ANNEX II (PART 2)

Technical documentation

6. PRODUCT VERIFICATION AND VALIDATION

The documentation shall contain the results and critical analyses of all verifications and validation tests and/or studies undertaken to demonstrate conformity of the device with the requirements of this Regulation and in particular the applicable general safety and performance requirements.

6.1. Pre-clinical and clinical data

(a)results of tests, such as engineering, laboratory, simulated use and
animal tests, and evaluation of published literature applicable to the device, taking into account its intended purpose, or to similar
devices, regarding the pre-clinical safety of the device and its
conformity with the specifications;
(b)detailed information regarding test design, complete test or study
protocols, methods of data analysis, in addition to data summaries
and test conclusions regarding in particular:
— the biocompatibility of the device including the identification of all materials in direct or indirect contact with the patient or user;
— physical, chemical and microbiological characterisation;
— electrical safety and electromagnetic compatibility;
— software verification and validation (describing the software
design and development process and evidence of the validation of
the software, as used in the finished device. This information shall
typically include the summary results of all verification, validation
and testing performed both in-house and in a simulated or actual
user environment prior to final release. It shall also address all of
the different hardware configurations and, where applicable,
operating systems identified in the information supplied by the
manufacturer);
— stability, including shelf life; and
— performance and safety.

Where applicable, conformity with the provisions of Directive 2004/10/EC of the European Parliament and of the Council (1) shall be demonstrated.

Where no new testing has been undertaken, the documentation shall incorporate a rationale for that decision. An example of such a rationale would be that biocompatibility testing on identical materials was conducted when those materials were incorporated in a previous version of the device that has been legally placed on the market or put into service;

(c)the clinical evaluation report and its updates and the clinical
evaluation plan referred to in Article 61(12) and Part A of Annex
XIV;
(d)the PMCF plan and PMCF evaluation report referred to in Part B of
Annex XIV or a justification why a PMCF is not applicable.

6.2. Additional information required in specific cases

(a)Where a device incorporates, as an integral part, a substance which,if used separately, may be considered to be a medicinal product within the meaning of point 2 of Article 1 of Directive 2001/83/EC,
including a medicinal product derived from human blood or human plasma, as referred to in the first subparagraph of Article 1(8), a
statement indicating this fact. In this case, the documentation shall
identify the source of that substance and contain the data of the tests conducted to assess its safety, quality and usefulness, taking accountof the intended purpose of the device.
(b)Where a device is manufactured utilising tissues or cells of human
or animal origin, or their derivatives, and is covered by this
Regulation in accordance with points (f) and (g) of Article 1(6, and
where a device incorporates, as an integral part, tissues or cells of
human origin or their derivatives that have an action ancillary to
that of the device and is covered by this Regulation in accordance
with the first subparagraph of Article 1(10), a statement indicating
this fact. In such a case, the documentation shall identify all
materials of human or animal origin used and provide detailed
information concerning the conformity with Sections 13.1. or 13.2.,
respectively, of Annex I.
(c)In the case of devices that are composed of substances or
combinations of substances that are intended to be introduced into
the human body and that are absorbed by or locally dispersed in thehuman body, detailed information, including test design, complete
test or study protocols, methods of data analysis, and data
summaries and test conclusions, regarding studies in relation to:
— absorption, distribution, metabolism and excretion;
— possible interactions of those substances, or of their products of
metabolism in the human body, with other devices, medicinal
products or other substances, considering the target population, andits associated medical conditions;
— local tolerance; and
— toxicity, including single-dose toxicity, repeat-dose toxicity,
genotoxicity, carcinogenicity and reproductive and developmental
toxicity, as applicable depending on the level and nature of exposure to the device.

In the absence of such studies, a justification shall be provided.

(d)In the case of devices containing CMR or endocrine-disrupting
substances referred to in Section 10.4.1 of Annex I, the justification
referred to in Section 10.4.2 of that Annex.
(e)In the case of devices placed on the market in a sterile or defined
microbiological condition, a description of the environmental
conditions for the relevant manufacturing steps. In the case of
devices placed on the market in a sterile condition, a description of
the methods used, including the validation reports, with respect to
packaging, sterilisation and maintenance of sterility. The validation
report shall address bioburden testing, pyrogen testing and, if
applicable, testing for sterilant residues.
(f)In the case of devices placed on the market with a measuring
function, a description of the methods used in order to ensure the
accuracy as given in the specifications.
(g)If the device is to be connected to other device(s) in order to operate as intended, a description of this combination/configuration
including proof that it conforms to the general safety and
performance requirements when connected to any such device(s)
having regard to the characteristics specified by the manufacturer.

(1) Directive 2004/10/EC of the European Parliament and of the Council of 11 February 2004 on the harmonisation of laws, regulations and administrative provisions relating to the application of the principles of good laboratory practice and the verification of their applications for tests on chemical substances (OJ L 50, 20.2.2004, p. 44).

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