KG LEGAL \ INFO
BLOG

Blog home > PHARMACEUTICAL, HEALTHCARE & LIFE SCIENCES LAW > “THE MOST EXPENSIVE PREVENTION IS ALSO CHEAPER THAN THE CHEAPEST TREATMENT” – LEGAL REGULATIONS FOR REPORTING PERFORMANCE TESTS OF A MEDICAL DEVICE FOR IN VITRO DIAGNOSTICS

“THE MOST EXPENSIVE PREVENTION IS ALSO CHEAPER THAN THE CHEAPEST TREATMENT” – LEGAL REGULATIONS FOR REPORTING PERFORMANCE TESTS OF A MEDICAL DEVICE FOR IN VITRO DIAGNOSTICS

Publication date: April 17, 2024

Medical devices for in vitro diagnostics.

In vitro diagnostic medical devices are intended for testing samples taken from the human body. This test is carried out outside the human body (in vitro) in laboratory conditions, as well as at home, in the case of products intended for self-testing. In accordance with the definition contained in Art. 2 point 2 of Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU (OJ EU, L. of 2017, No. 117, p. 176, as amended) (hereinafter: IVDR) medical device is a device that is a reagent, reagent product, calibrator, control material, kit, tool, instrument, hardware, software or system, whether used individually or in combination, intended by the manufacturer to be used in vitro for the examination of samples obtained from the human body, including blood and tissue obtained from donors, solely or principally for the purpose of providing information:

  1. about a process, physiological or disease state;
  2. congenital physical or mental developmental defect;
  3. predisposition to disease or illness;
  4. to determine safety and compatibility with potential recipients;
  5. to predict response or responses to treatment;
  6. to determine or monitor therapeutic activities.

Sample containers are also considered to be in vitro diagnostic medical devices.

A special type of in vitro diagnostic medical device is a “self-monitoring device”, which, in accordance with Art. 2(5) of the IVDR means a device intended by the manufacturer for use by lay persons, including devices used for inspection services offered to lay persons through information society services. The definition of “layman” is specified in Art. 2 point 31 of the IVDR and means a natural person who has no formal education in the relevant field of health care or medicine.

Performance study reporting.

Products, in accordance with Art. 47 of the IVDR Regulation, are divided into classes A, B, C and D (class A is the lowest risk class and class D is the highest risk). In accordance with Annex XII of the IVDR, the process of evaluating the performance of a device includes the analysis of data to demonstrate the scientific significance, analytical performance and clinical effectiveness of the product in accordance with its declared use by the manufacturer. The manufacturer is responsible for establishing and regularly updating a performance evaluation plan that specifies the characteristics and performance of the device and the procedures and criteria necessary to obtain appropriate clinical evidence. This assessment is conducted in a thorough and objective manner, taking into account both favorable and unfavorable outcomes. The level of detail and scope of the assessment plan corresponds to the characteristics of the product, including its risk, risk class, performance and intended use.

In Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC (OJ EU L. of 2017, No. 117, p. 1, as amended) (hereinafter: MDR) there is a close connection between testing the performance of a medical device and the risk management system. The European legislator notes the need to carefully adapt this system to the process of assessing the performance of a given device, taking into account the clinical risk that is analyzed as part of performance studies, effectiveness assessment and post-market monitoring. The risk management process and the performance evaluation process should be interconnected and regularly updated. The concept of product performance refers to the ability of the product to fulfill the purpose declared by the manufacturer. This consists of analytical performance and, where appropriate, clinical performance supporting this intended use. The provision of Art. 39 section 1 of the Polish Act on Medical Devices regulates performance testing in the following cases:

(a) where surgical sampling is performed solely for the purpose of performance testing;

(b) in the case of an interventional clinical performance study defined in accordance with Article 2 point 46 of the IVDR Regulation;

c) if the study involves additional invasive interventions or carries other risks for study participants.

Article 39 (1) 1 of the Act on Medical Devices also refers to testing the operation of a device that already has the CE marking in order to further assess its functioning in accordance with its declared use. In such cases, the examination includes, in accordance with Art. 70 section 1 and 2 of the IVDR Regulation, subjecting participants to additional treatments in addition to those performed under normal conditions of use of the device, and these additional treatments could be invasive or burdensome for participants.

The condition for legally initiating performance testing of an in vitro diagnostic medical device in the territory of the Republic of Poland, in accordance with Art. 41 of the Polish Act on Medical Devices, is for the sponsor to submit an application for permission to conduct such a study to the President of the Polish Office for Registration of Medicinal Products, Medical Devices and Biocidal Products (hereinafter: Polish Office for Registration of Medicinal Products and Medical Devices). The sponsor attaches the following information and documents to the application:

Clinical effectiveness study plan

As stated in section 2.3.2. of Annex XIII of the IVDR, the performance study shall be carried out on the basis of a performance study plan.

The action research plan shall specify the rationale, objectives, design and proposed analysis, methodology, monitoring and conduct of the performance study and its documentation. It contains in particular the following information:

  1. the unique identification number of the clinical performance study referred to in Article 66 section 1 of the IVDR Regulation;
  2. details relating to the sponsor, including his name, registered place of business address and contact details, and, where applicable, name and address of his registered place of business and contact details of his contact person or a legal representative who has – in accordance with Art. 58 section 4 of the IVDR Regulation – place of residence or registered office in the Union;
  3. information regarding the investigator(s), i.e. principal investigator, study coordinator or other investigators, their qualifications, contact details and information regarding the research center(s), such as number, qualifications, contact details and, in the case of self-monitoring devices, location and number of lay people participating in the study;
  4. the start date and planned duration of the clinical effectiveness study;
  5. identification and description of the device, its intended use, the analyte or analytes or marker or markers, traceability and manufacturer;
  6. information on the type of samples tested;
  7. a general summary of the clinical effectiveness study, the type of research design, such as observational or interventional, along with research goals and hypotheses, references to the current state of knowledge in the field of diagnostics or medicine;
  8. a description of the expected risks and benefits associated with the device and clinical performance testing in the context of the current state of knowledge in clinical practice and, excluding studies using residual samples, related medical procedures and patient care;
  9. instructions for use of the device or test protocol, the necessary training and experience of the user, appropriate calibration procedures and control measures, an indication of any other devices, medical devices, medicinal products or other articles to be included or excluded, and specifications of any comparator devices or comparator methods used as reference;
  10. a description and justification of the study design for clinical effectiveness, robustness and scientific validity, including statistical design, and details of the measures to be taken – such as randomization – to minimize measurement bias and the management of potential confounding factors;
  11. analytical performance in accordance with Annex I to the IVDR, Chapter I, Section 9.1(a) (a) with justification in the event of any omission;
  12. clinical performance parameters in accordance with IVDR Annex I, section 9.1(a) (b) to be specified, giving reasons in the event of any omission; and, except for studies using residual samples, the specific clinical outcomes/endpoints (primary/secondary) used and their justification, and the potential implications for individual health or public health management decisions;
  13. information on the performance study population: characteristics of participants, selection criteria, size of the performance study population, representativeness of the study population for the target population and, where appropriate, information on the participation of particularly vulnerable participants such as children, pregnant women, people with immunocompromised or elderly people;
  14. information on the use of data from residual sample banks, genetic or tissue banks, patient or disease registries, etc., together with a description of reliability and representativeness and methods of statistical analysis; ensuring an appropriate method for determining the actual clinical status of patient samples;
  15. monitoring plan;
  16. data management;
  17. decision algorithms;
  18. rules regarding any changes, including changes in accordance with Article 71 of the IVDR, in the clinical performance study plan or derogations from that plan, with an express prohibition on exemptions from the application of the clinical performance study plan;
  19. information on liability in relation to the device, in particular on control of access to the device, further actions in relation to the device used in clinical effectiveness testing and the return of unused, expired or defective devices;
  20. a statement of compliance with recognized ethical principles for medical research involving human subjects and good clinical practice for clinical effectiveness research, as well as with applicable regulatory requirements;
  21. a description of the informed consent process, including a copy of the patient information and consent forms;
  22. procedures for recording and reporting safety incidents, including definitions of events that are subject to mandatory recording and reporting, and reporting procedures and deadlines;
  23. criteria and procedures for suspension or early termination of a clinical effectiveness study;
  24. criteria and procedures for the follow-up of participants after completion of the performance study, procedures for the follow-up of participants in the event of interruption or early termination of the performance study, procedures for the follow-up of participants who withdrew their consent, and procedures for participants excluded from follow-up;
  25. procedures for sharing test results outside the study, including communicating them to performance study participants;
  26. rules for developing a clinical performance study report and publishing the results in accordance with the legal requirements and ethical principles referred to in section 2.2 of Annex XIII of the IVDR Regulation;
  27. a list of the technical and functional properties of the product, indicating those that are covered by a given performance test;
  28. bibliography.

In the case of tests using sample residues, it is not necessary to apply point (a). u), x), y) z). If any of the elements referred to earlier are considered inappropriate to be included in the performance study plan due to the choice of a particular study design, such as the use of residual samples or interventional clinical performance studies, a justification for this decision should be provided.

Performance study report

In accordance with section 2.3.3. and 3 of Annex XIII to the IVDR Regulation, the report on the clinical effectiveness study (performance study), signed by a physician or other duly authorized person, contains detailed documented information regarding the study protocol plan, results and conclusions of the study, even including negative results. All data and conclusions must be clear, free from measurement errors and clinically relevant. The report contains sufficient information to be understandable to laypeople without requiring them to refer to other documents. Additionally, where appropriate, the report includes any changes or deviations from the original study protocol, as well as explanations of any data exclusions.

Application form

The application form shall be completed in the appropriate manner, including the information listed in Annex XIV of the IVDR:

  1. the name, address and contact details of the sponsor and, where applicable, the name, address and contact details of his contact person or legal representative in accordance with Article 58 section 4 of the IVDR Regulation having their place of residence or registered office in the Union;
  2. the name, address and contact details of the manufacturer of the device to be subject to performance evaluation and, where applicable, of his authorized representative, if these details are different from those referred to in point (a);
  3. title of the performance study;
  4. unique identification number in accordance with Art. 66 section 1 of the IVDR Regulation;
  5. performance study status, i.e. first-time application, re-application, significant change;
  6. data or reference to the performance study plan, such as information about the performance study design phase;
  7. in the case of a repeat application for a device for which an application has already been submitted, the date or dates and reference number or numbers of the previous application or, in the case of a significant change, a reference to the original application. The sponsor shall mark all changes compared to the previous application together with the reasons for these changes, in particular whether any changes have been made to address the conclusions of previous assessments by the competent authority or ethics committee;
  8. if the application is submitted in parallel with an application for authorization of a clinical trial in accordance with Regulation Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use and repealing Directive 2001/20/EC (Journal of Laws EU. L. of 2014, No. 158, p. 1, as amended) – reference to the official registration number of this clinical trial;
  9. identification of the Member States and third countries in which the clinical performance study is planned to be conducted as part of a multicenter or multinational study at the time of submission of the application;
  10. a brief description of the performance study device, its classification and other information necessary to identify the device and the type of device;
  11. summary of the action study plan;
  12. where applicable, information on the comparative product, its classification and other information necessary to identify the comparative product;
  13. evidence provided by the sponsor that the clinical investigator and clinical site are able to conduct the clinical performance study in accordance with the performance study plan;
  14. data on the expected start date of the performance study and its duration;
  15. data enabling the identification of the notified body, if it has been involved already at the stage of submitting the application for authorization for the performance study;
  16. confirmation that the sponsor is aware that the competent authority may contact the ethics committee that is assessing or has assessed the application;
  17. a declaration signed by the natural or legal person responsible for the manufacture of the performance study device that the device is in compliance with the general safety and performance requirements laid down in Annex I, except for matters covered by the clinical performance study, and that all measures have been taken in respect of those matters precautions to protect the participant’s health and safety.

Researcher’s brochure

The investigator’s brochure, in accordance with Section 2 of Chapter I of Annex XIV of the IVDR, contains information on the performance study device that is relevant to the study and is available at the time of submission of the application. Investigators should be informed in a timely manner of any updates to the investigator’s brochure or other relevant information that becomes available. The researcher’s brochure is clearly marked and contains in particular the following information:

  1. identification and description of the device, including information on its intended use, risk classification and applicable classification rule in accordance with Annex VIII of the IVDR, the design and manufacture of the device and references to previous and similar generations of the device;
  2. the manufacturer’s instructions for installation, maintenance, hygiene and use, including storage and handling requirements, and, to the extent such information is available, the information to be included on the label and instructions for use, to be supplied with the product when it is placed on the market. In addition, information regarding any relevant training required;
  3. information regarding analytical performance;
  4. existing clinical data, in particular: — from the relevant available peer-reviewed scientific literature and available expert consensus opinions or the positions of relevant industry associations regarding the safety, performance, clinical benefit to patients, design characteristics, scientific validity, clinical effectiveness and intended use of the device or equivalent devices or similar, — other relevant available clinical data relating to the safety, scientific validity, clinical effectiveness, clinical benefit to patients, design characteristics and intended use of similar devices, including details of their similarities and differences with the device in question;
  5. a summary of the benefit-risk analysis and risk management, including information on known or foreseeable risks and warnings;
  6. in the case of devices containing tissues, cells and substances of human, animal or microbiological origin, detailed information on those tissues, cells and substances and on compliance with the relevant general safety and performance requirements and specific risk management in relation to those tissues, cells and substances and substances;
  7. a list detailing the fulfillment of the relevant general safety and performance requirements set out in Annex I of the IVDR, including the standards and common specifications applied, in whole or in part, and a description of the solutions used to meet the relevant general safety and performance requirements, in terms of the extent to which those standards and common specifications have not been met, are only partially met or are missing;
  8. a detailed description of the clinical procedures and diagnostic tests used during the performance study, and in particular information on any deviations from normal clinical practice.

Other information

a) proof that participants are covered by insurance or other compensation mechanism in the event of health damage, in accordance with Art. 65 of the IVDR and the relevant national law.
b) documents to be used to obtain informed consent, including a copy of the patient information and the informed consent document.
c) a description of the arrangements aimed at ensuring compliance with applicable regulations regarding the protection and confidentiality of personal data, in particular:

a. organizational and technical arrangements that will be implemented to prevent unauthorized access to processed information and personal data, their disclosure, dissemination, changes or loss,
b. a description of the measures that will be put in place to ensure the confidentiality of participants’ records and personal data,
c. a description of the measures that will be put in place in the event of a data breach to limit possible adverse effects.

d) full details of the technical documentation available, for example detailed risk analysis/management documentation or specific test reports (if requested by the competent authority considering the application).

Positive opinion of the bioethics committee

Pursuant to Art. 39 section 1 of the Polish Act on Medical Devices, the provisions of Art. 29 of the Act of December 5, 1996 on the professions of doctor and dentist (Journal of Laws of 2022, item 1731, as amended) apply to testing the operation of a medical device, taking into account the provisions of the Medical Devices Act. It follows that the bioethics committee expresses its opinion on the action research project, taking into account the conditions and ethical criteria for this type of research involving humans, and also assesses the purposefulness and feasibility of the project. The bioethics committee reviews the application of a sponsor who plans to conduct a performance study in Poland or introduce significant changes to an already conducted study, within no longer than 45 days of submitting the application along with complete documentation. This application must be submitted to the appropriate bioethics committee, depending on where the performance study is conducted. In the case of multi-center performance studies conducted in Poland on the basis of the same protocol, the application should be submitted to the bioethics committee responsible for the place where the study is conducted by the coordinator. Depending on the type of study or the scope of changes, the application may require additional documentation, in accordance with the provisions of Art. 39 section 8-10 of the Medical Devices Act. If the committee finds that the application or attached documents are incomplete or incorrectly prepared, it sets an appropriate deadline for the sponsor, no less than 7 days, to supplement or correct them, informing that failure to respond will result in the application being left without consideration. The Commission may also request additional information and documents from the sponsor. If the performance study is to cover minors or persons incapable of giving informed consent, and the committee does not have appropriate specialists, it is obliged to seek the opinion of these specialists from outside the committee. All committee decisions should be signed by all members participating in the committee’s work. Pursuant to Art. 39 section 7 of the Act on Medical Devices, the opinion of the bioethics committee may be appealed to the Bioethics Appeals Committee, regulated by the regulation of the Minister of Health of January 26, 2023 on the bioethics committee and the Bioethics Appeals Committee (Journal of Laws, Item 218).

Application validation

The procedure used to submit an application is based on the provisions contained in Art. 66 of the IVDR Regulation. According to this, the application is submitted via an electronic system that generates a unique European Union performance study identification number for all correspondence relating to the study. Within ten days of receiving the application, the Member State shall inform the sponsor whether the study is subject to the IVDR and whether the application is complete. Moreover, within one week of any change in the study documentation, the sponsor is obliged to update the relevant data in the electronic system and clearly mark this change in the documentation. If the study is not subject to the Regulation or the application is incomplete, the sponsor is notified and given a maximum of ten days to submit comments or complete the application via the electronic system, with the possibility of extending this deadline by a further 20 days in appropriate cases. If the sponsor does not respond within the deadline, the application will be deemed not to have been submitted. However, if the sponsor considers that the application is complete and subject to the regulation, but the responsible authority believes otherwise, the application is rejected. Upon receipt of comments or additional information, the authority shall notify the sponsor within five days whether the performance study is subject to the IVDR and whether the application is complete. Generally, the date of this notification is the date of validation of the application. When assessing the application, the authority may also request additional information from the sponsor. However, the sponsor may begin testing the performance of the device in the circumstances specified in Article. 66 section 7 of the IVDR Regulation.

Obtaining consent from the President of the Polish Office for Registration of Medicinal Products and Medical Devices

The application for testing the performance of an in vitro diagnostic medical device should be submitted to the competent authority, which in Poland is the Polish Office for Registration of Medicinal Products and Medical Devices. The report should include complete documentation of the study (indicated in the preceding points) and information regarding the medical device. After submitting the notification, the Polish Office for Registration of Medicinal Products and Medical Devices evaluates the documentation to ensure that the study will be conducted in accordance with applicable legal regulations and ethical standards.

Pursuant to the provisions of Art. 42 of the Act on Medical Devices, the President of the Polish Office for Registration of Medicinal Products and Medical Devices may issue or refuse to issue a permit to conduct performance studies through an administrative decision, which should be made within a period not exceeding 45 days from the date of application validation. However, this deadline may be extended by an additional 20 days if it is necessary to consult experts. The President of the Polish Office for Registration of Medicinal Products and Medical Devices may also, in justified cases, request from the sponsor additional information and documents necessary to issue a decision, in which case all deadlines are suspended from the date of requesting this information until the date of its receipt. A necessary condition for issuing a decision on matters related to the authorization to conduct a performance study is to obtain a prior positive opinion from the bioethics committee or the Bioethics Appeals Committee. If the President of the Polish Office for Registration of Medicinal Products and Medical Devices determines that participation in an action study could result in worse treatment for participants than under standard practice, or if doubts arise as to the safety of participants, the reliability of the data presented by the sponsor, or if, based on the collected evidence materials finds that the researcher and the research center are unable to conduct the study in accordance with the planned project, or when the tasks, scope of responsibilities and qualifications of individual categories of researchers have not been precisely defined, or when there are irregularities in the documentation regarding the opinion of the bioethics committee, insurance or obtaining informed consent of study participants, then the President of the Polish Office for Registration of Medicinal Products and Medical Devices refuses to issue permission to conduct an action study. Additionally, a document confirming the payment of the application and notification fee referred to in Art. 44 of the Medical Devices Act needs to be presented.

Obligations of the sponsor and investigator in connection with testing the performance of an in vitro diagnostic medical device

In addition to the obligations of the sponsor and researcher mentioned in the previous point during and in connection with submitting the application, both the Polish Medical Devices Act and the IVDR Regulation provide for a number of other obligations. These include:

Obligation to insure the sponsor and researcher

As indicated in Art. 40 section 1 of the Medical Devices Act and Art. 65 section 1 of the IVDR Regulation, both the sponsor and the investigator are obliged to have insurance against damage incurred by the participant resulting from participation in the performance study. Performance tests conducted solely within the scope of the intended use of the device bearing the CE marking are exempt from this obligation, when the test covers only procedures performed under normal conditions of use of the device (Article 40(2) of the Act on Medical Devices). These solutions are identical to the obligation specified in Art. 32 of the Medical Devices Act relating to clinical trials.

The Regulation of the Minister of Finance of December 2, 2022 on mandatory insurance of the sponsor and investigator in connection with conducting a clinical trial of a device or performance testing of an in vitro diagnostic medical device (Journal of Laws, item 2563) specifies the scope of compulsory insurance of the sponsor and investigator for damages caused in connection with conducting a clinical trial of the device or testing the operation of an in vitro diagnostic medical device, the date when the insurance obligation arises and the minimum insurance guarantee sum. Pursuant to § 2 section 1 of the Regulation on compulsory insurance of sponsors and investigators, the insurance covers the civil liability of the sponsor and investigator for damage caused by the action or omission of the insured person, which occurred during the period of insurance coverage, in connection with conducting a clinical trial of the device or testing the operation of an in vitro diagnostic medical device. This insurance covers all damages in the above scope. Additionally, § 2 section 4 of the Regulation on compulsory insurance of sponsors and investigators makes it impossible to contractually limit the liability of the insurance company. As stated in § 2 section 2 and 3 of the Regulation on compulsory insurance of sponsors and investigators, the insurance does not cover:

  1. damage consisting in damage, destruction or loss of items;
  2. damage resulting from war activities, martial law, riots, as well as acts of terrorism;
  3. contractual penalties resulting from action taken during the period of insurance coverage or failure to act during this period in connection with the clinical trial of the device conducted by the insured person or testing the operation of an in vitro diagnostic medical device.

Pursuant to § 3 of the Regulation on compulsory insurance of sponsors and investigators, the insurance obligation arises no later than on the day of submitting an application for authorization to conduct a clinical trial of a device or a performance test of an in vitro diagnostic medical device. However, § 4 section 1 of the Regulation on compulsory insurance of the sponsor and investigator specifies the minimum insured sum, during the insurance period not longer than 12 months, covering the duration of the clinical trial of the device or performance testing of the in vitro diagnostic medical device, in relation to one event, the effects of which are covered by the insurance contract, depending on the number of participants in a given study, is the equivalent in PLN:

  1. EUR 50,000 – if up to 10 people participate in the study;
  2. EUR 100,000 – if 11 to 25 people participate in the study;
  3. EUR 200,000 – if 26 to 50 people participate in the study;
  4. EUR 400,000 – if 51 to 100 people participate in the study;
  5. EUR 500,000 – if more than 100 people participate in the study.

Paragraph 4 section 2 of the Regulation on compulsory insurance of sponsors and investigators provides that the minimum guaranteed insurance sum, during the insurance period not longer than 12 months, covering the duration of the clinical trial of the device or the performance test of the in vitro diagnostic medical device, in relation to all events whose effects are covered by the insurance contract, depends on the number of participants in a given study and is the equivalent in PLN:

  1. EUR 250,000 – if up to 10 people participate in the study;
  2. EUR 500,000 – if 11 to 25 people participate in the study;
  3. EUR 1,000,000 – if 26 to 50 people participate in the study;
  4. EUR 2,000,000 – if 51 to 100 people participate in the study;
  5. EUR 2,500,000 – if more than 100 people participate in the study.

The above minimum guarantee amounts are specified jointly in relation to the sponsor and investigators participating in the clinical trial of the device or the performance study of the in vitro diagnostic medical device. The amounts are determined in accordance with § 4 section 3 and 4 of the Regulation on compulsory insurance of the sponsor and researcher using the average euro exchange rate announced by the National Bank of Poland in the year in which the insurance contract was concluded.

Obligation to keep records in a specific language

Article 46 of the Medical Devices Act indicates the language in which notifications, reports and summaries regarding the performance testing of an in vitro diagnostic medical device should be prepared. With regard to the last document, Art. 73 section 5 of the IVDR Regulation provides for the requirement to prepare it in the Polish language (in the case of research conducted on the territory of Poland. In the event of conducting research or applying for it to be carried out in another Member State, the language in question would be the language of that country). The remaining documents indicated in Art. 73 IVDR, may be prepared in Polish or English. The same solution is provided for reporting a serious adverse event, device defects that could have led to a serious adverse event if appropriate action or intervention had not been taken or if circumstances had been less favorable, and new findings in relation to adverse and serious events adverse events (Article 76 of the IVDR).

  • Obligation to keep documentation

Pursuant to Art. 47 of the Act on Medical Devices, documentation related to testing the performance of a medical device is kept for the period indicated in Section 3 of Chapter II of Annex X and V to the IVDR Regulation, which is at least 10 years from the end of the study or, if the device is subsequently placed on the market, for at least 10 years after the last product was placed on the market. The obligation to store documentation rests with the sponsor and its representative, and may be performed by an external entity with appropriate conditions, based on an agreement concluded with the sponsor or its representative. The documentation must be made available free of charge to the President of the Polish Office for Registration of Medicinal Products and Medical Devices upon request (Section 1 of Chapter II of Annex XIV to the IVDR Regulation).

  • The investigator’s obligation to control the compliance of the study with the approved performance study plan
  • The sponsor’s obligation to appoint a supervisor independent of the research center

A supervisor independent of the study site shall ensure that the performance study is conducted in accordance with the performance study plan, the principles of good clinical practice and the IVDR Regulation (Section 4 of Chapter II of Annex XIV to the IVDR Regulation). The supervisor may be a person who has appropriate knowledge, knows the test protocol and has read the documentation and knows the applicable procedures. An experienced supervisor ensures the study is completed on time and reduces unnecessary costs.

  • Obligation of the sponsor to conclude the agreement set out in Section 2 of Chapter II of Annex XIV to the IVDR

The sponsor shall enter into an appropriate agreement to ensure that the investigator or investigators report to the sponsor in a timely manner any serious adverse events or any other events referred to in Article 76 section 2 of the IVDR Regulation.

  • Sponsor’s obligation to notify significant changes to the performance study

If it is necessary to make changes to the performance study that may significantly affect the safety, health, rights of participants or the reliability of the clinical data obtained through this study, the sponsor is obliged, in accordance with the provisions of Art. 41 section 3 of the Medical Devices Act and Art. 71 of the IVDR Regulation, to notify the President of the Polish Office for Registration of Medicinal Products and Medical Devices within one week of the changes. The notification should be sent via an electronic system and include the justification and nature of the changes, as well as updated audit documents in which the modifications are clearly indicated. All documents and information provided as part of the notification should be prepared in Polish or English, with the exception of the general summary of the action study plan, which, like the information provided directly to study participants, should be prepared only in Polish. Moreover, the notification should be accompanied by the opinion of the relevant bioethics committee on significant changes in the performance study.

Performance study data

Managing the data obtained during the study is crucial to its results. Maintaining appropriate consistency when collecting, integrating and verifying data from action research enables efficient reporting and monitoring of the research and interpretation of its results. The provisions of the GDPR also require that the measures used to manage data ensure its protection against unauthorized access, disclosure, alteration or accidental loss. The method of collecting and managing data should be determined already at the research planning stage.

What are clinical trials of medical devices?

Clinical trials of medical devices enable confirmation that the devices are designed and manufactured in accordance with legal requirements. Clinical trials in Europe under the MDR are mandatory for high-risk and innovative medical devices. However, even class I devices (non-invasive devices used, among others, as mechanical barriers (e.g. for pressure or absorption of exudates), as well as other non-invasive medical devices, i.e. those that have not been included in other classes – class I also includes invasive devices for temporary use, reusable surgical instruments, as well as some active diagnostic devices) should have clinical evidence that demonstrates the safety and effectiveness of the device. Ensuring compliance with the safety and performance of medical devices is the main responsibility of their manufacturer, who, in accordance with Art. 2 point 30 of the MDR Regulation is a natural or legal person who manufactures or completely reproduces a product or who has a product designed, manufactured or completely reproduced and offers this product under his own name and surname or name or trademark. This obligation of the manufacturer is confirmed by carrying out a conformity assessment. The purpose of the assessment is to check whether medical devices operate in accordance with the design assumptions, do not pose a threat to the life or health of users, and whether the benefits of their use outweigh any possible risks. Potential side effects are also identified during the evaluation. Clinical assessment may be based on current scientific literature, analysis of the results of existing clinical trials or conducting own research.

Differences between reporting a clinical trial and a performance study.

In short, a clinical trial focuses on assessing the effectiveness and safety of new drugs or procedures, while a performance study aims to understand the biological mechanisms of action of these drugs or procedures. In addition to the differences resulting from the definitions of clinical trials and performance studies, many of the solutions presented when discussing the performance study application will also apply to the application of clinical trials. Without a doubt, the European legislator, and then the Polish one, when creating regulations relating to performance testing, relied on the regulations regarding clinical trials. Such identical solutions can be found in the regulations regarding both the submission of an application and the obligations of the sponsor and researcher (Articles 31-38 of the Medical Devices Act and the MDR Regulation with annexes). The differences can be seen in the design of a clinical trial, which usually involves randomized, controlled clinical trials in which patients are randomly assigned to receive an investigational drug or a placebo and then evaluated for effectiveness and safety. In contrast, an action study design may include in vitro studies, animal studies, in vivo studies in animal models, or clinical studies that focus on assessing the mechanisms of action of a drug or substance. In addition, the duration of a clinical trial may be longer because it usually requires testing a large number of patients and tracking the long-term effects of the therapy. Furthermore, the results of a clinical trial can be used to obtain regulatory approval of the product and to inform clinical practice on the effectiveness and safety of a given drug or procedure, while the results of a performance study can be used to design subsequent clinical trials, to further understand the mechanisms disease and treatment and to the further development of medical science.

Significant changes – harmonization of reporting and conducting clinical trials within the EU.

As indicated by the President of the Polish Office for Registration of Medicinal Products and Medical Devices in the Information of the President of the Office of January 25, 2022 on the regulatory harmonization of clinical trials in the EU – entry into force of the regulation on clinical trials and launch of the new Clinical Trials Information System,from January 31, 2022, there apply provisions on clinical trials (hereinafter: CTR) harmonizing the processes of submitting applications, assessing and supervising clinical trials in the European Union. The core of the changes introduced by CTR is the new Clinical Trial Information System (hereinafter: CTIS). CTIS is a single point of access for clinical trial sponsors and regulators to submit and evaluate clinical trial data, which includes a publicly accessible, searchable database for healthcare professionals, patients and the general public. In the past, sponsors had to submit clinical trial applications separately to the national competent authorities and ethics committees in each country to obtain regulatory approval to conduct a clinical trial, and registration and publication of results were also separate processes. Thanks to CTIS, sponsors can now apply for authorizations in up to 30 European Union and European Economic Area (EEA) countries at the same time and with the same documentation. From 31 January 2023, the submission of initial clinical trial applications via CTIS became mandatory, and by 31 January 2025, all ongoing trials approved under the current Clinical Trials Directive will be subject to the new regulation and will need to be transferred to CTIS. The European Medicines Agency (hereinafter: EMA) is responsible for maintaining CTIS. The European Commission, the heads of medicines agencies and the EMA have also launched the Acceleration Clinical initiative Trials in the EU, which aims to change the way clinical trials are initiated, designed and conducted.

UP