Last Updated on May 29, 2021 by LawEuro
Medicinal Products Act (Laws / Regulations of Germany)
CHAPTER THREE
Manufacture of medicinal products
Section 13
Manufacturing authorisation
(1) Any person who manufactures:
1. medicinal products within the meaning of Section 2 sub-section 1 or sub-section 2 number 1,
2. test sera, test antigens,
3. active substances, which are of human, animal or microbial origin or are manufactured using genetic engineering, or
4. other substances of human origin intended for the manufacture of medicinal products
on a commercial or professional basis shall require a permit by the competent authority. The same shall also apply to legal persons, non-incorporated associations and companies established under civil law which manufacture medicinal products for distribution to their members. Sentence 1 shall apply mutatis mutandis to a trial on the basis of which the release of the medicinal product is explained. This shall be without prejudice to Section 14 sub-section 4.
(1a) Sub-section 1 shall not apply to:
1. tissues within the meaning of Section 1a number 4 of the Transplantation Act which require a permit pursuant to Section 20b or 20c,
2. the procurement and the laboratory tests of autologous blood for the manufacture of biotechnologically processed tissue products which require a permit pursuant to Section 20b,
3. tissue preparations which require a permit pursuant to Section 20c,
4. reconstitution, in so far as medicinal products that are intended for use in clinical trials are not concerned.
(2) The following shall not require an authorisation pursuant to sub-section 1:
1. the owner of a pharmacy manufacturing medicinal products within the scope of the normal operation of a pharmacy, reconstituting or packaging including the labelling of medicinal products intended for clinical trials in so far as this corresponds to the trial protocol,
2. the body responsible for a hospital, in so far as it is authorised to distribute medicinal products pursuant to the Pharmacies Act, reconstituting or packaging including the labelling of medicinal products intended for clinical trials in so far as this corresponds to the trial protocol,
3. the veterinarian operating a veterinary in-house dispensary for:
a) the decanting, packaging or labelling of medicinal products without altering them,
b) the manufacture of medicinal products which contain substances or preparations from substances released exclusively for trade outside of pharmacies,
c) the manufacture of homeopathic medicinal products which, in so far as they are intended for administration to food-producing animals, contain only active substances listed in the Annex to Regulation (EU) No. 37/2010 as substances which do not require the stipulation of maximum levels,
d) the preparation of medicinal products from a finished medicinal product and medically non-active constituents,
e) the mixing of finished medicinal products for the immobilisation of zoo, wild and reserve animals,
in so far as these activities are undertaken for the animals in his/her care,
4. the wholesaler for:
a) the decanting of liquefied oxygen into small portable containers for individual patients in hospitals or in physicians’ practices including the required labelling,
b) decanting, packaging or labelling other medicinal products without altering them, provided the packages concerned are not intended for direct distribution to the consumer,
5. the retailer who, in possession of the expert knowledge defined in Section 50, decants, packages or labels medicinal products without altering them for direct distribution to the consumer,
6. the manufacturer of active substances that are intended for use in the manufacture of medicinal products, which are manufactured using a procedure described in the homeopathic section of the Pharmacopoeia.
(2a) The exceptions specified in sub-section 2 shall not apply to the manufacture of blood preparations, tissue preparations, sera, vaccines, allergens, test sera, test antigens advanced therapy medicinal products, xenogeneic medicinal products and radiopharmaceuticals. Sentence 1 shall not apply to the facilities specified in sub-section 2 number 1 or 2 in so far as
1. the decanting in an unchanged form for an individual patient, packaging or labelling of sera of non-human or non-animal origin authorised for marketing within the purview of this Act, or
2. the reconstitution or the decanting, packaging or labelling of medicinal products intended for clinical trials in so far as this corresponds to the trial protocol, or
3. the manufacture of test allergens
are concerned. The competent authority shall be notified of activities pursuant to sentence 2 numbers 1 and 3.
(2b) Furthermore, an authorisation pursuant to sub-section 1 shall not be required by a person who is a physician, a dentist or otherwise authorised to practise medicine on human beings in so far as the medicinal products are manufactured directly under his/her professional responsibility for personal use by a specific patient. Sentence 1 shall not apply to:
1. advanced therapy medicinal products and xenogeneic medicinal products, as well as
2. medicinal products intended for clinical trials in so far as it is not merely a case of reconstitution.
(2c) Sub-section 2b sentence 1 shall apply mutatis mutandis to veterinarians maintaining a veterinary in-house dispensary for use in animals treated by them.
(3) An authorisation issued pursuant to sub-section 1 concerning the decanting of liquefied medicinal gases into the delivery receptacle of a tanker truck also covers the decanting of liquefied medicinal gases, without altering them, from a delivery receptacle of a tanker truck into containers installed at a hospital or on the premises of other consumers.
(4) The decision on the granting of the authorisation shall be reached by the competent authority of the federal Land where the factory site is situated or is to be situated. As far as blood products, tissue preparations, sera, vaccines, allergens, advanced therapy medicinal products, xenogeneic medicinal products, medicinal products manufactured using genetic engineering as well as active substances and other substances intended for the manufacture of medicinal products and which are of human, animal or microbial origin or are manufactured using genetic engineering are concerned, the decision on the authorisation shall be reached in consultation with the competent higher federal authority.
Section 14
Decision on the manufacturing authorisation
(1) The authorisation may only be refused if:
1. there is not at least one person available with the expert knowledge required pursuant to Section 15 (qualified person pursuant to Section 14) who is responsible for the activity referred to in Section 19,
2. (no longer applicable),
3. the qualified person pursuant to number 1 or the applicant is not sufficiently reliable in the performance of his/her job,
4. the qualified person referred to in number 1 cannot consistently perform the duties incumbent upon him,
5. (no longer applicable),
5a. in enterprises that manufacture medicated feeding stuffs from medicated pre-mixes, the person responsible for supervising the technical side of the manufacturing procedure does not possess sufficient knowledge and experience in the field of mixing technology, or
5b. the physician under whose responsibility pre-treatment of the donor is carried out for the purpose of separating haematopoietic stem cells from peripheral blood or from other blood components, does not possess the expert knowledge required,
5c. in breach of Section 4 sentence 1 number 2 of the Transfusion Act, no physician in charge has been appointed or said person does not possess the necessary professional knowledge according to the state of the medical art or, in breach of Section 4 sentence 1 number 3 of the Transfusion Act, no physician is present when the withdrawal procedure is carried out on a human donor,
6. suitable premises and equipment for the intended manufacture, testing and storage of the medicinal products are not available, or
6a. the manufacturer is not in a position to ensure that the manufacture or the testing of the medicinal products is carried out according to the latest standards prevailing in science and technology, and in the procurement of blood and blood components, additionally, according to the provisions contained in Chapter Two of the Transfusion Act.
(2) (no longer applicable)
(2a) The physician in charge pursuant to Section 4 sentence 1 number 2 of the Transfusion Act can also be the qualified person pursuant to sub-section 1 number 1.
(2b) (no longer applicable)
(3) (no longer applicable)
(4) By way of derogation from sub-section 1 number 6, it shall be possible to conduct partly outside of the manufacturer’s factory site:
1. the manufacture of medicinal products for clinical trials on human beings at a commissioned pharmacy,
2. the changing of the expiry date of medicinal products for clinical trials on human beings at a trial site by a person commissioned by the manufacturer, in so far as these medicinal products are exclusively intended for use at this trial site,
3. the testing of medicinal products at commissioned enterprises,
4. the procurement or testing, including laboratory testing of the donor samples of substances of human origin intended for the manufacture of medicinal products, with the exception of tissues, in other enterprises or facilities,
which require no authorisation of their own, can be carried out on condition that they have the premises and equipment suitable for this purpose and it is guaranteed that the manufacture and testing are carried out in accordance with the obtaining state of scientific and technical knowledge and the qualified person pursuant to sub-section 1 number 1 is able to assume his/her responsibilities.
(5) Should there be any objections against the submitted documents, the applicant shall be given an opportunity to correct the flaws within an appropriate period of time. If the flaws are not corrected, the authorisation shall be refused.
Section 15
Expert knowledge
(1) Proof of the required expert knowledge on the part of the qualified person referred to in Section 14 shall be furnished by:
1. the licence to practise as a pharmacist, or
2. the certificate testifying to the successful completion of a course of university studies in pharmacy, chemistry, pharmaceutical chemistry and technology, biology, human or veterinary medicine, of at least four-years’ duration,
as well as a period of at least two years’ practical experience in the field of the qualitative and quantitative analysis and other quality testing of medicinal products. The minimum duration of the university studies can be three and a half years, if studies are followed by theoretical and practical training of at least one year, which includes an internship of at least six months at a public pharmacy and is completed with a university-level examination. The duration of the practical experience pursuant to sentence 1 can be reduced by one year if the university studies are of at least five years’ duration and by one and a half years if the university studies are of at least six years’ duration. Where two university courses or two courses recognized as equivalent co-exist and where one of these extends over four years and the other over three years, it is to be assumed that the certificate awarded on completion of the university course or its recognized three-year equivalent shall be considered to fulfil the condition of duration referred to in sentence 2, in so far as the certificates awarded on completion of both courses are recognized as equivalent.
(2) In the cases specified in sub-section 1 number 2, proof shall be furnished to the competent authority that the university studies comprised theoretical and practical instruction at least in the following basic subjects and that an adequate knowledge exists thereof:
experimental physics,
general and inorganic chemistry,
organic chemistry,
analytical chemistry,
pharmaceutical chemistry,
biochemistry,
physiology,
microbiology,
pharmacology,
pharmaceutical technology,
toxicology,
pharmaceutical biology.
The theoretical and practical instruction and sufficient knowledge may also be acquired at a university upon completion of university studies within the meaning of sub-section 1 number 2 and may be proved by examination.
(3) Sub-section 2 shall not apply to the manufacture and testing of blood preparations, sera of human or animal origin, vaccines, allergens, test sera and test antigens. In place of the evidence of practical experience required in sub-section 1, proof shall be furnished of at least three years’ experience in the field of medical serology or medical microbiology. By way of derogation from sentence 2, in place of the practical experience required in sub-section 1, proof shall be furnished of:
1. at least three years’ experience in manufacture or testing in plasma processing enterprises with a manufacturing authorisation, in addition to at least six months’ experience in the field of transfusion medicine or medical microbiology, virology, hygiene or analytic procedure, in the case of blood preparations produced from blood plasma for the purpose of fractionation,
2. at least two years’ experience in the field of transfusion medicine covering all the areas of manufacture and testing in the case of blood preparations made from blood cells and preparations made from fresh plasma as well as in the case of substances and blood components for the manufacture of blood preparations,
3. at least six months’ experience in transfusion medicine or one year’s experience in the manufacture of autologous blood preparations in the case of autologous blood preparations,
4. for haematopoietic stem cell preparations made from peripheral blood or umbilical cord blood, in addition to sufficient knowledge, at least two years’ experience in this field of activity especially in the technology on which it is based.
With regard to the pre-treatment of patients for the purpose of separating haematopoietic stem cells from peripheral blood or from other blood components, the responsible physician shall provide evidence of sufficient knowledge in addition to at least two years’ experience in this field of activity. The prerequisites contained in sub-section 1 remain valid for packaging and labelling.
(3a) Sub-section 2 shall not apply to the manufacturing and testing of advanced therapy medicinal products, xenogeneic medicinal products, tissue preparations, medicinal products for use in in-vivo diagnosis by means of marker genes, tissue preparations, radiopharmaceuticals and active substances. In place of the practical experience required in sub-section 1, proof must be furnished:
1. in the case of gene therapy medicinal products and medicinal products for use in in-vivo diagnosis by means of marker genes, at least two years’ experience in a medically relevant field, in particular of genetic engineering, microbiology, cell biology, virology or molecular biology,
2. in the case of somatic cell therapy medicinal products and biotechnologically processed tissue products, at least two years’ experience in a medically relevant field, in particular of genetic engineering, microbiology, cell biology, virology or molecular biology,
3. in the case of xenogeneic medicinal products, at least three years’ experience in a medically relevant field including at least two years’ activity particularly in one of the fields mentioned under number 1,
4. in the case of tissue preparations, at least two years’ experience in the manufacture and testing of such medicinal products in enterprises and facilities which require a manufacturing authorisation pursuant to this Act or possess a manufacturing authorisation under the legislation of the European Union,
5. in the case of radiopharmaceuticals, at least three years’ experience in the field of nuclear medicine or that of radiopharmaceutical chemistry, and
6. in the case of active substances other than those listed under sub-section 3 sentence 3 number 2, at least two years’ experience in the manufacture and testing of active substances.
(4) The period of practical experience specified in sub-section 1 shall be spent at a firm which has been granted a manufacturing authorisation by a Member State of the European Union, by another State Party to the Agreement on the European Economic Area or by a state with which an agreement exists as to the mutual recognition of certificates pursuant to Section 72a sentence 1 number 1.
(5) The period of practical experience shall not be required for the manufacturing of medicated feeding stuffs from medicated pre-mixes; sub-section 2 shall not apply.
(6) A legally exercised function as a qualified person, subsequent to an examination of the necessary expert knowledge by the competent authority, also entitles a person to exercise this function within the remit of another competent authority, unless there are substantiated grounds to suppose that the existing expert knowledge is insufficient for the new function.
Section 16
Limitation of the manufacturing authorisation
The authorisation shall be issued to the applicant for a specific factory site and for particular medicinal products and pharmaceutical forms of medicinal products and, in cases as defined in Section 14 sub-section 4, also for a specific factory site of the commissioned company or the other company. In so far as the authorisation includes the testing of medicinal products or active substances, the type of testing is to be specified.
Section 17
Deadlines for the granting of marketing authorisations
(1) The competent authority shall take the decision on the application for authorisation within a period of three months.
(2) If the holder of the authorisation makes an application for the authorisation to be modified in respect of the medicinal products to be manufactured or the premises and equipment as defined in Section 14 sub-section 1 number 6, the authority shall reach a decision within a period of one month. In exceptional cases, the deadline shall be extended by an additional two months. The applicant shall be notified thereof prior to the expiry of the deadline and notified of the grounds.
(3) If the authority gives the applicant the opportunity to correct the flaws pursuant to Section 14 sub-section 5, the deadlines shall be interrupted until such flaws have been corrected or until the expiry of the deadline set pursuant to Section 14 sub-section 5. The interruption of the deadline shall begin on the day the applicant receives the request to correct the flaws.
Section 18
Withdrawal, revocation, suspension
(1) The authorisation shall be withdrawn if it becomes known subsequently that one of the grounds for refusal, pursuant to Section 14 sub-section 1, existed at the time the authorisation was granted. The authorisation shall be revoked if one of the grounds for refusal subsequently developed; the suspension of the authorisation may be ordered instead of its revocation. Section 13 sub-section 4 shall apply mutatis mutandis.
(2) The competent authority may issue a provisional order mandating that the manufacture of a medicinal product be discontinued if the manufacturer fails to furnish the evidence required for manufacture and testing. The provisional order may be restricted to one batch.
Section 19
Areas of responsibility
The qualified person pursuant to Section 14 shall be responsible for ensuring that each batch of the medicinal product is manufactured and tested in accordance with the regulations applicable to the trade in medicinal products. He/she must certify the fulfilment of these provisions for each batch of medicinal products in a serially numbered register or comparable document before it is placed on the market.
Section 20
Obligations to notify
The marketing authorisation holder shall notify the competent authority in advance of any change in the information referred to in Section 14 sub-section 1 and submit evidence. Any unforeseen change in the qualified person referred to in Section 14, must be notified immediately.
Section 20a
Applicability to active substances and other substances
Section 13 sub-sections 2 and 4 and Sections 14 to 20 shall apply mutatis mutandis to active substances and to other substances of human origin intended for use in the manufacture of medicinal products, in so far as their manufacture or testing pursuant to Section 13 sub-section 1 requires an authorisation.
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