The Quality Metrics Initiative of the US Food and Drug Administration (FDA) for risk-based inspection planning is entering the decisive phase. Laboratories are directly affected. After an initially voluntary phase, the mandatory submission of quality metrics will begin in 2018. The EMA is still monitoring developments. The only question is: how much longer?
Do you already know IOOSR? No? Then it’s high time…
You know Out-of-Specification (OOS), Out-of-Expectation (OOE) and Out-of-Trend (OOT). But IOOSR? This abbreviation stands for “Invalidated Out-of-Specification Rate” and, along with the Lot Acceptance Rate (LAR) and the Product Quality Complaint Rate (PQCR), is one of the three key figures in the “FDA Quality Metrics Initiative”. It is calculated by relating the number of OOS results for finished goods, APIs and stability tests that were declared invalid due to a laboratory error to the total number of batches (lots). In plain language, this means that one of the key figures regularly reported to the FDA with monthly values comes from the laboratory. This fact shows the important role of laboratories in quality management and will bring the laboratory even further into the focus of regulatory authorities and management.
When does it really start?
After several years of research and testing, it will officially start in 2018. In principle, the initiative is not new. The FDA already started thinking about this in more concrete terms in 2002. In the last 5 years, however, the initiative has noticeably gained momentum: in 2013, the FDA published a memo to explore the topic. This originally focused on key figures that patients and doctors could also use as quality indicators. This was followed by “draft guidance documents” in July 2015 and most recently in November 2016. The latest draft now only contains three of the original four metrics, which should reduce the reporting burden. After a short voluntary test phase, the program is to start in 2018 with mandatory reporting of the metrics.
Will the European Medicines Agency (EMA) follow suit?
In our view, the EMA will probably follow suit sooner rather than later. Current statements at least strongly suggest this. So far, the EMA still believes that the risk level of a plant can be adequately assessed through inspections alone. However, regularly submitted quality metrics have the clear advantage that the authorities can intervene earlier – if the submitted metrics indicate a need for action. In any case, the EMA is monitoring the development of the Quality Metrics Initiative very closely, as can be seen from the recently published “Perspective on Quality Metrics”. In this publication, it reaffirms its existing approach, but shows great interest in helping to shape the course of development. If the FDA can demonstrate positive experiences in two to three years’ time at the latest, the EMA will probably no longer be able to avoid following suit. However, this development could also take place much faster, as the FDA and the EMA are already intensifying their cooperation independently of this issue, as was recently demonstrated by the recognition of inspection results between the EMA and the FDA agreed on March 2, 2017.
Implications for laboratories
Laboratories should start preparing for the reporting of key figures now. If the key figures are not already collected regularly, the corresponding infrastructure must be created – and with sufficient lead time for the start of the initiative. Even more important, however, is that poor values compared to other pharmaceutical companies can lead to a higher frequency of inspections. It is therefore important to measure yourself against other laboratories in advance in order to recognize where you stand in direct comparison with them and, if necessary, to work on improving the IOOSR value. And this effort is worthwhile, as IOOSR ties up laboratory capacity unnecessarily and the preparation of additional inspections or at shorter intervals takes up considerable capacity.
Geniu’s services in the area of quality metrics
- Establishment of a reliable key performance indicator system – not only for IOOSR – but also for the management of a laboratory as a whole
- Comparison (“benchmarking”) with other laboratories in relation to the IOOSR (and in relation to all other key figures in the laboratory)
- Optimization of laboratory processes to improve the IOOSR
