12.07.2016 |

LOGFILE No. 27/2016 – Quality Management System - What should it cover?

What typical situations must be controlled by a quality management system?

An excerpt from GMP Fundamentals

by Dr. Christine Oechslein

A quality management system should cover all of the processes and events that take place in the company on a day-to-day basis, from everyday routine processes to instructions in special cases. The scope of a QMS depends mainly on the number of different products and tasks that a company has to deal with.

A pharmaceutical quality management manual should cover the following topics and include SOPs, policies, master plans or other process instructions that describe the work processes and responsibilities in detail:

  • qualification of employees
  • document control: creation and approval of specifications, work instructions and batch documentation
  • qualification of buildings, facilities, machines, personnel and suppliers/service providers
  • zone concept and hygiene plan
  • process validation
  • storage and distribution
  • quality control and marketing authorisation
  • self-inspection and auditing
  • certain cornerstone principles of quality

Management responsibility

GMP does not only affect the employees in production, quality assurance and the laboratory. The top management (the executive board) is responsible for implementing and maintaining a functional quality management system and has to ensure that sufficient personnel, materials and resources are available to eliminate possible quality risks for the medicinal products (management responsibility). For this reason, the top management has to receive information on the quality of the manufactured products (product quality reviews, PQR) on a regular basis and implement any measures that are required (management review).

Outsourcing (contracting third parties)

The increasing cost pressures in health care are forcing companies to source input materials (active ingredients, excipients, packaging materials) from the least expensive suppliers. For the same reason parts of the work process are outsourced to contractors – sometimes even to low-wage countries. These contractors often sub-contract the work without informing the contract giver.

Out of sight, out of mind: When several companies are involved in a process, they often "blindly" rely on each other and forget to communicate quality-related requirements. In recent years, serious incidents have occurred again and again because important information was not shared between the contractual partners due to a lack of communication.

To minimise these risks to the patient, the legislator specifies the following: the marketing authorization holder (whose name is printed on the packaging of the medicinal product) bears the overall responsibility for the GMP activities that are outsourced to external contractors. This does not only apply to manufacturing or packaging processes and quality reviews, but to every outsourced activity.

Outsourcing refers to all activities involving any contract acceptor. For example:

  • suppliers of active ingredients, excipients and packaging materials
  • service providers in the areas of cleaning (including clean room clothing), maintenance and repair, calibration, qualification, installation of systems, IT service, training and consulting
  • contract manufacturers who carry out single manufacturing, packaging or sterilisation steps or the complete manufacturing process of the medicinal product. Contract manufacturers must have a manufacturing authorisation and are inspected by the authorities, even if they don't market medicinal products under their own names.
  • contract laboratories that carry out outsourced chemical, physical or microbiological tests, e.g. clean room monitoring
  • logistics service providers who store or transport medicinal products or starting materials for pharmaceutical companies

Before the task is outsourced, the contract giver must ensure that the contract acceptor is in a position to carry out the respective task, i.e. that the contract acceptor has the required expertise and experience and is aware of the regulatory requirements that apply (qualification of the contract acceptor). Depending on the impact that the outsourced activities have on the quality of the product, the suitability of the contract acceptor may be checked in different ways, e.g. by evaluating information provided by the contract acceptor, audit reports and failure statistics or even by carrying out comparison analyses, audits or outsourced audits.

If complex analyses or manufacturing steps are outsourced, there is a particularly high risk that these activities will not be carried out in exactly the same wayas before they were outsourced. For this reason, it is mandatory that the handover of the methods to be used and all other relevant information are documented in detail and that the successful handover is confirmed by both parties (technology transfer).

In addition, the responsibilities of the contract acceptors and the contract givers must be contractually defined and agreed (liability limitation agreement). In the case of contract manufacturing, it must be defined in writing whether the Qualified Person of the contract manufacturer is responsible for the market release of the finished product, or whether this task remains with the contract giver.

The contract acceptor is obliged to carry out the activities exactly as agreed in the contracts and specifications. Changes may only be carried out after consent has been obtained from the contract giver (change control).

The contract giver bears the ultimate responsibility for tasks outsourced to third parties.


Dr. Christine Oechslein
GMP Instructor, Germany

This text is an excerpt from our brand new hand book GMP Fundamentals


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