Last Updated on May 29, 2021 by LawEuro
Medicinal Products Act (Laws / Regulations of Germany)
CHAPTER TEN
PHARMACOVIGILANCE
Section 62
Organisation of the pharmacovigilance system of the competent higher federal authority
(1) In the interests of preventing direct or indirect hazards to human or animal health, it shall be the responsibility of the competent higher federal authority to centrally record and evaluate those risks associated with the administration of medicinal products, in particular adverse reactions, interactions with other products, risks associated with counterfeit medicinal products or counterfeit active substances as well as potential risks to the environment owing to the use of a veterinary medicinal product and to co-ordinate the measures to be adopted in accordance with this Act. For this purpose, the higher federal authority shall act in co-operation with the agencies of the World Health Organization, the European Medicines Agency, the medicinal product authorities of other countries, the health and veterinary authorities of the federal Laender, the medicinal product commissions of the chambers of the health professions and national pharmacovigilance centres as well as with others who, in the execution of their work, keep records on medicinal product risks. The competent higher federal authority may inform the public about medicinal product-related risks and envisaged measures. The competent higher federal authority shall operate a pharmacovigilance system. In so far as it is responsible for medicinal products for human use, it shall conduct regular audits of its pharmacovigilance system and report to the European Commission every two years, for the first time on 21 September 2013.
(2) The competent higher federal authority shall record all cases of suspected adverse reactions that come to its attention. Reports from patients and health care professionals can take any form, especially also electronic. Reports from marketing authorisation holders pursuant to Section 63c shall be transmitted electronically. By collecting information and, when necessary, following up on reports of suspected adverse reactions, the competent higher federal authority ensures that all suitable measures are taken, so as to clearly identify all biological medicinal products that are prescribed, dispensed or sold and pertaining to which reports of suspected adverse reactions have been made, whereby the name of the medicinal product and the number of the manufacturing batch are to be specified.
(3) In the case of medicinal products for human use, the competent higher federal authority shall transmit every serious suspected adverse reaction reported, that occurs on the territory governed by this Act within 15 days and on every reported non-serious suspected adverse reaction that occurs on the territory governed by this Act within 90 days electronically to the database referred to in Article 24 of Regulation (EC) 726/2004 (EudraVigilance database) and, if necessary, to the marketing authorisation holder. In the case of medicinal products for animal use, the competent higher federal authority shall transmit every serious suspected adverse reaction that is reported to it and occurs on the territory governed by this Act immediately, or at the latest within 15 days following the day on which it comes to the authority’s attention, to the European Medicines Agency and to the marketing authorisation holder, if the latter does not yet have knowledge of the occurrence. The competent higher federal authority shall work together with the European Medicines Agency and the marketing authorisation holder to determine in particular whether there has been duplication in the recording of reported suspected adverse reactions. Where necessary, the competent higher federal authority shall also involve patients, health care professionals or the marketing authorisation holder in the follow-up of the reports received.
(4) The competent higher federal authority shall control the management of the funds intended for the performance of pharmacovigilance activities, the operation of the communication networks and market surveillance in order to guarantee its independence in the performance of these pharmacovigilance activities.
(5) In the case of medicinal products for human use, the competent higher federal authority, in collaboration with the European Medicines Agency, shall take the following measures; it shall:
1. monitor the outcome of the risk minimisation measures contained in risk management plans as well as the conditions referred to in Section 28 sub-sections 3, 3a and 3b,
2. assess updates to the risk management system,
3. evaluate the data in the EudraVigilance database to determine whether there are new or changed risks, and whether this has an impact on the risk-benefit balance of medicinal products.
(6) The competent higher federal authority can inspect the collection and evaluation of medicinal product risks and the co-ordination of necessary measures in enterprises and facilities that manufacture, place on the market or clinically test medicinal products. To this end, the representatives of the competent higher federal authority, in consultation with the competent authority, can enter the production areas and business premises during regular working hours, inspect documents including the pharmacovigilance master file and request information. Sentence 1 also applies to undertakings commissioned by enterprises and facilities pursuant to sentence 1. A report of the inspection shall be drawn up. The report shall be submitted to the enterprises and facilities pursuant to sentence 1 for comments. If an inspection results in the conclusion that the marketing authorisation holder fails to meet the requirements of the pharmacovigilance system, as described in the pharmacovigilance master file, and above all the requirements of Chapter Ten, the competent higher federal authority shall draw the attention of the marketing authorisation holder to the detected deficiencies and give the latter the opportunity to submit comments. In such cases the competent higher federal authority shall inform the competent authorities of other Member States, the European Medicines Agency and the European Commission if enterprises and establishments that manufacture, place on the market or test medicinal products for human use are concerned.
Section 63
Graduated plan
By means of general administrative regulations subject to the approval of the Bundesrat, the Federal Government shall draw up a graduated plan detailing the execution of the tasks indicated in Section 62. This plan shall specify the details of the co-operation to take place between the authorities and the services involved at the various danger levels, the intervention of the pharmaceutical entrepreneurs as well as the participation of the Federal Government Commissioner for Patient Affairs and shall stipulate the various measures to be taken in compliance with the provisions of this Act. In the graduated plan, information means and channels may also be specified.
Section 63a
Graduated plan officer
(1) Anyone who, in his/her capacity as a pharmaceutical entrepreneur, places finished medicinal products which are medicinal products under the terms of Section 2 sub-section 1 or sub-section 2 number 1 on the market, shall appoint a qualified person who is resident in a Member State of the European Union having the required expert knowledge and the reliability necessary for exercising his/her function (graduated plan officer) to set up and manage a pharmacovigilance system and to collect and evaluate notifications on medicinal product risks that have become known and co-ordinate the necessary measures. Sentence 1 shall not apply to persons who do not require a manufacturing authorisation pursuant to Section 13 sub-section 2 sentence 1 numbers 1, 2, 3, 5 or sub-section 2b. The graduated plan officer shall be responsible for meeting the obligations to notify in so far as they concern medicinal product risks. He/she shall also ensure that additional information for the evaluation of the risk-benefit profile of a medicinal product, including his/her own evaluations, are sent immediately and in full, if requested by the competent higher federal authority. The details shall be stipulated by the Ordinance on the Manufacture of Medicinal Products and Active Substances. Persons other than those specified in sentence 1 shall not be authorised to perform the duties of the graduated plan officer.
(2) The graduated plan officer may be a qualified person pursuant to Section 14 or a responsible person pursuant to Section 20c at the same time.
(3) The pharmaceutical entrepreneur shall notify the competent authority and the competent higher federal authority about the identity of the graduated plan officer and shall make notification of any change beforehand. In the case of an unforeseen change in the person of the graduated plan officer, notification shall be made immediately.
Section 63b
General pharmacovigilance obligations of the marketing authorisation holder
(1) The marketing authorisation holder is obligated to set up and operate a pharmacovigilance system.
(2) The holder of a marketing authorisation is obligated, in the case of medicinal products for human use, to:
1. scientifically evaluate all of the information, examine risk minimisation and prevention measures and, if necessary, take risk minimisation and prevention measures immediately based on its pharmacovigilance system,
2. audit its pharmacovigilance system regularly at appropriate intervals; in the process, it shall make a note of the most important findings in its pharmacovigilance master file and ensure that corrective measures are taken to remedy deficiencies; once the corrective measures have been fully implemented, the note may be deleted,
3. maintain a pharmacovigilance master file and to make this file available upon request,
4. operate a risk management system for every medicinal product authorised after 26 October 2012 or for which a condition pursuant to Section 28 sub-section 3b sentence 1 number 1 has been imposed,
5. monitor the outcome of risk minimisation measures that are part of the risk management plan or have been imposed as conditions pursuant to Section 28 sub-sections 3, 3a to 3c, and
to update the risk management system and monitor pharmacovigilance data so as to determine whether there are new risks, whether risks have changed or whether there are changes to the risk-benefit balance of medicinal products.
(3) In connection with the authorised medicinal product, the marketing authorisation holder may not make any pharmacovigilance information public without notifying the competent higher federal authority and, in the case of medicinal products for human use, without also notifying the European Medicines Agency and the European Commission beforehand or simultaneously. He/she shall ensure that such information is presented objectively and is not misleading.
Section 63c
Documentation and reporting obligations of the holder of a marketing authorisation for medicinal products for human use in the case of suspected adverse reactions
(1) The marketing authorisation holder shall keep documents on all suspected adverse reactions as well as information on the quantities supplied.
(2) The marketing authorisation holder shall, moreover:
1. record every suspected serious adverse reaction on the territory governed by this Act, of which he/she gains knowledge and electronically notify the competent higher federal authority immediately, or at the latest within 15 days of acquiring this knowledge,
2. record every suspected serious adverse reaction in a third country of which he/she gains knowledge of and electronically notify the competent higher federal authority and the European Medicines Agency immediately, or at the latest within 15 days of acquiring this knowledge.
The competent higher federal authority can require that the marketing authorisation holder also record suspected non-serious adverse reactions that occur on the territory governed by this Act and electronically notify the competent higher federal authority of them immediately or at the latest 90 days after acquiring this knowledge.
(3) The marketing authorisation holder must guarantee that all reports of suspected adverse reactions from medicinal products for human use are available at a central location belonging to the enterprise within the European Union.
(4) Sub-sections 1 to 3, Section 62 sub-section 6 and Section 63b shall apply mutatis mutandis to:
1. the holder of a registration pursuant to Section 39a,
2. a pharmaceutical entrepreneur who is neither the holder of the marketing authorisation nor the holder of a registration pursuant to Section 39a and who places a medicinal product on the market that is subject to marketing authorisation or exempt from marketing authorisation or is a traditional herbal medicinal product.
Sub-sections 1 to 3 shall apply mutatis mutandis to:
1. to the holder of the registration pursuant to Section 38,
2. to a pharmaceutical entrepreneur who is not the holder of the registration pursuant to Section 38 and places a homeopathic medicinal product that is subject to registration or exempt from the obligation to obtain a registration on the market,
3. to the applicant before the marketing authorisation is granted.
Sub-sections 1 to 3 shall apply regardless of whether the medicinal product is still on the market or the marketing authorisation or registration still exists. The fulfilment of the obligations pursuant to sub-sections 1 to 3 can be totally or partly transferred to the marketing authorisation holder by means of a written agreement between the marketing authorisation holder and the pharmaceutical entrepreneur who is not the holder of the marketing authorisation.
(5) Sub-sections 1 to 4 shall not apply to medicinal products for which a marketing authorisation has been granted by the European Community or the European Union. For such medicinal products, the obligations of the pharmaceutical entrepreneur shall be those stipulated in Regulation (EC) No. 726/2004 in the latest applicable version on condition that, within the purview of this Act, an obligation on the part of the relevant competent higher federal authority to notify or to inform the Member States exists. In the case of medicinal products for which a marketing authorisation by the competent higher federal authority forms the basis for mutual recognition or for which a competent higher federal authority is the rapporteur in arbitration proceedings pursuant to Article 32 of Directive 2001/83/EC, the competent higher federal authority shall assume the responsibility for the analysis and surveillance of all serious suspected adverse reactions that occur in the European Union; this shall also apply to medicinal products that were authorised for marketing in the decentralised procedure.
Section 63d
Periodic safety update reports
(1) The marketing authorisation holder shall transmit periodic safety update reports containing the following:
1. a summary of the data that is of interest in assessing the benefits and risks of a medicinal product, including the results of all studies that can have an effect on the marketing authorisation,
2. a scientific evaluation of the medicinal product’s risk-benefit balance that is based on all of the available data, including data from clinical trials for therapeutic indications and population groups that are not covered by the marketing authorisation,
3. all of the data relating to the medicinal product’s volume of sales as well as all of the data at his/her disposal relevant to the volume of prescriptions, including an estimate of the number of persons using the medicinal product.
(2) The periodic safety update reports are to be transmitted electronically:
1. in the case of medicinal products for which frequency and dates of submission of the periodic safety update reports are stipulated in the marketing authorisation or in accordance with the procedure pursuant to Article 107c paragraph 4, 5 and 6 of Directive 2001/83/EC, to the European Medicines Agency,
2. in the case of medicinal products that were authorised before 26 October 2012 and for which frequency and dates of submission of the periodic safety update reports are not stipulated in the marketing authorisation, to the competent higher federal authority,
3. in the case of medicinal products that were only authorised domestically and for which no frequency and dates of submission of the periodic safety update reports are not stipulated in the marketing authorisation pursuant to Article 107c paragraph 4 of Directive 2001/83/EC, to the competent higher federal authority.
The safety reports shall be transmitted electronically to the competent higher federal authority.
(3) The frequency for the submission of periodic safety update reports pursuant to sub-section 1 shall be specified in the marketing authorisation. The date for submission will be calculated from the date on which the marketing authorisation is granted. The submission frequency and the submission dates can be laid down in the European Union according to the procedure pursuant to Article 107c paragraph 4 of Directive 2001/83/EC. The marketing authorisation holder can apply to the Committee on Medical Products for Human Use or to the co-ordination group pursuant to Article 27 of Directive 2001/83/EC to have a single reference date pursuant to Article 107c (6) of Directive 2001/83/EC stipulated in the European Union or that the frequency for the submission of periodic safety update reports is changed. In the case of medicinal products that are authorised before 26 October 2012 or are authorised only for the national market and for which the submission frequency and dates are not specified in the marketing authorisation or pursuant to Article 107c paragraph 4, 5 or 6 of Directive 2001/83/EC, the marketing authorisation holder shall transmit the periodic safety update reports pursuant to sub-section 1 immediately upon request or in the following cases:
1. if a medicinal product has not yet been placed on the market: at least every six months after the marketing authorisation has been granted and until it is placed on the market,
2. if a medicinal product has been placed on the market: at least every six months during the first two years following the first placing on the market, once a year in the following two years and at three-yearly intervals thereafter.
(4) By way of derogation from sub-section 1 periodic safety update reports shall be transmitted for medicinal products that are authorised for marketing pursuant to Section 22 sub-section 3 or Section 24b sub-section 2 only in the following cases:
1. if a condition pursuant to Section 28 sub-section 3 or 3a has been imposed,
2. if they are requested by the competent higher federal authority for an active substance, after the marketing authorisation has been granted, owing to reservations in connection with pharmacovigilance data or owing to reservations due to insufficient availability of periodic safety update reports,
3. if the frequency and dates for the submission of periodic safety update reports pursuant to Article 107c (4) of Directive 2001/83/EC were specified in the marketing authorisation,
The competent higher federal authority shall transmit the assessment reports on the requested periodic safety update reports pursuant to sentence 1 number 2 to the Pharmacovigilance Risk Assessment Committee which examines whether it is necessary to initiate the procedure pursuant to Article 107c paragraph 4 of Directive 2001/83/EC. Sentence 1 numbers 2 and 3 apply mutatis mutandis to the holder of registrations pursuant to Section 38 or Section 39a, as well as to the pharmaceutical entrepreneur who is not the holder of the marketing authorisation or the registration pursuant to Section 38 or Section 39a and who places a traditional herbal medicinal product that is subject to authorisation or registration or exempt from the obligation to obtain an authorisation or registration on the market.
(5) The competent higher federal authority shall assess the periodic safety update reports to determine whether there are new risks or whether risks have changed and whether there are changes to the risk-benefit balance of medicinal products and shall take the necessary measures. In the case of medicinal products for which a single Union reference date or a single frequency date for the submission of reports pursuant to Article 107c paragraph 4 of Directive 2001/83/EC has been stipulated, as well as for medicinal products that are authorised in more than one Member States and for which periodic safety update reports are specified in the marketing authorisation, the procedure pursuant to Articles 107e and 107g shall apply to the assessment.
(6) The fulfilment of the obligations pursuant to sub-sections 1 to 4 can be totally or partly transferred to the marketing authorisation holder by means of a written agreement between the marketing authorisation holder and the pharmaceutical entrepreneur who is not the holder of the marketing authorisation. Sub-sections 1 to 5 do not apply to parallel importers.
Section 63e
European procedure
With regard to the cases governed by Article 107i of Directive 2001/83/EC, the competent higher federal authority shall take the measures provided for therein. Articles 107i to 107k of Directive 2001/83/EC shall apply to the procedure.
Section 63f
General prerequisites for non-interventional post-authorisation safety studies
(1) Notification of non-interventional post-authorisation safety studies that are conducted voluntarily by the marketing authorisation holder shall be made to the competent higher federal authority. The competent higher federal authority can require that the marketing authorisation holder submit the protocol and the progress reports. The marketing authorisation holder shall transmit the final report to the competent higher federal authority within one year after data collection is completed.
(2) In the case of non-interventional post-authorisation safety studies that are conducted by the marketing authorisation holder pursuant to a condition imposed pursuant to Section 28 sub-sections 3, 3a or 3b, the procedure pursuant to Section 63g shall apply.
(3) It shall not be admissible to conduct non-interventional post-authorisation safety studies pursuant to sub-sections 1 and 2 if:
1. conducting the study promotes the use of the medicinal product,
2. payments for the participation of the health professionals involved in such studies is not restricted in type and amount to compensation for time and expenses incurred, or
3. an incentive is created for the preferential prescription or recommendation of specific medicinal products.
(4) The marketing authorisation holder shall also immediately notify the Federal Association of Panel physicians, the Central Federal Association of the Health Insurance Funds and the German Association of Private Health Insurance Funds of post-authorisation safety studies pursuant to sub-sections 1 and 2. In doing so, he/she shall also provide information on the location, time, purpose and the protocol of the study as well as the name and lifelong physician identification number of the participating physicians. In so far as participating physicians provide benefits that are reimbursed by the statutory health insurance, the type and amount of the compensation actually paid to them in each case shall be communicated as well as a copy of each of the contracts signed with them and, in each case, a description of the costs incurred for the participating physicians and a justification for the appropriateness of the compensation shall be submitted in the case of notifications pursuant to sentence 1. In so far as modifications are made to the information specified in sentence 3, the information pursuant to sentence 3 shall be communicated in its entirety, in the modified, updated form within four weeks following the end of each quarter; the compensation actually paid is to be communicated and assigned to the participating physicians giving the name and the lifelong physician identification number. Within one year following the completion of the data collection process, the number of patients participating in each case, and in total, as well as the type and amount of the compensation paid in each case and in total are to be communicated giving the total number of participating physicians. The information pursuant to this sub-section is to be transmitted electronically according to the format specifications provided for in Section 67 sub-section 6 sentence 13.
Section 63g
Special prerequisites for imposed non-interventional post-authorisation safety studies
(1) In the case of non-interventional post-authorisation safety studies that were imposed pursuant to Section 28 sub-sections 3, 3a or 3b, the marketing authorisation holder shall submit the draft study protocol before conducting the study to:
1. the competent higher federal authority in the case of a study that will only be conducted on the territory governed by this Act,
2. the Pharmacovigilance Risk Assessment Committee in the case of a study that will be conducted in several Member States of the European Union.
(2) A non-interventional post-authorisation safety study pursuant to sub-section 1 may only be commenced if the draft protocol in the case of studies pursuant to sub-section 1 number 1 has been authorised by the competent higher federal authority or, in the case of studies pursuant to sub-section 1 number 2, has been authorised by the Pharmacovigilance Risk Assessment Committee and the draft protocol submitted to the competent higher federal authority. The competent higher federal authority shall take a decision on the authorisation of the study within 60 days following the submission of the draft protocol. The authorisation shall be refused if the use of the medicinal product is to be promoted, the aims cannot be achieved with the study design in question or the study is a clinical trial pursuant to Section 4 sub-section 23 sentence 1.
(3) Once a study pursuant to sub-section 1 has started, any essential changes to the protocol must be authorised before implementation:
1. by the competent higher federal authority, if the study is being conducted only on the territory governed by this Act,
2. by the Pharmacovigilance Risk Assessment Committee, if the study is being conducted in several Member States of the European Union.
If the study described in sentence 1 number 2 is also being conducted on the territory governed by this Act, the marketing authorisation holder shall inform the competent higher federal authority of the authorised changes.
(4) On completion of a study pursuant to sub-section 1, the final study report shall be submitted:
1. to the competent higher federal authority in the cases pursuant to sub-section 1 number 1,
2. to the Pharmacovigilance Risk Assessment Committee in the cases pursuant to sub-section 1 number 2,
within twelve months after data collection is completed if the competent authority pursuant to sentence 1 number 1 or 2 has not waived the submission. The final report shall be transmitted electronically together with a short description of the study findings.
Section 63h
Documentation and notification obligations for medicinal products for animal use
(1) In the case of medicinal products for animal use, the marketing authorisation holder shall keep documents on all suspected adverse reactions in the European Union or in a third country, as well as information on the quantities supplied.
(2) Furthermore, in the case of medicinal products for animal use, the marketing authorisation holder shall record:
1. every serious suspected adverse reaction within the purview of this Act, of which he/she gains knowledge
2.
a) any serious unexpected suspected adverse reaction reported to him/her by a health professional, which did not occur in a Member State of the European Union,
b) in the case of medicinal products that contain components derived from starting materials of human or animal origin, every suspected case of infection that has come to his/her knowledge and which is a serious adverse reaction and was caused by the contamination of said medicinal product through pathogens and which did not occur in a Member State of the European Union,
and notify the competent higher federal authority and the European Medicines Agency immediately or at the latest within 15 days, and
3. notify the competent higher federal authority immediately of frequent cases of abuse or individual cases of considerable abuse that have been observed if such abuse can directly endanger health.
The obligation to notify pursuant to sentence 1 numbers 1 and 2 letter a) shall apply mutatis mutandis to adverse reactions in human beings owing to the use of a medicinal product intended for animal use.
(3) The marketing authorisation holder who was granted the marketing authorisation through the mutual recognition process or through the decentralised procedure, shall furthermore ensure, in the case of medicinal products for animal use, that every suspected case of:
1. a serious adverse reaction, or
2. adverse reaction in human beings owing to the use of a medicinal product for animal use
that occurs within the purview of this Act, is also made available to the competent authorities of the Member State that granted the marketing authorisation which provided the basis for the recognition or the Member State that was the rapporteur in arbitration proceedings pursuant to Article 36 of Directive 2001/82/EC.
(4) In the case of medicinal products for animal use, the competent higher federal authority shall be furnished with all of the available documents needed to assess the cases of suspected or observed abuse, as well as a scientific assessment.
(5) In the case of medicinal products for animal use, and, if not otherwise stipulated either by imposed conditions or in sentence 5 or 6, the marketing authorisation holder shall submit to the competent higher federal authority a periodic safety update report for the medicinal product based on the obligations laid down in sub-section 1 and in Section 63a sub-section 1 immediately upon request or at least every six months after the marketing authorisation has been granted and until the placing on the market. Furthermore, he/she shall submit such reports immediately upon request or at least every six months during the first two years following the first placing on the market and once a year in the following two years. Thereafter, he/she shall submit the reports at intervals of three years or immediately upon request. The periodic safety update reports on medicinal products shall also contain a scientific assessment of the benefits and risks of the medicinal product in question. Upon request, the competent higher federal authority can prolong the intervals between reports. In the case of medicinal products that are exempted from the marketing authorisation pursuant to Section 36 sub-section 1, the competent higher federal authority shall lay down the date for the submission of the periodic safety update reports in a notice to be published in the Federal Gazette. Sentences 1 to 6 shall not apply to the parallel importer.
(6) Sub-sections 1 to 5, Section 62 sub-section 6 and Section 63b sub-section 3 shall apply mutatis mutandis:
1. to the holder of a registration pursuant to Section 39a,
2. to a pharmaceutical entrepreneur who is neither the holder of the marketing authorisation nor the holder of a registration pursuant to Section 39a and who places a medicinal product on the market that is subject to marketing authorisation or exempt from marketing authorisation or is a traditional herbal medicinal product.
Sub-sections 1 to 4 shall apply mutatis mutandis to:
1. to the holder of the registration pursuant to Section 38,
2. to a pharmaceutical entrepreneur who is not the holder of the registration pursuant to Section 38 and places a homeopathic medicinal product that is subject to registration or exempt from the obligation to obtain a registration on the market,
3. to the applicant before the marketing authorisation is granted.
Sub-sections 1 to 4 shall apply regardless of whether the medicinal product is still on the market or the marketing authorisation or registration still exists. The fulfilment of the obligations pursuant to sub-sections 1 to 5 can be totally or partly transferred to the marketing authorisation holder by means of a written agreement between the marketing authorisation holder and the pharmaceutical entrepreneur who is not the holder of the marketing authorisation.
(7) Sub-sections 1 to 6 shall not apply to medicinal products for which a marketing authorisation has been granted by the European Community or the European Union. For these medicinal products, the obligations of the pharmaceutical entrepreneur pursuant to Regulation (EC) No. 726/2004 and his/her obligations pursuant to Regulation (EC) No. 540/95, in the latest applicable version in either case, shall apply provided that, within the purview of this Act, the obligation to notify or to inform the Member States exists for the relevant competent higher federal authority. In the case of medicinal products for which a marketing authorisation by the competent higher federal authority forms the basis for mutual recognition or for which a competent higher federal authority is the rapporteur in arbitration proceedings pursuant to Article 36 of Directive 2001/82/EC, the competent higher federal authority shall assume the responsibility for the analysis and surveillance of all serious suspected adverse reactions that occur in the European Union; this shall also apply to medicinal products that were authorised for marketing in the decentralised procedure.
Section 63i
Documentation and notification obligations in respect of blood and tissue preparations and tissues
(1) The holder of a marketing authorisation for blood preparations pursuant to Article 3 (6) of Directive 2001/83/EC or a marketing authorisation or approval for tissue preparations or for haematopoietic stem cell preparations pursuant to Directive 2004/23/EC of the European Parliament and of the Council of 31 March 2004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells (OJ L 102 of 7.4.2004, p. 48), last amended by Regulation (EC) No. 596/2009 (OJ L 188 of 18.7.2009, p. 14) or a marketing authorisation for tissue preparations pursuant to Section 21, shall keep documents on all suspected serious incidents or serious adverse reactions that have occurred in a Member State of the European Union, in a State Party to the Agreement on the European Economic Area or in a third country, as well as the number of recalls.
(2) The holder of a marketing authorisation or authorisation for blood or tissue preparations pursuant to sub-section 1, shall, furthermore, document every suspected serious incident and every suspected serious adverse reaction and shall notify the competent higher federal authority thereof immediately, or at the latest within 15 days of acquiring this knowledge. The notification shall contain all of the necessary information, especially the name or firm and address of the pharmaceutical entrepreneur, name and number or code of the blood or tissue preparation, date and documentation of the emergence of the suspicion of the serious incident or the serious adverse reaction, date and place where the removal of the blood components or tissue took place, enterprises or facilities supplied as well as information on the donor. Furthermore, in the case of tissue preparations and haematopoietic stem cell preparations derived from peripheral blood or umbilical cord blood, the EU tissue establishment code must be given, if available, and when making a notification of a suspected serious adverse reaction, the Single European Code, if available. The incidents or reactions notified pursuant to sentence 1 are to be examined with respect to their causes and effects and subsequently evaluated and notification of the results, together with the measures to trace and protect both the donor and the recipient, shall be made immediately to the competent higher federal authority.
(3) In the case of blood and tissue preparations as well as blood and blood components, and tissues that are not subject to marketing authorisation or approval, the blood and plasma donation facilities or the tissue establishments shall document every suspected serious incident and every suspected serious adverse reaction and notify the competent authority immediately thereof. The notification shall contain all the necessary information such as the name or firm and address of the donation or tissue establishment, name and number or code of the blood or tissue preparation, date and documentation of the occurrence of the suspected serious incident or the serious adverse reaction, date on which the blood or tissue preparation was manufactured as well as information on the donor. Furthermore, in the case of tissues and tissue preparations as well as haematopoietic stem cells and stem cell preparations derived from peripheral blood or umbilical cord blood, the EU tissue establishment code must be given, if available, and when making a notification of a suspected serious adverse reaction, the Single European Code, if available, must be given. Sub-section 2 sentence 4 shall apply mutatis mutandis. The competent authority shall transmit the notifications pursuant to sentences 1 to 3 as well as the notifications pursuant to sentence 4 to the competent higher federal authority.
(4) The holder of a marketing authorisation for blood or tissue preparations within the meaning of sub-section 1 shall submit, to the competent higher federal authority, on the basis of the obligations contained in sub-section 1, an updated report on the safety of the medicinal product immediately upon request or, where recalls, cases or suspected cases of serious incidents or serious adverse reactions are involved, at least once a year. Sentence 1 shall not apply to parallel importers.
(5) Section 62 sub-section 1, sentences 1 and 2, sub-sections 4 and 6 and Section 63 shall apply mutatis mutandis. Sections 63a and 63b sub-sections 1 and 2 shall apply mutatis mutandis to the holder of an authorisation for blood or tissue preparations. The details shall be laid down in the Ordinance on the Manufacture of Medicinal Products and Active Substances; the general administrative regulation pursuant to Section 63 sentence 1 shall apply. Furthermore, Sections 62 to 63h shall not apply.
(6) A serious incident within the meaning of the foregoing provisions is any undesired event in connection with the procurement, testing, processing, preserving, storage or supply of blood and blood components, tissues, tissue or blood preparations which could lead to the transmission of an infectious disease, the death of a patient, a life-threatening state, disability or invalidity of patients, the need for or prolongation of hospitalisation as well as to the genesis or prolongation of a disease. A serious incident is also any incorrect identification or confusion of germ cells or impregnated egg cells within the framework of medically-assisted insemination measures.
(7) A serious adverse reaction within the meaning of the foregoing provisions is an unintended reaction, including an infectious disease in the donor or recipient in connection with the procurement of tissues or blood or the transplanting of tissue or blood preparations, which is fatal or life-threatening or leads to disability or invalidity or requires hospitalisation or the prolongation of existing hospitalisation or causes or prolongs a disease.
(8) The holder of a marketing authorisation or an approval for blood or tissue preparations, within the meaning of sub-section 1, may not make public any information regarding the haemo- or tissue vigilance, in connection with a medicinal product that has a market authorisation or approval, without prior or simultaneous notification of the competent higher federal authority and the European Commission. He/she shall ensure that such information is made public in a manner that is objective and not misleading.
Section 63j
Exceptions
(1) The provisions of Chapter Ten shall not apply to medicinal products that are used as investigational medicinal products within the framework of a clinical trial.
(2) Section 63b, with the exception of sub-sections 1 and 3, sections 63d, 63e, 63f and 63g, shall not apply to medicinal products for animal use.
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