Opinion: Implications of the US-EU mutual recognition agreement to CMOs

Mark TePaske, senior director at Cambrex, outlines some of the potential implications for contract manufacturing organisations under the MRA to be effective by mid-2019

The US Food and Drug Administration (FDA) announced last years that it will recognise eight European drug regulation authorities — those of Austria, Croatia, France, Italy, Malta, Spain, Sweden and the UK — as being capable of conducting pharmaceutical manufacturing facility inspections that meet their requirements.

As a contract manufacturing organisation (CMO) with facilities in both the US and Europe, and serving a global market, Cambrex will be just one of those companies affected by the plans for mutual recognition. Mark TePaske, Cambrex's senior director of global regulatory affairs, quality and compliance, outlines some of the potential implications for such organisations.

The FDA’s announcement is an important development in the implementation phase of the amended Pharmaceutical Annex to the 1998 US-EU Mutual Recognition Agreement (MRA). This new reciprocal arrangement enables both EU and US regulators to use each other’s cGMP inspections of pharmaceutical manufacturing facilities, avoiding replication.

In June 2007, the EU had announced that it had found the US inspectorate to be capable, and four months later the FDA said that eight EU inspectorates had been determined to be capable – “capable” in this instance meaning that the inspectorate can effectively ensure public safety. FDA is now scheduled to complete its assessment of all 28 EU inspectorates by mid-2019, with the programme expected to be expanded as evaluations are completed.

The latest amendment to the MRA covers both surveillance and preapproval inspections, but is initially expected to be used for surveillance inspections only. FDA has stated that because of the special requirements of preapproval deadlines, such as unique application deadlines and a specialised focus on the product, it will not always be possible for FDA to rely on an inspectorate within the EU to conduct Prior Approval Inspections (PAIs). With time, the MRA may also prove to be reliable and efficient for PAIs.

Common goals and expectations

The decisions taken by the EU and FDA in 2017 were informed and intentional, and the latest phase of the MRA was accomplished through a co-operative process to establish common goals and expectations, a co-ordination of efforts, effective communication, mutual respect and commitment.

The MRA is applicable for facilities in the US and the EU, whereby EU authorities will inspect facilities in their own countries; similarly, FDA will inspect facilities within the US. The EU and the FDA have agreed to recognise each other’s inspections and can choose to forego conducting their own inspections in the other’s countries. Both FDA and the EU have reserved the right to inspect facilities in each other’s countries at any time.

Cambrex is a manufacturing organisation with facilities in Italy, Sweden and the United States; in May 2017, the company hosted simultaneous inspections by FDA and L’Agenzia Italiana del Farmaco. This new mutual recognition is expected to reduce the number and/or frequency of health authority inspections performed at Cambrex’s sites to obtain the same number of regulatory approvals.

The EU and US API cGMP regulations have been harmonised for many years now, and each of the Cambrex manufacturing sites has been required to satisfy the same regulations.

Regardless of where they are undertaken, inspections are performed to verify the suitability of facilities and equipment, with verification also undertaken to ensure that facilities are adequately staffed with knowledgeable and well-trained personnel who are following procedures that control all operations that may affect the quality of drugs to ensure patient safety. All of this must be properly documented and the raw data must be readily available for review during the inspection. Data must be collected, analysed, reported and retained in a manner that is accurate, truthful and completely and accurately represents what actually occurred.

A site needs to operate in a state of audit readiness at all times, but every inspection is time-consuming and exhausting, and involves a large number of site personnel. Harmonising the inspection process should ensure that patient safety is not compromised, while increasing the efficiency of the process for both regulators and manufacturers.

Editor's note: This is a version of the article originally appeared on our sister title Manufacturing Chemist.

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