During a webinar last year, the TGA announced they were intending to introduce changes to the medicinal cannabis regulations (including supplier assurance requirements for imported medicinal cannabis products). In light of that, a TGA consultation on potential reforms to medicinal cannabis manufacturing, labelling and packaging has just closed.
As a result, there are three key changes of which the medicinal cannabis industry should be aware:
- the introduction of child-resistant packaging
- the requirement of cannabis products to conform with Australian labelling requirements
- Good Manufacturing Practice (GMP) standards for imported medicinal cannabis products (equivalent to those that already apply to goods manufactured domestically).
As far as I’m concerned, S3 CBD is still some way off, thus this blog will focus exclusively on what supplier assurance activities sponsors must perform to ensure their S4/S8 imported medicinal cannabis products comply with GMP requirements.
The complexity of unapproved imported medicinal cannabis products
The majority of medicinal cannabis products on the Australian market are considered unapproved medicines. Typically, medicines in this category do not have to conform with the quality standards required by most therapeutic goods (minimum quality standards in TGO 93 notwithstanding for medicinal cannabis).
While the new GMP requirements for imported medicinal cannabis products are an improvement in my mind, it does place medicinal cannabis products in general into a bit of an awkward position amongst the regulations. In terms of requirements for approved vs unapproved medicines there is a bit of “column A/column B” mixing as highlighted in the table below (please note that some generalisations have been made):
|-||Specs||Unapproved medicines||Approved medicines||Locally manufactured medicinal cannabis||Imported medicinal cannabis|
|Can be accessed outside special access pathways||X||✔||X||X|
|Can be accessed via |
special access pathways
|Needs marketing approval/registration on the ARTG||X||✔||X||X|
|Requires GMP licence (if local) or GMP certificate (if overseas)||X*||✔||✔||X**|
*Caveat – there are exemptions from requiring a licence to manufacture therapeutic goods, but they must comply with GMP. This is the requirement of the ICH Guideline for Good Clinical Practice. Also see PIC/S Annex 13 Manufacture of investigational medicinal products.
**GMP licence or evidence of GMP manufacturing from imported medicinal cannabis suppliers is now required as a part of the latest regulatory changes.
So in this scenario, you have an unapproved medicine (medicinal cannabis) that requires most of the requirements of an approved medicine (GMP licence and supplier assurance activities) but still functions as an unapproved medicine (no product registration + limited access pathway)…you see the contradiction?
This would not be an issue if medicinal cannabis were like any other product (i.e. one that has to go through clinical trials and product registration before being accessed). However, given that both clinical trials and product registration are lengthy processes, I believe the regulators created this special (and complicated) exemption which allows for increased availability of cannabis via special access programs. Any additional risks would then be mitigated by GMP manufacturing and QC testing requirements.
What GMP applies to imported cannabis products?
The requirement to comply with child-resistant packaging and prescription labelling requirements do add a complication to the old medicinal cannabis supply pathway: imported medicinal cannabis product cannot be distributed in Australia unless they are compliant. This may mean that additional manufacturing steps are required to repackage or relabel products to local standards.
Unfortunately, packaging and labelling steps are considered to be GMP manufacturing steps (see the TGA’s Chapter 5, Part I – finished dosage form) so unless you get the original (overseas) manufacturer to perform these activities, sponsors importing medicinal cannabis products may need to get a GMP licence to conduct the remaining repackaging, labelling, and batch release activities.
3 scenarios have been outlined in the table below on the potential pathways for repackaging and labelling imported medicinal cannabis products:
|Scenario||GMP licence||Technical agreement||Supplier assurance||Batch release|
|Supplier conducts repack/label||Supplier requires foreign GMP licence||Required between sponsor and supplier||Sponsor performs on supplier||Conducted by supplier|
|Sponsor conducts repack/label in Australia||Sponsor requires TGA GMP licence (and Poisons licence if not already obtained).||Not required - can be covered by specifications, CofAs, and evidence of supplier assessment||Sponsor performs on supplier||Conducted by sponsor|
|Local third-party contract manufacturer conducts repack/label for sponsor.||Contract manufacturer requires TGA GMP licence (and equivalent Poisons licence).||Required between sponsor and contract manufacturer||Sponsor performs on contract manufacturer||Conducted by contract manufacturer|
Supplier assurance for imported medicinal cannabis products
As indicated in the table above, supplier assurance will be required for imported medicinal cannabis products.
PIC/S GMP does have requirements for supplier assurance (also called vendor assurance or supplier qualification) and companies will be expected to capture this vetting process in a Standard Operating Procedure that outlines how evidence is collected of a supplier’s GMP compliance.
You will also need to conduct ongoing supplier assessments as well as a periodic reassessment of the supplier’s capacities using a risk-based approach. Depending on your specific circumstances, and the number of suppliers you need to qualify, supplier assurance can get a little complicated. As a minimum, you may want to consider obtaining evidence of:
- GMP Licences – Check if your importer’s regulatory body has a mutual recognition agreement with Australia; if they do then the country’s pharmaceutical system is considered comparable to Australia’s. Ask for a copy of your supplier’s local GMP pharmaceutical manufacturing licence.
- Supplier audits – You can either perform this yourself, or ask a third party to conduct a GMP desktop audit (or gap analysis) of the supplier to see whether they are GMP compliant, if their labels are Australia-compliant, or remedial actions are required.
- Quality Agreements – A Quality or Technical Agreement may be used to outline any contracted activities with suppliers or contractors (i.e. repackaging and labelling requirements). This is detailed in PIC/S Chapter 7.
- Testing arrangements – What lab does your supplier use to test the imported products, or is testing going to be covered by a certified Australian lab? Is their lab certified to any standards? Do you have examples of the CofAs? Are those test methods validated? Do they match what is required by TGO 93? (Note: there is no longer a requirement to submit TGO 93 declaration forms, but products are still expected to meet the testing limits.)
- Transport arrangements – Is the product shipped at recommended storage temperatures? Have you done any temperature mapping or validated the transport pathway?
We recommend creating a supplier assessment questionnaire to assist with your information gathering (or just ask PharmOut for help!). The TGA also has a handy process flow on their website of expected supplier assessment activities.
To get started on your supplier assurance journey, why not sign up for one of PharmOut’s e-learning modules?
- Supplier qualification
- Remote Audit Training
- Release for supply
- Good Warehouse Practice
- Good Distribution Practice
If you want to learn more about setting up a supplier assurance program for your imported medicinal cannabis products, or want us to do label and packaging reviews for you against TGO91 or TGO 95, please get in touch with one of our friendly consultants here.
The following pages also have more information: