06.12.2016 |

LOGFILE No. 45/2016 – Rework: What has to be observed?

Rework: What has to be observed?

An excerpt from the GMP MANUAL

by Dr. Christian Gausepohl

When is rework necessary?

Rework can be carried out on intermediates, batches or partial quantities for different reasons (see Figure 1), including process errors caused by mechanical defects in the system or by staff. Ambiguity in the documentation can lead to rework if the quality of the manufactured product is not clearly traceable from the documentation. Deviations during in-process controls or release testing can also make additional processing steps necessary. Returned products can require rework in certain situations. For example, products without quality deficits can be repackaged. 

Figure 1 Some reasons for rework

How are quality and safety guaranteed?

Rework is generally looked at from two different points of view:

  • It is carried out to achieve or restore the required product quality. The use, sale and supply of the product needs to be ensured for economic reasons.
  • The possible impact on the quality, effectiveness and safety must be evaluated with regard to the safety of the medicinal product and patient.

During this process, the principles of risk management must always be applied. Potential risks must be identified and assessed, suitable control measures defined, and the results included when a release decision is made.

During rework, risks that often compete with one another must be taken into account:

  • patient safety
  • compliance with the manufacturing authorisation
  • inspection safety
  • manufacturing technologies
  • stability
  • supply readiness
  • economic risk

A comparison between the different requirements and risks can be useful. Figure 2 uses three different situations to show how this might be done.

Figure 2 Examples of individual risk distribution

Any decision affecting the processing steps and measures to be specified must always be agreed with QC (see Figure 3).

Figure 3 Requirements in the EU GMP Guidelines for decisions about rework

Figure 4 shows the basic rework options for different product classes. The factors that need to be taken into account are discussed in the following sections.

Figure 4 Product rework (overview)

What needs to be observed in cases of contract manufacturing?

Specific requirements apply during contract manufacturing. This means that process steps that have not been agreed in advance should not be carried out. This is important for the contract giver, especially with regard to the final batch release. Good practice includes getting the contract giver involved at an early stage, e.g. during deviation management. Decisions about the rework of products can then be made jointly.

The text is an excerpt from the GMP MANUAL.


Dr. Christian Gausepohl

Rottendorf Pharma GmbH, Ennigerloh