In the European Union, the IVD Directive that governs the regulatory market access for in vitro diagnostic medical devices, or IVDs, also includes requirements for the specific device’s technical documentation. A medical device’s technical documentation is an integral part of its regulatory approval, regardless of the type of medical device and its classification.
The type of information usually included may vary depending on the conformity assessment route and classification of IVD. Regardless of any variances, the technical documentation remains the main evidence of an IVD’s compliance to the IVD Directive’s essential requirements, and will continue to be in the coming IVD Regulation.
Manufacturers should therefore pay close attention to the technical documentation requirements in order to have a better foundation upon which to meet the new European IVD regulatory requirements.
Which IVDs need a Technical File?
Essentially, if an IVD carries a CE-marking and will be sold in the EEA, it needs a technical file. This is true even if the IVD is an IVD that is not classified in Annex II and does not need to go through a Notified Body for its regulatory approval, as competent authorities may always ask to review the technical documentation.
Article 9.7 in the IVDD (98/79/EC) states:
“The manufacturer must keep […] the technical documentation referred to in Annexes III to VIII […] for a period ending five years after the last product has been manufactured.”
The contents of each section depend not only on the IVD itself but also on the class of the IVD. While the technical documentation requirements found in Annex III are consistent regardless of the IVD’s classification, different classes have variations or additional documentation that reflects their different requirements:
|IVDs not in Annex II||Self-Testing IVDs||Annex II List A IVDs||Annex II List B IVDs|
Annex III including point 6
Either Annex IV or Annex V+VII (both routes include technical documentation requirements from Annex III)
Either Annex IV, or Annex V+VI or V+VII (all routes include technical documentation requirements from Annex III)
Note: In the European IVD regulatory scheme, the technical documentation is a living, breathing set of documents. Over time it will grow as it includes post-market data, design changes, risk management updates, and other changes that may affect the IVD’s conformity.
What Goes Into the Technical File?
The technical documentation is the proof that the device meets or exceeds the IVD Directive’s essential requirements, it is imperative that each requirement is completely addressed. Manufacturers use as an input into the different parts of the technical file an essential requirements checklist and the data that they reach by using the European harmonized standards and the Common Technical Specifications (CTS).
General Description of the Product including Variants:
The description should be sufficient for the reviewer to understand the design, characteristics, intended performances of the IVD and each variant, as well as the IVD’s classification. A description of the manufacturing methods and method of sterilization, including the technologies used and how they assure the intended characteristics and performances, should also be included in this section.
Documentation of the Quality System and Quality Assurance
The Quality System documentation includes the manufacturer’s quality manual, standard operating procedure, and any quality records that pertain to the device and the processes used to manufacture the device.
Documentation showing the device’s and the manufacturer’s quality assurance structure, including the organizational structure and responsibilities and how the manufacturer maintains and monitors quality control through the manufacturing process is also included.
Design Information, Descriptions, Calculations, and Inspections
The manufacturer should put information about the design and design processes for the IVD, including explanations and validations.
Some of the documents included in the design information section are:
• Master drawings and patterns,
• Manufacturing methods
• Process validation data
• Quality control procedures for raw materials
• Intermediate products and sub-assemblies
• Final product specifications
The design explanation section is an explanation of the design information. According to Annex III.3: “[…] the descriptions and explanations necessary to understand the […] characteristics, drawings, and diagrams, and the operation of the product.” Design validation information, the tests and calculations that were performed showing that the IVD’s design allows it to maintain conformity to the essential requirements, are also included.
Note: Self-testing IVDs undergo an EC design examination by a Notified Body to be CE-marked. Annex III.6.1 highlights the additional information to be included in the device’s technical documentation:
• Test reports (including results of studies performed with lay people) ;
• Data showing that the device is suitable for self-testing needs; and
• The labeling
• IFU information
While the labeling and IFU information is always included, the Notified Body reviews them in light of how the IVD is for lay-person use rather than professional use. It is important that IVD manufacturers build this difference into the design of their self-testing IVDs.
Note: IVDs classified in Annex II List A reviewed according to Annex IV undergo an EC design examination. According to Annex IV.4.2, the dossier includes the documents listed in Annex IV.3.2(c):
• Full technical documentation required in Annex III.3
• The additional documents required for self-testing IVDs
• The design control and validation procedures.
Tissues of Human Origin Information
This section includes all traceability information for the tissues of human origin (or animal origin if applicable). The traceability information should include the origin of the tissue and the conditions under which it was collected. The manufacturer should keep the records of it from their defined sources.
Risk Analysis and Risk Management File
The risk analysis and risk management file are an essential part of the technical documentation. It should incorporate and address all the known and reasonably foreseeable hazards for the IVD, the likelihood of occurrence, and how the manufacturer mitigates these risks. This risk analysis and risk management file demonstrates that the risks inherent to the IVD itself are acceptable when weighed against the benefits to the patient. The risk analysis should cover all stages of the life-cycle of the IVD, from its initial conception to final decommissioning and disposal.
If a manufacturer claims that an IVD is to be provided sterile or has a special microbiological state of cleanliness, the sterilization and cleaning procedures as well as the validation reports must be included.
Performance Evaluation Data
The manufacturer includes any performance evaluation data from devices for performance evaluation generated and collected during design, R&D, performances studies, and literature. According to Article 1.2.(e), an IVD for performance evaluation is “[…] intended by the manufacturer to be subject to one or more performance evaluation studies in laboratories for medical analysis or in other appropriate environments outside his own premises.” In other words, an IVD for performance evaluation is one that the manufacturer uses to benchmark its own IVD’s performance.
Labeling and IFU Information
The label information and the Instructions For Use (IFU) are an important part of the technical documentation, section 8 of the Essential Requirements requires them. The IFU should be written such that the user, taking account of their training and education, is able to safely and properly use the IVD. For example, IFUs for an IVD that is for self-testing may look much different from those for a professional user (E.R §8.7.t).
Stability studies are an important part of an IVD’s technical documentation. IVDs sometimes aren’t used immediately upon receipt like some other types of medical devices. Also, Stability tests are usually performed under real-time, in condition of use, in transport conditions with storage conditions stated by the manufacturer. Accelerated stability studies can be used to support the shelf-life.
IVD’s technical documentation requirements are robust and comprehensive. All IVDs need technical documentation. Even though an IVD may not need a Notified Body’s services to place a CE marking on the device, IVD manufacturers should not interpret this as an excuse for or way around the technical documentation requirements as competent authorities may always request the technical documentation. The changes in the European regulatory scheme for IVDs mean that IVD manufacturers who don’t currently need a notified body’s services will in the future. As a result, IVD manufacturers should examine their technical documentation to ensure it is up-to-date and as comprehensive as required in the IVDD.