Technical File Guidance for Preclinical Evaluations

[Roland chung]

Hi all,

MDD requires Technical File to include pre-clinical evaluation. I cannot find a guidance except for MEDDEV 2.7.1 which is actually for clinical evaluation. What should be included in the pre-clinical evaluation?

Regards,
Roland

 

[Ronen E]

Pre-clinical evaluation usually means design verification / bench tests, and sometimes animal tests (typically where a human clinical evaluation is planned but the risk is high or knowledge gaps are big).

 

[Roland chung]

Thanks for your input, Ronen.

Annex X of MDD states that Adequacy of demonstration of conformity with the essential requirements by performance evaluation, bench testing and pre-clinical evaluation alone has to be duly substantiated.

It seems that performance evaluation, bench testing and pre-clinical evaluation are different things.

 

[Ronen E]

Annex X of MDD states that Adequacy of demonstration of conformity with the essential requirements by performance evaluation, bench testing and pre-clinical evaluation alone has to be duly substantiated.

I'm not sure how you concluded that. "Bench testing" and "pre-clinical" are not mentioned in Annex X, and in my understanding all the references to "performance" in Annex X relate to the clinical performance of the device.

BSI's best practices guide provides a concise description of the preferred contents of the Technical File (preferred by BSI).

 

[Roland chung]

Annex X, 1.1d indeed has the statement mentioned above.

 

[mihzago]

In my opinion, as Ronen said, these are just different names for testing, evaluations, and analyses that happen prior to human investigation. Other types of tests could be biocompatibility, safety, usability, etc.
Since you mentioned MEDDEV 2.7.1, rev 4 describes a pre-clinical assessment, which is essentially an evaluation of existing clinical data.

 

[Marcelo]

The proposed MDR makes things a little more clear:

The adequacy of demonstration of conformity with the general safety and performance requirements based on the results of non-clinical testing methods alone, including performance evaluation, bench testing and pre-clinical evaluation, has to be duly substantiated in the technical documentation referred to in Annex II.

Pre-clinical and clinical data
(a)results of (engineering, laboratory, simulated use, animal) tests and evaluation of published literature applicable to the device and taking into account its intended purpose or substantially similar devices regarding the pre-clinical safety of the device and its conformity with the specifications;

Pre-clinical evaluation assessment
The notified body shall have documented procedures in place for the review of the manufacturer’s procedures and documentation relating to the evaluation of pre-clinical aspects. The notified body shall examine, validate and verify that the manufacturer’s procedures and documentation adequately address:
- the planning, conduct, assessment, reporting and, where appropriate, updating of the
pre-clinical evaluation, in particular of
= the scientific preclinical literature search and
= the preclinical testing for example laboratory testing, simulated use testing,
computer modelling, animal models,
- the nature and duration of body contact and the specific associated biological risks,
- the interface with the risk management process, and
- the appraisal and analysis of the available preclinical data and its relevance to
demonstrate conformity to the relevant requirements in Annex I.

Pre-clinical evaluation based on relevant pre-clinical testing and experimental data, in particular regarding in design calculations, in vitro tests, ex vivo tests, animal tests, mechanical or electrical tests, reliability tests, sterilisation validation, software verification and validation, performance tests, evaluation of biocompatibility and biological safety, as applicable.

 

[Ronen E]

Annex X, 1.1d indeed has the statement mentioned above.

I don't see a (d) section in Annex X s. 1.1:

1.1. As a general rule, confirmation of conformity with the requirements concerning the characteristics and performances referred to in Sections 1 and 3 of Annex I under the normal conditions of use of the device and the evaluation of the undesirable side-effects must be based on clinical data in particular in the case of implantable devices and devices in Class III. Taking account of any relevant harmonized standards, where appro-priate, the adequacy of the clinical data must be based on:

1.1.1. either a compilation of the relevant scientific literature currently available on the intended purpose of the device and the techniques employed as well as, if appropriate, a written report containing a critical evaluation of this compilation;

1.1.2. or the results of all the clinical investigations made, including those carried out in conformity with Section 2.

That's all of s. 1.1. If you're relating to the proposed MDR (I haven't looked for an Annex X 1.1d section there, if it exists), please note that it's only expected to come into effect around May 2017, and then there will be a 3 year transition period.

 

[Ronen E]

In my opinion, as Ronen said, these are just different names for testing, evaluations, and analyses that happen prior to human investigation. Other types of tests could be biocompatibility, safety, usability, etc.
Since you mentioned MEDDEV 2.7.1, rev 4 describes a pre-clinical assessment, which is essentially an evaluation of existing clinical data.

I haven't gone back to MEDDEV 2.7.1 rev 4 in a while, but if that's its choice of words I think it's a little poor. As far as I know and understand, the evaluation of existing clinical data is considered a type of clinical evaluation. A clinical evaluation can be either an investigation (trial) or a literature study. The latter is not in any way "pre-clinical"; when it is appropriate (ie enough relevant and acceptable data exists) there shouldn't be any subsequent clinical study except maybe periodic updates or responses to newly realised risks, so the word "pre-" would be meaningless in that context.

The quotes Marcelo included from the proposed MDR use slightly better language because they mention "pre-clinical literature search" and the like (not "pre-clinical assessment") to describe that activity, and they also go quite a long way to clarify what a pre-clinical evaluation actually includes.

 

[Roland chung]

I don't see a (d) section in Annex X s. 1.1:



That's all of s. 1.1. If you're relating to the proposed MDR (I haven't looked for an Annex X 1.1d section there, if it exists), please note that it's only expected to come into effect around May 2017, and then there will be a 3 year transition period.

I was talking about the MDD, not the MDR. Please check mdd 93/42/eec amended by 2007/47/ec.