16.05.2017 |

LOGFILE No. 19/2017 – Complex Product and Process Flows

A Challenge: Complex Product and Process Flows

An excerpt from the GMP Compliance Adviser (formerly GMP MANUAL), Chapter 14.J.8 and 14.J.8.1

3 min. reading time

by Rainer Gnibl

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.

Critical parts of the complex product and process flow

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:

  • suppliers (of active ingredients, excipients, packaging materials)
  • active ingredient distributors
  • printers (of packaging materials)
  • contract manufacturers
  • external test sites
  • technical service providers
  • external storage facilities
  • distribution logistics companies
  • transport companies
  • contract auditors
  • external marketing authorisation

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:

  • internal distribution (within an MIA or production site)
  • external distribution (different MIAs or production sites)

The required marketing authorisation compliance is related to the following components:

  • participants in the supply chain (suppliers, contract manufacturers, test operations)
  • starting substances and materials
  • manufacturing process and analytical testing

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:

  • import regulations
  • export regulations
  • mutual agreements
  • authorisation/registration requirements
  • reporting requirements for responsible personnel
  • official responsibilities

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:

  • translation errors
  • differences between bilingual documents
  • incorrectly interpreted abbreviations
  • legibility of hand-written documents
  • misunderstanding during oral communication
  • internal terminology
  • differences in the error culture

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.

This text is an excerpt from the GMP Compliance Adviser (formerly GMP MANUAL), Chapter 14.J.8 and 14.J.8.1


Rainer Gnibl
Government of Upper Bavaria, Munich