17/18 April 2024
"The ultimate responsibility for the performance of a medicinal product over its lifetime, its safety, quality and efficacy, lies with the marketing authorisation holder (MAH). However, the QP is responsible for ensuring that each individual batch has been manufactured and checked in compliance with laws in force in the Member State where certification takes place, in accordance with the requirements of the marketing authorisation (MA) and with Good Manufacturing Practice (GMP)." This is how it is described in Annex 16 of EU-GMP Guidelines (Certification by a Qualified Person and Batch Release). The Annex also describes in detail a QP's other responsibilities and activities in part 1.7., which may be delegated to key personnel and how the QP can rely on these activities and the Pharmaceutical Quality System.
But sometimes it is still not clear, where tasks and responsibilities of the QP end - and where not. There is no sharp cut. This also became obvious during a very interesting talk at the last QP Forum of the European QP Association on 01/02 December 2016 in Madrid. Discussing the manifold activities the QP is involved in should not indicate the QP is responsible for everything. But the QP should have a clear vision of what level of information and involvement is necessary to do the job.
In his talk on "Detection of Falsified Medicines and how the QP can support this", Paul Hargreaves from the U.K. Medicines and Healthcare Products Regulatory Agency (MHRA), explored some facts that a QP should know when it comes to the falsification of medicines. He started his talk with a provoking question. When a QP sees that the Sales Department is celebrating a number of large export orders, "What do you do? Celebrate with them? Or begin an investigation?" Maybe the QP finds out that the exports go to countries with no effective Drug Regulatory Authority. And the sales terms and conditions are "Ex Works". Should the QP begin "to get a bit worried now?" According to Paul Hargreaves' opinion the answer is yes. But should the QP really be worried about where the goods are going to? The QP certified the batch and everything was in specification. So why worry? Paul Hargreaves clearly pointed out that "when investigating falsified medicines, it is worrying that some QPs do not have a full and detailed knowledge of their own supply chain for imports and/or exports." And he presented some details of the supply chain, a QP should know and understand, as the QP plays an important role in this supply chain. "Transport, shipping, handling and customs documentation may provide the key evidence not only of criminal offences but also identify most of the key players involved in the falsification", he said.
Here are some examples of terms and documents a QP should be aware of:
Incoterms: The Incoterms rules are a series of pre-defined commercial terms published by the International Chamber of Commerce (ICC). They are widely used in International commercial transactions or procurement processes including medicinal products and APIs. There are eleven terms in place defining tasks, costs, and risks associated with the transportation and delivery of goods. But they are silent on title of goods.
CMR (Convention on the Contract for the International Carriage of Goods by Road aka International Consignment Note): The CMR will usually provide information as to which member state (MS) the medicines were delivered to. This information is usually found in the warehouse office.
SAD (Single Administrative Document) C88 and C99: The C88 can provide some useful cross-checks and contains many interesting information that can begin to reveal the true provenance of the falsified medicines (by indicating which countries medicines have originated from and transited through).
EORI number (Economic Operator Registration and Identification Scheme): Any economic operator established in the EU needs to have an EORI number. Economic operators established outside the EU have to be assigned an EORI number if they lodge a customs declaration, an Entry or an Exit Summary Declaration. The number is basically used for tracking imports and exports within the EU.
As a conclusion to this talk, one could say that the QP should know and understand these terms. These and numerous other sources of information necessitate that the QPs have to have at least a working knowledge of the whole supply chain in order to carry out their legal duties for batch release and Product Quality Review. And being a QP was never an easy option, was it? The days of a QP being expected to sit in and checking batch records and signing documentation are gone; communication with involved stakeholders on time is essential.