Maintenance of Active Pharmaceutical Ingredient (API) and other sites named on marketing authorisations
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Marketing and manufacturing authorisation holders are reminded that as all sites named on approved marketing authorisations (MAs) can be used for the activity they have been registered for without further variation or provision of evidence of Good Manufacturing Practice (GMP) compliance to the MHRA, it is important that all named sites are fully maintained as approved suppliers and thus available for use.
Through its inspection programme, the MHRA has encountered numerous examples of API manufacturing sites that are named on marketing authorisations but are not currently used and not fully maintained as approved suppliers. In some cases such API sites may never have supplied API for marketed product. This can also apply to other sites eg drug product manufacturing, importation or batch release sites.
Therefore in order to clarify MHRA expectations the following guidance is provided:
- All API manufacturing sites named on UK marketing authorisations (product licences) must be actively maintained as approved suppliers (in line with EU GMP expectations).
- The MHRA regards all API manufacturers that are registered on UK marketing authorisations to be approved to supply without further notice and with immediate effect; sites without proven documented GMP compliance status cannot be regarded as an effective back up supply source of starting material.
- As a minimum, and in order to comply with EU directives on the use of GMP compliant APIs, the supplier approval process must be supported by evidence of effective GMP compliance of the API manufacturing site(s). As per European Medicine Agency (EMA) guidance it is expected that this will be confirmed via audit of the API manufacturing site by or on behalf of the relevant manufacturing authorisation holder. Audits should have been conducted at intervals not exceeding three years, by persons with appropriate training and experience, to confirm the current GMP status of the site.
- Any API manufacturer listed on a UK marketing authorisation that has not been maintained as an approved supplier does not meet the EU requirements for starting materials to have been manufactured in compliance with EU GMP requirements.
- The MHRA can inspect API sites named on marketing authorisations at any time where GMP compliance status is unknown or suspected to be deficient. Confirmation of non-compliance can result in regulatory action being taken by the MHRA.
- Companies not wishing to maintain back up API manufacturers to GMP requirements should remove them from marketing authorisations by submission of a Type 1A variation change code A.7.
The MHRA will continue to monitor compliance with this guidance through its inspection programme of MIA holders and as necessary by inspection of marketing authorisation holders.
In addition to reviewing the approval status of API manufacturers named on marketing authorisations, holders are also requested to remove any other sites that are no longer used/maintained eg drug product manufacturing, importation or batch release sites etc by use of a Type 1A variation, change code A.7.