European Medicines Agency Proposes Pilot Program To Rationalize International GMP Inspection Activities

Main Category: Regulatory Affairs / Drug Approvals
Article Date: 08 Sep 2008 - 0:00 PDT

email to a friend   printer friendly   view / write opinions   rate article

As part of its collaboration with international medicines regulators on goods manufacturing practice (GMP) inspections, the European Medicines Agency (EMEA) has coordinated a group of participating regulators (EU Member States, the US Food and Drug Agency (FDA) and the Australian Therapeutic Goods Administration) and has published a proposal for coordinating inspection plans between them to avoid duplicating inspection work. The outline of the pilot project was drafted on 6 November 2007 and was published on the EMEA website on 22 July 2008.

The majority of international regulatory authorities are obliged by law to have systems in place to verify the GMP status of medicinal product manufacturers whose products are marketed on their territory. Most "developed" regulatory authorities ensure that such manufacturers on their territory are subject to routine GMP inspection. However, different approaches are taken to supervising the manufacture of medicinal products outside a national territory, and to supervising and inspecting active pharmaceutical ingredients. A number of countries have mutual recognition agreements (MRAs) or memoranda of understandings (MOUs) with other countries, which allow them to rely on results from inspections performed by other countries. However these MRAs or MOUs are often limited in scope, and subject to restrictions. A large number of other international collaboration activities are also in place, e.g. ICH, the WHO prequalification scheme, specific bilateral arrangements between countries, co-operation with EDQM etc.

Since the adoption of ICH guidelines on Quality Risk Management in 2005, applying risk-based approaches to the planning of inspections has grown more important and there is increasing interest in additional international collaboration. Recently, discussions between the EU and the US have focused on simplifying administration between the regions, and discussions at the FDA international summit in November 2006 highlighted co-operation on inspections as a priority.

In May 2007, EMEA launched the first phase of its EudraGMP database, which in further releases will make accessible certain GMP information on inspections performed by all EEA member states, as well as information from its MRA partners and other international partners. A further release of this database includes a module for sharing inspection plans.

The European industry associations have also raised the issue of international duplication of inspection and associated resources on a number of occasions. According to industry sources, the EU, US, FDA, and Brazil are the most active regulators inspecting in developing countries.

The objective of the paper is to outline a proposal for more coordinated international planning of inspections, taking into account risk-based approaches, building on equivalent GMP standards and mutual confidence between international regulators.

As an initial effort to improve international information sharing and to facilitate more risk-based approaches to planning inspections, it is proposed that a small group of interested regulators establish a pilot program to coordinate inspection planning. This is based on the system currently operating in the EU in which the EMEA outlines a yearly plan for centralized inspections and invites all Member States to contribute to this based on their own inspection plans. Each regulator reserves the right to perform their own dedicated inspection, should they consider this necessary.

The basic idea is as follows:

Each regulator identifies a contact point specifically for planning inspections. Regulators outline their preliminary inspection plans for the next 6-12 months. They provide this information to all other regulators involved in the pilot. A template for this information may be agreed. After reviewing each other's plans, they identify:

- If they have previously inspected the site

- If they plan to inspect the site within the same period

- If they have an interest in the site for some other reason (e.g. other products on the market or that are used in clinical trials in the territory concerned)

- If they have no interest.

They communicate this information to the other regulators involved by way of a form.

Based on the information received and the common areas of interest identified, the regulatory contact points set up a teleconference to discuss further sites of interest.

The object of this teleconference is as follows:

1. To investigate whether one party's investigation would cover the interest of the other parties

2. To ascertain if a joint or coordinated inspection could be organized

3. To see if one of the inspectorates could do the inspection and provide the outcomes to the other interested parties.

As part of the pilot phase it is proposed to restrict this exercise to inspections of active pharmaceutical ingredients, as most authorities already take a risk-based approach to these inspections and there are less legal complications in taking results of other regulators into account.

Collaboration with the inspectorate of the country where the inspection will take place should also be assured.

If initial information sharing is restricted to basic information, it is anticipated that no commercially confidential information will be involved and therefore no concerns are expected.

If an interest is identified between two or more regulators, each party signs a confidentiality agreement with respect to discussions concerning that site. Although not legally necessary, the company will be asked to sign an agreement allowing information to be shared between the parties concerned.

The pilot phase should last a year, after which the outcomes should be analysed and future action recommended.

Following a successful pilot phase, the following could be considered:

- Extension to a wider group of regulators
- Extension to additional types of pharmaceuticals
- Extension to other types of inspection (e.g. GCP, pharmacovigilance)
- Communication of information from regional databases
- Definition of common risk-based criteria and conventions for "lead" inspectorates.

European Society for Medical Oncology