Unlicensed Cannabis-Based Products for Medicinal (CBPM) Use – Latest MHRA guidance on the process for approving Manufacturing Authorisations / API Registrations – On the 16th of November 2022 the Medicines and Healthcare products Regulatory Agency (MHRA) released a blog with guidance on the process for approving Manufacturing Authorisations/ API Registrations in relation to unlicensed Cannabis-Based Products for Medicinal (CBPM) use.
An authorisation by the MHRA and Home Office (HO) is required for any companies wishing to manufacture CBPMs or Active Pharmaceutical Ingredients (APIs). If companies wish to cultivate, produce, supply, and possess cannabis they will require a Controlled Drug (CD) licence issued following a successful inspection carried out by the UK HO to ensure the security of controlled substances. To manufacture CBPMs and API an MHRA issued Manufacturing licence/ API registration is required, this will only be granted following a successful inspection by the MHRA.
Sites with an existing MHRA manufacturing licence/ API registration the Pharmaceutical Quality Management System will have already been inspected by the MHRA. If company wishes to handle cannabis-based materials the HO may be able to process the application for a new/ revised CD licence or the process described below may need to be followed depending on how activities differ to those already authorised. Submission of variation to the site licence may trigger an MHRA inspection, assessed on a case-by-case basis. Activities detailed on companies Manufacturing Authorisation/ API registration may need to be amended depending on the type of cannabis-based products to be handled.
Previously companies who applied to manufacture and hands CDs usually had existing MHRA licences to cover the scope of their manufacturing activities and could thus apply for the HO Licence to handle CDs. This has however change in recent years and there is an increasing number of companies who require authorisation by both the MHRA and the HO. This created difficulty as the necessary process validation and performance qualification activities required for the MHRA cannot be completed without handling CDs and a HO licence is required to handle CDs but prior to issuing a CD licence, the HO need assurance that companies are able to meet the requirements of the MHRA. This challenge has been reviewed by both government departments and the below outlines the approach required for companies who do not possess necessary authorisations from both the MHRA and HO.
Firstly, the site will need to apply to the MHRA for the appropriate licence or registration. Prior to application the site must be inspection ready and have the following in place:
- a pharmaceutical Quality Management System (QMS)
- suitable and qualified facility with all required equipment installed and at minimum Operationally Qualified
- appropriate staff to meet EU GMP requirements
Second, the MHRA will carry out a remote (Desk-Based) Inspection in which they will assess the QMS, Standard Operating Procedures (SOPs), Basic facility design, and Equipment. If the inspection is successful, this will be communicated to the HO however no GMP/GDP certificate will be issued at this time.
The site must then apply to the HO for their CD licence. The HO will only consider this following a successful MHRA remote (Desk-Based) inspection. The HO will then carry out an on-site inspection to assess the facilities and procedures suitability for handling cannabis-based materials. If the HO confirms acceptability, they will issue a CD Licence.
The site can complete the outstanding validation, process and analytical, once the HO Licence has been issued and the site is able to handle cannabis material. Once validation has been completed and reported, the site will provide confirmation that all activities are completed and advise the MHRA that they are inspection ready.
The MHRA will then carry out their on-site inspection in which they will review validation and other aspects which were not covered in the Remote (Desk-Top) Audit. On completion of a successful on-site inspection the MHRA will issue the appropriate authorisations and GMP/GDP certificates. If the inspection is unsuccessful the HO will be notified.
Medicines can only be supplied once the appropriate authorisations/ licences have been granted by both the MHRA and the HO.
If a company is a new virtual importation site and does not directly physically handle cannabis-based materials, by utilising a physical importation site that already hold appropriate MHRA and HO licences, a Home Office CD licence may still be required for the virtual importation site as well as an authorisation from MHRA.
The regulatory framework is based on the product not the process it is therefore important to understand where you, your activities, and your product fit in the supply chain in relation to the finished medicine that the patient will receive.
For more information and guidance please follow the links below:
- https://mhrainspectorate.blog.gov.uk/2022/11/16/mhra-process-for-approving-manufacturing-authorisations-or-api-registrations-in-relation-to-unlicensed-cannabis-based-products-for-medicinal-use/
- https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/869284/Cannabis_Guidance__unlicensed_CBPMs__updated_2020.pdf
