GMP Clearance Framework
What is a GMP Clearance?
The manufacture and control of medicinal ingredients and products must conform with the principles of Good Manufacturing Practice (GMP) standards in order to ensure their quality and safety. Compliance by various manufacturers involved in different steps of the process are verified by competent authorities through site inspections and review of manufacturer documentation. Typically, a successful audit leads to a GMP certificate being issued by the inspecting authority.
Since it is impractical and time-consuming for the TGA to carry out site inspections on all overseas manufacturers, an abbreviated process was developed to recognise other authorities’ certifications by means of ‘GMP clearances’ issued to Australian sponsors of the therapeutic goods.
The GMP clearance is specific to the site/location, the stages and steps that it is involved in during manufacture and control, the type and risk classification of the goods, and the sponsor responsible for supply in Australia. The clearance specifies an expiry period and should be maintained to avoid it lapsing.
Who requires it?
All overseas facilities that are identified on the sponsor’s ARTG entries require GMP clearances that cover the specified manufacturing steps, which will depend on the medicine’s risk classification. Whereas manufacturers of the active ingredients in lower risk goods such as complementary and OTC medicines are not specified on the ARTG and do not require a GMP clearance, prescription and biological medicines may include other steps such as specific control testing, cell bank manufacture and storage, etc.
Unlike medical devices where a single legal manufacturer may require manufacturer certification, all of the specified overseas sites require individual clearances.
What are the pathways in obtaining this?
Since foreign competent authorities may have different GMP standards and may apply different requirements for various types of goods, the TGA has several mechanisms for verifying GMP conformance. A GMP clearance can be obtained via:
• a Mutual Recognition Agreement (MRA) desktop assessment
• a Compliance Verification (CV) desktop assessment
• following an on-site inspection by the TGA, clearances can be issued to the requesting sponsors.
The MRA pathway is the simplest, cost and time effective approach for sponsors to obtain GMP clearances. It can be used only if the manufacturing site is located within the borders of an MRA country and inspected within the past 3 years by that country’s competent authority. A list of countries with an MRA arrangement with Australia may be found on https://www.tga.gov.au/international-agreements-and-arrangements-gmp-clearance.
GMP inspections and certifications by other competent authorities, including the US FDA, for other manufacturing sites may be eligible to use the CV pathway, when the manufacturer does not meet the criteria for the MRA pathway. Aside from the competent authority’s inspection, manufacturer documentation may be required to support the clearance. When compared to the MRA pathway, CV requires a longer processing time and is more complex.
The TGA on-site inspection pathway may be used if certification and documentation required for the MRA or CV pathway are not adequate, or if the TGA considers there is significant risk to warrant an inspection. This pathway should be considered as a last resort as it requires the longest processing time, it is costly and more complex.
What happens in a typical global supply chain?
Modern supply chains can be multifaceted with numerous manufacturing sites performing various steps of manufacture of a product. The relevant GMP, quality or technical agreements needs to be established and maintained between sponsors, manufacturers and/or any contracted manufacturing sites.
What are the steps in GMP clearance process?
Step 1 – Understanding your supply chain and establishing agreements
Step 2 – Identifying what manufacturing and control steps need to be listed in the registration record (ARTG) according to the product risk category, and which overseas manufacturing sites are involved in those steps (including alternative sites)
Step 3 – For each manufacturing site, identifying the appropriate GMP clearance pathway
Step 4 – Identifying what documentation is required
Step 5 – Creating your clearance application, which includes defining the scope to cover the registered steps and product category as a minimum
Step 6 – Providing your evidence with the application and paying fees
Step 7 – Application receipt, assessment and decision (by the TGA’s GMP Clearance Unit)
Step 8 – Keeping track of expiry dates
Step 9 – Maintaining your active GMP clearance, including varying the scope to include new products and/or responsibilities of the manufacturing site
TGA recently provided a target processing timeline which has been effective from 1 July 2019:
- MRA applications: 30 working days
- CV – Non-sterile API: 60 working days
- CV – Sterile API: 75 working days
- CV – Non-sterile product: 90 working days
- CV – Sterile product: 120 working days
Approval of the GMP clearance isn’t the end, sponsors have the responsibility for maintaining the currency and accuracy of their GMP clearance(s).
If any manufacturing or control step of your medicine is performed by an overseas site, be sure to reach out directly to discuss how Brandwood CKC can support you in your GMP clearance needs.
Looking to fly south for warmer weather? We have the skills in all aspects of Australian regulatory and reimbursement requirements and can assist you to prepare and file regulatory submissions to TGA. We can also hold Australian licenses on behalf of international manufacturers. Talk to us today about how to leverage international reviews to achieve TGA registration. Contact us for a free, no obligation discussion. Email [email protected] or call us: 1 888-271-5063 (US toll free) ♦ 400-842 7017 (Beijing – toll free) ♦ +61 2 9906 2984 (Sydney)