Register of SoHO entities
1. SoHO national authorities shall establish and maintain a register of SoHO entities on their territory. In carrying out that task, SoHO national authorities may make use of the EU SoHO Platform in accordance with Article 74(1). In such case, the SoHO national authority shall instruct SoHO competent authorities, where necessary, and SoHO entities to register directly on the EU SoHO Platform.
2. In cases where SoHO national authorities establish registries of SoHO entities outside the EU SoHO Platform, the SoHO competent authorities shall submit the information included in such registries to the EU SoHO Platform. SoHO competent authorities shall be responsible for ensuring that the information regarding the SoHO entities on their territory registered pursuant to Article 17 in the register of SoHO entities and on the EU SoHO Platform is consistent, and shall submit any changes in that information to the EU SoHO Platform without undue delay.
3. The Commission may adopt implementing acts concerning the set of data to be published for registered SoHO entities to facilitate the transfer of information from national registries to the EU SoHO Platform.
Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).
Registration of SoHO entities
1. SoHO competent authorities shall have procedures in place for the registration of SoHO entities in accordance with Article 35.
2. SoHO competent authorities shall verify that each SoHO entity registered in a national registry or the EU SoHO Platform has provided the information pursuant to Article 35(3) before publication of the registration on the EU SoHO Platform. Where national registries are in place, the SoHO competent authority shall submit the information on the registration to the EU SoHO Platform after carrying out that verification.
3. SoHO competent authorities shall verify whether an authorisation is required under Article 19, 25 or 26 for a registered SoHO entity, taking into account the declaration referred to in Article 35(4).
4. SoHO competent authorities shall identify whether the SoHO entity is a critical SoHO entity, in accordance with the criteria agreed by the SCB, taking into account the self-assessment carried out by the SoHO entity, where applicable, as referred to in Article 35(4). SoHO competent authorities shall update the registration information accordingly.
5. Where, on the basis of the information provided, an entity does not fall within the definition of a SoHO entity as set out in Article 3, point (33), the SoHO competent authority shall remove the registration from the EU SoHO Platform and, where applicable, from the national registry, and inform the entity without undue delay.
6. SoHO competent authorities shall:
(a)
acknowledge receipt of the registration without undue delay;
(b)
request the SoHO entity to provide supplementary details on the information provided in accordance with Article 35(3), if needed;
(c)
provide instructions on the procedures to be followed to apply for an authorisation, where relevant;
(d)
where applicable, inform the SoHO entity of its status as a critical SoHO entity and of the related obligations pursuant to Articles 64 and 67;
(e)
inform the SoHO entity that its registration has been verified and published on the EU SoHO Platform.
7. In the case of changes in the information registered by the SoHO entity in accordance with Article 35(6), SoHO competent authorities shall verify those changes and publish the updated registration on the EU SoHO Platform without undue delay, including in the case of cessation of SoHO activities of the SoHO entity concerned.
SoHO preparation authorisation system
1. SoHO competent authorities shall establish and maintain a system for granting SoHO preparation authorisations to SoHO entities located in their territory. Such a system shall include the reception and processing of applications and the approval of clinical-outcome monitoring plans to generate the evidence required for authorisation, where necessary, and shall allow for the suspension or withdrawal of authorisations.
2. SoHO competent authorities shall authorise SoHO preparations in accordance with Articles 19, 20 and 21 and, where applicable, Article 22.
3. The requirement of SoHO preparation authorisation shall be waived for SoHO that are intended to be distributed for the manufacture of products regulated by other Union legislation, as referred to in Article 2(6).
4. SoHO preparation authorisations shall be valid throughout the Union for the period set out in the authorisation granted pursuant to Article 19(2), point (e), or until the SoHO competent authority has suspended or withdrawn the authorisation. Where a Member State has adopted a more stringent measure in accordance with Article 4, which relates to a specific SoHO preparation, that Member State may decline to recognise the validity of the SoHO preparation authorisation of another Member State until the SoHO entity authorised for that SoHO preparation has demonstrated to that Member State compliance with that more stringent measure.
Authorisation of SoHO preparations
1. SoHO competent authorities shall provide guidelines and templates for the submission of applications for SoHO preparation authorisations in accordance with Article 39, and for the design of the clinical-outcome monitoring plans referred to in Article 21. When developing those guidelines and templates, SoHO competent authorities shall use the templates and take into account the relevant best practices documented and published by the SCB, as referred to in Article 69(1), point (d). SoHO competent authorities may establish simplified procedures for applications concerning modifications to previously authorised SoHO preparations. SoHO competent authorities may use the secure communication channel on the EU SoHO Platform for the exchange, with the SoHO entity, of documents relating to the application for authorisation of SoHO preparations.
2. Upon receipt of an application for a SoHO preparation authorisation, SoHO competent authorities shall:
(a)
acknowledge receipt of the application without undue delay;
(b)
assess the SoHO preparation pursuant to Article 20 and examine agreements between the applicant SoHO entity and any SoHO entity or third party contracted by that applicant SoHO entity to perform activities or relevant steps of the processing in relation to the SoHO preparation, where applicable;
(c)
request the applicant SoHO entity to provide supplementary information, if needed;
(d)
grant or refuse the approval for clinical-outcome monitoring plans, as appropriate, in accordance with Article 20(4), points (c) and (d), and indicate a time limit for the applicant SoHO entity to submit the results of the approved clinical-outcome monitoring;
(e)
on the basis of the assessment under point (b) of this paragraph, and of the results of the clinical-outcome monitoring referred to in point (d) of this paragraph, where applicable, grant or refuse the authorisation for the SoHO preparation and, indicate which conditions apply, if any.
3. SoHO competent authorities shall submit information regarding the authorisation granted in respect of the SoHO preparation, including a summary of the evidence used to authorise that SoHO preparation, to the EU SoHO Platform and, for that SoHO preparation, they shall amend accordingly the authorisation information of the SoHO entity concerned.
4. SoHO competent authorities shall conclude the SoHO preparation authorisation steps referred to in paragraph 2 of this Article, within the time limit set out for the authorisation taking into account best practices documented and published by the SCB, as referred to in Article 69(1), point (d). Such time limit may be extended for:
(a)
the duration of the consultations referred to in Article 13(2) and (3);
(b)
the time needed to prepare and submit a response to a request for additional information to the SoHO entity;
(c)
the time needed to perform clinical-outcome monitoring; or
(d)
the time needed to perform additional validation or to generate additional quality and safety data as requested by the SoHO competent authority.
5. For SoHO preparations that incorporate a medical device, as defined in Article 2, point (1), of Regulation (EU) 2017/745, as an integral part, and where that medical device has an action that is ancillary to that of the SoHO preparation, SoHO competent authorities shall verify that the medical device has been certified by the notified body under that Regulation.
6. Where a SoHO competent authority receives in the course of the conformity assessment procedure pursuant to Article 52 of Regulation (EU) 2017/745 a request for an opinion in relation to a medical device that incorporates a SoHO preparation as an integral part, and where that medical device has an action that is principal to that of the SoHO preparation, it shall provide an opinion regarding compliance of the SoHO preparation part with this Regulation, in accordance with Section 5.3.1 of Annex IX to that Regulation, and inform the SCB of the opinion provided.
7. SoHO competent authorities may, in accordance with national legislation, suspend the SoHO preparation authorisation where SoHO supervisory activities demonstrate, or give reasonable ground for suspecting, that such SoHO preparation, or any activities performed in respect of that preparation, do not comply with the conditions of its authorisation or with this Regulation. SoHO competent authorities shall, in accordance with national legislation, suspend the SoHO preparation authorisation when an imminent risk to the safety of SoHO donors, recipients or offspring from medically assisted reproduction, or an imminent risk of unnecessary wastage of critical SoHO, is identified.
SoHO competent authorities shall specify a period of time for the investigation of the suspected non-compliance and for SoHO entities to rectify a confirmed non-compliance, during which the suspension will remain in place.
8. Where SoHO competent authorities have confirmed cases of non-compliance as referred to in paragraph 7, and SoHO entities are not able to rectify them in the specified time period, SoHO competent authorities shall, in accordance with national legislation, withdraw the SoHO preparation authorisation from the SoHO entities concerned.
9. SoHO competent authorities may, in accordance with national legislation, withdraw the SoHO preparation authorisation if a suspension, as referred to in paragraph 7, is not sufficient to resolve the identified shortcomings.
10. In cases of suspension or withdrawal of a SoHO preparation authorisation, as referred to in paragraphs 7, 8 and 9, SoHO competent authorities shall, without undue delay, amend accordingly the authorisation information for the SoHO entity concerned on the EU SoHO Platform.
11. Where the procedures referred to in this Article have not been carried out, SoHO competent authorities may exceptionally authorise, at the request of the SoHO entity responsible for a planned human application of a SoHO preparation to a specific SoHO recipient within their territory, that human application provided that:
(a)
the specific SoHO recipient has no therapeutic alternative, the treatment cannot be postponed or the specific SoHO recipient’s prognosis is life-threatening;
(b)
the safety and effectiveness of the SoHO preparation can reasonably be assumed on the basis of the available clinical data; and
(c)
the SoHO recipient concerned is informed that the SoHO preparation concerned has not been authorised under this Regulation.
SoHO competent authorities may require that the SoHO entity concerned provide a summary of the clinical outcome in the specific case and shall inform the SoHO national authority of that exceptional authorisation without undue delay.
12. The Commission may adopt implementing acts concerning the procedures to authorise SoHO preparations pursuant to this Article.
Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).
Assessment of SoHO preparations
1. The assessment of a SoHO preparation shall include a review of all SoHO activities that are performed for that SoHO preparation and that might influence the quality, safety and effectiveness of that SoHO preparation.
2. SoHO preparation assessors who meet the requirements set out in Article 23 shall carry out the assessment of SoHO preparations.
3. Where a SoHO preparation that is subject to an application for SoHO preparation authorisation pursuant to Article 19 has been duly authorised in another SoHO entity in the same or in another Member State, SoHO competent authorities may authorise that SoHO preparation, provided that the SoHO competent authorities have verified, with the permission of the SoHO entities concerned, that the SoHO activities performed and the steps of the processing applied for that SoHO preparation are carried out by the applicant SoHO entity in such a manner that the quality, safety and effectiveness results of the SoHO preparation will be equivalent to those demonstrated in the SoHO entity where the SoHO preparation was first authorised.
4. Where a SoHO preparation that is subject to an application for SoHO preparation authorisation pursuant to Article 19 has not been authorised in another SoHO entity, or where the SoHO competent authority chooses not to take a SoHO preparation authorisation in another Member State into account, the SoHO competent authority shall:
(a)
assess the adequacy of the information provided by the applicant SoHO entity pursuant to Article 39(2), point (b);
(b)
initiate the consultation provided for in Article 13, if, during the assessment of the information referred to in point (a) of this paragraph, questions arise as to whether the SoHO preparation falls, in part or fully, within the scope of this Regulation or other Union legislation, taking into account the activities performed for the SoHO preparation and the intended human application;
(c)
evaluate the benefit-risk assessment carried out by the applicant SoHO entity pursuant to Article 39(2), point (c), including the scientific evidence and clinical data provided regarding the expected benefit and risk;
(d)
in cases where the evidence provided in accordance with point (c) of this paragraph is not sufficient to provide certainty that the benefit outweighs the risk or where the risk is more than negligible, evaluate the plan to gather further evidence of safety and effectiveness through clinical-outcome monitoring, and the plan’s proportionality to the level of risk and expected benefit of the SoHO preparation in accordance with Article 21;
(e)
consult the SCB, pursuant to Article 69(1) on the evidence necessary and sufficient for the authorisation of a particular SoHO preparation where the best practices referred to in paragraph 7 of this Article are not sufficient;
(f)
assess, in the case of a clinical-outcome monitoring plan previously approved pursuant to Article 19(2), point (d), the results of the clinical-outcome monitoring upon its completion and submission of the results by the applicant.
5. When assessing the SoHO preparation pursuant to paragraph 4, points (d) and (f), SoHO competent authorities shall verify, in the cases where the applicant SoHO entity has proposed to record, and recorded, the results of the clinical-outcome monitoring in an existing clinical registry, whether that clinical registry has data quality management procedures in place that ensure adequate accuracy and completeness of data.
6. SoHO competent authorities shall conduct the assessment referred to in paragraphs 3 and 4 of this Article by means of a remote document review. SoHO competent authorities may also, as part of the SoHO preparation assessment, carry out inspections pursuant to Articles 27, 28 and 29. Pursuant to Article 12, Member States shall ensure communication and cooperation between SoHO preparation assessors and inspectors.
7. When conducting the assessment steps referred to in paragraph 4 of this Article, SoHO competent authorities shall take into account the best practices documented and published by the SCB, as referred to in Article 69(1), point (d).
Clinical-outcome monitoring plans
1. In cases where the scientific evidence and clinical data provided as part of the benefit-risk assessment carried out by the applicant SoHO entity, as referred to in Article 20(4), point (c), is not sufficient, or where the risk is more than negligible, the SoHO competent authority shall approve a clinical-outcome monitoring plan submitted by the applicant SoHO entity. The approved clinical-outcome monitoring plan shall be the basis for the gathering of further evidence to allow for the assessment and authorisation of the new SoHO preparation or a new indication for the SoHO preparation.
2. Clinical-outcome monitoring plans shall not be approved in cases where scientific evidence and clinical data provided as part of the benefit-risk assessment indicate a relevant level of risk without a significant expected benefit.
3. The clinical-outcome monitoring plan shall include the following:
(a)
in cases of low risk, and an expected positive benefit-risk assessment, pro-active clinical follow-up of a pre-defined number of SoHO recipients;
(b)
in cases of moderate risk, and an expected positive benefit-risk assessment, in addition to point (a), a SoHO clinical study of a pre-defined number of SoHO recipients required to be able to assess pre-defined clinical end-points;
(c)
in cases of high risk, and an expected positive benefit-risk assessment, and in cases where the risk or the benefit are not evaluable due to a lack of scientific and clinical data or knowledge, in addition to point (a), a SoHO clinical study of a pre-defined number of SoHO recipients required to be able to assess pre-defined clinical endpoints with a comparison to standard therapy.
4. In the cases referred to in paragraph 3, points (b) and (c), SoHO competent authorities shall register each approved SoHO clinical study on the EU SoHO Platform, providing the following information:
(a)
the name and address of the SoHO entity carrying out the SoHO clinical study;
(b)
a description of the SoHO type and the intended clinical indication;
(c)
a summary of the processing methodology;
(d)
a summary of the study design;
(e)
the planned date of commencement and completion of the SoHO clinical study.
5. In cases where SoHO supervisory activities indicate a risk for SoHO donors, SoHO recipients or offspring from medically assisted reproduction, SoHO competent authorities may withdraw the previous approval of the clinical-outcome monitoring plan. In such cases, the record on the EU SoHO Platform shall be modified without undue delay.
Joint SoHO preparation assessments
1. At the request of one or more SoHO competent authorities, via their SoHO national authority to another SoHO national authority, SoHO preparation assessments referred to in Article 20 may be carried out by SoHO preparation assessors assigned by more than one Member State, as a joint SoHO preparation assessment.
2. With the prior consent of the SoHO national authority, the SoHO competent authority receiving a request for a joint SoHO preparation assessment shall make all reasonable efforts to accept such a request, taking into account its available resources.
3. The SoHO competent authorities participating in a joint SoHO preparation assessment shall conclude a written agreement prior to carrying out the joint SoHO preparation assessment. Such a written agreement shall specify at least the following:
(a)
the scope of the joint SoHO preparation assessment;
(b)
the roles of the participating SoHO preparation assessors during and following the joint SoHO preparation assessment;
(c)
the powers and responsibilities of each participating SoHO competent authority.
The SoHO competent authorities participating in the joint SoHO preparation assessment shall commit themselves in the agreement referred to in the first subparagraph to jointly accept the results of that assessment. That agreement shall be signed by all the participating SoHO competent authorities, including the respective SoHO national authorities.
4. Member States may set up joint SoHO preparation assessment programmes to facilitate frequent or routine joint SoHO preparation assessments. Member States may operate such programmes under a single written agreement as referred to in paragraph 3.
5. For the purpose of coordinating and performing joint SoHO preparation assessments, SoHO competent authorities shall take into account the relevant best practices documented and published by the SCB, as referred to in Article 69(1), point (d).
Specific requirements concerning SoHO preparation assessors
1. SoHO preparation assessors shall:
(a)
possess a diploma, certificate or other evidence of formal qualifications in the field of medical, pharmaceutical or life sciences, awarded on completion of a university course of study or a course recognised as equivalent by the Member State concerned;
(b)
have expertise in the processes being assessed or the human applications for which the SoHO preparations will be used.
2. The assessment of SoHO preparations referred to in Article 20 may be done jointly by a team of persons which collectively have the qualifications and experience set out in paragraph 1 of this Article.
3. In exceptional cases, SoHO competent authorities may consider that a person’s considerable and relevant experience exempts that person from the requirements set out in paragraph 1.
4. Before SoHO preparation assessors take up their duties, SoHO competent authorities shall provide SoHO preparation assessors with a specific induction training on the procedures to be followed for the assessment of SoHO preparations in accordance with Articles 20 and 21.
5. SoHO competent authorities shall ensure that the specific induction training is complemented by specialised training for assessment of processing methods and technologies used for specific types of SoHO preparations, as well as by continuous training, as appropriate, throughout the career of the SoHO preparation assessors. SoHO competent authorities shall make all reasonable efforts to ensure that SoHO preparation assessors participating in joint SoHO preparation assessments have completed the relevant Union training referred to in Article 70(1) and are included in the list referred to in Article 70(5).
6. SoHO preparation assessors may be assisted by technical experts provided that SoHO competent authorities ensure that those experts comply with the requirements of this Regulation, in particular with those set out in Articles 6, 75 and 76.
SoHO establishment authorisation system
1. SoHO competent authorities shall establish and maintain a system for receiving and processing applications for SoHO establishment authorisation in their territory. The system shall allow for the suspension and withdrawal of authorisations.
2. In accordance with Article 25, SoHO competent authorities shall authorise as SoHO establishments the SoHO entities that fall within the definition of a SoHO establishment as set out in Article 3, point (35).
3. SoHO competent authorities shall include all SoHO activities to be carried out by a SoHO establishment in the authorisation granted, including those SoHO activities to be carried out outside of the premises of the SoHO establishment.
4. SoHO competent authorities may decide that certain SoHO entities that do not fall within the definition of a SoHO establishment as set out in Article 3, point (35), also need to be authorised as SoHO establishments, in particular SoHO entities that:
(a)
have significant influence on the quality and safety of SoHO due to the scale, criticality or complexity of the SoHO activities they perform; or
(b)
carry out SoHO activities in connection with multiple SoHO establishments.
SoHO competent authorities shall inform the SoHO entity of such a decision and of the resulting obligation to comply with all provisions of this Regulation relating to SoHO establishments, including the submission of an application for SoHO establishment authorisation.
5. SoHO establishment authorisations shall be valid throughout the Union for the period set out in the terms of the authorisation, when such a time period has been defined, or until a SoHO competent authority has suspended or withdrawn the authorisation, or until the SoHO establishment has ceased to conduct SoHO activities. Where a Member State has adopted a more stringent measure in accordance with Article 4, which relates to a specific SoHO establishment authorisation, that Member State may decline to recognise the validity of the SoHO establishment authorisation of another Member State until it has verified compliance with that more stringent measure.
Authorisation of SoHO establishments
1. SoHO competent authorities shall provide guidelines and templates to allow that applications for SoHO establishment authorisations are submitted in accordance with Article 46. When developing those guidelines and templates, SoHO competent authorities shall take into account the relevant best practices documented and published by the SCB, as referred to in Article 69(1), point (d). SoHO competent authorities may use the secure communication channel on the EU SoHO Platform for the exchange, with the SoHO establishment, of documents relating to the application for a SoHO establishment authorisation.
2. Upon receipt of an application for a SoHO establishment authorisation, SoHO competent authorities shall:
(a)
acknowledge receipt of the application without undue delay;
(b)
assess the application;
(c)
examine agreements between the applicant SoHO establishment and any SoHO entities contracted by that SoHO establishment to perform SoHO activities;
(d)
request the applicant SoHO establishment to provide supplementary information, if needed;
(e)
carry out an on-site inspection of the applicant SoHO establishment pursuant to Article 27, and, where applicable, of SoHO entities or third parties contracted by the SoHO establishment pursuant to Article 28;
(f)
inform the applicant SoHO establishment, without undue delay, of the outcome of the assessment and inspections referred to in points (b), (c) and (e), and in point (d), where relevant;
(g)
grant or refuse the authorisation of the applicant SoHO establishment as a SoHO establishment, as appropriate, and indicate which SoHO and which SoHO activities for each SoHO are subject to the authorisation and which conditions apply, if any;
(h)
submit information regarding the authorisation granted in respect of the SoHO establishment, by amending the status of the SoHO entity to SoHO establishment on the EU SoHO Platform without undue delay;
(i)
assess and, as appropriate, authorise any significant changes made by the SoHO establishment to the information provided in the application and communicated to them pursuant to Article 46(2), and update that information on the EU SoHO Platform.
3. SoHO competent authorities may, in accordance with national legislation, suspend the SoHO establishment authorisation, or the authorisation of certain SoHO activities which the SoHO establishment is authorised to perform, where SoHO supervisory activities demonstrate, or give reasonable grounds for suspecting that the SoHO establishment concerned does not comply with the conditions of its authorisation or with this Regulation. SoHO competent authorities shall, in accordance with national legislation, suspend the SoHO establishment authorisation when an imminent risk to the safety of SoHO donors, recipients or offspring from medically assisted reproduction, or an imminent risk of unnecessary wastage of critical SoHO, is identified.
SoHO competent authorities shall specify a period of time for the investigation of a suspected non-compliance and for the SoHO establishment to rectify a confirmed non-compliance, during which the suspension will remain in place.
4. In cases where SoHO competent authorities have confirmed cases of non-compliance as referred to in paragraph 3 and SoHO establishments are not able to rectify them in the specified time period, SoHO competent authorities shall, in accordance with national legislation, withdraw the authorisation of those SoHO establishments.
5. SoHO competent authorities may, in accordance with national legislation, withdraw the SoHO establishment authorisation if a suspension, as referred to in paragraph 3, is not sufficient to resolve the identified shortcomings.
6. In cases of suspension or withdrawal of a SoHO establishment authorisation, as referred to in paragraphs 3, 4 and 5, SoHO competent authorities shall, without undue delay, amend accordingly the authorisation status of the SoHO establishment concerned on the EU SoHO Platform.
Authorisation of importing SoHO establishments
1. SoHO competent authorities shall authorise as importing SoHO establishments those SoHO entities that import SoHO, as referred to in Article 24(2).
2. Article 24(1), (3) and (5) and Article 25 shall apply, mutatis mutandis , to the authorisation of importing SoHO establishments.
3. Upon receipt of an application for an importing SoHO establishment authorisation, SoHO competent authorities shall act in accordance with Article 25(2). SoHO competent authorities shall also assess the procedures in place at the applicant importing SoHO establishment to ensure that the imported SoHO are equivalent, in terms of quality, safety and effectiveness, to SoHO preparations authorised in accordance with this Regulation.
4. With regard to Article 25(2), point (e), and in cases where the imported SoHO are not physically received by the importing SoHO establishment but are sent directly to the SoHO entity for human application to a specific SoHO recipient or to an operator for manufacturing a product regulated by other Union legislation, as referred to in Article 2(6), SoHO competent authorities may choose to carry out an inspection by means of remote document review.
5. SoHO competent authorities may require to inspect any third-country supplier to the applicant importing SoHO establishment prior to granting or refusing the importing SoHO establishment authorisation, in particular in cases where the application concerns regular and repeated import of SoHO from the same third-country supplier.
6. By way of derogation from paragraph 1, SoHO competent authorities may authorise imports of SoHO for immediate human application to a specific SoHO recipient, when requested by the SoHO entity responsible for that human application and when duly justified by the clinical circumstances on a case-by-case basis. SoHO competent authorities may also authorise imports of SoHO in emergency situations for immediate human application to SoHO recipients whose health would be seriously endangered without such an import of SoHO.
7. The Commission is empowered to adopt delegated acts in accordance with Article 77 to supplement this Regulation by laying down specific criteria for the assessment of the applications in the course of the authorisation of importing SoHO establishments.
8. Where, in the case of risk to quality and safety of imported SoHO, imperative grounds of urgency so require, the procedure provided for in Article 78 shall apply to delegated acts adopted pursuant to this Article.
Inspections of SoHO establishments
1. SoHO competent authorities of the Member States where SoHO establishments are located shall carry out inspections of those SoHO establishments, and, where applicable, of SoHO entities or third parties contracted by SoHO establishments.
2. SoHO competent authorities shall carry out the following inspections of SoHO establishments, as appropriate:
(a)
announced routine system inspections;
(b)
announced or unannounced inspections, in particular for the investigation of fraudulent or other illegal activities, or on the basis of information that indicates possible non-compliance with this Regulation;
(c)
announced or unannounced inspections targeted at a specific activity or topic as provided for in Article 20(6), Article 26(5), Article 29 and Article 33(6).
3. SoHO competent authorities that identify during inspections cases of non-compliance with this Regulation may include follow-up to those inspections, where necessary and proportionate, to verify that SoHO establishments have undertaken appropriate corrective and preventive actions.
4. SoHO competent authorities shall carry out on-site inspections. However, exceptionally, SoHO competent authorities may conduct inspections, in full or in part, by virtual means, or by remote document review, provided that:
(a)
such inspection modes do not pose a risk to the quality and safety of SoHO;
(b)
such inspection modes do not prejudice the effectiveness of inspections;
(c)
protection of SoHO donors, SoHO recipients or offspring from medically assisted reproduction is respected; and
(d)
the maximum interval between two on-site inspections pursuant to paragraph 9 is not exceeded.
5. SoHO competent authorities shall ensure that inspections are carried out by inspectors who meet the requirements set out in Article 30.
6. The inspections shall include the verification that SoHO establishments comply with the standards, or elements thereof, set out in Chapters VI and VII.
In cases where the SoHO establishments follow:
(a)
the technical guidelines published by the ECDC and by the EDQM referred to in Article 56(4), point (a), and Article 59(4), point (a), as applicable, the inspectors shall consider the standards set out in this Regulation to be met, insofar as they are addressed by such guidelines;
(b)
other guidelines as referred to in Article 56(4), point (b), and Article 59(4), point (b), adopted by the Member State in accordance with paragraph 7 of this Article, the inspectors shall consider the standards set out in this Regulation to be met, insofar as they are addressed by such guidelines;
(c)
guidelines other than those referred to in point (a) or (b) of this paragraph, or other technical methods that are not addressed in guidelines, applied in specific circumstances, as referred to in Article 56(4), point (c), and Article 59(4), point (c), the inspectors shall evaluate the steps taken by the SoHO establishments to ensure the adequacy of such guidelines or technical methods, and their compliance with the standards set out in this Regulation; for that evaluation, the SoHO establishments shall provide the inspectors with all the necessary information, pursuant to Article 56(7) and Article 59(7).
7. When adopting the guidelines referred to in paragraph 6, point (b), of this Article, the Member State shall, prior to the inspection, verify and document that those guidelines are adequate to achieve compliance with the standards set out in Chapters VI and VII and shall make those guidelines available on the EU SoHO Platform. Those guidelines shall be deemed to be adequate to achieve compliance with the standards of this Regulation where they have been established to be equivalent with the technical guidelines published by the ECDC and by the EDQM referred to in paragraph 6, point (a), of this Article.
8. Inspectors shall carry out one or more of the following activities:
(a)
inspect premises;
(b)
evaluate and verify compliance of the procedures and the SoHO activities performed with the requirements of this Regulation;
(c)
examine any documents or other records relating to the requirements of this Regulation;
(d)
where applicable, evaluate the design and implementation of the quality management system in place pursuant to Article 37;
(e)
evaluate compliance with the vigilance and the traceability systems;
(f)
take samples for analysis, copies of documents, and photographs or videos, if required;
(g)
evaluate the SoHO entity emergency plan in place in accordance with Article 67, where applicable;
(h)
order or propose to the SoHO competent authority, the suspension or cessation of any procedure or activity or impose other measures, where necessary and proportionate to the risk detected; in such case, the inspector shall take all the necessary steps without undue delay.
9. Following the inspection referred to in Article 25(2), point (e), SoHO competent authorities shall carry out periodic inspections pursuant to paragraph 2, point (a), of this Article, so that the interval between two on-site inspections shall not exceed, in any event, 4 years. The frequency of inspections shall take account of:
(a)
identified risks associated with the type of SoHO that are subject to the SoHO establishment authorisation and the SoHO activities carried out;
(b)
the SoHO establishments’ past record as regards the outcome of previous inspections and their compliance with this Regulation;
(c)
the certification or accreditation by international bodies, where relevant;
(d)
the reliability and effectiveness of the quality management system referred to in Article 37.
10. Following each inspection, the SoHO competent authorities shall draw up a report on the findings of the inspection and provide it to the SoHO establishment concerned. Where the result of the inspection so requires, the SoHO competent authorities shall, as appropriate, set out any corrective or preventive action needed or shall request the SoHO establishment to respond with a proposal for such actions, with associated dates for completion.
11. For the purpose of inspections referred to in paragraph 1 of this Article, SoHO competent authorities shall take into account the relevant best practices on inspections documented and published by the SCB, as referred to in Article 69(1), point (d).
12. The Commission may adopt implementing acts concerning technical elements of the procedures to be followed for inspections of SoHO establishments.
Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).
Inspections of SoHO entities, other than SoHO establishments, and of third parties
1. SoHO competent authorities may carry out, pursuant to Article 27(1), inspections of SoHO entities other than SoHO establishments, and of the third parties contracted, as necessary and proportionate to the risks associated with the SoHO and the SoHO activities registered for that SoHO entity, and to the SoHO entity’s past compliance records.
2. In the cases referred to in paragraph 1 of this Article, Article 27 shall apply, mutatis mutandis , to the inspection of SoHO entities other than SoHO establishments and of the third parties contracted.
Joint inspections
1. At the request of one or more SoHO competent authorities, via their SoHO national authority to another SoHO national authority, inspections pursuant to Article 27(1) and Article 28(1) may be carried out with the participation of inspectors sent for that purpose by another Member State as a joint inspection.
2. With the prior consent of the SoHO national authority, the SoHO competent authority receiving a request for a joint inspection shall make all reasonable efforts to accept such a request, taking into account its available resources, in cases where:
(a)
the SoHO entity to be inspected performs SoHO activities in more than one Member State, that have impact in the requesting Member State;
(b)
the SoHO competent authorities of the requesting Member State require specialist technical expertise of another Member State for that inspection;
(c)
the SoHO competent authorities of the Member State receiving the request agree that there are other reasonable grounds for conducting a joint inspection.
3. Where the SoHO competent authority receives a request for joint inspection of a SoHO entity, it may decline that request, in particular if:
(a)
there has been a joint inspection in that SoHO entity within the previous year; or
(b)
a joint inspection of that SoHO entity is already being planned.
4. The SoHO competent authorities participating in a joint inspection shall conclude a written agreement prior to carrying out the joint inspection. Such a written agreement shall specify at least the following:
(a)
the scope and objective of the joint inspection;
(b)
the roles of the participating inspectors during and following the inspection, including the designation of the SoHO competent authority leading the inspection;
(c)
the powers and responsibilities of each participating SoHO competent authorities.
The SoHO competent authorities participating in the joint inspection shall commit themselves in the agreement referred to in the first subparagraph to jointly accept the results of that inspection. That agreement shall be signed by all the participating SoHO competent authorities, including the respective SoHO national authorities.
5. The SoHO competent authority leading the joint inspection shall be a SoHO competent authority of the Member State in which the joint inspection takes place and shall ensure that the joint inspection is carried out in accordance with the national legislation of that Member State.
The SoHO competent authority supervising the SoHO entity to be inspected through a joint inspection shall inform that SoHO entity in advance about the joint inspection and its nature, unless there are reasonable and duly justified grounds to suspect that such prior communication would compromise the effectiveness of the joint inspection.
6. Member States may set up joint inspection programmes to facilitate routine joint inspections. Member States may operate such programmes under a single written agreement as referred to in paragraph 4.
7. For the purpose of coordinating and performing joint inspections, SoHO competent authorities shall take into account the relevant best practices documented and published by the SCB, as referred to in Article 69(1), point (d).
Specific requirements concerning inspectors
1. Inspectors shall possess a diploma, certificate or other evidence of formal qualifications in a relevant field, awarded on completion of a university course of study or a course recognised as equivalent by the Member State concerned.
In exceptional cases, SoHO competent authorities may consider that a person’s considerable and relevant experience exempts that person from the requirements set out in the first subparagraph.
2. Before inspectors take up their duties, SoHO competent authorities shall provide inspectors with a specific induction training. For the specific induction training, SoHO competent authorities shall take into account the relevant best practices documented and published by the SCB, as referred to in Article 69(1), point (d).
3. SoHO competent authorities shall ensure that the specific induction training includes at least the following:
(a)
the inspection techniques and procedures to be followed, including practical exercises;
(b)
an overview of relevant Union and national inspection guidance, where applicable, and the best practices documented and published by the SCB, as referred to in Article 69(1), point (d);
(c)
an overview of the authorisation systems in the Member State concerned;
(d)
the legal framework applicable to the performance of SoHO supervisory activities;
(e)
an overview of the technical aspects concerning SoHO activities;
(f)
SoHO technical guidelines as referred to in Articles 56 and 59;
(g)
an overview of the organisation and functioning of national regulatory authorities in the field of SoHO and related fields;
(h)
an overview of the national healthcare system and SoHO organisational structures in the Member State concerned.
4. SoHO competent authorities shall ensure that the specific induction training is complemented by specialised training for inspection of specific types of SoHO establishments and by continuous training, as appropriate. SoHO competent authorities shall make all reasonable efforts to ensure that inspectors participating in joint inspections have completed the relevant Union training referred to in Article 70(1) and are included in the list referred to in Article 70(5).
5. Inspectors may be assisted by technical experts provided that the SoHO competent authorities ensure that those experts comply with the relevant requirements of this Regulation.
Extraction, submission and publication of activity data
1. SoHO competent authorities shall verify that SoHO entities that have activity data collection and reporting obligations pursuant to Article 41 submit to their SoHO competent authorities, via the EU SoHO Platform, an annual report with those activity data. The EU SoHO Platform shall allow for the compilation of the annual reports submitted by the SoHO entities and provide the SoHO competent authorities with an annual aggregated report with the activity data from their SoHO entities.
2. By way of derogation from paragraph 1 of this Article, Member States may decide that SoHO entities shall submit the activity data referred to in Article 41(1) to SoHO competent authorities through national or international registries, in cases where such registries collect activity data matching the data sets indicated on the EU SoHO Platform. In such case, the SoHO competent authorities shall submit those activity data in accordance with the implementing acts adopted pursuant to Article 41(3).
3. SoHO competent authorities shall ensure that the annual aggregated report of activity data for their SoHO entities is made publicly available in their Member States, including via the internet. The annual aggregated report of activity data may also be published on the EU SoHO Platform after review and approval by SoHO national authorities.
4. The Commission shall compile the annual aggregated reports from the SoHO competent authorities and prepare an annual Union SoHO activity report. After having shared that report with the SoHO national authorities for their review and approval, the Commission shall publish the annual Union SoHO activity report and make it available on the EU SoHO Platform.
Traceability
1. SoHO competent authorities shall verify that SoHO entities have appropriate procedures in place to ensure traceability and coding of SoHO as referred to in Article 42.
2. SoHO competent authorities shall establish procedures for the unique identification of SoHO establishments that are to apply the Single European Code pursuant to Article 43. SoHO competent authorities shall ensure that such identification complies with the technical standards established for that coding system. For that purpose, SoHO competent authorities may use a SoHO establishment identification code generated by the EU SoHO Platform.
Vigilance
1. SoHO competent authorities shall be responsible for the supervision of vigilance associated with SoHO activities.
2. SoHO competent authorities shall provide guidance and templates for the submission of SAR or SAE notifications and investigation reports as referred to in Article 44. The guidance and templates provided shall take into account the best practices documented and published by the SCB as referred to in Article 69(1), point (d). SoHO competent authorities shall also establish procedures for the receipt of SAR or SAE notifications pursuant to Article 44.
3. Upon receipt of a SAR or SAE notification pursuant to Article 44(3), SoHO competent authorities shall:
(a)
verify that the notification includes the information referred to in Article 44(3);
(b)
respond to the submitting SoHO entity if additional documentation or corrections are required.
4. Upon receipt of a SAR or SAE notification pursuant to Article 44(3), SoHO competent authorities may:
(a)
provide advice on the investigation planned by the SoHO entity;
(b)
request advice from the SCB pursuant to Article 69(1).
Where the SAR notification concerns a transmission of a communicable disease that is rare, or unexpected for that SoHO type, SoHO national authorities shall inform the ECDC. In such cases, the SoHO national authority shall take into account any advice or information provided by the ECDC or its SoHO expert network.
5. Upon receipt of a SAR or SAE investigation report, SoHO competent authorities shall:
(a)
verify that the investigation report includes the information required pursuant to Article 44(7);
(b)
assess the results of the investigation and of the corrective and preventive actions described;
(c)
request additional documentation from the submitting SoHO entity, if required;
(d)
inform the submitting SoHO entity of the conclusion of the assessment, if corrections are required.
6. SoHO competent authorities may carry out inspections, pursuant to Article 27 or 28, as appropriate, when the SAR or SAE notification or the investigation report received indicates, or gives reasonable grounds for suspecting, that requirements of this Regulation have not been complied with, or they may carry out inspections to verify an accurate implementation of the corrective and preventive actions planned, or when they consider that a particular serious adverse reaction or serious adverse event might constitute a public health threat.
7. Where a SAR or SAE notification concerns a risk to public health, SoHO competent authorities shall, without delay, communicate essential information to other SoHO competent authorities via the SoHO rapid alert procedure referred to in Article 34. SoHO competent authorities receiving that information shall in turn communicate it to the general public, where relevant.
8. Upon receipt of a SAR or SAE notification with implications for quality, safety or supply of a product manufactured from a SoHO and regulated by other Union legislation, as referred to in Article 2(6), SoHO competent authorities shall inform, without undue delay and via their SoHO national authority, the relevant authorities competent for that product, pursuant to Article 13(6).
9. Upon receipt of information regarding a serious incident within the meaning of Article 2, point (65), of Regulation (EU) 2017/745, or information regarding a serious adverse reaction within the meaning of Article 1, point (12), of Directive 2001/83/EC, associated with a product manufactured from or with SoHO, where that information indicates a possible association with the quality or safety of the SoHO used to manufacture that product, the SoHO competent authorities shall communicate without undue delay the information to the SoHO establishment that released the SoHO, to facilitate possible actions to prevent further distribution of the SoHO implicated in the serious incident or serious adverse reaction.
10. Upon receipt of information regarding a serious incident and field safety corrective action within the meaning of Article 2, points (65) and (68), of Regulation (EU) 2017/745, as well as within the meaning of Article 2, points (68) and (71), of Regulation (EU) 2017/746 of the European Parliament and of the Council ( 19 ) , the SoHO competent authorities receiving such information shall communicate it to the SoHO entities that may be using the medical device concerned when carrying out their SoHO activities. The SoHO competent authorities shall also submit that information to their SoHO national authority, provided that the incident falls within the definition of a serious adverse reaction as set out in Article 3, point (45), of this Regulation or the definition of a serious adverse event as set out in Article 3, point (46), of this Regulation.
11. SoHO competent authorities or Member States shall ensure that the procedures referred to in paragraphs 1 to 6 of this Article provide for an adequate interconnection between the SAR and SAE notifications pursuant to this Article and the reporting system established in accordance with Article 11 of Directive 2010/53/EU, for instance where a SAR or SAE notification relates to SoHO donations by SoHO donors that also donated organs.
12. SoHO competent authorities shall submit to their SoHO national authority an annual summary of the SAR and SAE notifications and the investigation reports of confirmed serious adverse reactions and serious adverse events. That summary shall, where necessary, include recommendations arising from an analysis of the serious adverse reactions and serious adverse events reported.
13. SoHO national authorities shall submit an annual summary of confirmed SAR or SAE notifications and of the related investigation reports to the EU SoHO Platform before 30 June of the subsequent year and shall make an aggregated version of that summary publicly available in their Member State, including via the internet. SoHO national authorities shall include in the annual summary the numbers and types of SAR or SAE notifications reported to them that meet the thresholds of seriousness and imputability as set out in the best practices documented and published by the SCB, as referred to in Article 69(1), point (d).
14. The Commission shall aggregate the annual summaries of the SoHO national authorities, and prepare and publish an annual Union SoHO vigilance report, after having shared it with the SoHO national authorities for review and approval. That report shall include overall pattern analysis and recommendations.
15. The Commission may adopt implementing acts concerning the procedures to be followed for consultation and coordination between SoHO competent authorities and the ECDC concerning relevant SAR or SAE notifications and investigations.
Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).
SoHO rapid alerts
1. SoHO competent authorities shall, upon receipt of a SAR or SAE notification or other information with implications for quality, safety or supply of SoHO in more than one Member State, inform their SoHO national authority, which shall in turn launch a SoHO rapid alert on the EU SoHO Platform.
2. SoHO national authorities shall launch a SoHO rapid alert in particular in the following circumstances:
(a)
a risk to the quality or safety of SoHO has been identified concerning SoHO that have been distributed from their Member State to at least one other Member State;
(b)
an outbreak of a communicable disease has occurred in their Member State and they have put in place SoHO donor deferral or testing measures to mitigate the risks of transmission by SoHO;
(c)
a defect or serious supply interruption has occurred concerning equipment, devices, materials or reagents that are critical for the collection, processing, storage or distribution of SoHO and that might be used in other Member States;
(d)
other information is available to the SoHO national authorities that could reasonably be considered useful in other Member States to reduce risks to the quality or safety of SoHO and where the launch of a SoHO rapid alert is proportionate and necessary.
3. The ECDC, with the support of its SoHO expert network, may also launch a SoHO rapid alert on the EU SoHO Platform when surveillance of communicable diseases indicates a new risk to the safety of SoHO. The ECDC may indicate in such a SoHO rapid alert that it has provided guidelines on the mitigation of risks associated with communicable disease outbreaks, in particular concerning the eligibility and testing of SoHO donors.
4. SoHO national authorities that receive a SoHO rapid alert shall communicate relevant information to SoHO competent authorities in their Member State and to the relevant SoHO entities without undue delay with a view to ensuring that risk mitigating actions can be taken promptly and that relevant information available among professionals in the SoHO sector can be shared with the SoHO competent authorities. SoHO national authorities may also supplement the information provided in the SoHO rapid alert with further information such as details of relevant risk mitigating actions taken in their Member State.
5. SoHO national authorities and the ECDC shall take into account the relevant best practices documented and published by the SCB, as referred to in Article 69(1), point (d), when launching and handling a SoHO rapid alert.
Source: EUR-Lex (Publications Office of the EU), © European Union, reuse permitted under Commission Decision 2011/833/EU.
