Although the core of the text of the standard itself is unchanged from the ISO 14971:2007, the update of the Annex ZA has introduced major confusions and headache for manufacturers and certainly for Notified Bodies. In particular, this revision bans the use of the 'As Low As Reasonably Practicable' (ALARP) approach from the risk acceptance process and basically considers that the labelling is not a risk control measure that may decrease the occurrence of a risk. This is what I call A change!
The changes brought by the revision of the EN ISO 14971:2012 harmonized standard could have easily gone unnoticed. The standard indeed fully endorses the text of the current ISO 14971:2007 and the updates only pertain to the informative Annex ZA. While the Annexes ZA has very limited normative impact (for information only), their regulatory impact is however crucial. As always, the devil is in the details...
The Annex Z ensures the regulatory binding between the Essential Requirements of the Medical Devices Directive 93/42/EEC (MDD) and the use of harmonized standard to support compliance, in direct alignment with the Article 5 of the MDD. Said differently, the Annex Z of an harmonized standard corresponds to the current thinking of the European Commission about the relevance of a standard to respond to the Essential Requirements of the MDD. Usually, the interpretation of the European Commission is direct and no specific limits to the standard are made. The Annex ZA (the version 2012 includes 3 Annexes ZA, ZB and ZC - one for each Directive) introduces a particular degree of interpretation on how a manufacturer should apply the standard to respond to the Essential Requirements of the MDD. The direct impact is that a manufacturer thoroughly claiming the compliance to the ISO 14971:2007 without including the requirements of the Annex ZA may not be compliant with the MDD!
While some Notified Bodies have issued gap analyses to help (alert?) manufacturers, the application of the revised standard remains very obscure. In particular, the LRQA (No. 0088) has published an interesting document. Among the changes described by the Annex ZA, the following are of particular interest: the removal of the ALARP approach and the loss of impact of the labelling to mitigate a risk.
The end of the ALARP approachALARP approach is no longer accepted and neither Notified Bodies nor manufacturers should consider a risk as acceptable with regards to economic considerations. Risk reduction "as far as possible" applies instead. Additionally, all risks - regardless of their initial risk level - need to be individually reduced as far as possible and balanced against the expected benefits.
Consequently, the risk reduction should be performed regardless of the cost of the risk reduction measures. But where is it supposed to end and what could limit a Notified Body from requesting a manufacturer to further mitigate a risk with control measure costing millions?
In practice, an approach of risk reduction strategy performed together with a systematic assessment of the benefits/risks ratio should apply. It will then be a matter of interpretation and of application of a pragmatic approach.
While the valuable intent of the European Commission was certainly to force manufacturers to preserve patients safety at any price, the interpretation of the Annex ZA will probably end into an 'As Far As Possible but Nevertheless Pragmatic' approach: the AFAPNP is born!
The labelling: do as if nobody reads itAccording to the new Annex ZA, the occurence of a risk cannot be reduced by the labelling. The impact is typically that manufacturers cannot reduce the quotation of the risk only mitigated by a warning in the IFU... Putting this requirement in the perspective of (i) the removal of the ALARP approach and (ii) the 2nd Essential Requirement of the MDD which requests the mitigation by design, then protection and finally labelling, this means that a risk only mitigated by the labelling could never be accepted, unless a manufacturer drastically changes the design of his device regarldess of the cost. Let's illustrate this with the risk of allergic reaction to a material of an implant...People have allergies, so how can a manufacturer prevent from the risk of anaphylaxis (maximum severity) if it is not by the labelling? Should a surgeon instinctively know the composition of a device? Should a manufacturer change the materials of his device at any cost? In this case, should we immediately remove biological products from the market considering the potential allergies of the population? In practice, manufacturers will mitigate the risk by conducting hypersensitivity testing or the use of materials known for their low allergic potential. But still, people have allergies and only the IFU can provide the relevant information for the safe use.
My personal opinion is that the IFU is important and supports both instructive and legal values. Therefore, a pragmatic approach should again be observed when it comes to the mitigation by the labelling and the systematic assessment of the benefits/risks ratio for each individual risk should apply.