependent on the number of deficiencies identified during the inspection and the number of response(s) required to close out the inspection.
Refer to: Page 32 of the Australian manufacturing licences and overseas GMP Certification – a step-by-step guide, for a detailed description of the inspection closeout process.
An older blog can also provide more information: How long does it take for me to get a TGA license?
5. Define the Manufacturing Steps
The scope of the application for a new TGA manufacturing Licence, as specified in the Manufacturing Steps table, should fully reflect the activities (steps) to be licensed.
The Application/inspection will be assigned to an Inspector(s). When the Lead Inspector notifies the ‘Manufacturer’ of the scheduled inspection date, it is at that point that the ‘Manufacturer’ should indicate the state-of-readiness of the site relative to the Application, for the scheduled inspection. The Inspector will plan the inspection based on this conversation.
The inspector will request that a number of documents be sent to the TGA prior to the inspection. The list of documents will include the SMF but can include any document the inspector wants to see for example, the Validation Master Plan and document in the PQS. The list will vary from inspector to inspector; there are no rules.
6. Host On-site Inspection for your TGA Manufacturing Licence
The scope of the on-site inspection will include an inspection of the manufacturing facility, equipment and processes in addition to the Pharmaceutical Quality System (PQS).
At short notice, decreasing the scope of an inspection is less problematic than increasing the scope.
If the scope of the inspection is decreased, a Variation can be submitted at a later to include the omitted, desired manufacturing steps.
- Application and Inspection Fees
- Initial Application and inspection Fees
The Application and Inspection fees are as defined in the Australian Therapeutic Goods Legislation. The fees and charges are reviewed annually.
For example, the estimated TGA Costs for an Application and Issue of a TGA Manufacturing Licence (as at 01 July 2018) are as follows:
|Activity||Estimated Hours||Rate per inspector ($/hr)||Payment Timeline||Cost ($)|
|Licence application||N/A||N/A||Licence application||770|
|On-site inspection 1 inspector / 3 days (1)||24||970||Immediately prior to issue of Licence||23,280|
|On-site inspection – Specialist (2)||TBD||970||Immediately prior to issue of Licence||TBD|
|On-site close out inspection (3)||TBD||970||Immediately prior to issue of Licence||TBD|
|Manufacturing Licence (initial & annual fee)||N/A||N/A||Immediately prior to issue of Licence||4,590|
- Assumption the inspection will be assigned to a minimum of one (1) inspectors for 3 days.
- The inspection team could also include Specialists e.g. biotechnologists.
- The close out process may include an on-site close out inspection.
7. Ongoing Compliance
The TGA schedules routine follow-up inspections. The frequency of routine follow-up inspections depends on the level of compliance at previous inspections and level of risk of products being manufactured. Manufacturers are not required to submit applications for routine re-inspections; TGA Business Services will automatically generate an application for re-inspection based on the frequency recommended following the previous inspection.
Estimated costs for ongoing inspections will be dependent on the number of inspectors and the hours spent on site. In addition, there will be an Annual Licence fee
The TGA has developed a re-inspection frequency matrix for Registered medicines. The matrix reflects the higher level of risk associated with the use of these products.
|Risk Rating||Third and subsequent consecutive A1||Second consecutive A1||First A1||A2||A3|
|H||36 months + reduced scope inspection||36 months||24 months||18 months||12 months|
Refer to: Manufacturer inspections – a risk-based approach to frequency
The PIC/S Guide to GMP is the essential standard for those intending to manufacture medicines for supply within Australia. Unless there is a special exemption under the Therapeutic Goods Act, the manufacture of medicinal cannabis API and FDF will require PIC/S Part I and Part II compliance. Depending on the dosage form and the particular manufacturing process, compliance to the relevant PIC/S Annexes are also required, (e.g. if your FDF is a cream or ointment; if you use computerised systems, etc.) as well as relevant product standards such as TGO 93 (Medicinal Cannabis) and TGO 77 (Microbiological); or TGO 98 which replaced TGO 77. The information is intended as a guide only, regulations change all the time, like the TGO 77 above and therefore please check before making any final decision.
How we can help:
PharmOut has years of experience in designing and building pharmaceutical manufacturing sites in Australia. We are also experts in supporting ODC Medicinal Cannabis licence applications and TGA GMP manufacturing licenses.
Please contact us to discuss your needs or to ask any questions you may have.
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