GERMAN DRUG LAW
This section is intended to give you an impression of the content of the German Drug Law, "Arzneimittelgesetz" or "AMG". It reflects the legals situation as of late 2010.
This translation is not official - valid is the German version.
(THE DRUG LAW)
(ARZNEIMITTELGESETZ – AMG)
of the
FEDERAL REPUBLIC OF GERMANY
Non-official translation as of 2010
This version incorporates:
1. the version of the notification of the Law of 12th
December 2005 (Federal Law Gazette I p.
3394),
2. Article 12 of the Law of 14th
August 2006 (Federal Law Gazette I p.
1869), which entered
into force on 18th
August 2006.
3. Article 5 of the Law of 21st
December 2006 (Federal Law Gazette I p.
3294), which entered
into force on 28th
December 2006,
4. Article 2 of the Law of 21st
December 2006 (Federal Law Gazette I p.
3367), which entered
into force on 29th
December 2006,
5. Article 30 of the Law of 26th
March 2007 (Federal Law Gazette I p. 378),
which partially
entered into force on 1st
April 2007 and will partially enter into
force on 1st
January 2009
6. Article 2 of the Law of 14th
June 2007 (Federal Law Gazette I p. 1066),
which entered into
force on 30th
June 2007,
7. Article 2 of the Law of 20th
July 2007 (Federal Law Gazette I p. 1574),
which entered into
force on 1st
August 2007,
8. Article 2 of the Law of 24th
October 2007 (Federal Law Gazette I p.
2510), which entered
into force on 1st
November 2007,
9. Article 9 (1) of the Law of 23rd
November 2007 (Federal Law Gazette I p. 2631), which
entered into force on 1st
January 2008,
10. Article 2 of the Law of 15th
July 2009 (Federal Law Gazette I p. 1801),
which entered into
force on 21st
July 2009,
11. Article 1 of the Law of 17th
July 2009 (Federal Law Gazette I p. 1990,
p. 3578), which entered
into force on 23rd
July 2009,
12. Article 1 of the Ordinance of 28th
September 2009 (Federal Law Gazette I p. 3172), which
entered into force on 3rd
October 2009.
Medicinal Products Act
(The DRUG LAW)
(Arzneimittelgesetz – AMG)∗)
Summary of Contents
First Chapter
Purpose of the Act, definition of terms, scope
§ 1 Purpose of the Act
§ 2 The term ‘medicinal product’
§ 3 The term ‘substance’
§ 4 Definitions of additional terms
§ 4a Exceptions to the scope of the present Act
§ 4b Special provisions governing advanced therapy
medicinal products
∗)
This Act serves to incorporate:
Second Chapter
Requirements on medicinal products
§ 5 Prohibition in respect of unsafe medicinal products
§ 6 Empowerment in respect of health protection
§ 6a Prohibition of medicinal products for doping
purposes in sport
§ 7 Radiopharmaceuticals and medicinal products treated
with
ionizing radiation
§ 8 Prohibitions to prevent deception
§ 9 The party responsible for placing on the market
§ 10 Labelling
§ 11 Package leaflet
§ 11a Expert information
§ 12 Empowerment for labelling, package leaflet and
pack sizes
Third Chapter
Manufacture of medicinal products
§ 13 Manufacturing authorisation
§ 14 Decision on the manufacturing authorisation
§ 15 Expert knowledge
§ 16 Limitation of the manufacturing authorisation
§ 17 Deadlines for the granting of an authorisation
§ 18 Withdrawal, revocation, suspension
§ 19 Areas of responsibility
§ 20 Obligations to notify
§ 20a Applicability to active substances and other
substances
§ 20b Authorisation for the procurement of tissues and
the pertinent
laboratory testing
§ 20c Authorisation for the processing, preservation,
testing and
storage or the placing on the market of tissues or
preparations made from tissues
§ 20d Exception from the obligation to obtain an
authorisation for
tissues and tissue preparations
Fourth Chapter
Marketing authorisation for medicinal products
§ 21 Obligation to obtain a marketing authorisation
§ 21a Authorisation of tissue preparations
§ 22 Marketing authorisation documents
§ 23 Particular documents required for medicinal
products
intended for administration to animals
§ 24 Expertises
§ 24a Use of a previous applicant's documents
§ 24b Authorisation of a generic medicinal product,
document protection
§ 24c Additional requests
§ 24d General right of use
§ 25 Decision on marketing authorisation
§ 25a Prior examination
§ 25b Mutual-recognition procedure and decentralised
procedure
§ 25c Measures taken by the competent higher federal
authority on
decisions of the European Commission or the Council of
the
European Union
§ 26 Guidelines for the testing of medicinal products
§ 27 Deadlines for the granting of marketing
authorisations
§ 28 Power to impose conditions
§ 29 Obligation to notify, renewal of the marketing
authorisation
§ 30 Withdrawal, revocation, suspension
§ 31 Expiry, prolongation
§ 32 Official batch testing
§ 33 Costs
§ 34 Informing the public
§ 35 Empowerments in respect of marketing authorisation
and exemptions
§ 36 Empowerment in respect of standard marketing
authorisations
§ 37 Authorisation by the Commission of the European
Communities
or the Council of the European Union for placing on the
market,
marketing authorisations for medicinal products from
other states
Fifth Chapter
Registration of medicinal products
§ 38 Registration of homeopathic medicinal products
§ 39 Decision on the registration of homeopathic
medicinal products,
procedural provisions
§ 39a Registration of traditional herbal medicinal
products
§ 39b Registration documents for traditional herbal
medicinal products
§ 39c Decision on the registration of traditional
herbal medicinal products
§ 39d Other procedural provisions for traditional
herbal medicinal products
Sixth Chapter
Protection of human subjects in clinical trials
§ 40 General conditions for the clinical trial
§ 41 Special conditions for the clinical trial
§ 42 Ethics committee procedure, procedure for
authorisation by the
higher federal authority
§ 42a Withdrawal, revocation and suspension of the
authorisation
or of the favourable opinion
Seventh Chapter
Sale of medicinal products
§ 43 Pharmacy-only requirement, placing on the market
by
veterinarians
§ 44 Exceptions to the pharmacy-only requirement
§ 45 Authority to allow further exceptions to
pharmacy-only
requirement
§ 46 Authority to extend the pharmacy-only requirement
§ 47 Distribution channel
§ 47a Special distribution channels, obligation to keep
records
§ 47b Special distribution channels, diamorphine
§ 48 Prescription requirement
§ 49 (deleted)
§ 50 Retail trading of over-the-counter medicinal
products
§ 51 Sale by itinerant traders
§ 52 Prohibition of self-service
§ 52a Wholesale trading of medicinal products
§ 52b Supply of medicinal products
§ 53 Expert consultation
Eighth Chapter
Safety and quality control
§ 54 Internal regulations
§ 55 Pharmacopoeia
§ 55a Official compilation of test procedures
Ninth Chapter
Special provisions for medicinal products intended for
use in animals
§ 56 Medicated feedingstuffs
§ 56a Prescription, dispensing and use of medicinal
products by
veterinarians
§ 56b Exceptions
§ 57 Acquisition and possession by keepers of animals,
records
§ 58 Use in food-producing animals
§ 59 Clinical trial and residue testing in
food-producing animals
§ 59a Trade in substances and preparations from
substances
§ 59b Substances for conducting residue tests
§ 59c Obligations to keep records of substances which
can be
used as veterinary medicinal products
§ 60 Pet animals
§ 61 Powers of veterinary schools
Tenth Chapter
Observation, collection and evaluation of the risks of
medicinal products
§ 62 Organisation
§ 63 Graduated plan
§ 63a Graduated plan officer
§ 63b Documentation and notification obligations
§ 63c Special documentation and notification
obligations for blood
and tissue preparations
Eleventh Chapter
Supervision
§ 64 Conducting supervision
§ 65 Sampling
§ 66 Obligation to tolerate and collaborate
§ 67 General notification requirement
§ 67a Database-supported information system
§ 68 Obligation to inform and to report
§ 69 Measures by the competent authorities
§ 69a The supervision of substances which can be used
as
medicinal products for animals
§ 69b Use of specific data
Twelfth Chapter
Special provisions for the Federal Armed Forces,
Federal Police, Public Order Police, Civil Protection
§ 70 Application and enforcement of the Act
§ 71 Exceptions
Thirteenth Chapter
Import and export
§ 72 Import authorisation
§ 72a Certificates
§ 72b Import authorisation and certificates for tissues
and
specific tissue preparations
§ 73 Prohibition of introduction
§ 73a Export
§ 74 Participation of customs offices
Fourteenth Chapter
Information Officer, Pharmaceutical Consultant
§ 74a Information Officer
§ 75 Expert knowledge
§ 76 Duties
Fifteenth Chapter
Designation of the competent higher federal authorities
and other provisions
§ 77 Competent higher federal authority
§ 77a Independence and transparency
§ 78 Prices
§ 79 Authority to permit exceptions in times of crises
§ 80 Authority to issue procedural and compassionate
use regulations
§ 81 Relation to other laws
§ 82 General administrative regulations
§ 83 Approximation to Community legislation
Sixteenth Chapter
Liability for damages caused by medicinal products
§ 84 Absolute liability
§ 84a Right to disclosure
§ 85 Contributory negligence
§ 86 Extent of liability for damages in the case of
death
§ 87 Extent of liability for damages in the case of
bodily injury
§ 88 Maximum amounts
§ 89 Compensation in the form of annuities
§ 90 (deleted)
§ 91 Extended liability
§ 92 Mandatory provisions
§ 93 Several parties liable for damages
§ 94 Coverage provision
§ 94a Local jurisdiction
Seventeenth Chapter
Penal provisions and provisions on administrative fines
§ 95 Penal provisions
§ 96 Penal provisions
§ 97 Administrative fines
§ 98 Confiscation
§ 98a Extended forfeiture
Eighteenth Chapter
Transitional and interim provisions
First sub-chapter
§s 99 to 124 Transitional provisions arising out of the
Law on the Reform
of Drug Legislation
Second sub-chapter
§s 125 and 126 Transitional provisions arising out of
the First Act
Amending the Drug Law
Third sub-chapter
§s 127 to 131 Transitional provisions arising out of
the Second Act
Amending the Drug Law
Fourth sub-chapter
§ 132 Transitional provisions arising out of the Fifth
Act
Amending the Drug Law
Fifth sub-chapter
§ 133 Transitional provisions arising of the Seventh
Act
Amending the Drug Law
Sixth sub-chapter
§ 134 Transitional provisions arising out of the
Transfusion Act
Seventh sub-chapter
§ 135 Transitional provisions arising out of the Eighth
Act
Amending the Drug Law
Eighth sub-chapter
§ 136 Transitional provisions arising out of the Tenth
Act
Amending the Drug Law
Ninth sub-chapter
§ 137 Transitional provisions arising out of the
Eleventh Act
Amending the Drug Law
Tenth sub-chapter
§ 138 Transitional provisions arising out of the
Twelfth Act
Amending the Drug Law
Eleventh sub-chapter
§ 139 Transitional provisions arising out of the First
Act
Amending the Transfusion Act and the Regulations on
Medicinal Products
Twelfth sub-chapter
§ 140 Transitional provisions arising out of the
Thirteenth Act
Amending the Drug Law
Thirteenth sub-chapter
§ 141 Transitional provisions arising out of the
Fourteenth Act
Amending the Drug Law
Fourteenth sub-chapter
§ 142 Transitional provisions arising out of the
Tissues Act
Fifteenth sub-chapter
§ 143 Transitional provisions arising out of the Act on
improving measures
against doping in sport
Sixteenth sub-chapter
§ 144 Transitional provisions arising out of the Act
amending the
regulations on medicinal products and other regulations
Annex
FIRST CHAPTER
PURPOSE OF THE ACT, DEFINITION OF TERMS, SCOPE
§ 1
Purpose of the Act
It is the purpose of the present Act to guarantee, in
the interest of furnishing both human
beings and animals with a proper supply of medicinal
products, safety in respect of the trade in
medicinal products, ensuring in particular the quality,
efficacy and safety of medicinal products
in accordance with the following provisions.
§ 2
The term ‘medicinal product’
(1) Medicinal products are substances or preparations
made from substances which:
1. are intended for use on or in the human or animal
body and are intended for use as
remedies with properties for the curing, alleviating or
preventing of human or animal diseases
or disease symptoms or
2. can be used in or on the human or animal body or can
be administered to a human being
or an animal, either:
a) to restore, correct or to influence the
physiological functions through a pharmacological,
immunological or metabolic effect, or
b) to make a medical diagnosis.
(2) The following shall be considered as medicinal
products:
1. objects which contain a medicinal product pursuant
to sub-§ 1 or to the surface of
which a medicinal product specified in sub-§ 1 is
applied and which are intended to
come into either temporary or permanent contact with
the human or animal body,
1a. veterinary instruments in so far as they are
intended for single use and the labelling of
which indicates that they have been subjected to a
procedure for microbe reduction,
2. objects which, without being objects pursuant to
number 1 or 1a, are intended for the
purposes indicated in sub-§ 1 number 2 or 5, to be
introduced either temporarily or
permanently into the human or animal body, with the
exception of veterinary instruments,
3. wound dressings and surgical sutures in so far as
they are intended for use on or in animals
and are not covered by numbers 1, 1a or 2,
4. substances and preparations made from substances
which, also in combination with
other substances or preparations made from substances,
without being applied on or in
the human or animal body, are intended to diagnose the
nature, state or functions of the
animal body or to identify pathogens in animals.
(3) The term 'medicinal product' shall not apply to:
1. foodstuffs within the meaning of § 2 sub-§ 2 of the
Food and Feed Code,
2. cosmetic products within the meaning of § 2 sub-§ 5
of the Food and Feed
Code,
3. tobacco products within the meaning of § 3 of the
Provisional Tobacco Act,
4. substances or preparations made from substances
which are exclusively intended for the
external cleaning or hygiene or for influencing the
appearance or the body odour of an
animal, provided that no substances or preparations
made from substances are added
which are excluded from trade outside of pharmacies,
5. biocidal products pursuant to § 3b of the Act on the
Protection against Hazardous
Substances,
6. feedingstuffs within the meaning of § 3 numbers 11
to 15 of the Food and Feed
Code,
7. medical devices and accessories for medical devices
within the meaning of § 3 of the
Medical Devices Act unless they are medicinal products
within the meaning of § 2
sub-§ 1 number 2,
8. organs within the meaning of § 1a number 1 of the
Transplantation Act if they are intended
for transplanting to human beings.
(3a) Medicinal products are also products which are or
contain substances or preparations
made from substances which, taking into account all the
properties of the product, fall under
the definition contained in sub-§ 1 and, at the same
time, can fall under the definition
of a 'product' pursuant to sub-§ 3.
(4) As long as a product is authorised or registered as
a medicinal product pursuant to
the present Act, or is exempted from the need for
authorisation or registration by ordinance,
such product shall be considered as a medicinal
product. A product shall not be considered as
a medicinal product if its authorisation or
registration has been rejected by the competent
higher federal authority, on the grounds that it is not
a medicinal product.
§ 3
The term ‘substance’
For the purpose of the present Act, substances are:
1. chemical elements and chemical compounds as well as
their naturally occurring mixtures
and solutions,
2. plants, parts of plants and plant constituents,
algae, fungi or lichen whether in the processed
or crude state,
3. the bodies of animals, including those of living
animals, as well as parts of the body, body
constituents and metabolic products of human beings or
animals, whether in the processed
or crude state,
4. micro-organisms, including viruses, as well as their
constituents or metabolic products.
§ 4
Definitions of additional terms
(1) Finished medicinal products are medicinal products
which are manufactured beforehand
and placed on the market in packaging intended for
distribution to the consumer or other
medicinal products intended for distribution to the
consumer, in the preparation of which any
form of industrial process is used or medicinal
products which are produced commercially, except
in pharmacies. Finished medicinal products are not
intermediate products intended for further
processing by a manufacturer.
(2) Blood preparations are medicinal products which are
or which contain, as medically
active substances, blood, plasma or serum conserves
obtained from blood, blood components
or preparations made from blood components.
(3) Sera are medicinal products within the meaning of §
2 sub-§ 1 which
contain antibodies, fragments of antibodies or fusion
proteins with a functional antibody component
as their active substance and are used because of this
active substance. Sera shall not
be considered as blood preparations as defined in sub-§
2 or as tissue preparations as
defined in sub-§ 30.
(4) Vaccines are medicinal products within the meaning
of § 2 sub-§ 1, containing
antigens or recombinant nucleic acids and intended for
use in human beings or animals
for the production of specific antitoxins and
protective agents and, in so far as they contain recombinant
nucleic acids, intended exclusively for the prevention
or treatment of infectious diseases.
(5) Allergens are medicinal products within the meaning
of § 2 sub-§ 1, containing
antigens or haptens and intended for use on human
beings or animals for the diagnosis
of specific antitoxins or protective agents (test
allergens) or containing substances which are
used to achieve an antigen-specific reduction in the
case of a specific immunological oversensitivity
(therapeutic allergens).
(6) Test sera are medicinal products within the meaning
of § 2 sub-§ 2
number 4, which are obtained from blood, organs, parts
of organs or secretions from organs of
the healthy or the sick, or from beings who have been
sick or previously immunized, which contain
specific antibodies and which are intended to be used
on account of these antibodies, as
well as the control sera appertaining to these
medicinal products.
(7) Test antigens are medicinal products within the
meaning of § 2 sub-§ 2
number 4, which contain antigens or haptens and which
are intended to be used as such.
(8) Radiopharmaceuticals are medicinal products which
are or contain radioactive substances
and spontaneously emit ionizing radiation and which are
intended to be used on account
of these properties; radionuclides (precursors) which
have been manufactured for the radiolabelling
of other substances prior to administration as well as
systems with a fixed mother
radionuclide which forms a daughter radionuclide
(generators) shall also be regarded as radiopharmaceuticals.
(9) Advanced therapy medicinal products are gene
therapy medicinal products, somatic
cell therapy medicinal products or tissue engineered
products pursuant to Article 2, paragraph
1, letter a of Regulation (EC) No. 1394/2007 of the
European Parliament and the Council of 13th
November 2007 on advanced therapy medicinal products
and amending Directive 2001/83/EC
and Regulation (EC) No. 726/2004 (OJ EC No. L 324 of 10th
December 2007, p. 121).
(10) Medicated feedingstuffs are medicinal products in
the form of ready feedingstuffs,
manufactured from medicated pre-mixes and mixed feed
and intended to be placed on the
market for administration to animals.
(11) Medicated pre-mixes are medicinal products
intended exclusively for use in the
manufacture of medicated feedingstuffs. They shall be
regarded as finished medicinal
products.
(12) The withdrawal period is the period necessary
between the last administration of
the veterinary medicinal product in keeping with its
intended purpose to animals and the production
of foodstuffs from such animals, in order to protect
public health and ensure that such
foodstuffs do not contain residues in quantities in
excess of the maximum limits for pharmacologically
active substances laid down in Council Regulation (EEC)
No. 2377/90 of 26th
June
1990 laying down a Community procedure for the
establishment of maximum residue limits of
veterinary medicinal products used in foodstuffs of
animal origin (OJ L 224 p. 1).
(13) Side effects are those unintended, harmful
reactions which occur when a medicinal
product is administered in keeping with its intended
purpose. Serious side effects are side effects
which are fatal or life-threatening, require
hospitalisation or the prolongation of existing
hospitalisation, or lead to permanent or serious
disability, invalidity, congenital anomalies or
birth defects; in the case of medicinal products
intended for administration to animals, side effects
are also serious if they cause recurring or persistent
symptoms. Unexpected side effects
are side effects the nature, extent or outcome of which
differs from the medicinal product's
package leaflet. Sentences 1 to 3 also apply to such
side effects as occur as a result of interactions.
(14) Manufacturing is the producing, preparing,
formulating, treating or processing, filling
as well as decanting, packaging, labelling and release
of medicinal products.
(15) Quality is the nature of a medicinal product,
determined by identity, content, purity
and other chemical, physical and biological properties
or by the manufacturing procedure.
(16) A batch is the quantity of a medicinal product
produced from the same amount of
starting material in a standard manufacturing process
or, in the case of a continuous manufacturing
process, within a specific period of time.
(17) Marketing is the keeping in stock for sale or for
other forms of supply, the exhibiting
and offering for sale and the distribution to others.
(18) In the case of medicinal products requiring a
marketing authorisation or registration,
the pharmaceutical entrepreneur shall be the holder of
the marketing authorisation or registration.
The pharmaceutical entrepreneur is also any person who
places medicinal products
on the market under his/her own name.
(19) Active substances are substances which are
intended for use as medically active
constituents in the manufacture of medicinal products
or which, through their use in the manufacture
of medicinal products, are intended to become medically
active substances.
(20) (deleted)
(21) Xenogenic medicinal products are medicinal
products intended for use in or on humans
which are or contain living animal tissues or cells.
(22) Wholesale trade in medicinal products is any
professional or commercial activity for
the purpose of doing business which consists of the
procuring, storing, dispensing or exporting
of medicinal products, with the exception of the
dispensing of medicinal products to consumers
other than physicians, dentists, veterinarians or
hospitals.
(23) A clinical trial on human beings is any
investigation on human subjects intended to
investigate or verify the clinical or pharmacological
effects of medicinal products, or to identify
side-effects or to study the absorption, distribution,
metabolisation or excretion, with the aim of
ascertaining the safety or efficacy of the medicinal
product. Sentence 1 does not apply to noninterventional
trials. A non-interventional trial is a study, in the
context of which findings resulting
from persons' treatment with medicinal products are
analysed using epidemiological methods;
the treatment, including the diagnosis and monitoring,
shall not follow a predetermined trial
protocol but shall result exclusively from current
medical practice; in so far as a medicinal product
requiring a marketing authorisation or a medicinal
product requiring an authorisation pursuant
to § 21a sub-§ 1 is concerned, this shall be conducted,
moreover, according to
the specifications regarding its use contained in the
marketing authorisation or authorisation.
(24) The sponsor is a natural or legal person who
assumes responsibility for the commissioning,
organisation and financing of a clinical trial on human
beings.
(25) The investigator is generally a physician
responsible for the conduct of the clinical
trial on human beings at a site or, in justified
exceptional cases, another person whose profession,
owing to the scientific requirements and the experience
in the care of patients which it
calls for, qualifies him/her to conduct research on
human beings. If a clinical trial is being conducted
by several investigators at one site, the person in
charge of the team shall be the principal
investigator. If a clinical trial is being conducted at
various trial sites, the sponsor shall name
one investigator as the chief investigator.
(26) A homeopathic medicinal product is any medicinal
product prepared in accordance
with a homeopathic manufacturing procedure described in
the European Pharmacopoeia or, in
absence thereof, in the pharmacopoeias currently used
officially in the EU Member States. A
homeopathic medicinal product can also contain a number
of active substances.
(27) A risk linked to the use of a medicinal product
is:
a) any risk to patients’ health or public health linked
to the quality, safety or efficacy of the
medicinal product and, in the case of medicinal
products intended for use in animals, any
risk to human or animal health,
b) any risk of adverse effects on the environment.
(28) The risk-benefit balance is an assessment of the
positive therapeutic effects of the
medicinal product in relationship to the risk referred
to in sub-§ 27 letter a, and in the
case of medicinal products intended for use in animals,
also referred to in sub-§ 27 letter
b.
(29) Herbal medicinal products are medicinal products
which exclusively contain, as active
substances, either one or more herbal substances, one
or more herbal preparations, or
one or more such herbal substances in combination with
one or more such herbal preparations.
(30) Tissue preparations are medicinal products which
are tissues within the meaning of
§ 1a number 4 of the Transplantation Act or are
manufactured from such tissues. Human
sperm or egg cells including impregnated egg cells
(germ cells) and embryos are neither medicinal
products nor tissue preparations.
(31) Reconstitution of a finished medicinal product for
human use is the conversion of
the medicinal product into its usable form immediately
prior to its use according to the specifications
contained in the package leaflet or, within the
framework of the clinical trial, in accordance
with the trial protocol.
(32) Introduction is any type of shipment into, through
or from the territorial scope of the
present Act. Import is the conveyance of products which
fall under the Medicinal Products Act
from third countries which are not States Parties to
the Agreement on the European Economic
Area for free circulation.
(33) An anthroposophic medicinal product is a medicinal
product which has been developed
according to the anthroposophic understanding of humans
and nature, according to a
European Pharmacopoeia or, in the absence thereof, in
accordance with a homeopathic manufacturing
practice described in the pharmacopoeias currently used
officially in the EU Member
States, or according to a special anthroposophic
manufacturing procedure, and which is intended
for use according to the principles of the
anthroposophic understanding of humans and
nature.
§ 4a
Exceptions to the scope of the present Act
The present Act shall not apply to:
1. medicinal products which are manufactured using
pathogens or biotechnology and are intended
for use in the prevention, diagnosis or cure of
epizootics,
2. the procurement and marketing of germ cells for the
artificial insemination of animals,
3. tissues which are removed from a person in order to
reinsert them without changing their
material structure into the same person in one and the
same surgical procedure.
Sentence 1 number 1 shall not apply to § 55.
§ 4b
Special provisions governing advanced therapy medicinal
products
(1) In the case of advanced therapy medicinal products
which are:
1. prescribed by a doctor as an individual preparation
for an individual patient,
2. prepared on a non-routine basis according to
specific quality standards, and
3. used in a specialised facility for health care under
the professional responsibility
of a doctor,
within the scope of the present Act, Parts Four and
Seven of the present Act shall not apply.
The remaining provisions of the Act, as well as Article
14 (1) and Article 15 (1-6) of the Regulation
(EC) No. 1394/2007 shall apply mutatis mutandis
with the proviso that the official tasks and
powers laid down therein are assumed by the competent
authority or the competent higher federal
authority in keeping with the tasks entrusted to them
by the present Act and the holder of
the authorisation pursuant to sub-§ 3 sentence 1, takes
the place of the marketing authorisation
holder pursuant to the present Act or the marketing
authorisation holder pursuant to
Regulation (EC) No. 1394/2007.
(2) Prepared on a non-routine basis pursuant to sub-§ 1
sentence 1 number 2 are,
in particular, medicines:
1. which are manufactured in small quantities, and in
the case of which, based on a routine
manufacturing procedure, variations in the procedure
which are medically justified for an
individual patient, are carried out, or
2. which have not yet been manufactured in sufficient
quantities so that the necessary data
to enable a comprehensive assessment are not yet
available.
(3) Medicinal products pursuant to sub-§ 1 sentence 1
may only be supplied to
others if they have been authorised by the competent
higher federal authority. § 21a sub§s
2 to 8 shall apply mutatis mutandis. If the
necessary information and documents pursuant
to § 21a sub-§ 2 number 6 cannot be submitted, the
applicant can submit information
and documents regarding the mode of action, the
anticipated effect and possible
risks. The holder of the authorisation shall inform the
competent higher federal authority, at
specific intervals stipulated by the competent higher
federal authority by means of an ordinance,
about the scale of manufacture and about the data for
the comprehensive assessment
of the medicinal product. The authorisation shall be
withdrawn if it subsequently becomes
known that one of the prerequisites provided for in
sub-§ 1 sentence 1 had not been fulfilled;
it shall be revoked if one of the prerequisites no
longer exists. § 22 sub-§ 4
shall apply mutatis mutandis.
(4) Enquiries about the obligation to obtain an
authorisation for an advanced therapy
medicinal product shall be decided by the competent
authority in consultation with the competent
higher federal authority. § 21 sub-§ 4 shall apply
mutatis mutandis.
SECOND CHAPTER
REQUIREMENTS ON MEDICINAL PRODUCTS
§ 5
Prohibition in respect of unsafe medicinal products
(1) The placing on the market or the use of unsafe
medicinal products on another human
shall be prohibited.
(2) Medicinal products shall be considered unsafe if,
according to the current level of
scientific knowledge, there is reason to suspect that,
when used in accordance with their intended
purpose, they have harmful effects which exceed the
limits considered tolerable in the
light of current medical knowledge.
§ 6
Empowerment in respect of health protection
(1) The Federal Ministry of Health (the Federal
Ministry) is hereby empowered to specify,
restrict or prohibit, by ordinance subject to the
approval of the Bundesrat, the use of certain
substances, preparations from substances or objects in
the manufacture of medicinal products
and to forbid the marketing and use of medicinal
products which have not been manufactured
in compliance with these regulations in so far as this
is deemed necessary in the interest of risk
prevention or in order to prevent medicinal products
from posing a direct or indirect hazard to
human or animal health. The ordinance pursuant to
sentence 1 shall be issued by the Federal
Ministry of Consumer Protection, Food and Agriculture
in agreement with the Federal Ministry
in so far as the medicinal products are intended for
administration to animals.
(2) The ordinance referred to in sub-§ 1 shall be
promulgated in agreement with
the Federal Ministry for the Environment, Nature
Conservation and Nuclear Safety in the case
of radiopharmaceuticals and medicinal products in the
manufacture of which ionizing radiation
is used.
§ 6a
Prohibition of medicinal products for doping purposes
in sport
(1) The placing on the market, prescribing or
administering of medicinal products to others
for the purpose of doping in sport, is prohibited.
(2) Sub-§ 1 shall apply only to medicinal products
which contain substances belonging
to the groups of prohibited active substances or
substances contained in the Appendix
to the Anti-Doping Convention (Act of 2nd
March 1994 on the Anti-Doping Convention of 16th
November 1989, Federal Law Gazette 1994 II p. 334)
which are intended for use in the prohibited
measures listed therein in so far as human beings are
or are intended to be the subjects of
the doping. The package leaflet and the expert
information of these medicinal products shall
contain the following warning: "The use of the
medicinal product
[insert
name of the medicinal
product]
can lead to positive results in the event of a doping
test." If the misuse of the medicinal
product for doping purposes can endanger health, this
shall also be included. Sentence 2 shall
not apply to medicinal products which have been
manufactured using a homeopathic manufacturing
procedure.
(2a) The possession of medicinal products and active
substances which are or contain
substances listed in the annex to the present Act in
non-small quantities for the purpose of doping
in sports is prohibited in so far as human beings are
to be the subject of doping. The Federal
Ministry shall specify, in agreement with the Federal
Ministry of the Interior, after hearing
experts, by means of ordinance with the approval of the
Bundesrat, what constitutes the nonsmall
quantity of the substances mentioned in sentence 1. The
Federal Ministry is hereby empowered,
in agreement with the Federal Ministry of the Interior,
after hearing experts:
1. to include in the annex to the present Act
additional substances which can be used for
doping purposes in sport, are used in considerable
quantities for this purpose and the use
of which without a therapeutic assessment is dangerous,
and
2. to specify what constitutes a non-small quantity of
such substances
by ordinance with the consent of the Bundesrat.
By ordinance pursuant to sentence 3, subtances can be
deleted from the annex to the
present Act if the prerequisites contained in sentence
3 number 1 no longer exist.
(3) The Federal Ministry is hereby empowered to
specify, in agreement with the Federal
Ministry of the Interior, by ordinance subject to the
approval of the Bundesrat, additional sub-
24 -
stances or preparations made from substances to which
sub-§ 1 shall apply, in so far as
this is deemed necessary in order to prevent medicinal
products from posing a direct or indirect
hazard to human health through doping in sport.
§ 7
Radiopharmaceuticals and medicinal products treated
with ionizing radiation
(1) It shall be forbidden for radiopharmaceuticals or
medicinal products in the manufacture
of which ionizing radiation has been used to be placed
on the market unless the authorisation
to do so has been given by ordinance according to sub-§
2.
(2) The Federal Ministry is hereby empowered to
authorize, in agreement with the Federal
Ministry for the Environment, Nature Conservation and
Nuclear Safety, by means of an ordinance
subject to the approval of the Bundesrat, the
placing of radiopharmaceuticals on the
market or the use of ionizing radiation in the
manufacture of medicinal products in so far as this
is deemed, according to the current level of scientific
knowledge, to be justified for medical purposes
and in so far as it does not compromise human or animal
health. The ordinance may
prescribe the channel of distribution for the medicinal
products and specify that certain data
concerning their radioactivity are to appear on the
container, the outer packaging and the
package leaflet. The ordinance shall be issued by the
Federal Ministry of Consumer Protection,
Food and Agriculture in agreement with the Federal
Ministry and the Federal Ministry for the
Environment, Nature Conservation and Nuclear Safety, in
so far as medicinal products intended
for administration to animals are concerned.
§ 8
Prohibitions to prevent deception
(1) It shall be prohibited for medicinal products or
active substances:
1. which, by deviating from recognized pharmaceutical
principles, are of considerably reduced
quality,
1a. which are incorrectly labelled with regard to their
identity or origin (counterfeit medicinal
products, counterfeit active substances) or
2. which bear otherwise misleading names,
specifications or presentations to be manufactured
or placed on the market.
Deception shall be said to exist, in particular, in
cases where
a) claims are made to the effect that certain medicinal
products have a therapeutic efficacy
or effects which they do not possess or that active
substances exhibit an activity
which they do not,
b) the erroneous impression is given that success can
be expected with certainty or
that no harmful effects can be expected to occur when
the medicinal product is
used in accordance with its intended purpose or over a
prolonged period,
c) names, specifications or presentations having an
influence on the assessment of
the medicinal product or active substance are employed
to mislead others with regard
to its quality.
(2) It shall be prohibited for medicinal products whose
expiry date has elapsed to be
placed on the market.
§ 9
The party responsible for placing on the market
(1) Medicinal products which are placed on the market
within the purview of the present
Act shall bear the name or the company and the address
of the pharmaceutical entrepreneur.
This shall not apply to medicinal products intended for
use in a clinical trial on human subjects.
(2) Within the purview of the present Act, medicinal
products may only be placed on the
market by a pharmaceutical entrepreneur whose
registered place of business is situated within
the purview of the present Act, in another Member State
of the European Union or another
State Party to the Agreement on the European Economic
Area. If the pharmaceutical entrepreneur
appoints a local representative, this shall not release
him/her from his/her legal responsibility.
§ 10
Labelling
(1) Finished medicinal products which are medicinal
products within the meaning of
§ 2 sub-§ 1 or sub-§ 2 number 1, and are not intended
for clinical trials on
human beings or exempted from the obligation to obtain
a marketing authorisation, pursuant to
§ 21 sub-§ 2 number 1a or 1b, may only be placed on the
market within the pur-
26 -
view of the present Act provided that the following
information is displayed on the containers
and, where used, on the outer packaging in easily
legible and indelible characters, in easily
comprehensible German and pursuant to the details
referred to in § 11a:
1. the name or the company and the address of the
pharmaceutical entrepreneur and, if
available the name of the appointed local
representative,
2. the name of the medicinal product, followed by
details of the strength and pharmaceutical
form and, if applicable, information stating that it is
intended for administration to babies,
children or adults unless this information is already
included in the name,
3. the marketing authorisation number with the
abbreviation 'Zul.-Nr.',
4. the batch identification, if the medicinal product
is placed on the market in batches, with
the abbreviation 'Ch.-B.'; if it cannot be
placed on the market in batches, the date of
manufacture,
5. the pharmaceutical form,
6. the content by weight, volume or number of units,
7. the method of administration,
8. the active substances by type and quantity and other
constituents by type in so far as this
is imposed as a condition by the competent higher
federal authoritv pursuant to §
28 sub-§ 2 number 1 or provided for by an ordinance
pursuant to § 12 sub§
1 number 4, also in conjunction with sub-§ 2, or
pursuant to § 36 sub§
1; in the case of medicinal products intended for
parenteral or topical use, including
application to the eye, all constituents by type,
8a. in the case of medicinal products produced using
genetic engineering, the active substance
and the name of the genetically modified micro-organism
or cell line used in its
manufacture,
9. the expiry date with the instruction 'verwendbar
bis' (to be used by),
10. in the case of medicinal products which may only be
dispensed upon prescription by a
physician, dentist or veterinarian, the indication
'Verschreibungspflichtig' (prescription-
27 -
only), in the case of other medicinal products which
may only be dispensed to consumers
in pharmacies, the indication 'Apothekenpflichtig'
(pharmacy-only),
11. in the case of samples, the indication
'unverkäufliches Muster' (sample
1. are intended for the exclusive use of members of the
medical professions,
2. are placed on the market in containers with a net
content of not more than 20 millilitres or
not more than 20 grammes.
(2) Moreover, warnings, specific storage instructions
for the consumer as well as storage
instructions for experts shall be given, in so far as
this is deemed necessary according to
the current level of scientific knowledge or has been
imposed as a condition by the competent
higher federal authority pursuant to § 28 sub-§ 2
number 1 or provided for by an
ordinance.
(3) In respect of sera, information on the type of
living organism from which the sera
were obtained, in respect of virus vaccines,
information about the host system which was used
for the multiplication of the virus shall be indicated.
(4) In the case of medicinal products included in the
Register of Homeopathic Medicinal
Products, instead of the information referred to in
sub-§ 1 sentence 1 numbers 1 to 14
and in addition to the clearly recognisable
information: 'Homeopathic Medicinal Product”, the
following information shall be included:
1. the nature and quantity of the stocks and the degree
of dilution; in this regard, symbols
from the pharmacopoeias currently used officially,
should be utilised; the scientific name
of the stock can be supplemented by an invented name,
2. name and address of the pharmaceutical entrepreneur
and, if available, of his/her local
representative,
3. method of administration,
4. expiry date; sub-§ 1 sentence 1 number 9 and sub-§ 7
shall apply,
5. pharmaceutical form,
6. content by weight, volume or number of items,
7. information stating that medicinal products should
be kept out of the reach of children,
other special precautions for storage and warnings,
including additional information for
safe use if required or if stipulated in sub-§ 2,
8. batch identification,
9. registration number abbreviated to 'Reg.-Nr.'
and the phrase 'Registered homeopathic
medicinal product therefore no therapeutic indication
stated',
10. information advising the user to seek medical
advice if medical symptoms persist during
the use of the medicinal product,
11. for medicinal products to be dispensed only in
pharmacies, the information 'Apothekenpflichtig'
(pharmacy-only),
12. for samples, the information 'Unverkäufliches
Muster' (sample
proprietary name recommended by WHO or, in the absence
thereof, the common name
unless the name already contains the information on the
active substance,
2. the active substance by nature and quantity and
other constituents by nature, if this is
stipulated by conditions imposed by the competent
higher federal authority pursuant to
§ 28 sub-§ 2 number 1, or stipulated by an ordinance
pursuant to § 12
sub-§ 1 number 4, also in conjunction with sub-§ 2 or
pursuant to § 36
sub-§ 1,
3. the batch identification,
4. the marketing authorisation number,
5. the name or the company and the address of the
pharmaceutical entrepreneur and, if
available, the name of the local representative
appointed by him,
6. the animal species for which the medicinal product
is intended,
7. the method of administration,
8. the withdrawal, if the medicinal products are
intended for administration to food-producing
animals,
9. the expiry date pursuant to sub-§ 7,
10. if necessary, special precautions for the disposal
of unused medicinal products,
11. the indication that the medicinal products are to
be kept out of the reach of children, additional
special precautions for storage and warnings, including
additional information if required
for safe use or if stipulated in sub-§ 2,
12. the indication 'Für Tiere' (for animals),
13. the pharmaceutical form,
14. the content by weight, volume or number of units,
15. in the case of medicinal products which may only be
dispensed upon veterinary prescription,
the indication 'Verschreibungspflichtig'
(prescription-only), in the case of other medicinal
products which may only be dispensed to customers in
pharmacies, the indication
'Apothekenpflichtig'
(pharmacy-only),
16. in the case of samples, the indication
'Unverkäufliches Muster' (sample – not for sale).
Medicinal products intended for administration to
animals, which have been entered into
the Register for Homeopathic Medicinal Products, shall
be clearly and visibly labelled
'Homöopathisches Arzneimittel'
(homeopathic medicinal product); instead of the
information
pursuant to sentence 1 numbers 2 and 4, the information
pursuant to sub-§ 4 sentence 1
numbers 1, 9 and 10 shall be provided. Sentences 1 and
2 shall apply mutatis mutandis to medicinal
products which are exempted from registration pursuant
to § 28 sub-§ 1
sentence 3 or pursuant to § 60 sub-§ 1. In the case of
traditional herbal medicinal
products for administration to animals, the
registration number with the abbreviation 'Reg.-Nr.',
instead of the information pursuant to sentence 1
number 4; furthermore, the indications pursuant
to sub-§ 4a sentence 1 number 1 and, corresponding to
the administration to animals,
pursuant to number 2, shall be given. The information
pursuant to sentence 1 numbers 13 and
14 only need to be given on the outer packaging where
an outer packaging exists.
(6) For the designation of the constituents, the
following shall apply:
1. for the designation of the type, the World Health
Organization's international nonproprietary
names or, if such names do not exist, other common
scientific names shall be
used. The Federal Institute for Drugs and Medical
Devices shall stipulate, in agreement
with the Paul Ehrlich Institute and the Federal Agency
for Consumer Protection and Food
Safety, the names to be used and shall publish these in
a database pursuant to §
67a;
2. for the designation of quantity, units of measure
shall be used; if biological units or other
specifications regarding valence are customarily in
scientific use, then these shall be
used.
(7) The month and the year shall be given as the expiry
date.
(8) Blister packaging is to be affixed with the name or
the firm of the pharmaceutical entrepreneur,
the name of the medicinal product, the batch
identification and the expiry date. It
shall not be necessary to state the name and firm of a
parallel importer. In the case of contain-
32 -
ers with a nominal filling quantity of not more than
ten millilitres and single-dose ampoules, the
information specified in sub-§s 1, 1a, 2 and 5 need
only be displayed on the outer packaging;
the containers and the ampoules must, however, at least
bear the information specified
in sub-§ 1 sentence 1 numbers 2, 4, 6, 7, 9 as well as
pursuant to sub-§s 3 and 5
sentence 1 numbers 1, 3, 7, 9, 12 and 14; adequate
abbreviations may be used. Sentence 3
shall also apply to small containers other than those
mentioned therein in so far as divergent
requirements are placed on small containers in
procedures pursuant to § 25b.
(8a) In the case of fresh plasma preparations and
preparations of blood cells, at least
the information specified in sub-§ 1 sentence 1 numbers
1 and 2 must be included, without
stating the strength, pharmaceutical form and target
group, numbers 3, 4, 6, 7 and 9 as well
as the name and volume of the anticoagulant and, if
available, the additive solution, storage
temperature, blood group and, in the case of allogenic
preparations derived from red blood
cells, the rhesus formula as well and, in the case of
thrombocyte concentrates and autologous
preparations from red blood cells, also the rhesus
factor. In the case of autologous blood
preparations, the information 'Nur zur
Eigenbluttransfusion' (Only for Autologous Blood Donation)
must be given as well and, in the case of autologous
and directed blood preparations, also
an indication of the recipient.
(8b) In the case of tissue preparations, at least the
information pursuant to sub-§ 1
sentence 1 numbers 1 and 2 without the information
regarding the strength, the pharmaceutical
form and target group, number 3 or the authorisation
number with the abbreviation 'Gen.-Nr.'
(authorisation number), numbers 4, 6 and 9 as well as
the information 'Biologische Gefahr'
(Biological Danger) in the event that infectiosity has
been detected must be given. In the case
of autologous tissue preparations, the information
'Nur zur autologen Anwendung' (Only for
Autologous Use) must also be provided and, in the case
of autologous and targeted tissue
preparations, an additional indication as to the
recipient.
(9) Abbreviations customary in the medicinal product
trade may be used in the indications
given in compliance with sub-§s 1 to 5. The company to
be indicated under sub§
1 number 1 may be abbreviated, provided that the firm
is generally recognizable from
the abbreviation.
(10) For medicinal products which are intended for
administration to animals and for use
in a clinical trial or for residue testing, sub-§ 5
sentence 1 numbers 1, 3, 5, 7, 8, 13 and
14 as well as sub-§s 8 and 9 shall be applicable, in so
far as they are relevant. Where
relevant, these medicinal products shall be labelled
'Zur klinischen Prüfung bestimmt' (for clini-
33 -
cal trial) or 'Zur Rückstandsprüfung bestimmt'
(for residue testing). Blister packaging shall bear
the name, the batch identification and the information
pursuant to sentence 2.
(11) Partial amounts removed from finished medicinal
products, intended for use in humans,
may only be dispensed with labelling which corresponds
at least to the requirements
stipulated in sub-§ 8 sentence 1. Sub-§ 1b shall not
apply.
§ 11
Package leaflet
(1) Finished medicinal products which are medicinal
products within the meaning of
§ 2 sub-§ 1 or sub-§ 2 number 1 and are intended
neither for clinical trial nor
residue testing, or are exempted from the obligation to
obtain a marketing authorisation pursuant
to § 21 sub-§ 2 numbers 1a and 1b, may only be placed
on the market within
the purview of the present Act with a package leaflet
bearing the heading 'Gebrauchsinformation'
(Instructions for Use) and containing, in the same
order as below, in easily legible, readily
comprehensible German and in conformity with the
information referred to in § 11a:
1. for the purpose of identifying the medicinal
product:
a) the name of the medicinal product, § 10 sub-§ 1
sentence 1 number 2
and sub-§ 1a shall apply mutatis mutandis,
b) the substance or indication group or the mode of
action,
2. the therapeutic indications,
3. a list of information that must be read before
taking the medicinal product:
a) contra-indications,
b) corresponding precautions for use,
c) interactions with other medicinal products or other
products, if they are able to influence
the effect of the medicinal product,
d) warnings, especially if imposed by the competent
higher federal authority pursuant
to § 28 sub-§ 2 number 2 or stipulated by ordinance
pursuant to §
12 sub-§ 1 number 3,
4. the instructions under normal conditions of use,
relating to:
a) posology,
b) method of administration,
c) frequency of administration, if necessary stating
the exact time when the medicinal
product can or must be taken
and, if required, depending on the nature of the
medicinal product:
d) duration of treatment if a specific duration is
required,
e) warnings in the event of an overdose, forgotten
doses or warnings on the risk of
adverse consequences if the treatment is stopped,
f) the specific recommendation that a doctor or
pharmacist should be consulted in the
event of queries relating to the use,
5. side effects; if required according to the current
state of scientific knowledge, the necessary
countermeasures should be stated; the instruction to
the patient that he/she should
inform the physician or pharmacist of any side effect
that is not referred to in the package
leaflet,
6. mention of the expiry date stated on the packaging
and also:
a) a warning that the medicinal product may not be used
after expiry of this date,
b) if required, special precautions for storage and
information on shelf life after opening
of the container or after preparation of the
ready-to-use preparation by the user,
c) if required, a warning about specific visible signs
indicating that the medicinal product
may no longer be used,
d) complete qualitative composition in terms of active
substances and other constituents
and quantitative composition in terms of the active
substances, using the usual
common names for each of the medicinal product's
pharmaceutical forms; §
10 sub-§ 6 shall apply,
e) pharmaceutical form and content by weight, volume or
number of items for each of
the medicinal product's pharmaceutical forms,
f) name and address of the pharmaceutical entrepreneur
and, where applicable, of
his/her local representative,
g) name and address of the manufacturer or importer who
released the finished medicinal
product for placing on the market,
7. in the case of a medicinal product known by other
names in other Member States of the
European Union and approved for placing on the market
pursuant to Articles 28 to 39 of
Directive 2001/83/EC of the European Parliament and of
the Council of 6th
November
2001 on the Community code relating to medicinal
products for human use ( OJ L 311 p.
67), amended by Directives 2004/27/EC (OJ L 136 p. 34)
and 2004/24/EC of 31st
March 2004 (OJ L 136 p. 85), a list of the names
approved in the individual Member
States,
8. the date of the last revision of the package
leaflet.
Explanatory information on the terms listed in sentence
1 is admissible. In so far as information
referred to in sentence 1 is also rendered on the
package leaflet in another language,
the information provided in this language shall be
identical. Sentence 1 shall not apply to medicinal
products which do not require a marketing authorisation
pursuant to § 21 sub§
2 number 1. Additional information, which is not
stipulated by a regulation of the European
Community or is already permissible pursuant to such a
regulation, is permitted provided
it relates to the use of the medicinal product, is
important for the health education of patients
and is not inconsistent with the information referred
to in § 11a. With regard to the information
referred to in sentence 1 number 3 letters a to d,
account is to be taken of the special
situation of specific groups of persons such as
children, pregnant women or nursing mothers,
the elderly or persons with specific diseases, in so
far as this is deemed necessary in the light
of the current level of scientific knowledge;
furthermore, where necessary, the effects which the
use of the medicinal product could have on a person’s
ability to drive or to operate specific machines
should also be indicated.
(1a) A sample of the package leaflet and modified
versions shall be sent to the competent
higher federal authority unless the medicinal product
is exempted from the obligation to obtain
a marketing authorisation or registration.
(2) Furthermore, the package leaflet shall contain
references to constituents, the knowledge
of which is necessary for the safe and effective use of
the medicinal product, as well as
specific storage instructions for the consumer in so
far as this is deemed necessary according
to the current level of scientific knowledge or if
imposed as a condition by the competent higher
federal authority pursuant to § 28 sub-§ 2 number 2, or
provided for by ordinance.
(2a) In the case of radiopharmaceuticals, sub-§ 1 shall
apply mutatis mutandis
with the proviso that the precautions which are to be
taken by the user and the patient in the
preparation and administration of the medicinal
product, as well as special precautions for the
disposal of the containers used for transport and for
the disposal of medicinal products which
are not used, are taken.
(3) In the case of medicinal products included in the
register of homeopathic medicinal
products, sub-§ 1 shall apply mutatis mutandis
with the proviso that the information stipulated
in § 10 sub-§ 4, with the exception of the batch
identification, the expiry date
and the indication stipulated for samples, are
included, as well as the name and address of the
manufacturer who released the finished medicinal
product for placing on the market, where this
person is not the pharmaceutical entrepreneur. Sentence
1 shall apply mutatis mutandis to medicinal
products which are exempted from registration pursuant
to § 38 sub-§ 1
sentence 3.
(3a) In the case of sera, sub-§ 1 shall apply
mutatis mutandis with the proviso that
the type of living organism from which they are
derived, in the case of virus vaccines, the host
system used for virus multiplication and, in the case
of medicinal products derived from human
blood plasma for fractionation, the country of origin
of the blood plasma should be stated.
(3b) In the case of traditional herbal medicinal
products pursuant to § 39a, sub§
1 shall apply mutatis mutandis with the proviso
that the information referred to in sub§
1 sentence 1 number 2, shall state that the medicinal
product is a traditional medicinal
product, registered for the specific therapeutic
indication, exclusively on the basis of longstanding
use. In addition, the package leaflet should include
the advice referred to in §
10 sub-§ 4a sentence 1 number 2.
(3c) The marketing authorisation holder shall ensure
that at the request of patients’ organisations,
the package leaflet is made available in formats
appropriate for the blind and partially-
sighted persons in the case of medicinal products
intended for administration to humans.
(3d) In the case of spa-waters, notwithstanding the
requirements referred to in sub§
2, the information referred to in sub-§ 1 sentence 1
number 3 letter b number 4
letters e and f number 5, provided that the information
stated therein is stipulated, and number
6 letter c, can be omitted. Furthermore, in the case of
spa-waters, the order stipulated in sub§
1 is not compulsory.
(4) In the case of medicinal products which are
intended for administration to animals,
sub-§ 1 shall apply accordingly provided that, instead
of the information referred to in
sub-§ 1 sentence 1, the following information specified
in sub-§ 1 sentences 2 and
3 is given in the same order as below, in clearly
legible, readily comprehensible German and in
conformity with the information referred to in § 11a:
1. the name and address of the pharmaceutical
entrepreneur and, where applicable, of
his/her local representative, and the manufacturer who
released the finished medicinal
product for placing on the market,
2. name of the medicinal product, followed by details
of the strength and pharmaceutical
form; the common name of the active substance shall be
included if the medicinal product
contains only one active substance and its name is an
invented name; in the case of a
medicinal product that has been granted marketing
authorisation under Articles 31 to 43
of Directive 2001/82 EC of the European Parliament and
of the Council of 6th
November
2001 on the Community code relating to veterinary
medicinal products (OJ L 311 p.1),
amended by Directive 2004/28/EC (OJ L 136 p. 58), under
different names in Member
States of the European Union, a list of the names
authorised in each Member State,
3. therapeutic indications,
4. contra-indications and side-effects provided that
this information is relevant for use;
should it not be possible to provide information in
this respect, the indication 'keine
bekannt'
(none known) shall be given; the instruction that the user or animal keeper is
to
inform the veterinarian or pharmacist of any
side-effect that is not listed in the package
leaflet,
5. the animal species for which the medicinal product
is intended, dosage instructions for
each species, method and route of administration, if
necessary, instructions for use in
keeping with its intended purpose,
6. the withdrawal period, if the medicinal products are
intended for administration to foodproducing
animals; should a withdrawal period not be necessary,
this shall be indicated,
7. special precautions relating to storage,
8. special warnings in so far as this is imposed as a
condition by the competent higher federal
authority or provided for by an ordinance,
9. if necessary due to the current state of scientific
knowledge, special precautions for the
disposal of unused medicinal products or other special
precautions to avoid risks to the
environment.
The date of the last revision of the package leaflet
shall be stated. In respect of medicated
pre-mixes, indications for the correct manufacture of
medicated feedingstuffs and information
on the shelf life of the medicated feedingstuffs shall
be included. Additional information
is permitted in so far as it relates to the use of the
medicinal product, is important for the user or
animal keeper and is not inconsistent with the
information referred to in § 11a. In the
case of medicinal products for use in animals, which
are included in the Register of Homeopathic
Medicinal Products or which are exempted from the
registration pursuant to § 38
sub-§ 1 sentence 3 or pursuant to § 60 sub-§ 1
sentences 1, 2 and 4 shall
apply mutatis mutandis subject to the proviso
that the information stipulated in § 10 sub§
4, with the exception of the batch identification, the
expiry date and the indication stipulated
for samples must be provided. In the case of
traditional herbal medicinal products for use
in animals, a corresponding indication pointing to the
use in animals pursuant to § 10
sub-§ 4a sentence 1 number 2 shall be given in addition
to the indications pursuant to
sub-§ 3b sentence 1.
(5) Should it not be possible to provide the
information stipulated in sub-§ 1 sentence
1 number 3 letters a and c as well as number 5, the
indication "keine bekannt" (none
known) shall be given. Should additional information be
given on the package leaflet, it shall be
clearly set out and well separated from the information
specified in sub-§s 1 to 4.
(6) The package leaflet may be omitted provided that
the information specified in sub§s
1 to 4 is to be found either on the container or on the
outer packaging. Sub-§ 5
shall apply mutatis mutandis.
(7) Partial amounts removed from finished medicinal
products, intended for use in humans,
may only be dispensed together with a copy of the
package leaflet prescribed for the finished
medicinal product. Sub-§ 6 sentence 1 shall apply
mutatis mutandis. By way of
derogation from sentence 1, in the case of the regular
dispensing of partial amounts removed
from finished medicinal products and dispensed in new,
customised patient blisters in the context
of long-term medication, copies of the package leaflet
prescribed for the specific finished
medicinal product must only be inserted if they have
been modified compared with those previously
inserted.
§ 11a
Expert information
(1) The pharmaceutical entrepreneur shall be obliged to
make available upon request
to physicians, dentists, veterinarians, pharmacists
and, if the medicinal products concerned are
not subject to prescription, to other persons
practising medicine or dentistry professionally, instructions
for use by experts (expert information) for finished
medicinal products which are subject
to or exempted from the obligation to obtain a
marketing authorisation, are medicinal products
within the meaning of § 2 sub-§ 1 or sub-§ 2 number 1
and are not released
for trade outside of pharmacies. These instructions for
expert use shall bear the heading
"Fachinformation"
(expert information) and include the following
information written in clearly
legible type in conformity with the Summary of Product
Characteristics approved within the
framework of the marketing authorisation, and in the
following order:
1. the name of the medicinal product followed by the
strength and the pharmaceutical form;
2. information on the qualitative and quantitative
composition in terms of active substance
and other constituents, knowledge of which is required
for proper administration of the
product, with the usual common or chemical name
indicated; § 10 sub-§ 6
shall apply;
3. pharmaceutical form;
4. clinical information:
a) therapeutic indications,
b) posology and method of administration for adults
and, in so far the medicinal product
is indicated for administration to children, for
children,
c) contra-indications,
d) special warnings and precautions for use, and in the
case of immunological medicinal
products, any special precautions to be taken by
persons coming into contact
with and administering these medicinal products to
patients, together with any precautions
to be taken by the patient, if required as a result of
conditions imposed by
the competent higher federal authority pursuant to § 28
sub-§ 2 number
1 letter a or if stipulated by an ordinance,
e) interaction with other medicinal products or other
products if this is likely to influence
the effect of the medicinal product,
f) use during pregnancy and lactation,
g) effects on ability to drive or operate machinery,
h) side-effects,
i) overdosage: symptoms, emergency procedures,
antidotes;
5. pharmacological properties:
a) pharmacodynamic properties,
b) pharmacokinetic properties,
c) preclinical safety data;
6. pharmaceutical information:
a) list of other constituents,
b) main incompatibilities,
c) shelf life and where necessary, the shelf life after
reconstitution of the medicinal
product or after first opening the container,
d) special precautions for storage,
e) nature and contents of the container,
f) special precautions for disposal of an opened
medicinal product, or waste materials
derived from it, in order to avoid any risk to the
environment,
7. marketing authorisation holder,
8. marketing authorisation number;
9. the date of first authorisation or prolongation of
the authorisation,
10. date of revision of the expert information.
Additional information which is not stipulated by a
regulation of the European Community
or is already permissible pursuant to such a regulation
shall be permitted if it relates to the
use of the medicinal product and is not inconsistent
with the information referred to in sentence
2; such information must be clearly separate and
distinct from the information referred to in
sentence 2. Sentence 1 shall not apply to medicinal
products, which do not require a marketing
authorisation pursuant to § 21 sub-§ 2 or are
manufactured according homeopathic
procedures.
(1a) In the case of sera, the type of living organism
from which they are derived, in the
case of virus vaccines, the host system used for virus
multiplication and, in the case of medicinal
products derived from human blood plasma for
fractionation, the country of origin of the
blood plasma shall be indicated.
(1b) In respect of radiopharmaceuticals, details of the
internal radiation dosimetry, additional
detailed instructions for the extemporaneous
preparation and the quality control of this
preparation shall also be given and, where necessary,
the maximum storage time shall also be
indicated during which an intermediate preparation,
such as an eluate or the medicinal product
when ready for use, corresponds to its specifications.
(1c) In the case of medicinal products intended for use
in animals, the expert information
specified under number 4 'klinische Angaben'
(clinical information) must include the following
information:
a) information on each target animal species to which
the medicinal product is to be
administered,
b) instructions for use, specifying the target animal
species,
c) contra-indications,
d) special warnings for each target animal species,
e) special precautions for use, including special
precautions to be taken by the person
administering the medicinal product,
f) side-effects (frequency and seriousness),
g) use during pregnancy, lactation or lay,
h) interactions with other medicinal products and other
forms of interaction,
i) dosage and method of administration,
j) overdosage, emergency procedures, symptoms,
antidotes, if necessary,
k) withdrawal periods for all foodstuffs, including
those for which there is no withdrawal
period.
The information referred to in sub-§ 1 sentence 2
number 5 letter c is not necessary.
(1d) In the case of medicinal products available only
on prescription by a doctor, dentist
or veterinarian, the information
'Verschreibungspflichtig' (prescription only) should also be
added, for narcotics the information
'Betäubungsmittel' (narcotics), in the case of other medicinal
products available to consumers only in pharmacies, the
information 'Apotheken-pflichtig'
(pharmacy only); in the case of medicinal products
containing a substance or a preparation
pursuant to § 48 sub-§ 1 sentence 1 number 3
corresponding information shall be
given.
(1e) For marketing authorisations of medicinal products
pursuant to § 24b, the information
referred to in sub-§ 1 relating to therapeutic
indications, dosages or other objects
of a patent can be omitted if it is still covered by
patent law at the time of placing on the
market.
(2) The pharmaceutical entrepreneur shall be obliged to
make all modifications to the
expert information, which are relevant for therapy,
accessible to the experts in an appropriate
form. In so far as necessary, the competent higher
federal authority may, by imposition of a
condition, stipulate the form in which the changes are
to be made accessible to all or to certain
groups of experts.
(3) A sample of the expert information and revised
versions thereof shall be sent immediately
to the competent higher federal authority unless the
medicinal product is exempted from
the obligation to obtain a marketing authorisation.
(4) The obligations referred to in sub-§ 1 sentence 1
can also be fulfilled in the
case of medicinal products which are administered
exclusively by members of the health professions
by including the information referred to in sub-§ 1
sentence 2 in the package
leaflet. The package leaflet must be headed with the
title "Gebrauchsinformation und Fachinformation"
(instructions for use and expert information).
§ 12
Empowerment in respect of labelling, package leaflet
and package sizes
(1) The Federal Ministry is hereby empowered, in
agreement with the Federal Ministry
of Economics and Technology by ordinance subject to the
approval of the Bundesrat:
1. to extend the provisions of §s 10 and 11a to cover
other medicinal products and to
extend the expert information to include further
details,
2. to stipulate that the information indicated in §s 10
and 11 are to be made known to
the consumer in another way,
3. to stipulate that, for certain medicinal products or
certain groups of medicinal products,
warnings, warning symbols or recognition marks shall be
contained in or affixed to:
a) the containers, the outer packaging or the package
leaflet or
b) the expert information,
4. to stipulate that specific constituents are to be
listed by nature on the containers and
outer packaging or that attention should be drawn to
them in the package leaflet,
if this is deemed necessary in order to ensure the
proper handling and proper administration of
medicinal products within the purview of the present
Act and in order to prevent any direct or
indirect risk to human or animal health, which could
occur as a result of inadequate information.
(1a) Furthermore, the Federal Ministry is hereby
empowered to allow, by ordinance subject
to the approval of the Bundesrat, the use of
summarizing names for substances or preparations
from substances in the information provided on
containers and outer packaging or in
package leaflets or in expert information, as long as
active constituents are not involved and no
direct or indirect hazard to human or animal health
arising from a lack of information is to be
feared.
(1b) Furthermore, the Federal Ministry is hereby
empowered, in agreement with the
Federal Ministry of Economics and Technology, by means
of an ordinance subject to the approval
of the Bundesrat to regulate:
1. the labelling of starting materials intended for the
manufacture of medicinal products, and
2. the labelling of medicinal products intended for
clinical trials,
where it is deemed necessary to prevent a direct or
indirect hazard to human or animal health
owing to inadequate labelling.
(2) In the case of medicinal products intended for
administration to animals, the Federal
Ministry of Agriculture, Food and Consumer Protection
shall take the place of the Federal Ministry
in the cases provided for in sub-§ 1, 1a, 1b or 3, and
shall in each case issue the ordinance
in agreement with the Federal Ministry. The ordinance
pursuant to sub-§ 1, 1a or
1b shall be issued in agreement with the Federal
Ministry for the Environment, Nature Conservation
and Nuclear Safety in the case of radiopharmaceuticals
and medicinal products in the
manufacture of which ionizing radiation is used or
where, in the cases provided for in sub§
1 number 3, warnings, warning symbols or recognition
marks with regard to the information
stipulated in § 10 sub-§ 1 sentence 1 number 13 or
sub-§ 5 sentence
1 number 10, § 11 sub-§ 4 sentence 1 number 9 or § 11a,
sub-§ 1
sentence 2 number 6 letter f are required.
(3) Furthermore, the Federal Ministry is hereby
empowered to stipulate, by ordinance
not subject to the approval of the Bundesrat,
that medicinal products may only be placed on the
market in specific package sizes and that they shall be
labelled accordingly by the pharmaceutical
entrepreneur on the container or, if used, on the outer
packaging. The fixing of these
package sizes shall be done for specific active
substances and shall take into account the
therapeutic indications, the duration of application
and the pharmaceutical form. In fixing the
package size, the following sub-division shall, in
principle, be used as a basis:
1. packages for a short duration of application or
tolerance tests,
2. packages for an intermediate duration of
application,
3. packages for a relatively prolonged duration of
application.
THIRD CHAPTER
MANUFACTURE OF MEDICINAL PRODUCTS
§ 13
Manufacturing authorisation
(1) Any person who manufactures:
1. medicinal products within the meaning of § 2 sub-§ 1
or sub-§ 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 an
authorisation 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 § 14 sub-§ 4.
(1a) Sub-§ 1 shall not apply to:
1. tissues within the meaning of § 1a number 4 of the
Transplantation Act which require
an authorisation pursuant to § 20b or 20c,
2. the procurement and the laboratory tests of
autologous blood for the manufacture of biotechnologically
processed tissue products which require an
authorisation pursuant to §
20b,
3. tissue preparations which require an authorisation
pursuant to § 20c,
4. reconstruction, in so far as medicinal products
which are intended for use in clinical trials
are concerned.
(2) The following shall not require an authorisation
pursuant to sub-§ 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 Law on Pharmacies,
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 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 Annex II of Regulation (EEC) No. 2377/90,
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 decanting, packaging or labelling
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 § 50, decants,
packages or labels medicinal products without altering
them for direct distribution to the
consumer,
6. the manufacturer of active substances which are
intended for use in the manufacture of
medicinal products which are manufactured using a
procedure described in the homeopathic
§ of the Pharmacopoeia.
The exceptions specified in sentence 1 shall not apply
to the manufacture of blood
preparations, tissue preparations, sera, vaccines,
allergens, test sera, test antigens and radiopharmaceuticals.
(2a) (deleted)
(2b) Furthermore, an authorisation pursuant to sub-§ 1
shall not be required by a
person who is a physician or otherwise authorised to
practise medicine on humans 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 xenogenic
medicinal products, in so far as
these are or contain living somatic cells which have
been genetically modified or whose
biological properties have been changed using other
procedures, as well as
2. medicinal products intended for clinical trials in
so far as it is not merely a case of reconstitution.
(2c) Sub-§ 2b sentence 1 shall apply mutatis mutandis
to veterinarians maintaining
a veterinary house dispensary for use in animals
treated by them.
(3) An authorisation issued pursuant to sub-§ 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, xenogenic 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.
§ 14
Decision on the manufacturing authorisation
(1) An authorisation may only be refused if:
1. there is not at least one person available with the
expertise required pursuant to §
15 (qualified person pursuant to § 14) who is
responsible for the activity referred
to in § 19,
2. (deleted),
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. (deleted),
5a. in enterprises which manufacture medicated
feedingstuffs 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 blood stem cells or other blood
components, does not possess the
expert knowledge required,
5c. contrary to § 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 knowl-
48 -
edge according to the state of the medical art or,
contrary to § 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 Part Two of the
Transfusion Act.
(2) (deleted)
(2a) The physician in charge pursuant to § 4 sentence 1
number 2 of the Transfusion
Act can also be the qualified person pursuant to sub-§
1 number1.
(2b) (deleted)
(3) (deleted)
(4) By way of derogation from sub-§ 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 number 1
is able to assume his/her responsibilities.
(5) Should the documentation presented be deemed
flawed, the applicant shall be given
the opportunity to correct the flaws within an
appropriate period of time. If the flaws are not corrected,
the manufacturing authorisation shall be refused.
§ 15
Expert knowledge
(1) Proof of the required expert knowledge on the part
of the qualified person referred to
in § 14 shall be furnished by:
1. the licence to practise as a pharmacist, or
2. the diploma in pharmacy, chemistry, biology, human
or veterinary medicine attained upon
completion of university studies
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.
(2) In the cases specified in sub-§ 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-§ 1 number
2 and may be proved by examination.
(3) Sub-§ 2 shall not apply to the manufacture and
testing of blood preparations,
sera, vaccines, allergens, test sera and test antigens.
In place of the evidence of practical experience
required in sub-§ 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-§
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. in the case of preparations made from blood stem
cells, in addition to sufficient knowledge,
at least two year's 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 blood stem
cells or 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-§ 1 remain valid for packaging and
labelling.
(3a) Sub-§ 2 shall not apply to the manufacturing and
testing of advanced therapy
medicinal products, xenogenic 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-§ 1, proof
must be furnished of:
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 xenogenic 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 the present Act or possess a
manufacturing authorisation
under community legislation,
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-§ 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-§ 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 §
72a sentence 1 number 1.
(5) The period of practical experience shall not be
required for the manufacturing of
medicated feedingstuffs from medicated pre-mixes; sub-§
2 shall not apply.
§ 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 § 14 sub-§ 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.
§ 17
Deadlines for the granting of an authorisation
(1) The competent authority shall reach a decision on
the application for an authorisation
within 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 § 14 sub-§ 1 number 6, the authority
shall reach a decision
within one month. In exceptional cases, the deadline
shall be extended by a further two
months. The applicant shall be notified thereof prior
to the expiry of the deadline and shall be
informed of the grounds.
(3) If the authority gives the applicant the
opportunity to correct the flaws pursuant to
§ 14 sub-§ 5, the deadlines shall be interrupted until
such flaws have been corrected
or until the expiry of the deadline set pursuant to §
14 sub-§ 5. The interruption
of the deadline shall begin on the day the applicant
receives the request to correct the
flaws.
§ 18
Withdrawal, revocation, suspension
(1) The authorisation shall be withdrawn if it becomes
known subsequently that one of
the grounds for refusal, pursuant to § 14 sub-§ 1,
existed at the time the authorisation
was granted. The authorisation shall be revoked if one
of the grounds for refusal subse-
53 -
quently developed; the suspension of the authorisation
may be ordered instead of its revocation.
§ 13 sub-§ 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.
§ 19
Areas of responsibility
(1) The qualified person pursuant to § 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.
§ 20
Obligations to notify
The marketing authorisation holder shall notify the
competent authority in advance of
any change in the information referred to in § 14 sub-§
1 and submit evidence. Any
unforeseen change in the qualified person referred to
in § 14, must be notified immediately.
§ 20a
Applicability to active substances and other substances
§ 13 sub-§s 2 and 4 and §s 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 § 13 sub§
1 requires an authorisation.
§ 20b
Authorisation for the procurement of tissues and the
pertinent laboratory testing
(1) Any establishment seeking to procure tissues
intended for human applications within
the meaning of § 1a number 4 of the Transplantation Act
(removal establishments) or
seeking to conduct the laboratory testing necessary for
such procurement, shall require an authorisation
from the competent authority. Procurement within the
meaning of sentence 1 is the
direct or extracorporeal removal of tissues including
all measures which are intended to maintain
the tissues in a processable state, clearly
identifiable and transportable. The authorisation
may only be refused if:
1. an appropriately qualified person with the necessary
professional experience who, in the
case of a removal establishment, can also be the
medical person within the meaning of
§ 8d, sub-§ 1, sentence 1 of the Transplantation Act is
not present,
2. the additional personnel involved is insufficiently
qualified,
3. appropriate rooms for the specific tissue
procurement or for the laboratory testing are not
available, or
4. it is not guaranteed that the procurement of tissues
or the laboratory testing are conducted
according to the state of medical science and
technology and according to the
provisions contained in Parts 2, 3 and 3a of the
Transplantation Act.
The competent authority may dispense with an inspection
within the meaning of §
64 sub-§ 3 sentence 2, prior to the granting of an
authorisation pursuant to this provision.
The authorisation will be granted to the removal
establishment by the competent authority for a
specific facility and for a specific tissue and, to the
laboratory, for a specific site and for specific
activities. In the process, the competent authority may
involve the competent higher federal authority.
(2) An individual authorisation pursuant to sub-§ 1
shall not be required by a person
conducting such activities on a contractual basis for a
manufacturer or a processor who is
in possession of an authorisation pursuant to § 13 or §
20c for the processing of
tissue or tissue preparations. In this case, the
manufacturer or processor shall notify the locally
competent authority responsible for the removal
establishment or the laboratory of the latter
and shall include, with the notification, the
information and documents pursuant to sub-§
1 sentence 3. One month subsequent to the notification
pursuant to sentence 2, the manufacturer
or processor shall notify the competent authority
responsible for him/her of the removal
establishment or the laboratory unless the competent
authority responsible for the removal es-
55 -
tablishment or the laboratory has objected. In
exceptional cases, the deadline pursuant to sentence
3 can be extended for an additional two months. The
manufacturer or processor shall be
informed thereof before expiry of the deadline and
shall be informed of the grounds. If the competent
authority has objected, the deadlines pursuant to
sentences 3 and 4 shall be suspended
until the grounds for the objection have been
rectified. Sub-§ 1 sentences 3 to 6 shall apply
mutatis mutandis
provided that the authorisation pursuant to sub-§ 1
sentence 5 is
granted to the manufacturer or processor.
(3) The authorisation shall be withdrawn if it
subsequently becomes known that one of
the grounds for the rejection pursuant to sub-§ 1
sentence 3 existed at the time of the
granting of the authorisation. If one of these grounds
arises subsequently, the authorisation
shall be revoked; instead of the revocation, the
suspension of the authorisation can also be ordered.
The competent authority is entitled to prohibit the
procurement of tissue or the laboratory
testing temporarily if the removal establishment, the
laboratory, the manufacturer or the processor
fail to submit the necessary supporting documents for
the procurement of tissue or the
laboratory testing.
(4) Sub-§s 1 to 3 shall apply mutatis mutandis
for the procurement and the laboratory
testing of autologous blood for the manufacture of
biotechnologically processed tissue
products.
§ 20c
Authorisation for the processing, preservation, testing
and storage
or the placing on the market of tissues or preparations
made from tissues
(1) Any establishment which wishes to process,
preserve, test, store or place on the
market tissues or tissue preparations which are not
processed using industrial procedures and
the essential processing procedures of which are
sufficiently well known in the European Union,
requires, by way of derogation from § 13 sub-§ 1, an
authorisation from the
competent authority pursuant to the following
provisions. This shall also apply to tissues or tissue
preparations the processing procedures for which are
new but comparable with a known
procedure. The decision about whether to grant the
authorisation shall be taken by the compe-
56 -
tent authority of the Land in which the facility is
located or is to be located, in consultation with
the competent higher federal authority.
(2) The authorisation may only be refused if:
1. a person with the necessary expert knowledge and
experience pursuant to sub-§ 3
(responsible person pursuant to § 20c) responsible for
ensuring that the tissue
preparations and tissues are processed, preserved,
tested, stored or placed on the market
in keeping with the statutory provisions in force, is
not available,
2. additional participating personnel is insufficiently
qualified,
3. suitable premises and establishments are not
available for the envisaged activities,
4. it is not guaranteed that the processing including
the labelling, preservation and storage is
conducted according to state-of-the-art scientific and
technical procedures, or
5. a quality management system pursuant to the
principles of Good Practice has not been
installed or has not been kept up to date.
By way of derogation from sentence 1 number 3, the
testing of the tissues and tissue preparations
may be conducted outside of the factory site, in
commissioned factories which do not require
an authorisation of their own, if suitable rooms and
facilities are available there and if it is
guaranteed that testing is conducted in keeping with
the state of the art in science and technology
and the responsible person pursuant to § 20c is able to
assume his/her responsibilities.
(3) Proof that the responsible person pursuant to § 20c
possesses the necessary
expert knowledge, shall be provided by a certificate
testifying to the successful completion of
university studies in human medicine, biology,
biochemistry or a course of studies considered
equivalent as well as at least two years' practical
experience in the processing of tissues or tissue
preparations.
(4) 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. The
authorisation shall be granted for a specific
facility and for specific tissues or tissue
preparations.
(5) The competent authority shall take the decision on
the application for an authorisation
within three months. Should the holder of an
authorisation apply for a modification to the
authorisation, the authority shall take the decision
within 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 informed of the
grounds. If the authority gives the applicant
pursuant to sub-§ 4 sentence 1, the opportunity to
correct the flaws, the deadlines
shall be interrupted until such flaws have been
corrected or until the expiry of the deadline set
pursuant to sub-§ 4 sentence 1. The interruption of the
deadline shall begin on the day
the applicant receives the request to correct the
flaws.
(6) The holder of an authorisation shall notify the
competent authority in advance of any
change in the information referred to in sub-§ 2 and
shall submit evidence thereof; the
changes may be made only after receipt of a written
authorisation from the competent authority.
Any unforeseen change in the responsible person
pursuant to § 20c shall be notified immediately.
(7) The authorisation shall be withdrawn if it becomes
known subsequently that one of
the grounds for refusal, pursuant to sub-§ 2 existed at
the time the authorisation was
granted. The authorisation shall be revoked if one of
the grounds for refusal developed subsequently,
the suspension of the authorisation may be ordered
instead of its revocation. Sub§
1 sentence 3 shall apply mutatis mutandis. The
competent authority may issue a provisional
order mandating that the processing of tissues or
tissue preparations be discontinued if
the processor fails to furnish the evidence required
for processing. If the processing of tissues
or tissue preparations is terminated, the processor
shall ensure that stored tissue preparations
and tissues continue to be stored in a quality-assured
manner and are transferred to other
manufacturers, processors or distributors in possession
of an authorisation pursuant to sub§
1 or § 13 sub-§ 1. This shall also apply to the
information and data about
the processing which is necessary for the tracing of
these tissue preparations and tissues.
§ 20d
Exception from the obligation to obtain an
authorisation
for tissues and tissue preparations
An authorisation pursuant to § 20b sub-§ 1 and § 20c
sub-§ 1
shall not be required by a person who is a physician or
otherwise authorised to practise medicine
on humans and who performs the activities mentioned
therein, with the exception of the
placing on the market, in order to use the tissue or
tissue preparation personally on their patient.
This shall not apply to medicinal products which are
intended for clinical trials.
FOURTH CHAPTER
MARKETING AUTHORISATION FOR MEDICINAL PRODUCTS
§ 21
Obligation to obtain a marketing authorisation
(1) Finished medicinal products which are medicinal
products as defined in § 2
sub-§ 1 or sub-§ 2 number 1, may only be placed on the
market within the purview
of the present Act, if they have been authorised by the
competent higher federal authority or if
the Commission of the European Communities or the
Council of 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 of the European
Parliament and of the Council of 31st
March 2004 laying down Community procedures for the
authorisation and supervision of medicinal
products for human and veterinary use and establishing
a European Medicines Agency
(OJ EC No. L 136, p. 1), also in conjunction with
Regulation (EC) No. 1901/2006 of the European
Parliament and of the Council of 12th
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 27th
December 2006, p.1) or Regulation (EC)
No. 1394/2007. The same shall apply to medicinal
products which are not finished medicinal
products and which 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
which:
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
§ 4 sub-§ 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 the present
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 a marketing authorisation
pursuant to the provisions contained in § 21a sub-§ 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 the present Act
through filling and labelling in enterprises
authorised pursuant to § 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 feedingstuffs, manufactured in keeping
with their designated purpose from
medicated pre-mixes for which a marketing authorisation
has been issued pursuant to
§ 25,
4. are manufactured for individual animals or animals
belonging to a specific stock, in pharmacies
or in veterinary house dispensaries under the
prerequisites specified in sub§
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; rules of procedure shall be
specified in an ordinance pursuant
to § 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-§ 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 does not apply to the preparation of medicinal
product from a finished medicinal product and
medically non-active constituents nor 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
included in the list in Annex II of Regulation
(EEC) No. 2377/90.
(3) 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, upon request by 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, irrespective of an
application for a marketing authorisation pursuant
to sub-§ 3.
§ 21a
Authorisation of tissue preparations
(1) Tissue preparations which are not manufactured
involving an industrial process and
the essential processing procedures of which are
sufficiently well known in the European Union,
and the effects and side effects of which are known and
evident from scientific data may
only be placed on the market within the purview of the
present Act, if they have been authorised
by the competent higher federal authority, by way of
derogation from the marketing authorisation
obligations pursuant to § 21 sub-§ 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 blood
stem cell preparations intended for
autologous use or for targeted administration to a
specific person. The authorisation 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 processing
procedure must be evaluated to ascertain
that the procedures do not render the tissues
clinically ineffective or harmful to patients.
(1a) An authorisation pursuant to sub-§ 1 is not
required for tissue preparations
which are intended for clinical trials on human beings.
(2) The application for an authorisation 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
processor,
2. the name of the tissue preparation,
3. the therapeutic indications as well as the method of
administration and, in the case of tissue
preparations which are intended to be used for a
limited period of time, the duration
of the application,
4. information about the procurement and laboratory
testing of the tissues, as well as the
processing, preservation, testing and storage of the
tissue preparation,
5. the type of preservation, the shelf life, and the
conditions for storage,
6. a description of the functionality and the risks of
the tissue preparation,
7. documents containing the results of microbiological,
chemical and physical examinations
and the methods used in their determination, in so far
as these documents are necessary,
as well as
8. all of the information and documents which is
relevant to the purpose of evaluation of the
medicinal product.
§ 22 sub-§ 4 shall apply mutatis mutandis.
(3) In respect of the information pursuant to sub-§ 2
number 3, scientific findings
which are also able to compare with empirical medical
findings prepared according to scientific
methods can be submitted. These could 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
an authorisation within 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
the authorisation in writing, together
with an authorisation number. The authority may combine
the authorisation with the imposition
of conditions. § 28 shall apply mutatis mutandis.
(6) The competent higher federal authority may only
refuse an authorisation if:
1. the documents submitted are incomplete,
2. the tissue preparation does not correspond to the
current state of scientific knowledge, or
3. the tissue preparation does not fulfil the envisaged
function or the benefit-risk ratio is unfavourable.
(7) The applicant, or subsequent to the authorisation,
the holder of the authorisation
shall immediately notify the competent higher federal
authority of any changes in the information
pursuant to sub-§s 2 and 3 and include the
corresponding documents with the notification.
In the event of a change in the documents pursuant to
sub-§ 3, the change may
only be carried out if the competent higher federal
authority has consented.
(8) The authorisation shall be withdrawn if it
subsequently becomes known that one of
the grounds for refusal, pursuant to sub-§ 6 numbers 2
and 3 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 authorisation may
also be ordered. Before a decision is reached pursuant
to sentences 1 to 3, the holder of the
authorisation shall be heard unless danger is imminent.
If the authorisation 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 the present
Act.
(9) By way of derogation from sub-§ 1, tissue
preparations which 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 a certificate from the competent
higher federal authority before the first placing on
the market within the purview of the present
Act. Before issuing the certificate, the competent
higher federal authority shall examine whether
the processing of the tissue preparations meet 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 the present Act and its ordinances.
The competent higher federal authority
must issue the certificate if the authorisation
certificate or another certificate from the competent
authority of the country of origin demonstrates the
equivalence of the requirements pursuant
to sentence 2 and the proof of authorisation 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 informed 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 the present Act. The certificate 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.
§ 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; § 10 sub-§ 6
shall apply,
4. the pharmaceutical form,
5. the effects,
6. the therapeutic indications,
7. the contra-indications,
8. the side effects,
9. the interactions with other products,
10. the dosage,
11. information on the medicinal product's 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-§ 1 sentence 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 4th
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. a detailed description of the pharmacovigilance and,
if applicable, the risk management
system which the applicant will introduce,
6. evidence that the applicant has access to a
qualified person pursuant to § 63a who
is equipped with the necessary resources to perform the
duties referred to in § 63b,
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 16th
December 1999 on orphan
medicinal products (OJ L 18 p. 1).
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 experiments or clinical trials carried
out using the medicinal product in question.
(3) Instead of the results specified in sub-§ 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 side effects 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 which 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-§ 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 the present
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 § 21 sub-§ 3 sentence 2.
(5) If an application is made for a marketing
authorisation in respect of a medicinal
product manufactured outside the purview of the present
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
imported 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 import the medicinal product into the territory
governed by the present Act.
(6) If the medicinal product has already been granted a
marketing authorisation in another
state or in several other states, a copy of such
authorisation 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 authorized 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 which is meant to appear on the
container, the outer packaging and the
package leaflet as well as by the draft of the Summary
of Product Characteristics which shall
also represent the expert information pursuant to § 11a
sub-§ 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.
§ 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 § 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
Annex I, II or III of Regulation (EEC) No. 2377/90, a
certificate confirming that an application
pursuant to Annex V for the establishment of maximum
residues pursuant to the
aforementioned Regulation had been submitted to the
European Medicines Agency at
least 6 months previously, and
3. (deleted)
Sentence 1 number 2 shall not apply if § 25 sub-§ 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 feedingstuff. Furthermore, it shall be
justified and proved by documents that the medicated
pre-mixes are suited for the intended
manufacture of the medicated feedingstuff, and
particularly that they allow a homogeneous and
stable distribution of the active substances in the
medicated feedingstuffs taking into consideration
the manufacturing methods applied in the production of
mixed feed; furthermore, the shelflife
of medicated feedingstuffs 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 feedingstuffs, 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-§ 1, as well as from the
evidence regarding the suitability of
the medicated pre-mixes for the intended manufacture of
the medicated feedingstuff and the
test results of the test methods pursuant to sub-§ 2.
Instead of the documents, the evidence
and test results referred to in sentence 1, other
scientific findings may be submitted.
§ 24
Expertises
(1) Expertises in which the test methods, test results
and residue test procedures are
summarized and assessed, shall be included with the
required documents pursuant to §
22 sub-§ 1 number 15, sub-§s 2 and 3 and § 23. In
particular, the following
information shall be included in detail in the
expertises presented:
1. the analytical expert opinion shall state whether
the medicinal product is of appropriate
quality in accordance with recognized pharmaceutical
practice, 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
side effects 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
by Regulation (EEC) No. 2377/90.
(2) In so far as scientific documentation is presented
pursuant to § 22 sub-§
3 and § 23 sub-§ 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.
§ 24a
Use of a previous applicant's documents
The applicant can refer to the documents referred to in
§ 22 sub-§s 2, 3, 3c
and § 23 sub-§ 1, including the expertise report
referred to in § 24 sub§
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
§ 26. The previous applicant shall respond to a request
for agreement, within a period of
three months. A partial reference is not admissible.
§ 24b
Authorisation of a generic medicinal product, document
protection
(1) In the case of a generic medicinal product within
the meaning of sub-§ 2, reference
can be made, without the previous applicant’s
agreement, to the documents referred to
in sentence 1 of § 22 sub-§ 2 sentence 1 numbers 2 and
3 and § 23 sub§
1, including the expert report referred to in § 24
sub-§ 1 sentences 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-§ 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-§
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§
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 de-
72 -
viations 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-§ 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-§ 1 sentence 3 and sub-§ 6 shall not apply to
generic medicinal
products intended for use in animals. The period
referred to in sub-§ 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 § 22 sub-§ 3 and relates to a
food-producing species and was
obtained on submission of new residue tests pursuant to
Regulation (EEC) No. 2377/90 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.
§ 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 de