Sharing Supply-Chain Security - Pharmaceutical Technology

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Sharing Supply-Chain Security
A panel of industry and regulatory experts, including FDA, discuss efforts to secure the global pharmaceutical supply chain. This article contains bonus online-exclusive material.

Pharmaceutical Technology
Volume 33, Issue 11

Susanne Keitel on certification standards and sharing inspection information

Susanne Keitel, PhD
Keitel is director of the European Directorate for the Quality of Medicines and Healthcare (EDQM) of the Council of Europe in Strasbourg, France. EDQM is also responsible for the European Pharmacopoeia (PhEur).

EDQM developed a program to certify suitability of the monographs of PhEur to adequately control the quality of a substance from a specific source (i.e., certification of suitability [CEP]), which has been running since 1994. This procedure provides active substance manufacturers as well as brokers and distributors with the option of filing their quality documentation for the active substance with EDQM for a centralized assessment, rather than filing individual drug master files in different European Union member states or including the information in individual marketing authorization applications.

The focus of the procedure is to ensure that impurities are adequately controlled. Hence, a certificate will often include additional tests and specifications to be conducted for a given active substance from a specific source in addition to the mandatory pharmacopeial tests.

Table I: Legislation and programs targeting the global pharmaceutical supply chain.
In 1997, it was decided that it would be prudent not only to rely on paper assessment, but also to include inspections of manufacturing sites and processes. Based on a mandate from the European Commission, EDQM is now running GMP inspections for APIs—these inspections also assess compliance with the dossier. Inspections are normally conducted by a team of inspectors from EDQM and European national competent authorities. These inspections completely follow EU rules. This means that inspections of API manufacturing sites are not done routinely, but following a risk-based selection of sites according to the triggers identified at a European level and published... on the EMEA website.

EDQM today faces a situation where the vast majority of inspections are conducted outside of Europe, predominantly in India and China, reflecting the global shift in API production. The outcome of the inspections indicates the need for closer surveillance. In 2008, EDQM conducted 28 on-site inspections, leading to 16 certificates (CEPs) being suspended. Between January 209 and June 2009, EDQM performed 17 inspections, leading to 8 certificate suspensions. This means that 35% of the sites covered were found to be non-GMP compliant. It is important to stress that this is not representative of the entire API market. In contrast, it does indicate that the triggers used in the risk-based approach in the selection of inspection sites are the right ones.

In the case of a negative inspection outcome, European competent authorities and the local competent authority of the country where the inspection took place are informed (local inspectorates are routinely invited to participate in any inspection performed in their respective country). The competent authorities then take appropriate action.

Industry qualified importers proposal
As demonstrated by the number of suspended CEPs, there is a clear need for a broader coverage of inspection sites. EDQM therefore welcomes EMEA's pilot project to exchange information on API inspections with the FDA and Australia's Therapeutic Goods Administration. In fact, EDQM participates in this exercise on the European side.... Due to the absence of mutual recognition agreements, it will not be possible to take action based on information received from the partners in this pilot project. However, the information received from the partners will be very useful when applying risk-based selection of sites for inspection. For example, why should a site already covered by a partner and found to be GMP-compliant be high on the priority list of another partner?

Current EU pharmaceutical legislation requires the qualified person (QP) of the holder of the manufacturing authorization certify that all API used in the product has been manufactured according to GMP.

This has to be certified in every single marketing authorization application or subsequent variation. Based on the outcome of inspections carried out in the framework of EDQM's certification scheme, I have the impression that not all QPs really take their responsibility serious enough to ensure an audit—else it would be difficult to explain why we still see so many deficiencies. The planned revision of the pharmaceutical legislation, the EU Pharmaceutical Package, is [expected] to explicitly require the performance of audits. The draft legislation requires that any contracted auditor be accredited by the national competent authority of a member state. Hence, the draft legislation foresees more stringent requirements for the future. Based on our experience in conducting inspections of API manufacturing site, we consider this a move into the right direction.


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