Last Updated on May 29, 2021 by LawEuro
Medicinal Products Act (Laws / Regulations of Germany)
CHAPTER FOUR
Marketing authorisation of medicinal products
Section 21
Obligation to obtain a marketing authorisation
(1) Finished medicinal products that are medicinal products as defined in Section 2 sub-section 1 or sub-section 2 number 1, may only be placed on the market within the purview of this Act, if they have been authorised by the competent higher federal authority or if the European Community or the European Union has granted an authorisation for them to be placed on the market pursuant to Article 3 paragraph 1 or 2 of Regulation (EC) No. 726/2004 also in conjunction with Regulation (EC) No. 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use and amending Regulation (EEC) No. 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No. 726/2004 (OJ L 378 of 27.12.2006, p. 1) or Regulation (EC) No. 1394/2007. The same shall apply to medicinal products that are not finished medicinal products and are intended for administration to animals, provided they are not intended for distribution to pharmaceutical entrepreneurs holding an authorisation for the manufacture of medicinal products.
(2) A marketing authorisation (Zulassung) shall not be required for medicinal products that:
1. are intended for administration to human beings and the essential manufacturing stages of which, owing to the documented frequency with which they are the subject of medical and dental prescriptions, are carried out in a pharmacy in an amount of up to one hundred packages ready for dispensing in the space of one day within the framework of the existing pharmacy operating licence,
1a. are medicinal products manufactured from substances of human origin, which are either intended for autologous use or for targeted administration to a specific person, or are prepared on prescription for individual persons, unless medicinal products pursuant to Section 4 sub-section 4 are concerned,
1b. are medicinal products other than those referred to in number 1a, which are manufactured for pharmacies which are in possession of a prescription for a patient from medicinal products authorised within the purview of this Act:
a) as cytostatic preparations or for parenteral nutrition, as well as in other medically justified cases of special need if it is necessary in order to provide adequate care for the patient and no other medicinal product with a marketing authorisation is available, or
b) as a blister from unchanged medicinal products, or
c) are decanted in an unchanged form,
1c. are intended for use in human beings, show antibacterial or antiviral efficacy and are intended for the treatment of a dangerous communicable disease – the spread of which renders necessary an immediate supply of specific medicinal products in excess of normal requirements – and are manufactured from active substances, which have been stored for this purpose by Federal and Land health authorities, or agencies designated by them, provided that they are manufactured in a pharmacy for dispensing within the framework of the existing pharmacy operating licence of for dispensing to other pharmacies,
1d. are tissue preparations which are subject to the obligation to obtain an approval pursuant to the provisions contained in Section 21a sub-section 1,
1e. are curative waters, moor muds for baths or other peloids, which are not manufactured in advance and are not intended to be placed on the market in a specific packaging for sale to the consumer, or which are intended exclusively for external use or for inhalation on the premises,
1f. are medicinal gases and are manufactured for individual persons from medicinal products authorised within the purview of this Act through filling and labelling in enterprises authorised pursuant to Section 50 to conduct retail trade in medicinal products outside of pharmacies,
1g. are therapeutic allergens manufactured to order for individual patients,
2. are intended for use in clinical trials on human beings,
3. are medicated feeding stuffs, manufactured in keeping with their designated purpose from medicated pre-mixes for which a marketing authorisation has been issued pursuant to Section 25,
4. are manufactured for individual animals or animals belonging to a specific stock, in pharmacies or in veterinary in-house dispensaries under the prerequisites specified in sub-section 2a,
5. are intended for use in clinical trials on animals or in residue tests, or
6. are made available free of charge under the conditions specified to in Article 83 of Regulation (EC) No. 726/2004 for administration to patients with a seriously debilitating disease or whose disease is life-threatening, and who cannot be treated satisfactorily with an authorised medicinal product; this applies equally to medicinal products which do not fall under the categories stipulated in Article 3 first or second paragraph of Council Regulation (EC) No. 726/2004; procedure shall be specified in an ordinance pursuant to Section 80.
(2a) Medicinal Products which contain substances and preparations from substances which have not been released for trade outside of pharmacies, may only be manufactured pursuant to sub-section 2 number 4 if a medicinal product authorised for the treatment of the animal species in question or for the specific therapeutic indications is not available, if the necessary medicinal treatment of the animals would otherwise be seriously jeopardized and if no direct or indirect danger to the health of human beings and animals is to be feared. The manufacture of medicinal products pursuant to sentence 1 is only admissible in pharmacies. Sentence 2 shall not apply to the preparation of medicinal products from a finished medicinal product and medically non-active constituents or to the mixing of finished medicinal products intended for the immobilisation of zoo, wild and reserve animals. For the purposes of sentence 1, the decanting, packaging or labelling of medicinal products in unchanged form shall not be considered as manufacturing, in so far as:
1. no finished medicinal products are available commercially in package sizes suitable for the individual case, or
2. in other cases, the container or any other form of pharmaceutical packaging coming into direct contact with the medicinal product is not damaged.
Sentences 1 to 4 shall not apply to homeopathic medicinal products which are either registered or exempt from registration and, should they be intended for use in food-producing animals, if they contain only the active substances listed the Annex to Regulation (EU) No. 37/2010 as substances which do not require the stipulation of maximum levels.
(3) The application for a marketing authorisation shall be made by the pharmaceutical entrepreneur. For a finished medicinal product manufactured in pharmacies or at other retail dealers using standardized procedures, and distributed to the consumer under a standardized name, the application for a marketing authorisation shall be made by the party responsible for the issue of the master formula. If a finished medicinal product is manufactured for several pharmacies or other retail dealers and is to be distributed to the consumer under their name and under a standardized name, then the manufacturer shall apply for the marketing authorisation.
(4) Furthermore, at the request of the competent authority of the Land, the competent higher federal authority shall decide on the obligation to obtain a marketing authorisation for a specific medicinal product, the obligation to obtain approval for a tissue preparation or a clinical trial, irrespective of an application for a marketing authorisation pursuant to sub-section 3 or an application for approval pursuant to Section 21a sub-section 1 or Section 42 sub-section 2. The competent Land authority shall include a reasoned opinion on the classification of the medicinal product or the clinical trial with the application.
Section 21a
Approval of tissue preparations
(1) Tissue preparations that are not manufactured using an industrial process and the essential processing procedures of which are sufficiently well known in the European Union, and the effects and adverse reactions of which are known and evident from scientific data, may only be placed on the market within the purview of this Act, if they have been approved by the competent higher federal authority, by way of derogation from the marketing authorisation obligations pursuant to Section 21 sub-section 1. This shall also apply to tissue preparations the processing procedures for which are new but comparable with a known procedure. Sentence 1 shall apply mutatis mutandis to haematopoietic stem cell preparations derived from peripheral blood or umbilical cord blood intended for autologous use or for targeted administration to a specific person. The approval shall cover the procedures for the procurement, processing and testing, the choice of donors and the documentation for each operational step as well as the quantitative and qualitative criteria for tissue preparations. Especially the critical operational steps must be evaluated to ascertain that the functionality and the safety of the tissues are guaranteed.
(1a) An approval pursuant to sub-section 1 is not required for tissue preparations that are intended for clinical trials on human beings.
(2) The application for approval shall be accompanied by the following information and documents to be supplied by the applicant:
1. the name or the company and the address of the applicant and the processors,
2. the name of the tissue preparation,
3. the components of the tissue preparation by nature, pharmaceutical form and package size,
4. the therapeutic indications as well as the method of administration and, in the case of tissue preparations that are intended to be used for a limited period of time, the duration of the application,
5. Information on the procurement of the tissue and on the laboratory testing necessary for such procurement,
6. Information on the method of manufacture, including the processing procedures, the test procedures with their in-process and finished process controls, as well as the use of beta, gamma or x-rays,
7. Information on the method of preservation, shelf-life, retention and storage conditions of the tissue preparations,
8. Information on the functionality and the risks of tissue preparations,
9. documents containing the results of microbiological, chemical, biological or physical examinations and the methods used in their determination, in so far as these documents are necessary,
10. documents containing the results of pharmacological and toxicological tests,
11. a risk-benefit assessment,
12. all of the information and documents which is relevant to the purpose of evaluation of the medicinal product, as well as
13. in the case of haematopoietic stem cell preparations, also information on the dosage and quantity of active substance.
The results and the information pursuant to sentence 1 numbers 7 to 10, as well as the results of clinical trials or other medical trials are to be documented in such a way that the type, scope and date of the tests are evident. Section 22 sub-sections 4, 5 and 7 sentence 1 shall apply mutatis mutandis.
(3) In respect of the information pursuant to sub-section 2 numbers 4, 8 and 10, scientific findings which are also able to compare with empirical medical findings prepared according to scientific methods can be submitted. These can include studies conducted by the manufacturer of the tissue preparation, data from publications or subsequent assessments of the clinical findings on the manufactured tissue preparations.
(4) The competent higher federal authority shall reach a decision on the application for approval within a period of five months. If the applicant is given the opportunity to correct flaws, the deadlines shall be interrupted until such flaws have been corrected or until the expiry of the deadline set for the correction of the flaws. The interruption of the deadline shall begin on the day the applicant receives the request to correct the flaws.
(5) The competent higher federal authority shall grant approval in writing, together with an approval number. The authority may combine the approval with the imposition of conditions. Section 28 and Section 34 shall apply mutatis mutandis.
(6) The competent higher federal authority may only refuse approval if:
1. the documents submitted are incomplete,
2. the tissue preparation does not correspond to the current state of scientific knowledge,
3. the tissue preparation does not fulfil the envisaged function or the risk-benefit balance is unfavourable, or
4. the placing of the tissue preparation on the market would violate legal regulations or a regulation, directive, decision or resolution by the European Community or the European Union.
(7) The applicant, or subsequent to the approval, the holder of the approval shall immediately notify the competent higher federal authority of any changes in the information pursuant to sub-sections 2 and 3 and include the corresponding documents with the notification. The holder of the approval shall be required to inform the competent higher federal authority of new or changed risks in connection with the tissue preparation or of changes in the tissue preparation’s risk-benefit balance. Section 29 sub-sections 1a, 1d and 2 shall apply mutatis mutandis. The following changes may be made only if the competent higher federal authority has granted its approval:
1. a change in the information on the nature, the duration of the administration, or the therapeutic indications,
2. a limitation of the risks,
3. a change in either the type or quantity of the excipients,
4. a change in the pharmaceutical form,
5. a change in the information on the procurement of the tissue and on the laboratory testing necessary for such procurement,
6. a change in the processing procedure or the test procedure,
7. a change in the method of preservation and an extension of the shelf life,
8. a change in the method of retention and storage of the tissue preparation, and
9. in the case of haematopoietic stem cell preparations, also a modification of the information on the dosage or the quantity of active substance.
The decision on the application for approval must be taken within three months. Section 27 sub-section 2 shall apply mutatis mutandis.
(8) The approval shall be withdrawn if it subsequently becomes known that one of the grounds for refusal, pursuant to sub-section 6 numbers 2 to 4 existed at the time the authorisation was granted. The authorisation shall be revoked if one of the grounds for refusal subsequently developed. In both cases, the temporary suspension of the approval may also be ordered. Before a decision is reached pursuant to sentences 1 to 3, the holder of the approval shall be heard unless danger is imminent. If the approval has been withdrawn, revoked or suspended, the tissue preparation may not be placed on the market, nor shall it be introduced into the purview of this Act.
(9) By way of derogation from sub-section 1, tissue preparations and haematopoietic stem cell preparations derived from peripheral blood or umbilical cord blood pursuant to sub-section 1 sentence 3 that are allowed to be placed on the market in a Member State of the European Union or in another State Party to the Agreement on the European Economic Area, shall require an attestation from the competent higher federal authority before the first introduction into the purview of this Act for the purpose of being used. Before issuing the attestation, the competent higher federal authority shall examine whether the processing of the tissue preparations meets the requirements with respect to the removal and processing procedures including the donor selection procedures and the laboratory examinations, and whether the quantitative and qualitative criteria for the tissue preparations meet the requirements of this Act and its ordinances. The competent higher federal authority must issue the attestation if the approval certificate or another attestation from the competent authority of the country of origin demonstrates the equivalence of the requirements pursuant to sentence 2 and the proof of approval in the Member State of the European Union or in another State Party to the Agreement on the European Economic Area is submitted. The competent higher federal authority shall be notified on time of any change in the requirements pursuant to sentence 2 prior to any further introduction of the tissue preparation into the purview of this Act. The attestation is to be withdrawn if one of the prerequisites pursuant to sentence 2 had not been met; it shall be revoked if one of the prerequisites pursuant to sentence 2 is, subsequently, no longer met. Section 73 sub-section 3a shall apply mutatis mutandis.
Section 22
Marketing authorisation documents
(1) The applicant shall attach the following information to his/her application for a marketing authorisation:
1. the name or the company and the address of the applicant and the manufacturer,
2. the name of the medicinal product,
3. the constituents of the medicinal product by type and quantity; Section 10 sub-section 6 shall apply,
4. the pharmaceutical form,
5. the effects,
6. the therapeutic indications,
7. the contra-indications,
8. the adverse reactions,
9. the interactions with other products,
10. the dosage,
11. the medicinal product’s method of manufacture,
12. the method of administration and, in the case of medicinal products which should only be administered for a limited period of time, the duration of the administration,
13. the package sizes,
14. the method of preservation, shelf-life, storage conditions, results of stability tests,
15. the methods of quality control (test methods).
(1a) The information pursuant to sub-section 1 numbers 1 to 10 must be provided in the German language, the other information in German or in English; other information or documents can also be provided or submitted in English instead of in German, within the framework of the marketing authorisation procedure, in so far as information for use in the labelling, the package leaflet or the expert information are not concerned.
(2) Furthermore, the following information shall be submitted:
1. the results of physical, chemical, biological or microbiological examinations and the methods used in their determination (analytical test),
2. the results of the pharmacological and toxicological tests,
3. the results of clinical trials or other medical, dental or veterinary tests,
4. a statement to the effect that clinical trials conducted outside the European Union were conducted under ethical conditions which are equivalent to the ethical conditions laid down in Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use (OJ L 121 of 1.5.2001, p. 34),
5. in the case of medicinal products for human use, a summarised description of the applicant’s pharmacovigilance system which must contain the following:
a) evidence that the applicant has the services of a qualified person at his/her disposal pursuant to Section 63a, as well as the Member State in which this person is domiciled and works and his/her contact information,
b) the name of the place where the pharmacovigilance system master file for the medicinal product in question is kept, and
c) a declaration signed by the applicant that he/she possesses the necessary funds in order to fulfil the tasks and obligations listed in Chapter Ten,
5a. in the case of medicinal products for human use, the risk management plan containing a description of the risk-management system which the applicant will introduce for the medicinal product in question, together with a summary,
6. in the case of medicinal products for animal use, a detailed description of the applicant’s pharmacovigilance system, proof that the applicant has the services of a qualified person pursuant to Section 63a at his/her disposal and, in so far as necessary, of the risk-management system which this applicant will introduce, as well as proof of the necessary infrastructure for reporting all suspected adverse reactions pursuant to Section 63h,
7. a copy of each orphan medicinal product designation pursuant to Regulation (EC) No. 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products (OJ L 18, p. 1),
8. in the case of medicinal products for human use, a confirmation by the medicinal product manufacturer that he/she or another person designated by contract has satisfied him/herself, by means of an inspection on site, that good manufacturing practice is being applied in the manufacture of the active substances; the confirmation must also contain the date of the audit.
The results pursuant to sentence 1 numbers 1 to 3 shall be substantiated by documentary evidence in such a way that the type, scope and exact time of the tests are clearly evident. The application for a marketing authorisation shall be accompanied by all of the relevant information and documents necessary for the assessment of the medicinal product, whether favourable or unfavourable. This shall also apply to incomplete or discontinued toxicological or pharmacological tests or clinical trials carried out using the medicinal product in question.
(3) Instead of the results specified in sub-section 2 numbers 2 and 3, other scientific documents may be presented:
1. in the case of a medicinal product which contains active substances that have been used for at least ten years in the European Union for general medical or veterinary purposes, the effects and adverse reactions of which are known and evident from scientific data,
2. in the case of a medicinal product which, in its composition, is comparable to a medicinal product pursuant to number 1,
3. for the constituents of the medicinal product, in the case of a medicinal product which is a new combination of constituents that are already known; however, other documents containing scientific findings may also be presented for the combination as such, if the efficacy and safety of the medicinal product according to its composition, dosage, pharmaceutical form and therapeutic indications can be determined by these documents.
Furthermore, the medical experience gained by the specific schools of therapy must also be taken into consideration.
(3a) If the medicinal product contains more than one active substance, evidence shall be provided to prove that every active substance contributes to the positive assessment of the medicinal product.
(3b) In the case of radiopharmaceuticals which are generators, a general description of the system, including a detailed description of those components of the system which are able to influence the composition or quality of the secondary radioactive nuclide preparation, as well as the particular qualitative and quantitative characteristics of the eluate or the sublimate, are to be provided.
(3c) Documents should also be submitted for the evaluation of possible environmental risks and if the storage of the medicinal product or its administration or the disposal of its waste requires special safety precautions or measures to avoid endangering the environment or impairing the health of human beings, animals or plants, this shall also be stated. Information on how to reduce these dangers shall also be submitted and substantiated. In the case of medicinal products intended for use in animals, the results of the tests to evaluate possible environmental risks shall be submitted; sub-section 2 sentences 2 to 4 shall apply mutatis mutandis.
(4) If an application is made for a marketing authorisation in respect of a medicinal product manufactured within the purview of this Act, proof shall be furnished that the manufacturer is entitled to manufacture the medicinal product. This shall not apply in the case of an application pursuant to Section 21 sub-section 3 sentence 2.
(5) If an application is made for a marketing authorisation in respect of a medicinal product manufactured outside the purview of this Act, proof shall be furnished that the manufacturer is entitled to manufacture medicinal products in accordance with the legal regulations laid down by the country of manufacture and, in the event that the medicinal product is introduced from a country which is not a Member State of the European Union or a State Party to the Agreement on the European Economic Area, that the importer is in possession of an authorisation to introduce the medicinal product into the territory governed by this Act.
(6) If the medicinal product has already been granted a marketing authorisation in a foreign state, a copy of such authorisation and, in the case of medicinal products for human use, a copy of the summary of the safety data including the data from the periodic safety update reports, where available, and the reports on suspected adverse reactions shall be included. Where an application for a marketing authorisation has been denied in whole or in part, the details of that decision shall be furnished and the grounds for it explained. Where an application for a marketing authorisation is currently being examined in one or several Member States of the European Union, this shall be stated. Copies of the summaries of the product characteristics and package leaflets approved by the competent authorities of the Member States or, where these documents are not available, the versions of these documents proposed by the applicant in the course of a procedure pursuant to sentence 3, shall also be included. Furthermore, where an application for the recognition of the marketing authorisation of another Member State is submitted, the declarations required under Article 28 of Directive 2001/83/EC or in Article 32 of Directive 2001/82/EC shall be submitted along with the other information stipulated therein. Sentence 5 shall not apply to medicinal products which have been manufactured according to homeopathic manufacturing procedures.
(7) The application for a marketing authorisation shall be accompanied by the wording of the information that is meant to appear on the container, the outer packaging and the package leaflet as well as the draft of the Summary of Product Characteristics, which shall also represent the expert information pursuant to Section 11a sub-section 1 sentence 2, where such expert information is stipulated. In the case of medicinal products intended for administration to human beings, the results of evaluations of the package leaflet conducted in collaboration with patient target groups shall also be submitted to the competent higher federal authority. The competent higher federal authority may require the submission of one or more samples or mock-ups of the sales presentation of the medicinal product, including the package leaflets, as well as starting materials, intermediate products and substances which are used in the manufacture or testing of the medicinal products, in a quantity sufficient to conduct the test and in a state suitable to the conduct of said test.
Section 23
Particular documents required for medicinal products intended for administration to animals
(1) In respect of medicinal products intended for administration to food-producing animals, the following information shall be given in addition to those specified in Section 22:
1. information about the withdrawal period shall be given and shall be substantiated by documents on the results of the residue tests and particularly on the fate of the pharmacologically active constituents and their metabolic products in the animal body and on the influence on foodstuffs of animal origin, in so far as these results are necessary for the assessment of withdrawal periods taking stipulated maximum levels into account, and
2. in the case of a medicinal product with a pharmacologically active constituent not listed in Table 1 of the Annex to Regulation (EU) No. 37/2010, an attestation confirming that an application pursuant to Article 3 of Regulation (EC) No. 470/2009 of the European Parliament and of the Council of 6 May 2009 laying down Community procedures for the establishment of residue limits of pharmacologically active substances in foodstuffs of animal origin, repealing Council Regulation (EEC) No. 2377/90 and amending Directive 2001/82/EC of the European Parliament and of the Council and Regulation (EC) No. 726/2004 of the European Parliament and of the Council (OJ L 152 of 16.6.2009, p. 11), in the latest applicable version, had been submitted to the European Medicines Agency at least 6 months previous to the application for marketing authorisation.
3. (repealed)
Sentence 1 number 2 shall not apply if Section 25 sub-section 2 sentence 5 applies.
(2) In the case of medicated pre-mixes, the particulars of the mixed feed intended as carrier shall be given with the designation of the type of feeding stuff. Furthermore, it shall be justified and proved by documents that the medicated pre-mixes are suited for the intended manufacture of the medicated feeding stuff, and particularly that they allow a homogeneous and stable distribution of the active substances in the medicated feeding stuffs taking into consideration the manufacturing methods applied in the production of mixed feed; furthermore, the shelf-life of medicated feeding stuffs shall be indicated, grounds provided and proved by documents. Moreover, a routine test method suitable for the quantitative and qualitative analysis of the active substances in the medicated feeding stuffs, shall be described and documents on test results submitted as proof.
(3) The nature and scope of as well as the date on which the tests were carried out shall be inferable from the documents containing the results of the residue tests and the residue test procedures pursuant to sub-section 1, as well as from the evidence regarding the suitability of the medicated pre-mixes for the intended manufacture of the medicated feeding stuff and the test results of the test methods pursuant to sub-section 2. Instead of the documents, the evidence and test results referred to in sentence 1, other scientific findings may be submitted.
Section 24
Expert opinions
(1) Expert opinions in which the test methods, test results and residue test procedures are summarized and assessed, shall be included with the required documents pursuant to Section 22 sub-section 1 number 15, sub-sections 2 and 3 and Section 23. In particular, the following information shall be included in detail in the expert opinions presented:
1. the analytical expert opinion shall state whether the medicinal product is of appropriate quality in accordance with recognized pharmaceutical rules, whether the proposed test methods comply with the prevailing standard of scientific knowledge and are suitable for quality assessment,
2. the pharmacological-toxicological expert opinion shall state the medicinal product’s toxic effects and pharmacological properties,
3. the clinical expert opinion shall state whether the medicinal product has the required effect in the specified therapeutic indications, whether it is tolerated, whether the prescribed dosage is appropriate and which contra-indications and adverse reactions exist,
4. the expert opinion on the residue test shall state whether, and if so, how long after the administration of the medicinal product, residues occur in the foodstuffs obtained from the animals which have undergone treatment, how these residues are to be assessed and whether the prescribed withdrawal period is sufficient.
Moreover, the expert opinion shall state whether the type and quantity of residue present after the prescribed withdrawal period has elapsed are below the maximum levels stipulated in the Annex to Regulation (EU) No. 37/2010.
(2) In so far as scientific documentation is presented pursuant to Section 22 sub-section 3 and Section 23 sub-section 3 sentence 2, it must be evident from the expert opinion, that the documents on scientific findings were elaborated under analogous application of the Guidelines for the Testing of Medicinal Products.
(3) The expert opinion shall be accompanied by information regarding the name, training and professional practice of the expert as well as his/her professional relationship with the applicant. The experts shall confirm with their dated signature that they are the authors of the expert opinion.
Section 24a
Use of a previous applicant’s documents
The applicant can refer to the documents referred to in Section 22 sub-sections 2, 3, 3c and Section 23 sub-section 1, including the expert opinion referred to in Section 24 sub-section 1 sentence 2 submitted by an earlier applicant (previous applicant), if he/she submits the previous applicant’s written agreement, including confirmation that the documents referred to meet the requirements of the Guidelines for the Testing of Medicinal Products pursuant to Section 26. The previous applicant shall respond to a request for agreement, within a period of three months. A partial reference is not admissible.
Section 24b
Authorisation of a generic medicinal product, document protection
(1) In the case of a generic medicinal product within the meaning of sub-section 2, reference can be made, without the previous applicant’s agreement, to the documents referred to in sentence 1 of Section 22 sub-section 2 sentence 1 numbers 2 and 3 and Section 23 sub-section 1, including the expert report referred to in Section 24 sub-section 1 sentence 2 numbers 2 to 4 for the previous applicant’s medicinal product (reference medicinal product), provided that the reference medicinal product has been authorised for at least eight years or was authorised at least eight years previously; this shall also apply to authorisation in another Member State of the European Union. A generic medicinal product authorised pursuant to this provision shall not be placed on the market until ten years have elapsed following the first authorisation of the reference medicinal product. The period referred to in sentence 2 shall be extended to a maximum of eleven years if, during the first eight years of authorisation, the marketing authorisation holder obtains authorisation for one or more new therapeutic indications which during the scientific evaluation conducted prior to their authorisation by the competent higher federal authority are held to bring significant clinical benefit in comparison with existing therapies.
(2) Authorisation as a generic medicinal product pursuant to sub-section 1 shall require that the medicinal product in question has the same qualitative and quantitative composition of active substances and the same pharmaceutical form as the reference medicinal product and that the bioequivalence has been demonstrated in bioavailability studies. The different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance shall be considered to be one and the same active substance unless their properties differ significantly with regard to safety or efficacy. In such cases, the applicant must submit additional proof of the safety or efficacy of the different salts, esters, ethers, isomers, mixture of isomers, complexes or derivatives of the active substance. The various immediate release oral pharmaceutical forms shall be considered to be one and the same pharmaceutical form. The applicant shall not be required to submit bioavailability studies if he/she can otherwise demonstrate that the generic medicinal product meets the relevant bioequivalence criteria in accordance with current scientific knowledge. In cases where the medicinal product does not meet the requirements of a generic medicinal product or where the bioequivalence cannot be demonstrated through bioequivalence studies or in the case of a change in the active substance, therapeutic indication, strength, pharmaceutical form or route of administration vis-à-vis the reference medicinal product, the results of appropriate preclinical tests or clinical trials shall be provided. In the case of medicinal products intended for use in animals, the corresponding safety studies and in the case of medicinal products intended for use in food-producing animals, the results of corresponding residue tests shall also be submitted.
(3) If the reference medicinal product was not authorised by the competent higher federal authority but by the competent authority of another Member State, the applicant shall indicate in the application form, where the reference medicinal product is or has been authorised. In this case, the competent higher federal authority shall ask the competent authority of the other Member State to transmit within one month a confirmation that the reference medicinal product is or has been authorised, together with the full composition of the reference medicinal product and other documents relevant to the authorisation of the generic medicinal product. In the case where the reference medicinal product has been authorised by the European Medicines Agency, the competent higher federal authority shall ask the latter for the information and documents referred to in sentence 2.
(4) If the competent authority of another Member State where an application is submitted requests information or documents referred to in sub-section 3 sentence 2 of the competent higher federal authority, the latter shall respond to this request within one month, provided that at least eight years have elapsed since the reference medicinal product was first authorised.
(5) Where a biological medicinal product which is similar to a biological reference medicinal product does not meet the conditions for generic medicinal products, referred to in sub-section 2 owing to, in particular, differences relating to raw materials or differences between the manufacturing processes of the biological medicinal product and the reference biological medicinal product, the results of appropriate preclinical tests or clinical trials relating to these deviations must be provided. The type and quantity of the supplementary data to be provided must comply with the relevant criteria according to current scientific knowledge. The results of other tests from the documents submitted for the reference medicinal product’s authorisation shall not be provided.
(6) In addition to the provisions laid down in sub-section 1, where an application is made for a new therapeutic indication for a known active substance that has been in general medical use for at least ten years in the European Union, a non-cumulative period of one year of data exclusivity shall be granted for the data gained from significant preclinical or clinical studies carried out in connection with the new therapeutic indication.
(7) Sub-section 1 sentence 3 and sub-section 6 shall not apply to generic medicinal products intended for use in animals. The period referred to in sub-section 1 sentence 2 shall be extended:
1. to thirteen years in the case of veterinary medicinal products intended for use in fish or bees,
2. in the case of veterinary medicinal products intended for one or more food-producing species, containing a new active substance that had not been authorised in the Community by 30th April 2004, by one year for each extension of the marketing authorisation to another food-producing species which takes place within the five years following the granting of the initial marketing authorisation. This period shall not, however, exceed a total of thirteen years for a marketing authorisation for four or more food-producing species.
The prolongation of the ten-year period to eleven, twelve or thirteen years for a veterinary medicinal product intended for a food-producing species shall be granted only if the marketing authorisation holder also originally applied for the setting of maximum residues limits for the species covered by the authorisation.
(8) If the extension of a marketing authorisation is for a veterinary medicinal product registered pursuant to Section 22 sub-section 3 and relates to a food-producing species and was obtained on submission of new residue tests and new clinical trials, the data obtained in the aforementioned tests shall be covered by an exclusivity period of three years after the granting of the authorisation.
Section 24c
Additional requests
If several holders of a marketing authorisation have to be requested to submit additional documents, the competent higher federal authority shall notify every holder of a marketing authorisation of the documents necessary for the further assessment as well as of the names and addresses of the other holders of a marketing authorisation who are involved. The competent higher federal authority shall give those holders of the marketing authorisation who are involved the opportunity to decide among themselves as to who will submit the documents within a period of time to be determined by the authority. If an agreement is not reached, the competent higher federal authority shall decide and immediately inform all persons concerned. Unless the other holders of a marketing authorisation choose to forgo the marketing authorisation granted for their own pharmaceutical product, they shall be obliged to contribute proportionally to the expenditure incurred in the preparation of the documents, calculated according to the number of marketing authorisation holders involved; they are jointly and severally liable. Sentences 1 to 4 shall apply mutatis mutandis to persons using standard marketing authorisations, as well as in cases where documents with the same contents are requested from several applicants in ongoing marketing authorisation procedures.
Section 24d
General right of use
The competent higher federal authority is hereby empowered to utilize the documents submitted to it, with the exception of those referred to under Section 22 sub-section 1 numbers 11, 14 and 15 as well as sub-section 2 number 1, and the expert opinion pursuant to Section 24 sub-section 1 sentence 2 number 1, in fulfilling its tasks under this Act, provided that at least eight years have elapsed since the medicinal product first received a marketing authorisation in one of the Member States of the European Union or a procedure pursuant to Section 24c has not yet been terminated, or in so far as Sections 24a and 24b do not contain more special provisions for referring to the documents of a previous applicant.
Section 25
Decision on marketing authorisation
(1) The marketing authorisation, together with a marketing authorisation number, shall be issued in writing by the competent higher federal authority. The marketing authorisation shall only be applicable to the medicinal product specified in the marketing authorisation notice and, in the case of medicinal products manufactured according to homeopathic manufacturing procedures, it shall also apply to the degree of dilution specified in results published pursuant to Section 25 sub-section 7 sentence 1 of the version in force prior to 17 August 1994 and specified in the marketing authorisation notice.
(2) The competent higher federal authority may only refuse to grant the marketing authorisation if:
1. the documents submitted, including such documents as are to be submitted pursuant to a regulation of the European Community or the European Union, are incomplete,
2. the medicinal product has not been sufficiently tested in accordance with the confirmed state of scientific knowledge or the other scientific information material referred to in Section 22 sub-section 3 does not correspond to the confirmed state of scientific knowledge,
3. the medicinal product is not manufactured in accordance with recognised pharmaceutical rules or does not meet appropriate quality standards,
4. the therapeutic efficacy attributed to the medicinal product by the applicant is lacking or is insufficiently substantiated by the applicant in accordance with the confirmed state of scientific knowledge,
5. the benefit/risk profile is unfavourable,
5a. in the case of a medicinal product containing more than one active substance, insufficient grounds are provided to demonstrate that each active substance contributes towards a positive assessment of the medicinal product, whereby the special features of the particular medicinal product should be considered in a risk evaluation,
6. the withdrawal period given is insufficient,
6a. in the case of medicated pre-mixes, the test methods used for the qualitative and quantitative detection of the active substances in the medicated feedstuffs cannot be routinely conducted,
6b. the medicinal product is intended for use in food-producing animals and contains a pharmacologically active constituent not listed in Table 1 of the Annex to Regulation (EU) No. 37/2010,
7. the placing of the medicinal product on the market or its administration to animals would violate legal regulations or a regulation, directive, decision or resolution by the European Community or the European Union.
The marketing authorisation may not be refused pursuant to sentence 1 number 4, because therapeutic results have been achieved in only a limited number of cases. Therapeutic efficacy is lacking if the applicant fails to prove, according to the confirmed state of scientific knowledge at the time, that a therapeutic effect can be produced with the medicinal product. Medical experience in the particular therapeutic field shall be considered. Pursuant to sentence 1 number 6b, the marketing authorisation may be refused if the medicinal product is intended for the treatment of individual equidae to which the conditions referred to in Article 6 paragraph 3 of Directive 2001/82/EC apply and if it fulfils the other conditions in Article 6 paragraph 3 of Directive 2001/82/EC.
(3) The marketing authorisation shall be refused for a medicinal product which differs, in the nature or the quantity of its active substances, from a medicinal product bearing the same name which has been authorised for marketing or is already on the market. Deviating from sentence 1, a difference in the quantity of active substances shall be harmless if the medicinal products differ in their pharmaceutical form.
(4) If the competent higher federal authority is of the opinion that a marketing authorisation cannot be granted on the basis of the documents submitted, it shall notify the applicant, stating reasons. The applicant shall then have the opportunity to correct the flaw within an appropriate deadline which may not exceed six months. In the event that the flaws are not corrected within this deadline, the marketing authorisation shall be refused. After the decision has been taken to refuse the marketing authorisation, the submission of documents in order to correct flaws shall not be allowed.
(5) The marketing authorisation shall be granted on the basis of the examination of the documents submitted as well as on the basis of the expert opinions. In the assessment of the documents, the competent higher federal authority may utilize its own scientific results, call in experts or request expert opinions. The competent higher federal authority may examine authorisation-related data and documents also in connection with a marketing authorisation pursuant to Article 3 paragraph 1 or 2 of Regulation (EC) No. 726/2004 in enterprises and facilities which develop, manufacture, test or clinically investigate medicinal products. For this purpose, persons commissioned by the competent higher federal authority, in consultation with the respective competent authorities, may enter the operating and business premises during usual business hours to inspect documents and request information. Moreover, in making a decision in respect of the marketing authorisation, the competent higher federal authority is also entitled to have the documents assessed by independent counter-experts and shall apply the results of their evaluation in deciding on the marketing authorisation and, in so far as medicinal products which are subject to mandatory prescription under Section 48 sub-section 2 number 1 are concerned, as a basis for the draft of the marketing authorisation decision which is to be submitted to the marketing authorisation commission pursuant to sub-section 6 sentence 1. The competent higher federal authority may commission, as a counter-expert pursuant to sentence 5, any person who possesses the requisite expert knowledge and the reliability required to do the work of a counter-expert. Upon request, the applicant shall be permitted to peruse the expert opinions. If the applicant requires that experts be called in whom he himself selects, these persons shall also be heard. Sub-section 6 sentences 5 and 6 shall apply mutatis mutandis for the appointment of experts and counter-experts.
(5a) The competent higher federal authority shall also prepare an assessment report on the quality, safety and efficacy documents submitted containing a statement on the findings of pharmaceutical and pre-clinical tests as well as clinical trials and, for medicinal products for human use, also on the risk-management and on the pharmacovigilance system; in the case of medicinal products intended for use in food-producing animals, the assessment report shall also relate to the results of residue tests. The assessment report should be updated if any new information becomes available.
(5b) Sub-section 5a shall not apply to medicinal products which have been manufactured according to homeopathic manufacturing procedures in so far as these medicinal products are subject to Article 16 paragraph 2 of Directive 2001/83/EC or Article 19 paragraph 2 of Directive 2001/82/EC.
(6) Prior to the decision on the marketing authorisation of a medicinal product which is attributed to the phytotherapy, homeopathy or anthroposophy schools of therapy and which is subject to prescription pursuant to Section 48 sub-section 2 number 1, a marketing authorisation commission shall be consulted. The hearing shall cover the contents of the documents presented, the expert opinions, the reports requested, the comments of the experts summoned, the result of the tests and the reasons which played an essential role in the decision taken on the marketing authorisation or the assessment of the counter-experts. Should the higher federal authority diverge from the result of the hearing in deciding on the application, it shall set forth its reasons for doing so. The Federal Ministry shall appoint the members of the marketing authorisation commission in agreement with the Federal Ministry of Food and Agriculture, in so far as medicinal products intended for administration to animals are concerned, taking into account the proposals of the chambers of the medical professions, the professional societies of medical practitioners, dentists, veterinarians, pharmacists, alternative practitioners as well as the main central associations of the pharmaceutical entrepreneurs, patients and consumers responsible for representing their interests. In appointing the commission’s members, consideration shall be given to the individual peculiarities of the medicinal products. The experts to be appointed to the marketing authorisation commission shall be persons who possess scientific knowledge and have gained practical experience in the specific therapeutic indications as well as in the school of therapy in question (phytotherapy, homeopathy, anthroposophy).
(7) For medicinal products not subject to prescription pursuant to Section 48 sub-section 2 number 1, commissions shall be set up for specific therapeutic indications or schools of therapy at the competent higher federal authority. Sub-section 6 sentences 4 to 6 shall apply mutatis mutandis. In preparing the decision regarding the prolongation of marketing authorisations pursuant to Section 105 sub-section 3 sentence 1, the competent higher federal authority may involve the competent commission. If the decision pursuant to sentence 3 affects medicinal products from a specific school of therapy (phytotherapy, homeopathy, anthroposophy), the competent commission shall be involved if the intention is to refuse the prolongation pursuant to Section 105 sub-section 3 sentence 1 totally, or if the decision is of fundamental importance; the competent commission shall be afforded a period of two months in which to respond. In cases where the competent higher federal authority does not take the comments of the commission into account in making its decision under sentence 4, it shall set forth its reasons for not doing so.
(7a) In order to improve the safety of medicinal products for children and young people, a Commission on Medicinal Products intended for Children and Young People shall be set up at the Federal Institute for Drugs and Medical Devices. Sub-section 6 sentences 4 to 6 shall apply mutatis mutandis. In preparing the decision regarding an application for a marketing authorisation for a medicinal product which is also intended for use in children and young people, the competent higher federal authority shall involve said commission. Furthermore, the competent higher federal authority is entitled to involve the commission when preparing a decision regarding an application for a marketing authorisation of a medicinal product, other than that specified in sentence 3, for which the administration to children or young people is envisaged. The commission has the opportunity to issue an opinion. In cases where the competent higher federal authority does not take the commission’s opinion into account in making its decision, it shall set forth its reasons. Furthermore, in the case of medicinal products which have not been authorised for administration to children and young people, the commission may establish the prerequisites for their administration to children and young people in accordance with recognised scientific principles. In the case of medicinal products from the phytotherapeutic, homeopathic and anthroposophic schools of medicine, the tasks and authority conferred by sentences 3 to 7 shall be assumed by the commissions pursuant to sub-section 7 sentence 4.
(8) In the case of sera, vaccines, blood preparations, tissue preparations, allergens, xenogeneic medicinal products, which are not medicinal products pursuant to Section 4 sub-section 9, the competent higher federal authority shall grant the marketing authorisation either on the basis of an examination of the documents submitted, its own tests or based on observation of the tests carried out by the manufacturer. For this purpose, persons commissioned by the competent higher federal authority, in consultation with the respective competent authorities, may enter the operating and business premises during usual business hours and carry out inspections, both of said premises and of the company’s means of transport. At the request of the competent higher federal authority, the applicant shall submit information on the manufacturing process. Sub-sections 6, 7 and 7a shall not apply to these medicinal products.
(8a) Sub-section 8 sentences 1 to 3 shall apply mutatis mutandis to test methods pursuant to Section 23 sub-section 2 sentence 3.
(9) If an application is submitted for different strengths, pharmaceutical forms, administration routes or presentations of a medicinal product, at the applicant’s request, these can be the subject of a uniform comprehensive marketing authorisation; this shall also apply to subsequent amendments and extensions. This shall require a uniform authorisation number to which further codes must be added to allow differentiation between the different pharmaceutical forms or concentrations. For authorisations pursuant to Section 24b sub-section 1, individual authorisations of a reference medicinal product shall be regarded as a uniform comprehensive authorisation.
(10) The marketing authorisation shall be without prejudice to the pharmaceutical entrepreneur’s penal or civil liability.
Section 25a
Prior examination
(1) The competent higher federal authority can have the application for a marketing authorisation examined by independent experts to determine whether it is complete and whether the medicinal product has been sufficiently tested according to the current, recognized state of scientific knowledge. Section 25 sub-section 6 sentence 5 shall apply mutatis mutandis.
(2) Should flaws within the meaning of sub-section 1 be identified, the expert shall grant the applicant an opportunity to correct such flaws within a period of three months.
(3) If, on the basis of the final opinion delivered by the expert, the application for a marketing authorisation continues to be incomplete or flawed within the meaning of Section 25 sub-section 2 number 2 after the deadline has passed, the marketing authorisation shall not be granted. Section 25 sub-sections 4 and 6 shall not apply to the prior examination.
(4) If the competent higher federal authority establishes that an identically worded marketing authorisation application is being checked in another EU Member State, it shall reject the application and inform the applicant that a procedure pursuant to Section 25b shall apply.
(5) If the competent higher federal authority referred to in Section 22 is informed that an application relates to a medicinal product already authorised in another EU Member State, it shall reject the application unless it was submitted pursuant to Section 25b.
Section 25b
Mutual-recognition procedure and decentralised procedure
(1) If the applicant is applying for a marketing authorisation or authorisation in more than one EU Member State, the applicant shall submit an application based on identical documents in these Member States; this can be worded in English.
(2) If the medicinal product has already been approved or given a marketing authorisation in another EU Member State when the application is submitted, this marketing authorisation shall be recognised on the basis of the assessment report sent by this State, unless there is reason to believe that the authorisation of the medicinal product represents a serious risk to public health or, in the case of medicinal products for use in animals, a serious risk to human or animal health or the environment. In this case, the competent higher federal authority shall proceed pursuant to Article 29 of Directive 2001/83/EC or Article 33 of Directive 2001/82/EC.
(3) If the medicinal product does not have a marketing authorisation at the time of the application, the competent higher federal authority, provided that it is a reference Member State within the meaning of Article 28 of Directive 2001/83/EC or Article 32 of Directive 2001/82/EC, shall prepare drafts of the assessment report, the summary of the product characteristics of the medicinal product, the labelling and package leaflet and transmit them to the competent Member States and to the applicant. Section 25 sub-section 5 sentence 5 shall apply mutatis mutandis.
(4) With regard to recognition of the marketing authorisation granted by another Member State, Chapter 4 of Directive 2001/83/EC and Chapter 4 of Directive 2001/82/EC shall apply.
(5) In the case of a divergent decision with regard to the marketing authorisation, its suspension or revocation, Articles 30, 32, 33 and 34 of Directive 2001/83/EC and Articles 34, 36, 37 and 38 of Directive 2001/82/EC shall apply. In the case of a decision pursuant to Article 34 of Directive 2001/83/EC or Article 38 of Directive 2001/82/EC, a decision about the marketing authorisation shall be reached based on the decision taken or a resolution adopted pursuant to these Articles by the European Community or the European Union. Preliminary proceedings pursuant to Section 68 of the Rules of the Administrative Courts shall not take place in the case of remedies against decisions of the competent higher federal authority referred to in sentence 2. In addition, Section 25 sub-section 6 shall not apply.
(6) Sub-sections 1 to 5 shall not apply to medicinal products manufactured using a homeopathic manufacturing procedure, in so far as these medicinal products are subject to Article 16 paragraph 2 of Directive 2001/83/EC or Article 19 paragraph 2 of Directive 2001/82/EC.
Section 25c
Measures taken by the competent higher federal authority on decisions or resolutions of the European Community or the European Union
The competent higher federal authority shall take the necessary measures to implement decisions or resolutions adopted by the European Community or the European Union pursuant to Article 127a of Directive 2001/83/EC or pursuant to Article 95b of Directive 2001/82/EC.
Section 26
Guidelines for the testing of medicinal products
(1) The Federal Ministry shall be empowered, with the approval of the Bundesrat, to regulate by ordinance the requirements for the information, documents and expert opinions specified in Sections 22 to 24, also in conjunction with Section 38 sub-section 2 and Section 39b sub-section 1, as well as for their examination by the competent higher federal authority. The regulations must comply with the prevailing state of scientific knowledge and are to be continually adjusted to it; animal tests, in particular, shall be replaced by other test methods if this is reasonable in the light of the state of scientific knowledge and considering the purpose of the test. The ordinance shall be issued, in so far as radiopharmaceuticals and medicinal products in the manufacture of which ionizing radiation is used are concerned, and in so far as tests for ecotoxicity are concerned, in agreement with the Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety and, in so far as medicinal products intended for administration to animals are concerned, in agreement with the Federal Ministry of Food and Agriculture.
(2) The competent higher federal authority and the commissions specified in Section 25 sub-section 7 shall apply the Guidelines for the Testing of Medicinal Products analogously to the documents on scientific findings specified in Section 22 sub-section 3 and Section 23 sub-section 3 sentence 2, whereby consideration shall be given to the peculiarities of the individual medicinal product. Documents on empirical medical findings prepared in accordance with scientific methods shall also be deemed to be documents on scientific findings.
Section 27
Deadlines for the granting of marketing authorisations
(1) The competent higher federal authority shall reach its decision on the application for a marketing authorisation within a period of seven months. The decision on the recognition of a marketing authorisation shall be taken within a period of three months following receipt of the assessment report. An assessment report is to be drawn up within a period of three months.
(2) If the competent higher federal authority gives the applicant the opportunity to correct the flaws pursuant to Section 25 sub-section 4, then the deadline shall be interrupted until the flaws are corrected or until the deadline set pursuant to Section 25 sub-section 4 has expired. The interruption of the deadline shall begin on the day the applicant receives the request to correct the flaws. The same shall apply to the deadline granted to the applicant, at his/her request, for the purpose of giving his/her opinion, including the calling in of experts.
(3) In the case of procedures pursuant to Section 25b sub-section 3, the period for completion of the procedure shall be extended by three months, pursuant to the provisions contained in Article 28 of Directive 2001/83/EC and Article 32 of Directive 2001/82/EC.
Section 28
Power to impose conditions
(1) The competent higher federal authority may combine the marketing authorisation with the imposition of conditions. In the case of conditions imposed pursuant to sub-sections 2 to 3d for the protection of the environment, the competent higher federal authority shall decide, in agreement with the Federal Environmental Agency, when the impact on the environment needs to be evaluated. For this purpose, the competent higher federal authority shall transmit the data and documents, necessary for its evaluation of the environmental impact, to the Federal Environmental Agency. Conditions may also be imposed subsequently.
(2) The conditions specified in sub-section 1 may be imposed in order to ensure that:
1. the labelling of the containers and outer packaging complies with the regulations laid down in Section 10; in this connection, it may be prescribed that the following details shall be given:
a) instructions or warnings, in so far as they are necessary to prevent a direct or indirect health hazard to human beings or animals by administration of the medicinal product,
b) keeping instructions for the consumer and storage instructions for experts, in so far as they are deemed necessary in order to maintain the required medicinal product quality,
2. the package leaflet complies with the regulations laid down in Section 11; in this connection it may be prescribed that the following details shall be given:
a) the instructions or warnings specified in number 1 letter a and
b) keeping instructions for the consumer, in so far as they are deemed necessary in order to maintain the required medicinal product quality,
2a. the expert information complies with the provisions of Section 11a; in this connection it may be stipulated that the following details shall be given:
a) the instructions or warnings specified in number 1 letter a,
b) particular storage and keeping instructions, in so far as they are deemed necessary to maintain the required medicinal product quality,
c) references to conditions pursuant to sub-section 3,
3. the details given pursuant to Sections 10, 11 and 11a comply with the documents submitted for the marketing authorisation and that, in this connection, standardized and generally comprehensible terms as well as a standardized wording, also in keeping with the recommendations and opinions of the committees of the European Medicines Agency, are used, whereby the provision of information regarding additional contra-indications, adverse reactions and interactions remains admissible; the competent higher federal authority may generally make use of this authority for reasons of medicinal product safety, transparency or to ensure a rational method of working; in this connection, provisions may be imposed prescribing that certain therapeutic indications be omitted in respect of prescription-only medicinal products, if there is reason to fear that by giving such details, the therapeutic aim will be jeopardized,
4. the medicinal product is placed on the market in package sizes appropriate to the therapeutic indications and the envisaged duration of administration,
5. the medicinal product is placed on the market in a container of a particular form with a specific seal or some other kind of safety measure, in so far as it is deemed necessary to guarantee compliance with the dosage instructions or to prevent the danger of misuse by children.
(2a) Warnings pursuant to sub-section 2 can also be stipulated so as to ensure that the medicinal product is only prescribed by physicians with a certain speciality and administered only under their supervision or in clinics or special clinics, or in collaboration with such institutions, where necessary, so as to avoid any direct or indirect danger to the health of human beings in its administration, especially when the administration of the medicinal product appears to be completely safe only in the presence of special knowledge or in special therapeutic facilities.
(3) Furthermore, the competent higher federal authority may impose conditions prescribing that additional analytical and pharmaceutical-toxicological tests or clinical trials are to be carried out and a report be submitted on the results, if there is sufficient indication that the medicinal product can have a high therapeutic value and that, therefore, it is in the public interest to have the medicinal product introduced onto the market forthwith, even though further important details are still required to facilitate a comprehensive assessment of the same. The competent higher federal authority shall review the findings of these tests and trials on an annual basis. Sentence 1 shall apply mutatis mutandis to documents on the residue test procedure pursuant to Section 23 sub-section 1 number 2.
(3a) The competent higher federal authority may, in issuing the marketing authorisation for medicinal products for human use may impose, in addition, that:
1. specific measures contained in the risk-management system be taken to ensure the safe use of the medicinal product if it is necessary in the interest of medicinal product safety,
2. post-authorisation safety studies must be conducted if this is in the interest of medicinal product safety,
3. obligations regarding the recording or reporting of suspected adverse reactions that go beyond those listed in Chapter Ten be observed if this is necessary in the interest of medicinal product safety,
4. other necessary measures regarding the safe and effective use of the medicinal product be taken if this is necessary in the interest of medicinal product safety,
5. an appropriate pharmacovigilance system be introduced if this is necessary in the interest of medicinal product safety,
6. where reservations exist regarding individual aspects of the efficacy of the medicinal product, that can only be dispelled after its placing on the market, post-authorisation efficacy studies be conducted in keeping with the requirements stipulated in Article 21a first sentence letter f of Directive 2001/83/EC.
(3b) In the case of medicinal products for human use, the competent higher federal authority can, after the marketing authorisation has been granted, impose conditions to the effect that:
1. a risk-management system and a risk-management plan is introduced if this is in the interest of medicinal product safety,
2. post-authorisation safety studies must be conducted if this is in the interest of medicinal product safety,
3. a post-authorisation efficacy study must be conducted if findings regarding the disease or the clinical methodology indicate that earlier efficacy evaluations need to be significantly revised; the obligation to conduct this post-authorisation efficacy study subsequent to the granting of the marketing authorisation must be in keeping with the requirements stipulated in Article 22a sub-section 1 letter b second sentence of Directive 2001/83/EC.
Should the prerequisites for the imposition of conditions pursuant to sentence 1 number 2 exist for more than one medicinal product, and should these medicinal products be authorised for marketing in several Member States, the competent higher federal authority shall, after consulting the Pharmacovigilance Risk Assessment Committee pursuant to Article 56 (1) (aa) of Regulation (EC) No. 726/2004, advise the affected marketing authorisation holders to conduct a joint post-authorisation safety study.
(3c) Furthermore, the competent higher federal authority may impose conditions prescribing that, in the manufacture and control of such medicinal products and their starting materials which are of biological origin or are manufactured using biotechnology,
1. specific requirements have to be fulfilled and specific measures and procedures implemented,
2. documents have to be submitted substantiating the suitability of specific measures and procedures, including documents bearing on validation,
3. the introduction or modification of specific requirements, measures or procedures requires the prior approval of the competent higher federal authority,
in so far as this is deemed necessary to ensure adequate quality or to prevent risks. The conditions imposed shall be immediately enforceable. The lodging of an objection or action to rescind shall have no suspensive effect.
(3d) In the case of medicinal products intended for use in animals, the competent higher federal authority can, furthermore, mandate in justified individual cases that additional documents with which an evaluation of possible environmental risks will be conducted, as well as additional results of tests to evaluate possible environmental risks, be submitted in so far as this is necessary for a comprehensive assessment of the impact of the medicinal product on the environment. The competent higher federal authority shall check compliance with any condition imposed pursuant to sentence 1 immediately after the date for the submission of documents has expired. Sub-section 1 sentences 2 and 3 shall apply mutatis mutandis.
(3e) In the case of medicinal products for animal use, the competent higher federal authority can furthermore impose as a condition the introduction, subsequent to marketing authorisation, of a risk-management system that describes the combination of activities and measures in the area of pharmacovigilance, including the assessment of the efficacy of such measures and that, after marketing authorisation, findings arising from the use of the medicinal product are systematically collected, documented and evaluated and that the findings of this investigation are reported to it by a specific deadline if this is in the interest of medicinal product safety.
(3f) In the case of conditions pursuant to sub-sections 3, 3a, 3b and 3e, the competent higher federal authority can stipulate the type, scope and duration of the studies or tests, as well as activities, measures and evaluations within the framework of the risk-management system. The results shall be documented in such a way as to show the type, scope and date of the studies or tests.
(3g) The holder of a marketing authorisation for medicinal products for human use shall include all of the conditions pursuant to sub-sections 3, 3a and 3b into his/her risk-management system. The competent higher federal authority shall inform the European Medicines Agency of the marketing authorisations it has granted subject to conditions pursuant to sub-sections 3, 3a and 3b.
(3h) The competent higher federal authority can impose appropriate measures to improve the identifiability of adverse reaction reporting in the case of biological medicinal products for human use.
(4) Should the marketing authorisation be subject to a condition, the deadline envisaged in Section 27 sub-section 1 shall be interrupted until the deadline granted to the applicant for comment has expired. Section 27 sub-section 2 shall apply mutatis mutandis.
Section 29
Obligation to notify, renewal of the marketing authorisation
(1) The applicant shall notify the competent higher federal authority forthwith, enclosing the corresponding documents, in the event of any changes in the information or documents referred to in Sections 22 to 24a and 25b. The marketing authorisation holder shall comply with the requirement referred to in sentence 1 once the marketing authorisation has been granted.
(1a) The marketing authorisation holder shall notify the competent higher federal authority immediately of all prohibitions or restrictions by the competent authorities of each country where the medicinal product in question is placed on the market and of all other new information that could affect the assessment of the benefit and risks of the medicinal product in question. In the case of medicinal products for human use this information includes both positive and negative results of clinical trials or other studies that may refer to all indications and population groups and not only to those specified in the marketing authorisation as well as information regarding the use of the medicinal product beyond the terms of the marketing authorisation. The marketing authorisation holder shall also submit to the competent higher federal authority, upon request, all information and documents demonstrating that the risk-benefit balance is still favourable. In the case of medicinal products for human use, the competent higher federal authority can request a copy of the pharmacovigilance system master file at any time. The marketing authorisation holder shall submit the pharmacovigilance system master file at the latest seven days after receiving the request. Sentences 1 to 3 shall not apply to the parallel importer.
(1b) The marketing authorisation holder shall notify the competent higher federal authority immediately of the date on which the medicinal product is to be placed on the market, taking into consideration the different pharmaceutical forms and strengths authorised.
(1c) The marketing authorisation holder shall notify the competent higher federal authority in compliance with sentence 2 in the event of temporary or permanent cessation of the marketing of the medicinal product. Notification shall be submitted at least two months before the suspension of marketing. This shall not apply in the event of circumstances over which the marketing authorisation holder has no control.
(1d) The marketing authorisation holder shall submit all sales data for the medicinal product as well as all data available on prescription levels if the competent higher federal authority requests them for reasons of medicinal product safety.
(1e) The marketing authorisation holder shall notify the competent higher federal authority of the changed frequency and dates for the submission of the periodic safety update reports within the procedure pursuant to Article 107c paragraph 4, 5 or 6 of Directive 2001/83/EC. Changes in the dates or frequencies given in the manufacturing authorisation, arising from sentence 1, shall become effective six months after their publication on the European internet website.
(1f) In the case of medicinal products for human use, the marketing authorisation holder is required to inform the competent higher federal authority and the European Medicines Agency of new or changed risks or of changes in the medicinal products’ risk-benefit balance.
(1g) The holder of a marketing authorisation for medicinal products for human use shall notify the competent higher federal authority immediately of the grounds for temporarily or permanently ceasing to market or recalling the medicinal product, renouncing or failing to apply for the prolongation of the marketing authorisation. In particular, the marketing authorisation holder shall explain whether the measure pursuant to sentence 1 is based on one of the grounds listed in Section 25 sub-section 2 sentence 1 numbers 3, 4 or number 5, Section 30 sub-section 2 sentence 1 number 1 or Section 69 sub-section 1 sentence 2 number 4 or number 5. The notification pursuant to sentence 1 shall also be made if the measure is taken in a third country and is based on one of the grounds pursuant to sentence 2. If a measure pursuant to sentence 1 or sentence 3 is based on one of the grounds listed in sentence 2, the marketing authorisation holder shall also notify the European Medicines Agency thereof.
(2) In the case of a change in the name of the medicinal product, the marketing authorisation notice shall be amended accordingly. A pharmaceutical entrepreneur may place the medicinal product on the market under its current name for a further period of one year, wholesalers and retailers for a further period of two years, beginning on the following 1 January or 1 July after the promulgation of the change in the Federal Gazette.
(2a) A change:
1. in the information pursuant to Sections 10, 11 and 11a bearing on the dosage, nature and duration of the administration, the therapeutic indications, if it does not concern an addition or modification of an indication which is to be classified under another area of therapy, a limitation of the contra-indications, adverse reactions or interactions with other substances,
2. in the active substances, excluding the medically active constituents,
3. in a pharmaceutical form which is comparable with the one authorised for marketing,
3a. in treatment with ionizing radiation,
4. in the context of considerable changes in the manufacturing process, the pharmaceutical form, specification or impurity profile of the active substance or the medicinal product that can have a clear effect on the quality, safety or efficacy of the medicinal product, as well as any changes in manufacturing procedures using genetic engineering technology; in the case of sera, vaccines, preparations derived from blood, allergens, test sera, test antigens, every change in the manufacturing or test procedures or the indication of a longer shelf-life,
5. in the package size, and
6. in the withdrawal period of a medicinal product for animal use,
may be made only if the competent higher federal authority has granted its approval. Sentence 1 number 1 shall also apply to the extension of the target species in the case of medicinal products not intended for use in food-producing animals. The approval shall be deemed to be granted if no objection to the change has been filed within a period of three months.
(2b) By way of derogation from sub-section 1, the:
1. the closure of a location used in the manufacture if the medicinal product or its active substance or for its packaging or batch release,
2. any minor changes to an approved physico-chemical test procedure if the appropriate validation studies can demonstrate that the updated test procedure is at least equivalent to the former test procedure,
3. changes to the specification of an active substance or other substances used in the manufacture of medicinal products in order to comply with a monograph of the pharmacopoeia if the change is made exclusively to comply with the pharmacopoeia and the specifications for product specific properties remain unchanged,
4. changes to the packaging material if the latter does not come into contact with the medicinal product and the delivery, use, safety or stability of the medicinal product is demonstrably not affected, or
5. changes in the context of the tightening of specification limits where the change is not a consequence of any commitment from previous assessments to review specification limits and does not result from unexpected events arising during manufacture.
can be reported to the competent higher federal authority within twelve months following their introduction.
(3) In the following cases an application shall be made for renewal of the marketing authorisation for a medicinal product:
1. in the case of a change in the composition of the active substances either in type or quantity,
2. in the case of a change in the pharmaceutical form unless a change pursuant to sub-section 2a number 3 is concerned,
3. in the case of an extension of the therapeutic indications, in so far as this does not constitute a change pursuant to sub-section 2a number 1, and
3a. in the case of the introduction of manufacturing procedures using genetic engineering.
The competent higher federal authority shall decide on the obligation to obtain a marketing authorisation pursuant to sentence 1.
(4) Sub-sections 1, 1a sentences 4 and 5 sub-sections 1e to 1g, 2, 2a to 3 shall not be applicable to medicinal products which have been granted a marketing authorisation 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 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.
(5) Sub-sections 2a to 3 shall not apply to medicinal products governed by Commission Regulation (EC) No. 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products (OJ L 334 of 12.12.2008, p. 7) in the latest applicable version. Sub-sections 2a to 3 apply to:
1. homeopathic medicinal products for human use that are subject to authorisation and were authorised before 1 January 1998 or were deemed to be authorised,
2. the blood preparations listed in Article 3 (6) of Directive 2001/83/EC, and
3. tissue preparations authorised pursuant to Section 21, unless they are manufactured by a method involving in industrial process.
Section 30
Withdrawal, revocation, suspension
(1) A marketing authorisation shall be withdrawn if it becomes subsequently known that one of the grounds for refusal of marketing authorisations, as defined in Section 25 sub-section 2 numbers 2, 3, 5, 5a, 6 or 7, existed at the time of issuance; the marketing authorisation shall be revoked if one of the grounds for refusal pursuant to Section 25 sub-section 2 numbers 3, 5, 5a, 6 or 7 has subsequently developed. The marketing authorisation shall furthermore be withdrawn or revoked, if:
1. it comes to light that the medicinal product is lacking in therapeutic efficacy,
2. in the cases referred to in Section 28 sub-section 3, the therapeutic efficacy has not been sufficiently proved according to the prevailing standard of scientific knowledge.
Therapeutic efficacy is lacking if it is clear that no therapeutic results can be achieved with the medicinal product. In the cases referred to in sentence 1, the suspension of the marketing authorisation may also be ordered for a limited period of time.
(1a) Furthermore, the authorisation may be partially or fully withdrawn or revoked if necessary to comply with a decision or resolution by the European Community or the European Union pursuant to Article 34 of Directive 2001/83/EC or pursuant to Article 38 of Directive 2001/82/EC. No preliminary procedure pursuant to Section 68 of the Rules of the Administrative Courts shall be held in the event of an appeal against decisions by the competent higher federal authority pursuant to sentence 1. In the cases referred to in sentence 1, the suspension of the marketing authorisation may also be ordered for a limited period of time.
(2) The competent higher federal authority may:
1. withdraw the marketing authorisation if incorrect or incomplete information is given in the documents specified in Sections 22, 23 or 24 or if one of the grounds for the refusal of a marketing authorisation, as defined in Section 25 sub-section 2 number 6a or 6b existed at the time when it was granted,
2. revoke the marketing authorisation, if one of the grounds for refusal as defined in Section 25 sub-section 2 numbers 2, 6a or 6b subsequently developed or if one of the conditions imposed pursuant to Section 28 has not been met and the flaw has not been corrected within a reasonable period of time which is to be specified by the competent higher federal authority; in this regard, the conditions referred to in Section 28 sub-sections 3 and 3a should be reviewed annually,
3. revoke the marketing authorisation in consultation with the competent authority, if the quality tests specified for the medicinal product are either not carried out at all or are not carried out adequately,
4. revoke the marketing authorisation in consultation with the competent authority if becomes apparent that the medicinal product was not manufactured in accordance with recognised pharmaceutical rules.
In these cases, the suspension of the marketing authorisation may also be ordered for a limited period of time.
(2a) In the cases referred to in sub-sections 1 and 1a, the marketing authorisation shall be amended if, as a result, the reason for rejection referred to in sub-section 1 becomes inapplicable, or in order to comply with the decision referred to in sub-section 1a. In the cases referred to in sub-section 2, the marketing authorisation can be amended by imposing a condition if this is sufficient to comply with the requirements of medicinal product safety.
(3) Before a decision is reached pursuant to sub-sections 1 to 2a, the holder of the marketing authorisation shall be heard, unless danger is imminent. This also applies if a decision by the competent higher federal authority on changes to the authorisation, conditions for the authorisation, the withdrawal or the suspension of the authorisation is based on an agreement by the co-ordination group pursuant to Article 107g, 107k or Article 107q of Directive 2001/83/EC. A preliminary procedure pursuant to Section 68 of the Rules of the Administrative Courts shall not take place in the cases referred to in sentence 2. In the cases set forth in Section 25 sub-section 2 number 5, the decision can be implemented immediately. The lodging of an objection or action to rescind shall have no suspensive effect.
(4) If the marketing authorisation of a medicinal product has been withdrawn or revoked or if the marketing authorisation has been suspended, the medicinal product:
1. shall neither be placed on the market,
2. nor shall it be introduced into the purview of this Act.
It shall be permitted to return the medicinal product, appropriately marked, to the pharmaceutical entrepreneur. The competent authority may order the return of a medicinal product.
Section 31
Expiry, prolongation
(1) The marketing authorisation shall expire:
1. if the authorised medicinal product is not placed on the market within three years of the granting of the marketing authorisation, or if the authorised medicinal product that was placed on the market in accordance with the marketing authorisation is not placed on the market for three successive years,
2. by written renouncement,
3. five years after it was granted, unless an application for prolongation is filed,
a) in the case of medicinal products for human use, at the latest nine months,
b) in the case of medicinal products for animal use, at the latest six months,
prior to the expiry date.
3a. in the case of a medicinal product intended for administration to food-producing animals, and which contains a pharmacologically active constituent listed in Table 2 of the Annex to Regulation (EU) No. 37/2010, at the end of a period of 60 days following its publication in the Official Journal of the European Union unless, within this deadline, the therapeutic indications with respect to food-producing animals have been waived pursuant to Section 29 sub-section 1; in the case of a notification of changes pursuant to Section 29 sub-section 2a, the aim of which is to remove the relevant pharmacologically active constituent, the 60-day deadline shall be interrupted until the decision by the competent higher federal authority or until the expiry of the deadline pursuant to Section 29 sub-section 2a sentence 2 and the authorisation shall be suspended during this period after the 60-day deadline has expired; the half-sentences 1 and 2 shall apply mutatis mutandis in so far as Regulation (EC) No. 1234/2008 is applicable as regards the alteration of the medicinal product,
4. if the prolongation of the marketing authorisation is refused.
In the cases referred to in the sentence 1 number 1, the competent higher federal authority can allow exceptions if required to protect human or animal health.
(1a) A marketing authorisation which is prolonged shall be valid for an unspecified period unless, in the case of prolongation pursuant to sub-section 1 sentence 1 number 3, the competent higher federal authority considers it necessary to grant a prolongation of a further five year period pursuant to the provisions of sub-section 1 sentence 1 number 3, in conjunction with sub-section 2, also taking into account the exposure of an insufficient number of patients to the medicinal product for human use in question, in order to ensure the continued safe placing of the medicinal product on the market.
(2) The application for prolongation shall be supplemented by a report giving details of whether, and to what extent, the criteria by which the medicinal product is assessed have altered over the previous five years. To this end, the marketing authorisation holder shall submit to the competent higher federal authority a revised version of the quality, safety and efficacy documents including all amendments made since the marketing authorisation was granted; in the case of medicinal products intended for use in animals, a consolidated list of amendments shall be submitted instead of the revised version. In respect of medicinal products intended for administration to food-producing animals, the competent higher federal authority may furthermore demand that the report comprise details of experience gained in the residue test procedure.
(3) The marketing authorisation in the cases referred to in sub-section 1 sentence 1 number 3 or sub-section 1a, shall be prolonged based on an application pursuant to sub-section 2 sentence 1 for a further five years within the six months prior to its expiry on condition that none of the grounds for refusal pursuant to Section 25 sub-section 2 numbers 3, 5, 5a, 6, 6a, 6b or 7 exist, that the marketing authorisation is not to be withdrawn or revoked pursuant to Section 30 sub-section 1 sentence 2 and that no use is to be made of the possibility of withdrawal pursuant to Section 30 sub-section 2 number 1 or of revocation pursuant to Section 30 sub-section 2 number 2. Section 25 sub-section 5 sentence 5 and sub-section 5a shall apply mutatis mutandis. In respect of the decision regarding prolongation, it shall be verified whether findings exist which could influence the subordination of the medicinal product to the prescription requirement.
(4) If the marketing authorisation expires pursuant to sub-section 1 number 2 or 3, the medicinal product may be placed on the market for a further two years, commencing on the 1 January or 1 July following the promulgation of the expiry pursuant to Section 34. This shall not apply if the competent higher federal authority ascertains that a condition for the withdrawal or the revocation of the marketing authorisation as defined in Section 30 existed; Section 30 sub-section 4 shall apply.
Section 32
Official batch testing
(1) A batch of a serum, a vaccine or an allergen may only be placed on the market, without prejudice to the marketing authorisation, if it has been released by the competent higher federal authority. The batch shall be released if a test (official batch test) has shown that the batch has been manufactured and tested by methods of manufacture and control which comply with the prevailing standard of scientific knowledge and that it possesses the required quality, efficacy and safety. The batch shall also be released if the competent authority of another Member State of the European Union has decided, on the basis of an experimental investigation, that the prerequisites stated in sentence 2 are met.
(1a) The competent higher federal authority shall reach a decision pursuant to sub-section 1 within two months of receipt of the batch sample to be tested. Section 27 sub-section 2 shall apply mutatis mutandis.
(2) The Federal Ministry shall issue general administrative regulations on the requirements to be set by the higher federal authority for methods of manufacture and control, as defined in sub-section 1, following consultation with experts from the fields of medical and pharmaceutical science and practice and shall promulgate them as Guidelines for the Testing of Medicinal Products in the Federal Gazette. The regulations must comply with the prevailing standard of scientific knowledge and are to be continually adjusted to it.
(3) Section 25 sub-section 8 and Section 22 sub-section 7 sentence 3 shall apply mutatis mutandis to the execution of the official batch testing.
(4) Release, pursuant to sub-section 1 sentence 1, shall not be necessary if the medicinal products specified therein are exempted by ordinance according to Section 35 sub-section 1 number 4, or by the competent higher federal authority; the competent higher federal authority shall grant an exemption if the manufacturing and test methods of the manufacturer have reached a level of development which guarantees the quality, efficacy and safety required.
(5) The release as defined in sub-section 1 or the exemption by the competent higher federal authority as defined in sub-section 4 shall be withdrawn if one of their conditions has not been fulfilled; it shall be revoked if one of the conditions is subsequently no longer fulfilled.
Section 33
Fees and expenses
(1) The competent higher federal authority shall levy charges (fees and expenses) for the decisions on marketing authorisations, on the approval of tissue preparations, on the approval of medicinal products for advanced therapies, batch releases, the processing of applications, activities in the context of the compilation and evaluation of risks of medicinal products, for the protest procedure against an administrative act issued on the basis of this Act or the determination of fees and expenses on the basis of an ordinance pursuant to sub-section 2 sentence 1 or Section 39 sub-section 3 sentence 1 or Section 39d sub-section 9, as well as for other individually attributable public services, including independent consulting and information services, in so far as these do not consist of oral information and simple written information within the meaning of Section 7 number 1 of the Federal Act on Fees, in compliance with this Act and pursuant to Regulation (EC) No. 1234/2008 (fees and expenses).
(2) The Federal Ministry is hereby empowered to determine, in agreement with the Federal Ministry for Economics and Energy, and, in so far as medicinal products intended for administration to animals is concerned, also with the Federal Ministry of Food and Agriculture, by ordinance not subject to the approval of the Bundesrat, which elements are liable to a fee, and to establish fixed rates or rate schedules in the process, as well as the reimbursement of expenses also by way of derogation from the provisions contained in the Administrative Costs Act. The amount of fees payable for decisions on the marketing authorisations, on the approval of tissue preparations, the approval of medicinal products for advanced therapies, batch releases, as well as other individually attributable public services shall be determined in each case according to the expenditure for personnel and material, including in particular the costs for the marketing authorisation procedure in the case of sera, vaccines and allergens and also the expenditure for the tests and for the development of appropriate testing procedures. The amount of fee payable for the decision in respect of a batch release shall be determined by the average costs for personnel and material; in addition, appropriate consideration shall be given to the significance, the economic value or other benefit derived from the release by the party liable to pay the fee.
(3) By way of derogation from Section 18 sub-section 1 sentence 1 of the Federal Act on Fees, the right to the payment of fees and expenses, which are to be charged pursuant to Section 33 sub-section 1, in conjunction with the Ordinance on Therapy Allergens, shall lapse three years after the notification of the final decision on the marketing authorisation.
(4) If a protest pursuant to sub-section 1 is successful, necessary expenses shall be reimbursed according to Section 80 sub-section 1 of the Administrative Procedures Act, up to the level of the fees envisaged in an ordinance pursuant to sub-section 2 sentence 1 or Section 39 sub-section 3 sentence 1 or Section 39d sub-section 9, for the rejection of a corresponding protest procedure and, in the case of framework fees, up to the level of their mean value.
(5) The Federal Institute for Drugs and Medical Devices shall charge fees for the use of monographies for medicinal products which are exempted from the obligation to obtain a marketing authorisation pursuant to Section 36. In such a case, flat-rate fee agreements can be concluded with the associations to which the users belong. Sub-section 2 sentence 3 shall apply mutatis mutandis to the determination of fees.
(6) The competent higher federal authority shall be reimbursed by the competent authority of the Land for costs incurred by the former within the framework of the co-operation measures pursuant to this Act, if these costs are borne by the party responsible.
Section 34
Informing the public
(1) The competent higher federal authority shall promulgate the following in the Federal Gazette:
1. the granting and prolongation of a marketing authorisation,
2. the withdrawal of a marketing authorisation,
3. the revocation of a marketing authorisation,
4. the suspension of a marketing authorisation,
5. the expiry of a marketing authorisation,
6. the ascertainment pursuant to Section 31 sub-section 4 sentence 2,
7. the change in the name pursuant to Section 29 sub-section 2,
8. the withdrawal or revocation of the release of a batch pursuant to Section 32 sub-section 5,
9. a decision to prolong a protection period pursuant to Section 24b sub-section 1 sentence 3 or sub-section 7, or to grant a data protection period pursuant to Section 24b sub-section 6 or 8.
Sentence 1 numbers 1 to 5 and number 7 shall apply mutatis mutandis to decisions or resolutions adopted by the European Community or the European Union.
(1a) In the case of medicinal products for human use, the competent higher federal authority shall make the following information available to the public immediately via an internet website and, if necessary, by other means as well:
1. information on the granting of a marketing authorisation together with the package leaflet and the expert information in the currently approved version,
2. the public assessment report containing the information pursuant to Section 25 sub-section 5a for each therapeutic indication applied for as well as a generally comprehensible summary containing a section on the conditions for the use of the medicinal product,
3. summaries of the risk management plans,
4. information on the conditions along with time limits and deadlines for fulfilment,
5. pharmacovigilance-related reservations.
In the case of information pursuant to sentence 1 numbers 2 and 5, industrial and commercial secrets and personal data shall be deleted unless their disclosure is necessary for the protection of public health. If the pharmacovigilance reservations pursuant to sentence 1 number 5 refer to medicinal products that are authorised in several Member States, the publication shall take place in consultation with the European Medicines Agency. In the case of medicinal products for animal use, the competent higher federal authority shall immediately provide the public with information on the granting of the marketing authorisation together with the expert information, the assessment report pursuant to sentence 1 number 2 and, if the therapeutic indication of the medicinal product also extends to food producing animals, also on residue tests after deleting industrial and commercial secrets. Sentences 1 and 4 also apply to changes in the aforementioned information.
(1b) In the case of medicinal products for human use, the withdrawal of an application for authorisation as well as the refusal of the marketing authorisation and the grounds are to be made publicly accessible. In addition, decisions relating to the withdrawal, revocation or suspension of a marketing authorisation shall also be made publicly available. The competent higher federal authority is empowered, in the case of medicinal products for human use, to disclose information regarding the submission of a proper application for authorisation, the submission of a proper application for the approval of a confirmatory clinical trial, as well as on the approval or refusal of a confirmatory clinical trial.
(1c) Sub-sections 1a and 1b sentences 1 and 2 shall not apply to medicinal products approved pursuant to Regulation (EC) No. 726/2004.
(1d) The competent higher federal authority shall make the information referred to in sub-sections 1a, 1b and 1f available in electronic format. After taking the decision, the competent higher federal authority shall make available the information pursuant to sub-sections 1 and 1b, referring to the lack of enforceability.
(1e) The competent higher federal authority shall publish at least the following supplementary information through its internet website for medicinal products pursuant to Section 67a sub-section 2 in addition to the information provided for in sub-section 1a sentence 1 numbers 1 to 4 and sub-section 1a sentence 2:
1. the list of medicinal products pursuant to Article 23 of Regulation (EC) No. 726/2004,
2. information on the notification channels for informing the competent higher federal authority of suspected adverse reactions to medicinal products to be used by health professionals and patients, including the internet forms made available by the competent higher federal authority.
(1f) In the case of medicinal products for human use, the competent higher federal authority can make approved educational material available to the public through an internet portal and, where required, by other means as well, in so far this is necessary in the interest of medicinal product safety.
(1g) In the case of medicinal products that are intended for human use and subject to official batch testing pursuant to Section 32, the competent higher federal authority may publish information on the number of batches released. Information on the size of the released batches may be published, if necessary to protect the health of the public.
(2) The competent higher federal authority may promulgate an administrative act based on this Act in the Federal Gazette if more than 50 addressees are affected. Two weeks after publication of the administrative act in the Federal Gazette, the act shall be considered to be promulgated. Other notifications by the competent higher federal authority, including the letters giving the parties affected the opportunity to submit comments pursuant to Section 28 sub-section 1 of the Administrative Procedures Act, may also be published in the Federal Gazette if more than 50 addressees are affected. Sentence 2 shall apply mutatis mutandis.
Section 35
Empowerments in respect of marketing authorisation and exemptions
(1) The Federal Ministry is hereby empowered to issue ordinances, subject to the approval of the Bundesrat, in order to:
1. (repealed)
2. extend the provisions on the marketing authorisation to medicinal products that are not subject to the obligation to obtain a marketing authorisation pursuant to Section 21 sub-section 1, as well as to medicinal products that have been exempted from the marketing authorisation under Section 21 sub-section 2 number 1g, in so far as it is deemed necessary to prevent direct or indirect hazards to human and animal health,
3. extend the provisions on the release of a batch and on official batch testing to other medicinal products which are subject to variation in their composition or in their content of active substances, in so far as it is deemed necessary to prevent direct or indirect hazards to human or animal health,
4. exempt certain medicinal products from the official batch testing, if the manufacturing and testing procedures of the manufacturer have attained a level of development which guarantees quality, efficacy and safety.
(2) The ordinances, pursuant to sub-section 1 numbers 2 to 4, shall be issued in agreement with the Federal Ministry for Economics and Energy and, in the case of radiopharmaceuticals and medicinal products in the manufacture of which ionizing radiation is used, in agreement with the Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety and, in the case of medicinal products intended for administration to animals, in consultation with the Federal Ministry of Food and Agriculture.
Section 36
Empowerment in respect of standard marketing authorisations
(1) The Federal Ministry is hereby empowered to exempt, by ordinance subject to the approval of the Bundesrat and subsequent to consultation with experts, certain medicinal products or groups of medicinal products or medicinal products presented in particular pharmaceutical forms from the obligation to obtain a marketing authorisation, in so far as no direct or indirect danger to human or animal health is to be feared, since it is evident that the requirements with regard to the necessary quality, efficacy and safety have been met. For the sake of the protection of human or animal health, the exemption may be made dependent on a particular manufacturing procedure, composition, labelling, package leaflet, expert information or pharmaceutical form and be limited to certain methods of administration, therapeutic indications or fields of application. It is admissible for the pharmaceutical entrepreneur to provide information regarding additional contra-indications, adverse reactions and interactions.
(2) When selecting the medicinal products to be exempted from the obligation to apply for a marketing authorisation, account must be taken of the legitimate interests of the consumer of the medicinal product, the health professions and the pharmaceutical industry. The pharmaceutical entrepreneur is free to choose the name of the medicinal product.
(3) The ordinances pursuant to sub-section 1 shall be issued in agreement with the Federal Ministry for Economics and Energy and, in the case of radiopharmaceuticals and medicinal products in the manufacture of which ionizing radiation is used, in agreement with the Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety and, in the case of medicinal products intended for administration to animals, in consultation with the Federal Ministry of Food and Agriculture.
(4) In cases where it is necessary to make immediate changes to information regarding contra-indications, adverse reactions and interactions dosages, package sizes and precautions for use and, on condition that the validity of the ordinance having the force of law does not exceed a maximum period of one year, the hearing of experts and the approval of the Bundesrat shall not be necessary prior to the promulgation of an ordinance pursuant to sub-section 1. The deadline may be prolonged once for a further year if the procedure pursuant to sub-section 1 cannot be completed within the one-year period.
(5) The monographies on which the ordinance pursuant to sub-section 1 is based shall be regularly examined by the competent higher federal authority and, where necessary, adapted to the currently recognised technological and scientific state-of-the-art. In the process, the monographs shall be examined to determine whether the requirements regarding the necessary quality, efficacy and safety, including a positive risk-benefit balance, can continue to be considered fulfilled for medicinal products exempted from the obligation to obtain a marketing authorisation.
Section 37
Authorisation by the European Community or the European Union for placing on the market, marketing authorisation of medicinal products from other states
(1) The marketing authorisation issued by the European Community or the European Union pursuant to Regulation (EC) No. 726/2004, also in conjunction with Regulation (EC) No. 1901/2006 or Regulation (EC) No. 1394/2007 shall rank equally with a marketing authorisation issued pursuant to Section 25 in so far as the provisions of Section 11a, Section 13 sub-section 2a, Section 21 sub-sections 2 and 2a, Sections 40, 56, 56a, 58, 59, 67, 69, 73, 84 or 94 are geared to a marketing authorisation. The marketing authorisation issued for a medicinal product by another state shall be considered a valid marketing authorisation as defined in Section 21, in so far as this is stipulated in an ordinance issued by the Federal Ministry.
(2) The Federal Ministry is hereby empowered to issue an ordinance pursuant to sub-section 1, which shall not be subject to the approval of the Bundesrat, in order to implement a directive of the Council or where the marketing authorisation of medicinal products is mutually recognized in international treaties as being of equivalent value. The ordinance shall be issued in agreement with the Federal Ministry of Food and Agriculture in so far as medicinal products intended for administration to animals are concerned.
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