Complaints and Recalls: new EU-GMP Chapter 8 published

GMP News: Complaints and Recalls: new EU-GMP Chapter 8 published,Z-QAMPP_n.html

the European Commission has published the final Chapter 8 of the EU Guidelines for GMP (Complaints, Quality Defects and Product Recalls). The chapter has been revised completely. Whereas the current one has less than two pages focusing on complaints and recalls only, the revision is six pages long, 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

Throughout its chapters, the new version of Chapter 8 introduces Quality Risk Management principles and appropriate root cause analysis work when investigating quality defects and complaints. The scope includes complaints including quality defects (this is also new) and recall issues with respect to marketed medicinal products and investigational medicinal products (IMPs) that have been released to clinical trials. The new chapter 8 is better aligned with the wording of Directive 2003/94/EC with regard to when a quality defect/complaint should be reported to the competent authority.

Besides investigating and determining the cause(s) of quality defects/complaints, the revised chapter 8 also wants to ensure that appropriate corrective and preventative actions are put in place to avoid recurrence of the issue. CAPA has already been introduced in the revision of chapter 1 and is now also be recognised in chapter 8. The effectiveness “should be monitored and assessed”.

When it comes to product recalls, the new chapter also addresses risk mitigation and risk-based thinking into the recall decision-making process. In this context, the Manufacturer and Marketing Authorisation Holder shall ensure continuity of supply for critical medicinal products where alternative products may not be readily available. Consultation with the Competent Authority is inevitable.

The Qualified Person (QP) who is involved in the certification for release of the concerned product will play an important role. If the QP is not directly responsible for managing complaint and quality defect investigations and for deciding the measures to be taken, he or she “should be made formally aware of any investigations, any risk-reducing actions and any recall operations, in a timely manner”. For all respective actions like for example handling, reviewing and investigating complaints, sufficient personnel and resources should be made available.

The revised chapter details the requirements for written procedures like SOPs. They should at least address the following:

  • The description of the reported quality defect.
  • The determination of the extent of the quality defect.
  • Handling of samples
  • The assessment of the risk(s) posed by the quality defect.
  • How decisions and assessments are made
  • Notification to the relevant authorities and other internal and external communications
  • Root cause analysis and CAPAs.

There should also be established written procedures in relation to recall activities or the implementation of any other risk-reducing actions, so that recall operations can be initiated promptly and at any time.

So called Mock Recalls are now also described in more detail. Evaluations of the effectiveness “should extend to both within office-hour situations as well as out-of-office hour situations and, when performing such evaluations, consideration should be given as to whether mock-recall actions should be performed. This evaluation should be documented and justified. ”

Overall, the goal is to achieve information-based and scientific decisions in relation to risk-mitigating actions. It should also be highlighted that there may be more than one cause associated with a quality defect/complaint. However all likely causes should be thoroughly investigated leading to more effective preventative actions being identified and put in place.

To find more details please see the final Chapter 8: Complaints, Quality Defects and Product Recalls.

If a Facility stores Medicinal Products for more than 36 Hours GDP will apply

GMP News: If a Facility stores Medicinal Products for more than 36 Hours GDP will apply,S-GDP_n.html

Since the EU Good Distribution Practice (GDP) Guide has been revised, a number of questions regarding its interpretation have been raised. One of these questions relates to storage facilities and so called distribution hubs. In the past, many facilities which have been involved in the supply chain were not managed under GDP and didn’t posses a licence for their activities.

The British Medicines Authority MHRA published a press release on 18 August 2014 to explain what they consider to be a facility which must be licensed and which needs to implement the GDP requirements. According to the MHRA: “The GDP Inspectorate is raising awareness of the impact of the new regulations to those parties that are either directly or indirectly affected and any freight consolidator or freight forwarder either in the air, sea or road transport sector that is either holding ambient medicinal products on site for more than 36 hours or has cold room facilities will require a Wholesale Distribution Authorisation WDA(H) in order to comply with the Human Medicines Regulations 2012 [SI 2012/1916] (as amended) and with the Falsified Medicines Directive 2011/62/EU.”

Source: MHRA Press Release: MHRA position on freight consolidation depots (freight forwarders)

FDA publishes ICH Q4B – Annex 6 on Uniformity of Dosage Units

GMP News: FDA publishes ICH Q4B – Annex 6 on Uniformity of Dosage Units—Annex-6-on-Uniformity-of-Dosage-Units_8438,8571,Z-QCM_n.html

On 16 June 2014, the FDA published the ICH harmonised Guideline entitled “Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions on Uniformity of Dosage Units General Chapter (Q4B Annex 6)”. This ICH Guideline thus came into force in the USA, too.

The objective of the ICH Q4B Working Group is to reach mutual recognition by regulatory authorities in the ICH regions for all testing methods listed in the ICH Q6A Guideline on Specifications. Through this, comparable testing laid down in the different pharmacopeias shouldn’t be performed separately when it has been assessed by the authorities that those are similar and interchangeable.

The Annex 6 states that the following official texts :

  • Ph.Eur. 2.9.40 (Uniformity of Dosage Units
  • JP 6.02 Uniformity of Dosage Units
  • USP General Chapter <905> Uniformity of Dosage Units

can be used as interchangeable. Nevertheless, certain restrictions listed under the section “Analytical Procedures” have to be considered.

To get more details please see the complete FDA “Q4B – Annex 6 Uniformity of Dosage Units General Chapter“.

PS: At the QbD/PAT Conference from the University of Heidelberg from 15-16 October 2014, Dr Øyvind Holte from the Norwegian Medicines Agency will present the uniformity of dosage units using large sample sizes (Ph.Eur. 2.9.47). Dr Øyvind Holte is a member of both the EDQM PAT working party and the EMA PAT team.