SoHO entity registration
1. Entities shall register as a SoHO entity before commencing any of the SoHO activities referred to in Article 2(1), point (c).
Entities may request from a SoHO competent authority within their territory an opinion on whether the activities they are carrying out are subject to the registration requirements set out in this Chapter.
2. SoHO activities shall only be carried out by persons who operate within a registered SoHO entity.
3. In order to register as a SoHO entity, the SoHO entity shall provide the following information:
(a)
name of the SoHO entity and all addresses where SoHO activities are performed by the SoHO entity;
(b)
name and contact details of the responsible person as referred to in Article 36;
(c)
acknowledgment from the SoHO entity that it may be inspected pursuant to Article 28 and that it will cooperate with the relevant SoHO competent authority in any matter relating to the conduct of SoHO supervisory activities in accordance with this Regulation;
(d)
a list of the SoHO concerned and of the SoHO activities referred to in Article 2(1), point (c), that the SoHO entity carries out; where the SoHO entity carries out the SoHO activity referred to in Article 2(1), point (c)(iv), it shall also provide the name of the SoHO establishment responsible for the SoHO release prior to distribution;
(e)
where applicable, a list of SoHO establishments for which the SoHO entity performs SoHO activities covered by an agreement;
(f)
where applicable, details of any accreditation or certification received from an external body;
(g)
where applicable, information regarding activities carried out and regulated under other Union legislation, as referred to in Article 13(1).
4. SoHO entities shall declare, when registering, whether they need an authorisation pursuant to Article 19, 25 or 26. They shall also carry out a self-assessment of whether they meet the criteria for being a critical SoHO entity and communicate the result.
5. In Member States where the EU SoHO Platform is used for registration of SoHO entities, as referred to in Article 16(1), entities falling within the definition of a SoHO entity as set out in Article 3, point (33), shall register directly on the EU SoHO Platform in accordance with the instructions from their SoHO competent authorities.
6. SoHO entities shall register without undue delay changes to information registered pursuant to paragraph 3, points (a), (b) and (d) to (g). Where such changes indicate SoHO activities, including processing and storage, or release, or import or export of SoHO, those SoHO entities shall apply for an authorisation as SoHO establishment.
7. Where a registered SoHO entity partially or totally ceases to carry out its SoHO activities, it shall communicate this change on the register for SoHO entities without undue delay, indicating to which SoHO entity it will transfer SoHO for storage, and the data referred to in Article 42, where applicable.
8. Where the SoHO stored is intended for autologous or within-relationship use, or is a highly matched SoHO for a specific SoHO recipient, and the SoHO entity ceases SoHO activities affecting the storage or the possible use of such SoHO, it shall inform the persons from whom such SoHO were collected, and provide them with information about the new SoHO entity that will store such SoHO.
Responsible person
1. SoHO entities shall appoint a person responsible, within their entity, for ensuring that SoHO activities carried out by the SoHO entity comply with the requirements of this Regulation applicable to those SoHO activities.
2. The responsible person shall be in possession of 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 and shall have at least 2 years of experience in the relevant field.
3. SoHO entities shall inform their SoHO competent authority of the name and contact details of the responsible person. Where the responsible person is permanently or temporarily replaced, SoHO entities shall without undue delay inform their SoHO competent authorities of the name and contact details of the new responsible person and the date on which the responsibility of that person is assumed.
4. The responsible person may fulfil the role of releasing officer, as referred to in Article 49, or the role of physician, as referred to in Article 50, provided that that person is in possession of the required qualifications or experience as laid down in those Articles.
Quality management system
1. SoHO entities shall establish, maintain and update a quality management system that is appropriate, taking into account their SoHO activities and that achieves a high level of quality of SoHO.
2. SoHO entities shall design the quality management system in a way that ensures that SoHO activities are carried out in a consistent manner, by personnel that have documented and periodically assessed competence to perform the tasks allocated to them and that SoHO activities are carried out in facilities that are designed and maintained in a manner that prevents SoHO contamination, or cross-contamination between SoHO, or loss of traceability. In that respect, SoHO entities shall take into account the technical guidelines for quality management published by the EDQM, together with the EDQM good practice guidelines, as indicated on the EU SoHO Platform. Alternative approaches to the design of the quality management system may be applied where SoHO entities can demonstrate to their SoHO competent authorities that they achieve an equivalent level of quality.
3. SoHO entities shall put in place procedures and specifications covering, where applicable to their SoHO activities, the following:
(a)
documentation of roles, responsibilities of personnel and organisation;
(b)
selection, training and competence assessment of personnel;
(c)
the procurement qualification, validation and monitoring of premises, materials and equipment, including IT systems;
(d)
other documentation relevant for the quality management system put in place;
(e)
quality control, and monitoring of key performance indicators of SoHO activities;
(f)
quarantine and release;
(g)
withdrawal of SoHO from the inventory of released SoHO and recalls;
(h)
internal audits;
(i)
management of contracted third parties;
(j)
management of cases where procedures have not been followed or specifications have not been met;
(k)
complaints;
(l)
management of traceability and vigilance, pursuant to Articles 42, 43 and 44;
(m)
continuity planning.
4. SoHO entities shall review the quality management system at regular intervals to verify its effectiveness and introduce corrective and preventive actions, if deemed necessary.
5. The Commission may adopt implementing acts regarding selected elements and specifications of the quality management system in order to ensure uniform quality management.
Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).
SoHO preparation authorisation
1. SoHO entities shall not release or, in the context of autologous or within-relationship use, shall not prepare and immediately apply to a SoHO recipient, SoHO preparations without prior SoHO preparation authorisation, other than in the context of the implementation of an approved clinical-outcome monitoring plan as part of a SoHO preparation authorisation.
2. SoHO entities may request an opinion from their SoHO competent authorities on the applicability of the authorisation requirements in this Regulation to their SoHO activities prior to submitting an application for a SoHO preparation authorisation.
3. SoHO entities may request from their SoHO competent authorities a derogation from the requirement for a SoHO preparation authorisation in health emergency situations referred to in Article 65, or for a specific SoHO recipient when justified by the clinical circumstances as referred to in Article 19(11).
Application for SoHO preparation authorisation
1. SoHO entities shall submit applications for SoHO preparation authorisation to the SoHO competent authority in their territory.
2. Applications for SoHO preparation authorisation shall include the following:
(a)
the name and contact details of the applicant SoHO entity responsible for the SoHO preparation authorisation;
(b)
details of the SoHO activities performed for that SoHO preparation and including at least:
(i)
a description of the SoHO used for the SoHO preparation;
(ii)
a list of the specific SoHO donor eligibility criteria, including SoHO donor tests specific for the SoHO preparation;
(iii)
a summary of SoHO collection procedures and any specific quality control tests and checks carried out on the collected SoHO prior to processing;
(iv)
a description of the steps of the processing applied, including details of relevant materials and equipment used, environmental conditions and the process parameters and controls at each step;
(v)
a description of equipment, reagents and materials coming into direct contact with the SoHO during processing and their certification status in accordance with Regulation (EU) 2017/745, where applicable, and, in the case of the use of in-house developed equipment, reagents or materials, evidence of the validation of their quality;
(vi)
any specific conditions and time limits for storage and transport, including validation of those conditions and limits;
(vii)
a specification of the SoHO preparation, including quality control and release parameters;
(viii)
data resulting from process validation and equipment qualification;
(ix)
details of any SoHO entities or third parties contracted to perform activities or relevant steps of the processing applied to the SoHO preparation;
(x)
the clinical indications for which the SoHO preparation is to be applied and the clinical data justifying this indication;
(xi)
where relevant, non-clinical data on the effectiveness and toxicity of the SoHO preparation;
(c)
the results of a benefit-risk assessment conducted in respect of the combination of SoHO activities performed for the SoHO preparation, together with the intended clinical indication for which the application for SoHO preparation authorisation is submitted, taking into account:
(i)
whether the SoHO preparation is described in, and aligned with, an EDQM SoHO monograph included in the technical guidelines referred to in Article 59(4), point (a), or a specification included in the other guidelines referred to in Article 59(4), point (b) or (c);
(ii)
whether the SoHO preparation meets the quality criteria defined in a monograph or specification as referred to in point (i) of this point and whether it is intended to be used for the indication and with the mode of human application to which that monograph or specification refers, where such details are provided in that monograph, or whether it meets the requirements set out in the other guidelines referred to in Article 59(4), point (b);
(iii)
information regarding previous use and authorisation of the SoHO preparation or a comparable SoHO preparation in other SoHO entities, as available on the EU SoHO Platform;
(iv)
where applicable, clinical functionality evidence generated as part of conformity assessment procedures, in accordance with Regulation (EU) 2017/745, of a certified medical device that is critical to the specific processing for the SoHO preparation, in cases where the applicant SoHO entity has access to such data;
(v)
documentation of a standardised process of identification, quantification and evaluation of any risks to SoHO donors, SoHO recipients or the offspring from medically assisted reproduction arising from the chain of activities performed for the SoHO preparation and taking into account the technical guidelines published by the EDQM for the performance of such risk assessments, as referred to in Article 56(4), point (a), and Article 59(4), point (a);
(d)
in cases where the indicated risk is greater than negligible, or the expected clinical effectiveness is unknown, a proposed plan for clinical-outcome monitoring for the purpose of providing further evidence, where necessary, for the SoHO preparation authorisation, in line with the results of the benefit-risk assessment and pursuant to point (c);
(e)
an indication of the data which is to be regarded as proprietary and which is to be accompanied, where appropriate, by a verifiable justification.
3. If the application for SoHO preparation authorisation includes clinical-outcome registration, in accordance with Article 20(5), the applicant shall provide details of the clinical registry to the SoHO competent authority and request approval for its use.
4. Where applicable, in accordance with Article 20(4), point (d), and Article 21, SoHO entities shall prepare and distribute the SoHO preparation concerned solely for the implementation and within the limitations, of a clinical-outcome monitoring plan that has been approved by the SoHO competent authority, pursuant to Article 19(2), point (d), and submit the results and their analysis to their SoHO competent authority in accordance with the time limit set in the approval.
5. The applicant SoHO entity remains responsible for collecting the clinical-outcome monitoring data and shall be in a position to make those data available upon request from the SoHO competent authority.
6. SoHO entities shall not make any significant change as to the steps of the processing applied or the activities performed for an authorised SoHO preparation, without the prior written SoHO preparation authorisation from the SoHO competent authorities. Significant changes for which an application for an updated SoHO preparation authorisation shall be required shall be those having an impact on the intended clinical indication or on the quality, safety or effectiveness of the SoHO preparation.
7. The SoHO entity authorised for the SoHO preparation shall be based in the Member State where the application for the SoHO preparation authorisation is submitted.
SoHO clinical studies
1. Where SoHO entities carry out, in the context of approved clinical-outcome monitoring plans, SoHO clinical studies as referred to in Article 21(3), points (b) and (c), with SoHO preparations that are not yet authorised, the SoHO entities shall comply with the requirements set out in this Regulation and in particular with the standards laid down in Chapters VI and VII.
2. Before commencing a SoHO clinical study for the risk level referred to in Article 21(3), point (c), SoHO entities shall:
(a)
apply for a favourable opinion from a relevant ethics committee and shall communicate such an opinion to their SoHO competent authority; such an opinion shall address the ethical, legal and methodological aspects of the SoHO clinical study in order to determine the capacity of the study, as designed, to draw robust conclusions;
(b)
await approval by the SoHO competent authority of the clinical-outcome monitoring plan, as referred to in Article 19(2), point (d), and Article 21.
3. When applying SoHO to SoHO recipients in the context of a SoHO clinical study, SoHO entities shall ensure that the intended SoHO recipients, or persons granting consent on their behalf, are informed that the SoHO preparation concerned has not yet been authorised in accordance with this Regulation and that the SoHO preparation is being applied in the context of a SoHO clinical study that forms part of the authorisation process for that SoHO preparation.
4. The person responsible for the SoHO clinical study shall be adequately qualified and trained.
5. In the course of a SoHO clinical study, SoHO entities shall comply with the vigilance and reporting requirements set out in Article 44.
Activity data collection and reporting
1. SoHO entities shall collect and report data relating to any of the following SoHO activities:
(a)
SoHO donor registration;
(b)
collection;
(c)
distribution;
(d)
import;
(e)
export;
(f)
human application.
2. The data collected pursuant to paragraph 1 shall comprise the data set indicated on the EU SoHO Platform.
3. The Commission shall adopt implementing acts laying down technical procedures for setting and updating the list of data sets to be reported to ensure uniformity and compatibility and comparability of the annual activity data reports, and for extraction, submission and publication of activity data.
Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).
4. SoHO entities shall submit to the EU SoHO Platform an annual report of the data collected pursuant to this Article before 30 June of the subsequent year.
5. By way of derogation from paragraph 4 of this Article, where Member States require SoHO entities to report activity data as referred to in Article 31(2), the SoHO entities shall submit their annual report of activity data to the indicated registries before 30 June of the subsequent year.
Traceability and coding
1. SoHO entities shall implement a traceability system, in order to unambiguously link each SoHO donor or the person from whom SoHO are collected for autologous or within-relationship use, to their SoHO and to all the documents, samples, SoHO preparations and SoHO entities that are associated with that SoHO at any point.
Importing SoHO establishments shall ensure an equivalent level of traceability with regard to imported SoHO.
2. The traceability system referred to in paragraph 1 of this Article shall be able to:
(a)
identify the SoHO donor or the person from whom SoHO are collected for autologous or within-relationship use and the SoHO establishment releasing the SoHO;
(b)
identify the SoHO recipient at the SoHO entity applying the SoHO to the SoHO recipient, or the manufacturer of products regulated by other Union legislation, as referred to in Article 2(6);
(c)
locate and identify all relevant data relating to the quality and safety of the SoHO and any materials or equipment that have come into contact with those SoHO that might pose a risk to their quality or safety.
3. SoHO entities distributing SoHO shall apply a code that contains the information required by the traceability system referred to in paragraph 1 of this Article. SoHO entities shall ensure that the code generated:
(a)
is unique within the Union;
(b)
is machine-readable, unless the size or storage conditions mean that a machine-readable code cannot be applied;
(c)
does not reveal the identity of the SoHO donor or the person from whom SoHO are collected in the case of autologous use;
(d)
complies with technical rules for the Single European Code referred to in Article 43, where applicable as indicated in that Article.
The first subparagraph shall not apply in the context of autologous or within-relationship use of SoHO collected in the same SoHO entity where they are applied.
4. SoHO entities shall include the codes referred to in paragraph 3, on the labels applied to the SoHO, prior to its distribution, or on the documents accompanying the distributed SoHO, where it can be guaranteed that such documents will not be separated from the SoHO or will be kept digitally linked to the SoHO concerned.
5. SoHO entities shall use a labelling system that meets the labelling requirements set out in the relevant technical guidelines referred to in Article 56(4) and Article 59(4).
6. SoHO entities shall keep the data necessary to ensure traceability, appropriately safeguarded and accessible to the SoHO competent authority, for a minimum of 30 years from the SoHO distribution date or, where applicable, from the date of disposal or export. They may store the data in electronic form. Where a SoHO entity ceases its activity, the traceability data shall be transferred to a contracted SoHO entity for the remaining part of the traceability period, after informing the SoHO competent authority.
7. The Commission shall adopt implementing acts concerning the minimum SoHO donor and SoHO recipient data to be kept to ensure traceability.
Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).
European coding system
1. SoHO entities shall apply a Single European Code to SoHO distributed for human application. In cases where SoHO are transferred for further processing in another SoHO entity or released for manufacture of products regulated by other Union legislation, as referred to in Article 2(6), or exported to third countries, SoHO entities shall, at least, apply the elements of the Single European Code that allow for the identification of the donation. The Single European Code shall also appear on the primary packaging of the SoHO concerned or on a label attached thereto, or on the documents referring to that SoHO where it can be ensured that such documents accompany the SoHO concerned.
2. Paragraph 1 of this Article shall not apply to:
(a)
reproductive SoHO for within-relationship use;
(b)
blood or blood components for transfusion or for the manufacture of medicinal products;
(c)
SoHO applied to a SoHO recipient without being stored;
(d)
SoHO imported into the Union by way of derogation and authorised directly by SoHO competent authorities pursuant to Article 26(6);
(e)
SoHO that are imported to or collected in the same SoHO entity where they are applied.
3. The Commission shall adopt implementing acts concerning the format of the Single European Code and the requirements related to its application to SoHO entities and to SoHO at the point of distribution.
Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 79(2).
Vigilance and reporting
1. SoHO entities shall maintain a system for detecting, investigating and recording information concerning adverse reactions and adverse events, including those detected during clinical-outcome monitoring as part of a SoHO preparation authorisation application as referred to in Article 39.
2. SoHO entities shall make all reasonable efforts to encourage prospective parents of children born from third-party donation to communicate information concerning serious genetic conditions as soon as they emerge in the children, to the SoHO entity where they were treated. The SoHO entity shall communicate, without undue delay, that information to the SoHO establishment that released the reproductive SoHO for human application with a view to investigating the suspected serious adverse reaction and preventing further distribution of SoHO from the implicated SoHO donor, in accordance with national legislation on the storage and use of reproductive SoHO.
3. In cases where SoHO entities detect or suspect that an adverse reaction or adverse event falls within the definition of a serious adverse reaction as set out in Article 3, point (45), or the definition of a serious adverse event as set out in Article 3, point (46), they shall submit a notification to their SoHO competent authorities without undue delay and shall include the following information:
(a)
a description of the suspected serious adverse reaction or serious adverse event;
(b)
a preliminary assessment of the level of imputability, where applicable;
(c)
details of any immediate steps taken to limit harm, where applicable;
(d)
a preliminary assessment of the seriousness of the consequences of the suspected serious adverse reaction or serious adverse event.
4. SoHO entities other than SoHO establishments shall communicate adverse reactions or adverse events to the SoHO establishment for which they carry out SoHO activities on the basis of an agreement or to the SoHO establishment that distributed the SoHO to them, as appropriate. In such cases, the SoHO establishments which receive the communication shall be responsible for the investigation and shall report to their SoHO competent authorities when the adverse reaction or adverse event concerned is deemed to be a serious adverse reaction or serious adverse event.
SoHO entities other than those referred to in the first subparagraph shall investigate and report serious adverse reactions or serious adverse events directly to their SoHO competent authorities.
5. Upon receipt of information regarding a serious incident and field safety corrective action within the meaning of Regulation (EU) 2017/745 or (EU) 2017/746, concerning a medical device or in vitro diagnostic medical device that is used by a SoHO entity, the SoHO entity receiving such information shall communicate it to its SoHO competent authority.
6. SoHO entities shall have in place a procedure to accurately, efficiently and verifiably withdraw from distribution or use those SoHO affected, or suspected to be affected, by serious adverse reactions or serious adverse events, as referred to in paragraph 3, as appropriate. In the case of reproductive SoHO, such procedure shall be in accordance with national legislation.
7. SoHO entities shall conduct an investigation of each serious adverse reaction or serious adverse event detected by, or communicated to, them in accordance with paragraph 4. On completion of that investigation, SoHO entities shall provide an investigation report to their SoHO competent authorities. The SoHO entities shall include in the report:
(a)
a full description of the investigation of the serious adverse reaction or serious adverse event and the final assessment of the imputability of the serious adverse reaction to the collection process or to the human application of the SoHO, where applicable;
(b)
the final assessment of the seriousness of the harm to a SoHO donor, a SoHO recipient or the offspring from medically assisted reproduction or for public health in general, including a risk assessment of the likelihood of recurrence, where relevant;
(c)
a description of the corrective or preventive actions that have been taken to limit any harm or to prevent recurrence.
8. SoHO entities shall communicate information concerning a serious adverse reaction or serious adverse event to other SoHO entities engaged in the collection, processing, testing, storage and distribution of SoHO collected from the same SoHO donor, or otherwise possibly affected. They shall only communicate information necessary and appropriate in order to facilitate traceability and ensure quality and safety of SoHO in such cases, and shall, in particular, limit the information to details necessary to take risk mitigating actions. A risk assessment of the seriousness and likelihood of recurrence shall be included in the communication. SoHO entities shall, where relevant, also communicate such information to organ procurement organisations in cases where the SoHO donor who is implicated in the serious adverse reaction or serious adverse event has also donated organs or to manufacturers in cases where SoHO collected from that SoHO donor have been distributed to manufacture products regulated by other Union legislation, as referred to in Article 2(6).
Source: EUR-Lex (Publications Office of the EU), © European Union, reuse permitted under Commission Decision 2011/833/EU.
