The globalisation of the supply chain for starting materials and the ever-growing global distribution of manufacturing activities including batch release presents the Qualified Person with a great challenge. Figure 1 contains an example of the product and process flow of a generic medicinal product.
Figure 1 Global product and process flows
Using the diagram, the critical parts of the supply chain can be identified that can easily become the focus during batch certification because of their impact on the quality of the medicinal product.
The greatest problem results from the large number of interfaces with third parties which provide the certifying Qualified Person with proper information about batch certification so that marketing authorisation and GMP/GDP compliance can be guaranteed.
These can include:
The distribution (delegation or outsourcing) of the pharmaceutical responsibilities and activities of the Qualified Person must not only be carried out physically. From the point of view of the certifying Qualified Person, it must also be recorded in writing and, where applicable, contractually agreed. Only then can the actual responsibility be demonstrably and legally handed over.
This applies to:
The required marketing authorisation compliance is related to the following components:
Unauthorised modification of just one of these components compromises compliance with the MA.
The more complex the product and product flow becomes, the greater the challenge for the Qualified Person to ensure MA and GMP/GDP compliance for the entire life cycle of the medicinal product.
This can only be achieved using a seamlessly implemented and functioning change management system. It must cover all of the participating parties and it must be functional at their respective sites.
The potentially different and/or country-specific statutory requirements in the states involved in the supply chain must also be observed. This applies to:
If the supply chain or product leaves the EU, the QP certifying the import can no longer rely on confirmation by a QP in the third country, because he/she must be working in the EU under an EU manufacturing and/or import authorisation.
Language and cultural barriers should not be underestimated. Examples of these might include:
If the PQS elements that are used to minimise the risk of the critical parts of the complex product and process flow are looked at, it is clear that they are almost identical to those that were identified during the process to safeguard the certification requirements and are used by the QP during batch certification.
Government of Upper Bavaria, Munich