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Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use

EU Directive 2001/83 · Adopted 6 November 2001 · Extends to United Kingdom

Original text. legislation.gov.uk does not revise this item, so later amendments are not shown here. Changes made to it are listed under each provision when known.

Directive 2001/83/EC of the European Parliament and of the Council

of 6 November 2001

on the Community code relating to medicinal products for human use

THE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION,

Having regard to the Treaty establishing the European Community, and in particular Article 95 thereof,

Having regard to the proposal from the Commission;

Having regard to the opinion of the Economic and Social Committeef1,

Acting in accordance with the procedure laid down in Article 251 of the Treatyf2,

Whereas:

(1)

Council Directive 65/65/EEC of 26 January 1965 on the approximation of provisions laid down by law, regulation or administrative action relating to medicinal productsf3, Council Directive 75/318/EEC of 20 May 1975 on the approximation of the laws of Member States relating to analytical, pharmaco-toxicological and clinical standards and protocols in respect of the testing of proprietary medicinal productsf4, Council Directive 75/319/EEC of 20 May 1975 on the approximation of provisions laid down by law, regulation or administrative action relating to proprietary medicinal productsf5, Council Directive 89/342/EEC of 3 May 1989 extending the scope of Directives 65/65/EEC and 75/319/EEC and laying down additional provisions for immunological medicinal products consisting of vaccines, toxins or serums and allergensf6, Council Directive 89/343/EEC of 3 May 1989 extending the scope of Directives 65/65/EEC and 75/319/EEC and laying down additional provisions for radiopharmaceuticalsf7, Council Directive 89/381/EEC of 14 June 1989 extending the scope of Directives 65/65/EEC and 75/319/EEC on the approximation of provisions laid down by law, regulation or administrative action relating to medicinal products and laying down special provisions for proprietary medicinal products derived from human blood or human plasmaf8, Council Directive 92/25/EEC of 31 March 1992 on the wholesale distribution of medicinal products for human usef9, Council Directive 92/26/EEC of 31 March 1992 concerning the classification for the supply of medicinal products for human usef10, Council Directive 92/27/EEC of 31 March 1992 on the labelling of medicinal products for human use and on package leafletsf11, Council Directive 92/28/EEC of 31 March 1992 on the advertising of medicinal products for human usef12, Council Directive 92/73/EEC of 22 September 1992 widening the scope of Directives 65/65/EEC and 75/319/EEC on the approximation of provisions laid down by law, regulation or administrative action relating to medicinal products and laying down additional provisions on homeopathic medicinal productsf13 have been frequently and substantially amended. In the interests of clarity and rationality, the said Directives should therefore be codified by assembling them in a single text.

(2)

The essential aim of any rules governing the production, distribution and use of medicinal products must be to safeguard public health.

(3)

However, this objective must be attained by means which will not hinder the development of the pharmaceutical industry or trade in medicinal products within the Community.

(4)

Trade in medicinal products within the Community is hindered by disparities between certain national provisions, in particular between provisions relating to medicinal products (excluding substances or combinations of substances which are foods, animal feeding-stuffs or toilet preparations), and such disparities directly affect the functioning of the internal market.

(5)

Such hindrances must accordingly be removed; whereas this entails approximation of the relevant provisions.

(6)

In order to reduce the disparities which remain, rules should be laid down on the control of medicinal products and the duties incumbent upon the Member States' competent authorities should be specified with a view to ensuring compliance with legal requirements.

(7)

The concepts of harmfulness and therapeutic efficacy can only be examined in relation to each other and have only a relative significance depending on the progress of scientific knowledge and the use for which the medicinal product is intended. The particulars and documents which must accompany an application for marketing authorization for a medicinal product demonstrate that potential risks are outweighed by the therapeutic efficacy of the product.

(8)

Standards and protocols for the performance of tests and trials on medicinal products are an effective means of control of these products and hence of protecting public health and can facilitate the movement of these products by laying down uniform rules applicable to tests and trials, the compilation of dossiers and the examination of applications.

(9)

Experience has shown that it is advisable to stipulate more precisely the cases in which the results of toxicological and pharmacological tests or clinical trials do not have to be provided with a view to obtaining authorization for a medicinal product which is essentially similar to an authorized product, while ensuring that innovative firms are not placed at a disadvantage.

(10)

However, there are reasons of public policy for not conducting repetitive tests on humans or animals without over-riding cause.

(11)

The adoption of the same standards and protocols by all the Member States will enable the competent authorities to arrive at their decisions on the basis of uniform tests and by reference to uniform criteria and will therefore help to avoid differences in evaluation.

(12)

With the exception of those medicinal products which are subject to the centralized Community authorization procedure established by Council Regulation (EEC) No 2309/93 of 22 July 1993 laying down Community procedures for the authorization and supervision of medicinal products for human and veterinary use and establishing a European Agency for the Evaluation of Medicinal Productsf14 a marketing authorization for a medicinal product granted by a competent authority in one Member State ought to be recognized by the competent authorities of the other Member States unless there are serious grounds for supposing that the authorization of the medicinal product concerned may present a risk to public health. In the event of a disagreement between Member States about the quality, the safety or the efficacy of a medicinal product, a scientific evaluation of the matter should be undertaken according to a Community standard, leading to a single decision on the area of disagreement binding on the Member States concerned. Whereas this decision should be adopted by a rapid procedure ensuring close cooperation between the Commission and the Member States.

(13)

For this purpose, a Committee for Proprietary Medicinal Products should be set up attached to the European Agency for the Evaluation of Medicinal Products established in the abovementioned Regulation (EEC) No 2309/93.

(14)

This Directive represents an important step towards achievement of the objective of the free movement of medicinal products. Further measures may abolish any remaining barriers to the free movement of proprietary medicinal products will be necessary in the light of experience gained, particularly in the abovementioned Committee for Proprietary Medicinal Products.

(15)

In order better to protect public health and avoid any unnecessary duplication of effort during the examination of application for a marketing authorization for medicinal products, Member States should systematically prepare assessment reports in respect of each medicinal product which is authorized by them, and exchange the reports upon request. Furthermore, a Member State should be able to suspend the examination of an application for authorization to place a medicinal product on the market which is currently under active consideration in another Member State with a view to recognizing the decision reached by the latter Member State.

(16)

Following the establishment of the internal market, specific controls to guarantee the quality of medicinal products imported from third countries can be waived only if appropriate arrangements have been made by the Community to ensure that the necessary controls are carried out in the exporting country.

(17)

It is necessary to adopt specific provisions for immunological medicinal products, homeopathic medicinal products, radiopharmaceuticals, and medicinal products based on human blood or human plasma.

(18)

Any rules governing radiopharmaceuticals must take into account the provisions of Council Directive 84/466/Euratom of 3 September 1984 laying down basic measures for the radiation protection of persons undergoing medical examination or treatmentf15. Account should also be taken of Council Directive 80/836/Euratom of 15 July 1980 amending the Directives laying down the basic safety standards for the health protection of the general public and workers against the dangers of ionizing radiationf16, the objective of which is to prevent the exposure of workers or patients to excessive or unnecessarily high levels of ionizing radiation, and in particular of Article 5c thereof, which requires prior authorization for the addition of radioactive substances to medicinal products as well as for the importation of such medicinal products.

(19)

The Community entirely supports the efforts of the Council of Europe to promote voluntary unpaid blood and plasma donation to attain self-sufficiency throughout the Community in the supply of blood products, and to ensure respect for ethical principles in trade in therapeutic substances of human origin.

(20)

The rules designed to guarantee the quality, safety and efficacy of medicinal products derived from human blood or human plasma must be applied in the same manner to both public and private establishments, and to blood and plasma imported from third countries.

(21)

Having regard to the particular characteristics of these homeopathic medicinal products, such as the very low level of active principles they contain and the difficulty of applying to them the conventional statistical methods relating to clinical trials, it is desirable to provide a special, simplified registration procedure for those homeopathic medicinal products which are placed on the market without therapeutic indications in a pharmaceutical form and dosage which do not present a risk for the patient.

(22)

The anthroposophic medicinal products described in an official pharmacopoeia and prepared by a homeopathic method are to be treated, as regards registration and marketing authorization, in the same way as homeopathic medicinal products.

(23)

It is desirable in the first instance to provide users of these homeopathic medicinal products with a very clear indication of their homeopathic character and with sufficient guarantees of their quality and safety.

(23)

It is desirable in the first instance to provide users of these homeopathic medicinal products with a very clear indication of their homeopathic character and with sufficient guarantees of their quality and safety.

(24)

The rules relating to the manufacture, control and inspection of homeopathic medicinal products must be harmonized to permit the circulation throughout the Community of medicinal products which are safe and of good quality.

(25)

The usual rules governing the authorization to market medicinal products should be applied to homeopathic medicinal products placed on the market with therapeutic indications or in a form which may present risks which must be balanced against the desired therapeutic effect. In particular, those Member States which have a homeopathic tradition should be able to apply particular rules for the evaluation of the results of tests and trials intended to establish the safety and efficacy of these medicinal products provided that they notify them to the Commission.

(26)

In order to facilitate the movement of medicinal products and to prevent the controls carried out in one Member State from being repeated in another, minimum requirements should be laid down for manufacture and imports coming from third countries and for the grant of the authorization relating thereto.

(27)

It should be ensured that, in the Member States, the supervision and control of the manufacture of medicinal products is carried out by a person who fulfils minimum conditions of qualification.

(28)

Before an authorization to market an immunological medicinal product or derived from human blood or human plasma can be granted, the manufacturer must demonstrate his ability to attain batch-to-batch consistency. Before an authorization to market a medicinal product derived from human blood or human plasma can be granted, the manufacturer must also demonstrate the absence of specific viral contamination, to the extent that the state of technology permits.

(29)

The conditions governing the supply of medicinal products to the public should be harmonized.

(30)

In this connection persons moving around within the Community have the right to carry a reasonable quantity of medicinal products lawfully obtained for their personal use. It must also be possible for a person established in one Member State to receive from another Member State a reasonable quantity of medicinal products intended for his personal use.

(31)

In addition, by virtue of Regulation (EC) No 2309/93, certain medicinal products are the subject of a Community marketing authorization. In this context, the classification for the supply of medicinal products covered by a Community marketing authorization needs to be established. It is therefore important to set the criteria on the basis of which Community decisions will be taken.

(32)

It is therefore appropriate, as an initial step, to harmonize the basic principles applicable to the classification for the supply of medicinal products in the Community or in the Member State concerned, while taking as a starting point the principles already established on this subject by the Council of Europe as well as the work of harmonization completed within the framework of the United Nations, concerning narcotic and psychotropic substances.

(33)

The provisions dealing with the classification of medicinal products for the purpose of supply do not infringe the national social security arrangements for reimbursement or payment for medicinal products on prescription.

(34)

Many operations involving the wholesale distribution of medicinal products for human use may cover several Member States simultaneously.

(35)

It is necessary to exercise control over the entire chain of distribution of medicinal products, from their manufacture or import into the Community through to supply to the public, so as to guarantee that such products are stored, transported and handled in suitable conditions. The requirements which must be adopted for this purpose will considerably facilitate the withdrawal of defective products from the market and allow more effective efforts against counterfeit products.

(36)

Any person involved in the wholesale distribution of medicinal products should be in possession of a special authorization. Pharmacists and persons authorized to supply medicinal products to the public, and who confine themselves to this activity, should be exempt from obtaining this authorization. It is however necessary, in order to control the complete chain of distribution of medicinal products, that pharmacists and persons authorized to supply medicinal products to the public keep records showing transactions in products received.

(37)

Authorization must be subject to certain essential conditions and it is the responsibility of the Member State concerned to ensure that such conditions are met; whereas each Member State must recognize authorizations granted by other Member States.

(38)

Certain Member States impose on wholesalers who supply medicinal products to pharmacists and on persons authorized to supply medicinal products to the public certain public service obligations. Those Member States must be able to continue to impose those obligations on wholesalers established within their territory. They must also be able to impose them on wholesalers in other Member States on condition that they do not impose any obligation more stringent than those which they impose on their own wholesalers and provided that such obligations may be regarded as warranted on grounds of public health protection and are proportionate in relation to the objective of such protection.

(39)

Rules should be laid down as to how the labelling and package leaflets are to be presented.

(40)

The provisions governing the information supplied to users should provide a high degree of consumer protection, in order that medicinal products may be used correctly on the basis of full and comprehensible information.

(41)

The marketing of medicinal products whose labelling and package leaflets comply with this Directive should not be prohibited or impeded on grounds connected with the labelling or package leaflet.

(42)

This Directive is without prejudice to the application of measures adopted pursuant to Council Directive 84/450/EEC of 10 September 1984 relating to the approximation of the laws, regulations and administrative provisions of the Member States concerning misleading advertisingf17.

(43)

All Member States have adopted further specific measures concerning the advertising of medicinal products. There are disparities between these measures. These disparities are likely to have an impact on the functioning of the internal market, since advertising disseminated in one Member State is likely to have effects in other Member States.

(44)

Council Directive 89/552/EEC of 3 October 1989 on the coordination of certain provisions laid down by law, regulation or administrative action in Member States concerning the pursuit of television broadcasting activitiesf18 prohibits the television advertising of medicinal products which are available only on medical prescription in the Member State within whose jurisdiction the television broadcaster is located. This principle should be made of general application by extending it to other media.

(45)

Advertising to the general public, even of non-prescription medicinal products, could affect public health, were it to be excessive and ill-considered. Advertising of medicinal products to the general public, where it is permitted, ought therefore to satisfy certain essential criteria which ought to be defined.

(46)

Furthermore, distribution of samples free of charge to the general public for promotional ends must be prohibited.

(47)

The advertising of medicinal products to persons qualified to prescribe or supply them contributes to the information available to such persons. Nevertheless, this advertising should be subject to strict conditions and effective monitoring, referring in particular to the work carried out within the framework of the Council of Europe.

(48)

Advertising of medicinal products should be subject to effective, adequate monitoring. Reference in this regard should be made to the monitoring mechanisms set up by Directive 84/450/EEC.

(49)

Medical sales representatives have an important role in the promotion of medicinal products. Therefore, certain obligations should be imposed upon them, in particular the obligation to supply the person visited with a summary of product characteristics.

(50)

Persons qualified to prescribe medicinal products must be able to carry out these functions objectively without being influenced by direct or indirect financial inducements.

(51)

It should be possible within certain restrictive conditions to provide samples of medicinal products free of charge to persons qualified to prescribe or supply them so that they can familiarize themselves with new products and acquire experience in dealing with them.

(52)

Persons qualified to prescribe or supply medicinal products must have access to a neutral, objective source of information about products available on the market. Whereas it is nevertheless for the Member States to take all measures necessary to this end, in the light of their own particular situation.

(53)

Each undertaking which manufactures or imports medicinal products should set up a mechanism to ensure that all information supplied about a medicinal product conforms with the approved conditions of use.

(54)

In order to ensure the continued safety of medicinal products in use, it is necessary to ensure that pharmacovigilance systems in the Community are continually adapted to take account of scientific and technical progress.

(55)

It is necessary to take account of changes arising as a result of international harmonisation of definitions, terminology and technological developments in the field of pharmacovigilance.

(56)

The increasing use of electronic networks for communication of information on adverse reactions to medicinal products marketed in the Community is intended to allow competent authorities to share the information at the same time.

(57)

It is the interest of the Community to ensure that the pharmacovigilance systems for centrally authorised medicinal products and those authorised by other procedures are consistent.

(58)

Holders of marketing authorisations should be proactively responsible for on-going pharmacovigilance of the medicinal products they place on the market.

(59)

The measures necessary for the implementation of this Directive should be adopted in accordance with Council Decision 1999/468/EC of 28 June 1999 laying down the procedures for the exercise of implementing powers conferred on the Commissionf19.

(60)

The Commission should be empowered to adopt any necessary changes to Annex I in order to take into account scientific and technical progress.

(61)

This Directive should be without prejudice to the obligations of the Member States concerning the time-limits for transposition of the Directives set out in Annex II, Part B.

HAVE ADOPTED THIS DIRECTIVE:

Annotations to the whole text

Footnotes

f1

OJ C 368, 20.12.1999, p. 3.

f2

Opinion of the European Parliament of 3 July 2001 (not yet published in the Official Journal) and Council Decision of 27 September 2001.

f3

OJ 22, 9.2.1965, p. 369/65. Directive as last amended by Directive 93/39/EEC (OJ L 214, 24.8.1993, p. 22).

f4

OJ L 147, 9.6.1975, p. 1. Directive as last amended by Commission Directive 1999/83/EC (OJ L 243, 15.9.1999, p. 9).

f5

OJ L 147, 9.6.1975, p. 13. Directive as last amended by Commission Directive 2000/38/EC (OJ L 139, 10.6.2000, p. 28).

f6

OJ L 142, 25.5.1989, p. 14.

f7

OJ L 142, 25.5.1989, p. 16.

f8

OJ L 181, 28.6.1989, p. 44.

f9

OJ L 113, 30.4.1992, p. 1.

f10

OJ L 113, 30.4.1992, p. 5.

f11

OJ L 113, 30.4.1992, p. 8.

f12

OJ L 113, 30.4.1992, p. 13.

f13

OJ L 297, 13.10.1992, p. 8.

f14

OJ L 214, 24.8.1993, p. 1. Regulation as amended by Commission Regulation (EC) No 649/98 (OJ L 88, 24.3.1998, p. 7).

f15

OJ L 265, 5.10.1984, p. 1. Directive repealed with effect from 13 May 2000 by Directive 97/43/Euratom (OJ L 180, 9.7.1997, p. 22).

f16

OJ L 246, 17.9.1980, p. 1. Directive as amended by Directive 84/467/Euratom (OJ L 265, 5.10.1984, p. 4), repealed with effect from 13 May 2000 by Directive 96/29/Euratom (OJ L 314, 4.12.1996, p. 20).

f17

OJ L 250, 19.9.1984, p. 17. Directive as amended by Directive 97/55/EC (OJ L 290, 23.10.1997, p. 18).

f18

OJ L 298, 17.10.1989, p. 23. Directive as amended by Directive 97/36/EC (OJ L 202, 30.7.1997, p. 60).

f19

OJ L 184, 17.7.1999, p. 23.

Contents

  1. Title I: DEFINITIONS
  2. 1Article 1
  3. Title II: SCOPE
  4. 2Article 2
  5. 3Article 3
  6. 4Article 4
  7. 5Article 5
  8. Title III: PLACING ON THE MARKET
  9. Chapter 1: Marketing authorization
  10. 6Article 6
  11. 7Article 7
  12. 8Article 8
  13. 9Article 9
  14. 10Article 10
  15. 10aArticle 10a
  16. 10bArticle 10b
  17. 10cArticle 10c
  18. 11Article 11
  19. 12Article 12
  20. Chapter 2: Specific provisions applicable to homeopathic medicinal products
  21. 13Article 13
  22. 14Article 14
  23. 15Article 15
  24. 16Article 16
  25. Chapter 2a: Specific provisions applicable to traditional herbal medicinal products
  26. 16aArticle 16a
  27. 16bArticle 16b
  28. 16cArticle 16c
  29. 16dArticle 16d
  30. 16eArticle 16e
  31. 16fArticle 16f
  32. 16gArticle 16g
  33. 16hArticle 16h
  34. 16iArticle 16i
  35. Chapter 3: Procedures relevant to the marketing authorization
  36. 17Article 17
  37. 18Article 18
  38. 19Article 19
  39. 20Article 20
  40. 21Article 21
  41. 21aArticle 21a
  42. 22Article 22
  43. 22aArticle 22a
  44. 22bArticle 22b
  45. 22cArticle 22c
  46. 23Article 23
  47. 23aArticle 23a
  48. 23bArticle 23b
  49. 24Article 24
  50. 25Article 25
  51. 26Article 26
  52. Chapter 4: Mutual recognition procedure and decentralised procedure
  53. 27Article 27
  54. Chapter 4: Mutual recognition and decentralised procedure
  55. 28Article 28
  56. 29Article 29
  57. 30Article 30
  58. 31Article 31
  59. 32Article 32
  60. 33Article 33
  61. 34Article 34
  62. 35Article 35
  63. 36Article 36 Repealed
  64. 37Article 37
  65. 38Article 38
  66. 39Article 39
  67. Title IV: MANUFACTURE AND IMPORTATION
  68. 40Article 40
  69. 41Article 41
  70. 42Article 42
  71. 43Article 43
  72. 44Article 44
  73. 45Article 45
  74. 46Article 46
  75. 46aArticle 46a
  76. 46bArticle 46b
  77. 47Article 47
  78. 47aArticle 47a
  79. 48Article 48
  80. 49Article 49
  81. 50Article 50
  82. 51Article 51
  83. 52Article 52
  84. 52aArticle 52a
  85. 52bArticle 52b
  86. 53Article 53
  87. Title V: LABELLING AND PACKAGE LEAFLET
  88. 54Article 54
  89. 54aArticle 54a
  90. 55Article 55
  91. 56Article 56
  92. 56aArticle 56a
  93. 57Article 57
  94. 58Article 58
  95. 59Article 59
  96. 60Article 60
  97. 61Article 61
  98. 62Article 62
  99. 63Article 63
  100. 64Article 64
  101. 65Article 65
  102. 66Article 66
  103. 67Article 67
  104. 68Article 68
  105. 69Article 69
  106. Title VI: CLASSIFICATION OF MEDICINAL PRODUCTS
  107. 70Article 70
  108. 71Article 71
  109. 72Article 72
  110. 73Article 73
  111. 74Article 74
  112. 74aArticle 74a
  113. 75Article 75
  114. Title VII: WHOLESALE DISTRIBUTION AND BROKERING OF MEDICINAL PRODUCTS
  115. 76Article 76
  116. 77Article 77
  117. 78Article 78
  118. 79Article 79
  119. 80Article 80
  120. 81Article 81
  121. 82Article 82
  122. 83Article 83
  123. 84Article 84
  124. 85Article 85
  125. 85aArticle 85a
  126. 85bArticle 85b
  127. Title VIIA: SALE AT A DISTANCE TO THE PUBLIC
  128. 85cArticle 85c
  129. 85dArticle 85d
  130. Title VIII: ADVERTISING
  131. 86Article 86
  132. 87Article 87
  133. 88Article 88
  134. Title VIIIa: INFORMATION AND ADVERTISING
  135. 88aArticle 88a
  136. 89Article 89
  137. 90Article 90
  138. 91Article 91
  139. 92Article 92
  140. 93Article 93
  141. 94Article 94
  142. 95Article 95
  143. 96Article 96
  144. 97Article 97
  145. 98Article 98
  146. 99Article 99
  147. 100Article 100
  148. Title IX: PHARMACOVIGILANCE
  149. Chapter 1: General provisions
  150. 101Article 101
  151. 102Article 102
  152. 103Article 103
  153. 104Article 104
  154. 104aArticle 104a
  155. 105Article 105
  156. Chapter 2: Transparency and communications
  157. 106Article 106
  158. 106aArticle 106a
  159. Chapter 3: Recording, reporting and assessment of pharmacovigilance data
  160. Recording and reporting of suspected adverse reactions
  161. 107Article 107
  162. 107aArticle 107a
  163. Periodic safety update reports
  164. 107bArticle 107b
  165. 107cArticle 107c
  166. 107dArticle 107d
  167. 107eArticle 107e
  168. 107fArticle 107f
  169. 107gArticle 107g
  170. Signal detection
  171. 107hArticle 107h
  172. Urgent Union procedure
  173. 107iArticle 107i
  174. 107jArticle 107j
  175. 107kArticle 107k
  176. Publication of assessments
  177. 107lArticle 107l
  178. Chapter 4: Supervision of post-authorisation safety studies
  179. 107mArticle 107m
  180. 107nArticle 107n
  181. 107oArticle 107o
  182. 107pArticle 107p
  183. 107qArticle 107q
  184. Chapter 5: Implementation, Delegation and Guidance
  185. 108Article 108
  186. 108aArticle 108a
  187. 108bArticle 108b
  188. Title X: SPECIAL PROVISIONS ON MEDICINAL PRODUCTS DERIVED FROM HUMAN BLOOD AND PLASMA
  189. 109Article 109
  190. 110Article 110
  191. Title XI: SUPERVISION AND SANCTIONS
  192. 111Article 111
  193. 111aArticle 111a
  194. 111bArticle 111b
  195. 112Article 112
  196. 113Article 113
  197. 114Article 114
  198. 115Article 115
  199. 116Article 116
  200. 117Article 117
  201. 117aArticle 117a
  202. 118Article 118
  203. 118aArticle 118a
  204. 118bArticle 118b
  205. 118cArticle 118c
  206. 119Article 119
  207. Title XII: STANDING COMMITTEE
  208. 120Article 120
  209. 121Article 121
  210. 121aArticle 121a
  211. Title XIII: GENERAL PROVISIONS
  212. 122Article 122
  213. 123Article 123
  214. 124Article 124
  215. 125Article 125
  216. 126Article 126
  217. 126aArticle 126a
  218. 126bArticle 126b
  219. 127Article 127
  220. 127aArticle 127a
  221. 127bArticle 127b
  222. Title XIV: FINAL PROVISIONS
  223. 128Article 128
  224. 129Article 129
  225. 130Article 130
  226. Annex I: ANALYTICAL, PHARMACOTOXICOLOGICAL AND CLINICAL STANDARDS AND PROTOCOLS IN RESPECT OF THE TESTING OF MEDICINAL PRODUCTS
  227. Introduction and general principles
  228. (1)Division (1)
  229. (2)Division (2)
  230. (3)Division (3)
  231. (4)Division (4)
  232. (5)Division (5)
  233. (6)Division (6)
  234. (7)Division (7)
  235. (8)Division (8)
  236. (9)Division (9)
  237. (10)Division (10)
  238. (11)Division (11)
  239. Part I: STANDARDISED MARKETING AUTHORISATION DOSSIER REQUIREMENTS
  240. MODULE 1: ADMINISTRATIVE INFORMATION
  241. 1.1Table of contents
  242. 1.2Application form
  243. Summary of product characteristics, labelling and package leaflet
  244. 1.3.1Summary of product characteristics
  245. 1.3.2Labelling and package leaflet
  246. 1.3.3Mock-ups and specimens
  247. 1.3.4Summaries of product characteristics already approved in the Member States
  248. 1.4Information about the experts
  249. 1.5Specific requirements for different types of applications
  250. 1.6Environmental risk assessment
  251. 2MODULE 2: SUMMARIES
  252. 2.1Overall table of contents
  253. 2.2Introduction
  254. 2.3Quality overall summary
  255. 2.4Non-clinical overview
  256. 2.5Clinical overview
  257. 2.6Non-clinical summary
  258. 2.7Clinical Summary
  259. MODULE 3: CHEMICAL, PHARMACEUTICAL AND BIOLOGICAL INFORMATION FOR MEDICINAL PRODUCTS CONTAINING CHEMICAL AND/OR BIOLOGICAL ACTIVE SUBSTANCES
  260. 3.1Format and presentation
  261. Content: basic principles and requirements
  262. (1)Division (1)
  263. (2)Division (2)
  264. (3)Division (3)
  265. (4)Division (4)
  266. (5)Division (5)
  267. (6)Division (6)
  268. (7)Division (7)
  269. (8)Division (8)
  270. (9)Division (9)
  271. (10)Division (10)
  272. (11)Division (11)
  273. (12)Division (12)
  274. Active substance(s)
  275. 3.2.1.1General information and information related to the starting and raw materials
  276. 3.2.1.2Manufacturing process of the active substance(s)
  277. 3.2.1.3Characterisation of the active substance(s)
  278. 3.2.1.4Control of active substance(s)
  279. 3.2.1.5Reference standards or materials
  280. 3.2.1.6Container and closure system of the active substance
  281. 3.2.1.7Stability of the active substance (s)
  282. Finished medicinal product
  283. 3.2.2.1Description and composition of the finished medicinal product
  284. 3.2.2.2Pharmaceutical development
  285. 3.2.2.3Manufacturing process of the finished medicinal product
  286. 3.2.2.4Control of excipients
  287. 3.2.2.5Control of the finished medicinal product
  288. 3.2.2.6Reference standards or materials
  289. 3.2.2.7Container and closure of the finished medicinal product
  290. 3.2.2.8Stability of the finished medicinal product
  291. MODULE 4: NON-CLINICAL REPORTS
  292. 4.1Format and Presentation
  293. 4.2Content: basic principles and requirements
  294. 4.2.1Pharmacology
  295. 4.2.2Pharmaco-kinetics
  296. 4.2.3Toxicology
  297. MODULE 5: CLINICAL STUDY REPORTS
  298. 5.1Format and Presentation
  299. 5.2Content: basic principles and requirements
  300. 5.2.1Reports of bio-pharmaceutics studies
  301. 5.2.2Reports of studies pertinent to pharmaco-kinetics using human bio-materials
  302. 5.2.3Reports of human pharmaco-kinetic studies
  303. 5.2.4Reports of human pharmaco-dynamic studies
  304. Reports of efficacy and safety studies
  305. 5.2.5.1Study Reports of Controlled Clinical Studies Pertinent to the Claimed Indication
  306. 5.2.5.2Study reports of uncontrolled clinical studies reports of analyses of data from more than one study and other clinical study reports
  307. 5.2.6Reports of post-marketing experience
  308. 5.2.7Case reports forms and individual patient listings
  309. IISPECIFIC MARKETING AUTHORISATION DOSSIERS AND REQUIREMENTS
  310. 1WELL-ESTABLISHED MEDICINAL USE
  311. 2ESSENTIALLY SIMILAR MEDICINAL PRODUCTS
  312. 3ADDITIONAL DATA REQUIRED IN SPECIFIC SITUATIONS
  313. 4SIMILAR BIOLOGICAL MEDICINAL PRODUCTS
  314. 5FIXED COMBINATION MEDICINAL PRODUCTS
  315. 6DOCUMENTATION FOR APPLICATIONS IN EXCEPTIONAL CIRCUMSTANCES
  316. 7MIXED MARKETING AUTHORISATION APPLICATIONS
  317. IIIPARTICULAR MEDICINAL PRODUCTS
  318. BIOLOGICAL MEDICINAL PRODUCTS
  319. 1.1Plasma-derived medicinal product
  320. a)Principles
  321. b)Content
  322. c)Evaluation and Certification
  323. 1.2Vaccines
  324. a)Principles
  325. b)Content
  326. c)Evaluation and Certification
  327. RADIO-PHARMACEUTICALS AND PRECURSORS
  328. 2.1Radio-pharmaceuticals
  329. Module 3
  330. Module 4
  331. Module 5
  332. 2.2Radio-pharmaceutical precursors for radio-labelling purposes
  333. Module 3
  334. Module 4
  335. Module 5
  336. 3HOMEOPATHIC MEDICINAL PRODUCTS
  337. Module 3
  338. Module 4
  339. 4HERBAL MEDICINAL PRODUCTS
  340. Module 3
  341. (1)Herbal substances and herbal preparations
  342. (2)Herbal Medicinal Products
  343. 5ORPHAN MEDICINAL PRODUCTS
  344. Part IV: ADVANCED THERAPY MEDICINAL PRODUCTS
  345. 1INTRODUCTION
  346. 2DEFINITIONS
  347. 2.1Gene therapy medicinal product
  348. 2.2Somatic cell therapy medicinal product
  349. SPECIFIC REQUIREMENTS REGARDING MODULE 3
  350. 3.1Specific requirements for all advanced therapy medicinal products
  351. Specific requirements for gene therapy medicinal products
  352. Introduction: finished product, active substance and starting materials
  353. 3.2.1.1Gene therapy medicinal product containing recombinant nucleic acid sequence(s) or genetically modified microorganism(s) or virus(es)
  354. 3.2.1.2Gene therapy medicinal product containing genetically modified cells
  355. 3.2.1.3Division 3.2.1.3
  356. 3.2.1.4Division 3.2.1.4
  357. 3.2.1.5Division 3.2.1.5
  358. 3.2.2Specific requirements
  359. Specific requirements for somatic cell therapy medicinal products and tissue engineered products
  360. 3.3.1Introduction: finished product, active substance and starting materials
  361. 3.3.2Specific requirements
  362. 3.3.2.1Starting materials
  363. 3.3.2.2Manufacturing process
  364. 3.3.2.3Characterisation and control strategy
  365. 3.3.2.4Excipients
  366. 3.3.2.5Developmental studies
  367. 3.3.2.6Reference materials
  368. Specific requirements for advanced therapy medicinal products containing devices
  369. 3.4.1Advanced therapy medicinal product containing devices as referred to in Article 7 of Regulation (EC) No 1394/2007
  370. 3.4.2Combined advanced therapy medicinal products as defined in Article 2(1)(d) of Regulation (EC) No 1394/2007
  371. SPECIFIC REQUIREMENTS REGARDING MODULE 4
  372. 4.1Specific requirements for all advanced therapy medicinal products
  373. 4.2Specific requirements for gene therapy medicinal products
  374. 4.2.1Pharmacology
  375. 4.2.2Pharmacokinetics
  376. 4.2.3Toxicology
  377. Specific requirements for somatic cell therapy medicinal products and tissue engineered products
  378. 4.3.1Pharmacology
  379. 4.3.2Pharmacokinetics
  380. 4.3.3Toxicology
  381. SPECIFIC REQUIREMENTS REGARDING MODULE 5
  382. Specific requirements for all advanced therapy medicinal products
  383. 5.1.1Division 5.1.1
  384. 5.1.2Division 5.1.2
  385. 5.1.3Division 5.1.3
  386. 5.1.4Division 5.1.4
  387. 5.1.5Division 5.1.5
  388. 5.1.6Division 5.1.6
  389. 5.1.7Division 5.1.7
  390. 5.1.8Division 5.1.8
  391. Specific requirements for gene therapy medicinal products
  392. 5.2.1Human pharmacokinetic studies
  393. 5.2.2Human pharmacodynamic studies
  394. 5.2.3Safety studies
  395. Specific requirements for somatic cell therapy medicinal products
  396. 5.3.1Somatic cell therapy medicinal products where the mode of action is based on the production of defined active biomolecule(s)
  397. 5.3.2Biodistribution, persistence and long-term engraftment of the somatic cell therapy medicinal product components
  398. 5.3.3Safety studies
  399. Specific requirements for tissue engineered products
  400. 5.4.1Pharmacokinetic studies
  401. 5.4.2Pharmacodynamic studies
  402. 5.4.3Safety studies
  403. Annex II
  404. ARepealed Directives, with their successive amendments (referred to by Article 128)
  405. BTime-limits for transposition into national law (referred to by Article 128)
  406. Annex IIICORRELATION TABLE