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On 13 August 2014, the European Commission published revised version of Chapter 8: Complaints, Quality Defects and Product Recalls of the EU GMP Guide. The new chapter will become effective on 1 March 2015.

Extensive changes have been made to this chapter and in practice, it has been revised completely.

The principle: “In order to protect public and animal health, a system and appropriate procedures should be in place to record, assess, investigate and review complaints including potential quality defects, and if necessary, to effectively and promptly recall medicinal products for human or veterinary use and investigational medicinal products from the distribution network. (…)”.

Revised version of Chapter 8 introduces Quality Risk Management principles to the investigation and assessment of quality defects and to the decision-making process in relation to product recalls corrective and preventative actions and other risk-reducing actions.

In addition, revised version is defining expectations for:

  • Personnel and Organisation,
  • Procedures for handling and investigating complaints including possible quality defects,
  • Investigation and Decision-making,
  • Root Cause Analysis and Corrective and Preventative Actions,
  • Product Recalls and other potential risk-reducing actions.

Personnel and Organisation

In the sphere of Personnel and Organisation appropriately trained and experienced personnel should be in place for managing complaint and quality defect investigations and for deciding the measures to be taken to manage any potential risk(s) presented by those issues, including recalls. The use of inter-disciplinary teams should be considered.

“Sufficient trained personnel and resources should be made available for the handling, assessment, investigation and review of complaints and quality defects and for implementing any risk-reducing actions. Sufficient trained personnel and resources should also be available for the management of interactions with competent authorities.”

The Qualified Person involved in the certification for release of the concerned batch or batches should be made formally aware of any investigations, any risk-reducing actions and any recall operations, in a timely manner.

Procedures for handling and investigating complaints including possible quality defects

This part of new Chapter 8 states that: “(…) All complaints should be documented and assessed to establish if they represent a potential quality defect or other issue. Special attention should be given to establishing whether a complaint or suspected quality defect relates to falsification. (…)”.

In case, when a quality defect investigation is initiated, procedures should be in place to address at least the following:

  1. The description of the reported quality defect.
  2. The determination of the extent of the quality defect. The checking or testing of reference and/or retention samples should be considered as part of this, and in certain cases, a review of the batch production record, the batch certification record and the batch distribution records (especially for temperature-sensitive products) should be performed.
  3. The need to request a sample, or the return, of the defective product from the complainant and, where a sample is provided, the need for an appropriate evaluation to be carried out.
  4. The assessment of the risk(s) posed by the quality defect, based on the severity and extent of the quality defect.
  5. The decision-making process that is to be used concerning the potential need for risk-reducing actions to be taken in the distribution network, such as batch or product recalls, or other actions.
  6. The assessment of the impact that any recall action may have on the availability of the medicinal product to patients/animals in any affected market, and the need to notify the relevant authorities of such impact.
  7. The internal and external communications that should be made in relation to a quality defect and its investigation.
  8. The identification of the potential root cause(s) of the quality defect.
  9. The need for appropriate Corrective and Preventative Actions (CAPAs) to be identified and implemented for the issue, and for the assessment of the effectiveness of those CAPAs.

Investigation and Decision-making

This part of revised chapter clarifies applying of Quality Risk Management principles in order to support decisions regarding the degree of investigation and action taken in relation to the validity and extent of all reported quality defects. “The decisions that are made during and following quality defect investigations should reflect the level of risk that is presented by the quality defect as well as the seriousness of any non-compliance with respect to the requirements of the marketing authorisation/product specification file or GMP. (…)”.

The requirements reflecting the reporting of quality defects to the Competent Authorities are also clarified and better aligned with the wording of Directive 2003/94/EC. “Quality defects should be reported in a timely manner by the manufacturer to the marketing authorisation holder/sponsor and all concerned Competent Authorities in cases where the quality defect may result in the recall of the product or in an abnormal restriction in the supply of the product.”

Root Cause Analysis and Corrective and Preventative Actions

This part of the Chapter 8 constitutes of four sections and includes requirements of applying an appropriate level of root cause analysis during the investigation of quality defects. Besides that, in response to a quality defect appropriate CAPAs should be identified and taken, and effectiveness of such actions should be monitored and assessed.

Product Recalls and other potential risk-reducing actions

The last part of revised document requires of establishing written procedures in order to undertake any recall activity or implement any other risk-reducing actions.

This part also addresses using of Quality Risk Management principles into the recall decision-making process, and in addition to recalls indicates other potential risk-reducing actions that may be considered in order to manage the risk presented by quality defects (e.g. the issuance of cautionary communications to healthcare professionals).

The mock-recall actions are also described in more detail in revised chapter. The evaluations of the effectiveness of the arrangements in place for recalls should be extended to both within office-hour situations as well as out-of-office hour situations, consideration should be given as to whether mock-recall actions should be performed. This evaluation should be documented and justified.

There is important obligation of marketing authorisation holder/sponsor to inform in advance all concerned competent Authorities in cases where products are intended to be recalled. “It should also be considered whether the proposed recall action may affect different markets in different ways, and if this is the case, appropriate market-specific risk-reducing actions should be developed and discussed with the concerned competent Authorities. Taking account of its therapeutic use the risk of shortage of a medicinal product which has no authorised alternative should be considered before deciding on a risk-reducing action such as a recall. (…)”.