ISO 14155, who in medical devices is not familiar with that standard with respect to clinical investigation of medical devices for human subjects? Not that long after the EU had harmonised the 2009 version that introduced a more project management oriented approach (the 2003 harmonised version ceased to apply in the EU as of 21 March 2010) the IEC published the long-awaited new version of the ISO 14155 with its new requirements and which consolidates the two parts.
According to the ISO summary the scope of 14155:2011 is
good clinical practice for the design, conduct, recording and reporting of clinical investigations carried out in human subjects to assess the safety or performance of medical devices for regulatory purposes.
The principles set forth in ISO 14155:2011 also apply to all other clinical investigations and should be followed as far as possible, depending on the nature of the clinical investigation and the requirements of national regulations.
ISO 14155:2011 specifies general requirements intended to protect the rights, safety and well-being of human subjects, ensure the scientific conduct of the clinical investigation and the credibility of the results, define the responsibilities of the sponsor and principal investigator, and assist sponsors, investigators, ethics committees, regulatory authorities and other bodies involved in the conformity assessment of medical devices.
Remember, ISO 14155:2011 does not apply to in vitro diagnostic medical devices.
Companies should start to prepare for the implementation of IsO 14155:2011 because there are quite a few changes compared to the old standards. It’s important to realize that there is no transitional period after the EU harmonises the standard and your company’s clinical investigations will need to meet the new standard. Companies should rather use the period of publication by ISO and harmonisation by the EU (which may be several months) as sunshine period for becoming compliant. This is particularly important for
- studies that will be finalised in this Sunshine period; and
- studies that are in the process of being set up and start after the publication of the harmonised EN 14155:2011.
Companies should make sure that they have informed themselves how the entry into force by way of the new standard being harmonised by the EU will impact their ongoing and planned studies. Companies that get it wrong may face a difficult discussion with their notified body that will not be able to accept the clinical investigation, which will delay issuance of the CE certificate and may cause companies to have to redo administrative work, or, in the worst case, a trial that was not set up according to the new rules.
medicaldeviceslegal 
Great post! I followed the link posted on LinkedIn.
Hi Erik,
I was hoping for clarification on AE collection in clinical investigations. In pharma trials, it is typical to collect only SAEs (i.e. no more AEs) 30 days after the last dose of the investigational drug. In the case of an implantable device, however, when is it reasonable to stop collecting AE data and only collect ADEs, SAEs, incidents and deficiencies? 6.4.1 of ISO 14155:2011 seems to suggest that we must always collect them (that means collecting, say, colds and flu data even 12 months after an implant) whereas A.14.d appears to suggest that it is up to the sponsor in the CIP to define such timelines.
Any guidance?
Patrick
Hi Patrick, thanks for the comment; sorry it took me a while to answer. I don’t think EN 14155:2011 obliges to collect all types of AE data once the clinical investigation (the trial) has ended. 6.4.1 says “All adverse events shall be documented in a timely manner throughout the clinical investigation.”, so there is a cutoff when the clinical investigation ends. A.14.d is by definition limited to the trial period I would think, as the CIP is limited to the trial (see 9.6.b). The question is what the legal obligations of the sponsor/manufacturer are once the trial has finished, because with implantable devices you have a patient walking around with a non-CE marked implant in him/her. Then you are into the provisions of incident reporting under the Medical Devices Directive or Active Implantable Medical Devices Directive, as these are not limited to CE marked devices only but cover all medical devices (CE marked, custom made and investigational). Those incidents have to be reported in accordance with the applicable MEDDEV (http://ec.europa.eu/consumers/sectors/medical-devices/files/meddev/2_12_1-rev_6-12-2009_en.pdf) and member states in the EU have the competence to require incident reporting as set out in articles 10 MDD and 8 AIMDD, which may impose such reporting obligations on a number of parties involved with the incident. However, if the trial has ended, everything has been closed out and handed over to the manufacturer, it is not a clinical trial issue anymore. One observation: I think it is important that the manufacturer/sponsor (as part of the risk assessment in A.4.c of ISO 14155:2011) makes a good appreciation of the duration of the clinical trial necessary to make sure that most of the expected possible AE associated with the investigational device fall within the duration of the trial. I hope this answers your question; if not, we can discuss it further.
Best regards,
Erik
Hey, very nice site. I came across this on Google, and I am stoked that I did. I will definately be coming back here more often. Wish I could add to the conversation and bring a bit more to the table, but am just taking in as much info as I can at the moment.
iso 9000
Dear Eric,
Would you expand on what this statement means “The principles set forth in ISO 14155:2011 also apply to all other clinical investigations and should be followed as far as possible, depending on the nature of the clinical investigation and the requirements of national regulations?” Does this apply to post marketing surveillance studies?
thank you
Hi Christine, indeed, that’s what I propose. Even though registry / pms studies are mostly not interventional, using the same bes practices is recommended for a number of reasons. For example, why change the best practices with respect to obtaining and processing case reports and how to put a study together? Also, it ensures that the investigators have as little changes compared to what they are used to.
I read your post . it was amazing.Your thought process is wonderful.The way you tell about things is awesome. They are inspiring and helpful.Thanks for sharing your information and stories.
iso 9000
Thank you very much for the kind words! Spread the word, and if there are any subject that you think deserve attention, let me know. I will be happy to consider them for future postings on the blog.
Hi Erik,
Is ISO 14155 a stand alone Certifiable standard or does it piggy-back on ISO 9001 or ISO 13485.
Hi Amit, ISO 14155 does not piggyback on ISO 9001 or ISO 13485 which are both concerned with quality systems. ISO 14155 is about clinical trials and good clinical practices for clinical trials with medical devices. The only standard ISO 14155 says that it borrows from is ISO 14971:2007, Medical devices — Application of risk management to medical devices.
Dear Erik,
The principles set forth in ISO 14155:2011 do they apply to Investigator sponsored Trials? is there a difference between IST’s that serve the conformity assessment versus that don’t with respect to the need to comply with ISO14155?
Many thanks
Hi Irene, ISO 14155:2011 applies fully to investigator sponsored trials, as follows from the definition of clinical investigation in clause 3.40: “sponsor: individual or organization taking responsibility and liability for the initiation or implementation of a clinical investigation. NOTE When an investigator initiates, implements and takes full responsibility for the clinical investigation, the investigator also assumes the role of the sponsor and is identified as the sponsor-investigator.” From the perspective of GCP there is no difference between trials for different purposes – if an investigation qualifies as a clinical investigation in the meaning of ISO 14155 it should meet all the requirements in that standard.
Best regards,
Erik
Many thanks!
Hi Erik,
Thanks for creating this website. It was indeed very informative. I have a question for you with regards to auditing in the medical device arena. In your opinion do you think it would be most beneficial to have certification in ISO13485:2003 or 14155:2011 when conducting audits in the GCP, GLP, and PV regulatory environments?
Hi Nathalie, you don’t need to be certified under either of these standards to do audits, but you have to know them really well if you are auditing others for compliance to those standards. Or am I misunderstanding your question perhaps?