Dr. Ralf Büllesbach giving his talk at the PTS Conference in Düsseldorf
Last year, the European Commission closed the public consultation on Chapter 8 of the EU GMP Guide, Part I (Complaints, Quality Defects and Product Recalls) and published commentaries on it. On the occasion of the GMP conference organised by the PTS Training Service in December of last year in Düsseldorf, Dr. Ralf Büllesbach (Bayer Pharma AG) presented his thoughts on the challenges posed by the practical implementation of the revised chapter.
Among other things, the participants learned what is likely to be overlooked or underestimated when operating procedures and templates for processing such cases are being implemented. Ralf Büllesbach: After all, dealing with complaints, quality defects and product recalls is virtually synonymous with mastering crises. Such crises emerge suddenly; no one is immune. There is no one in the pharmaceutical manufacturing sector who has not been confronted at some point with this complex set of issues.”
A person’s response to a crisis is defined first and foremost by the complexity of the environment (global enterprise, company network across several countries or a smaller, local business) and the role played by the individual (manufacturer, distributor or supplier).
Dr. Büllesbach outlined the reasons for the revision:
Dr. Büllesbach then went into detail on individual passages of the revised chapter.
"...guard against a recurrence of the issue."
This means that the objective of CAPA (corrective and preventive actions) is to make certain that the same defects do not occur again. In any event, these actions are taken on the basis of a thorough root cause analysis. Ralf Büllesbach: “Only if the root causes have been identified and other potential causes ruled out or investigated is a CAPA programme feasible over time and capable of providing protection from recurrence of the problem. It is equally important to follow up by reviewing the effectiveness of a CAPA cycle.”
"…record, investigate and review complaints including potential quality defects..."
Complaints must always be followed by an investigation. Incidentally, quality defects are not all that need to be investigated. For example, the investigation also covers defects in the application or the medication which occur due to misunderstood or unclear instructions. Moreover, all cases must be subjected to periodic reviews. Here, however, Dr. Büllesbach warns against excessive “data obsession”. The important thing is not that every single complaint should be scrutinised again. “However, with a certain number of cases it becomes possible to recognise signals and trends, to study types of defects in a structured manner and to compare them across multiple product groups. This review must always focus primarily on the risk to the patient, and the efficacy of the actions taken must be evaluated.”
"Principles of quality risk management should be applied..."
The following principle applies with reference to quality risk management: The sum of the effort, formalities and documentation in the risk management process should be proportionate to the risk. Utilisation of precious resources should commensurate with the risk involved. Each individual issue must therefore be assigned first of all to a risk class.
Classification of the risk should be scientifically based and should always be done while bearing in mind the potential risk to the patient. In the initial phase, this means gathering as much information as possible. Of course this requires intensive effort, but it is justified in light of the fact that critical adverse events are prevented in this way.
A second step calls for defining a schedule and an action plan for the various risk categories. A rule of thumb is: The higher the risk class, the shorter the processing time. Incidents with a high risk potential therefore require a high degree of commitment and rapid processing. The case should be thoroughly investigated and closed within seven days after receipt of the complaint. The targeted timeframe of 30 days maximum for all other issues cannot always be maintained. It is even quite possible to double this time, for instance if complaint samples have not yet been submitted.
"If these persons do not include the Qualified Person….the latter should be made formally aware of…"
When it comes to mastering crises, the authorised persons and the organisation of workflows play a major role. The following points should be considered:
The guideline contains a detailed section on investigations of complaints and possible quality defects. Internal rules, for instance, must stipulate
The following questions relate to samples:
Speed and professional competence above all else are essential for the investigations. Clear strategies are helpful here, as is a readily available, interdisciplinary team empowered with the necessary authorisations. A contact person for the competent authority should be appointed from the very beginning. The authorities network closely within the EU; the catchphrase is “Rapid Alert”. Preparations for informing the public should also be in place in case of dire emergency.
"Any retrieval of product from the distribution network as a result of a quality defect should be regarded and managed as a recall."
The term “batch traceability” is often mentioned in this connection, since it should be possible to trace batches quickly for product recalls. Written procedures are required for this. Ralf Büllesbach: “The effectiveness of the processes intended for high-risk products should be verified and drilled repeatedly with mock recalls.”
Here are some of the hazards and stumbling blocks lying in wait for those who deal with complaints, quality defects and product recalls:
Dr. Büllesbach concluded with an appeal: “The pharmaceutical industry is notorious for not wanting to hear much at all from customers. Unfortunately, this pushes the positive effect of complaint management much too far into the background. As in other branches of industry, this negative view of complaint management must change. The important thing is to find something positive in the feedback from consumers.”
GMP Conference, PTS Training Service, 3rd/4th December 2013, Düsseldorf
Draft of Chapter 8 “Complaints and Product Recalls“ of the EU-GMP Guide
Maas & Peither AG, GMP-Publishing