This information relates to the blog post - Overview of compliance management escalation processes used by the GMP Inspectorate
Dates of inspection:
Post inspection consideration of regulatory action – UK MIA, MIA(IMP) and overseas manufacturers
The inspection conducted at the above named facility has identified potentially critical GMP / GDP deficiencies. Following independent review by a senior or expert inspector, the final classification of the deficiencies will be confirmed in writing within 14 days. You will have a further 14 days from the date of receipt to respond with your proposals for corrective action.
The deficiencies may provide grounds for the Licensing Authority to require the issuance of a Statement of Serious Non-Compliance with GMP.
For sites located in the UK there may also be grounds for action under regulation 23 of the Human Medicines Regulations 2012 (as amended) for refusal to grant a manufacturing or import authorisation application, or under regulation 26 to take formal action against an existing manufacturing or import authorisation.
It is normal practice for a licence holder or applicant to be given the opportunity to respond to the reported GMP / GDP deficiencies prior to taking regulatory action against the licence, unless it is considered necessary to suspend a licence with immediate effect in the interests of safety. The implications of regulatory action are as follows:
- The issuance of a Statement of Serious Non-compliance with GMP will prevent batch certification and release to market of medicinal products from the date of publication, unless otherwise indicated. Any previous GMP certificates will be withdrawn. The Statement of Serious Non-compliance with GMP will also be publicly visible on the EudraGMDP website (http://eudragmdp.ema.europa.eu/). Any batches manufactured between the date of publication of the document and any subsequent return to GMP compliance (confirmed following re-inspection) will not be considered suitable for batch certification or release.
- For sites located in the UK: Action against your manufacturing licence or authorisation (either suspension in full or variation to remove specified activities, facilities or sites) will be preceded by a notice period of at least 28 days, unless the Licensing Authority considers that immediate action is required to protect public health. It is a criminal offence under regulation 34(1) of the Human Medicines Regulations to manufacture or distribute medicinal products without the required licence.
- For sites located in the UK: Action to remove named persons from a manufacturing authorisation (e.g. Qualified Persons). A Qualified Person removed from a manufacturing authorisation would not be permitted to certify medicinal products manufactured under that authorisation. Furthermore, unless there are other persons already named on the manufacturing authorisation as responsible for the relevant role, the licence holder will also have to submit a variation to propose a replacement in order to maintain a valid authorisation.
Regulatory action may also lead to recommendations to the Licensing Division to consider action against relevant marketing authorisations or clinical trial applications. No new applications (MA or CTA) naming the site will be approved.
There are opportunities for the licence holder to submit representations in response to a notice of proposed regulatory action, which will be outlined in correspondence from the Licensing Authority if such action is proposed. This is in addition to the post inspection responses to address the identified deficiencies.
The above actions are not a permanent barrier to manufacturing or distribution activity, and regulatory restrictions will be lifted if the manufacturer / licence holder is able to demonstrate (usually upon re-inspection) the effective implementation of corrective actions which address the identified GMP deficiencies.
Any action taken will consider the potential impact to supply chain for products considered medically critical (products for which there is no available therapeutic alternative, as agreed by the national competent authority). Any restricted regulatory actions taken in the interests of maintaining the supply of medically critical products will be notified to you by the Licensing Authority as subsequent correspondence.
The regulatory action process is administered on behalf of the Licensing Authority by the Inspection Action Group (IAG). This multidisciplinary group meets regularly, usually fortnightly, to deal with ongoing business and to consider new referrals. Ad hoc meetings may be called by the Chairman for urgent cases. You may wish to provide an interim response to the IAG for discussion at their next meeting, prior to submitting your formal response to the written inspection deficiency notice. The date of the next meeting can be obtained from your inspector.
It is very important for the company to maintain open communication channels with the IAG throughout the process, and notify any significant changes in GMP compliance (positive or negative), including delays in implementing corrective action commitments, in a timely manner. Contact details will be provided in the initial correspondence from IAG to the company.