H2020_PHC-2

Dissemination

PU Public

PP Restrict

RE Restrict

CO Confide

1

2

3

DELIVERABLE4

5

6

Grant Agreement number: 6437967

Project Title: openMedicine8

9

D3.1 Assessment of the WP2 solution for ‘other’10

medicinal products11

12

Version: 1.013

Status: final14

15

Authors:16

Anna Gawrońska-

Błaszczyk

ILiM

17

18

19

Funded by

the European Union

014-single-stage

Level

X

ed to other programme participants (including the Commission Services

ed to a group specified by the consortium (including the Commission Services

ntial, only for members of the consortium (including the Commission Services)

openMedicine – D3.1

Page 2 of 52 24/06/2016

Revision History, Status, Abstract, Keywords, Statement of20

Originality21

22

Revision History23

Revision Date Author Organisation Description

1. 29-03-

2016

José Costa

Teixeira

HL7 Content-related comments

2. 29-03-

2016

IsabelLázaroSalcedo

AEMPS Content-related comments

3. 07-04-

2016

Jos Devlies Custodix Content-related comments

4. 20-04-

2016

IsabelLázaroSalcedo

AEMPS Content-related comments

5. 22-04-

2016

José Costa

Teixeira

HL7 Content-related comments

6. 23-04-

2016

Christian

Hay

NEN Content-related comments

7. 26-04-

2016

IsabelLázaroSalcedo

AEMPS Content-related comments

8. 03-05-

2016

José Costa

Teixeira

HL7 Content-related comments

9. 07-05-

2016

Jos Devlies Custodix Content-related comments

10. 12-05-

2016

Paolo Alcini EMA Content-related comments

11. 13-05-

2016

Jos Devlies Custodix Content-related comments

12. 13-05-

2016

Isabel

Lázaro

Salcedo

AEMPS Content-related comments

13 30-05-

2016

Paolo Alcini EMA Final Review

14 13-06- Jo Goulding Health and External Review

openMedicine – D3.1

Page 3 of 52 24/06/2016

2016 Social Care

Information

Centre

24

25

26

Date of delivery Contractual: 31.03.2016 Actual: xx.xx.20xx

Status final X /draft

27

Abstract

(for dissemination)

This document presents the definition of alternative and

complementary use case where unambiguous identification of

a medicinal or/and pharmaceutical product is needed.

Keywords Unambiguous identification of medicinal products, alternative and

complementary use cases

28

29

openMedicine – D3.1

Page 4 of 52 24/06/2016

Statement of originality30

This deliverable contains original unpublished work except where clearly indicated otherwise.31

Acknowledgement of previously published material and of the work of others has been made32

through appropriate citation, quotation or both.33

openMedicine – D3.1

Page 5 of 52 24/06/2016

Table of Content34

35

Revision History, Status, Abstract, Keywords, Statement of Originality .........................236

Executive Summary D3.1.....................................................................................................637

1.1. Introduction .................................................................................................................838

1.1. Scope of the WP ....................................................................................................839

1.2. Goal of D3.1 ...........................................................................................................940

1.3. Adopted approach and methodology ......................................................................941

2. References.................................................................................................................1142

3. Terms and definitions ...............................................................................................1343

4. Current and future identification and description methods...................................1444

5. Summary of approach and model developed in WP2.............................................1545

6. Inventory of ‘other’ medicinal products ..................................................................2246

6.1. Products mentioned in Directive 2001/83 by name and products included in47Regulation (EC) No 726/2004...............................................................................2348

6.2. Products excluded from Directive 2001/83 ...........................................................2449

6.3. Products in scope of Directive 2001/83 and additionally regulated .......................2550

6.4. Other sources of information ................................................................................2551

6.5. Inventory of ‘other’ medicinal products .................................................................2752

7. Analysis of chosen products with reference to the WP2 solution.........................3653

7.1. Non-pre-packaged medicinal products .................................................................3654

7.2. Pre-packaged medicinal products additionally regulated ......................................3955

7.3. Identification of substances ..................................................................................4456

7.4. Gap analysis regarding ‘other’ medicinal products................................................4557

7.5. Conclusions..........................................................................................................5158

59

openMedicine – D3.1

Page 6 of 52 24/06/2016

Executive Summary D3.160

Relationship to overall goal of the project, to other work in this WP/other WPs:61

WP2 has developed a generic solution for the identification and the description of62

medicinal and pharmaceutical products for human use considering commonly63

prescribed regulated medicinal products for humans. WP3 is focused on assessing64

WP2 options for other than pre-packed medicinal products and identify possible gaps65

in the WP2 approach regarding identification and description of the product(s) and66

their content. Task 3.1 is focused on listing ‘other’ medicinal product types,67

identification of EU regulatory requirements and other relevant documents in order to68

highlight the reason for additional or separate regulations towards these products69

and in order to determine whether there is a potential need for any identifiers or70

attributes not foreseen in WP2. Moreover, this task is focused on determination of71

identification concepts developed in WP2 as applicable for ‘other’ medicinal products72

as well as identification of gaps and any limitations that might occur. Conclusions will73

be a starting point for task 3.2. This task in turn will focus on modification of the WP274

model so that ‘other’ medicinal products can be identified and described in a cross-75

border environment. Within the scope of task 3.2 the WP2 model will be extended76

and various scenarios will be provided in order to illustrate specific identification77

needs of individual medicinal products.78

Objective:79

The main goal of WP3 is to assess WP2 options for other than pre-packaged80

medicinal products (branded and not branded) and identify possible gaps in the WP281

approach regarding identification and description of the product(s) and their content.82

The scope of this deliverable is that of identifying – based on the WP2 solution -83

potential gaps and additional needs for the identification and the description of84

medicinal and pharmaceutical products when applied to ‘other’ medicinal products.85

Approach/methods applied:86

Various documents, predominantly legal ones, have been taken into consideration87

and analysed in order to determine product types for consideration in WP3 as well as88

any possible identification needs to be addressed.89

Work process:90

The development of the document was led by the Task Leader and supported91

actively by project members in accordance with individual competences. Numerous92

internal reviews took place in order to design and develop the report. Finally, an93

external review took place according to the adopted quality assurance methods.94

Results:95

The following types of products have been identified for consideration of this96

deliverable:97

openMedicine – D3.1

Page 7 of 52 24/06/2016

non-pre-packaged medicinal products (branded and not branded),98

pre-packaged medicinal products towards which there might occur additional99

identification needs (e.g. additionally regulated).100

Discussion/Conclusions/Recommendations:101

Analysis performed for the sake of this deliverable allowed to develop an inventory of102

other products that are not included in WP2, aggregating them into two groups (pre-103

packaged and non-pre-packaged), verify what identification concepts and data-sets104

developed in WP2 are applicable and finally determine any additional needs105

regarding identification of ‘other’ medicinal products. In the course of the analysis, it106

has been found that the WP2 solution is applicable for the majority of ‘other’107

medicinal products groups identified for the sake of WP3 and especially D3.1.108

However, there are some examples of products (e.g. magistral formulas – also109

known as extemporaneous preparations, officinal formulas and radionuclides in the110

form of sealed sources) that might need some additional guidance and extension of111

the WP2 model. This issue will be addressed in T3.2 and D3.2 will include further112

information regarding possible identification and description methods with respect to113

these products for the sake of e-prescription (but also patient summary, etc.) in the114

cross-border context this information will include, among others: a prescription for115

each of these products as well as an extract of an Electronic Health Record116

documenting a treatment with these products.117

openMedicine – D3.1

Page 8 of 52 24/06/2016

1.1. Introduction118

1.1. Scope of the WP119

The main goal of WP3 is to assess WP2 options for other than pre-packaged120

medicinal products and identify possible gaps in the WP2 approach regarding121

identification and description of the product(s) and their content. WP2 has adopted122

a generic solution for the identification and the description of medicinal and123

pharmaceutical products for human use considering commonly prescribed regulated124

medicinal products for humans. The main focus of this WP is to:125

list ‘other’ products that are not included in WP2, aggregating them into two126

groups (pre-packaged and non-pre-packaged),127

verify if identification concepts and data-sets developed in WP2 are applicable,128

determine if there are any additional needs regarding identification of ‘other’129

medicinal products,130

develop an appropriate solution to be able to cover all ‘other’ medicinal131

products for human use (if needed).132

WP2 was focused on branded pre-packaged medicinal products including all133

products authorised in accordance with Regulation (EC) No 726/2004 and134

Directive 2001/83/EC of the community code relating to medicinal products for135

human use by a medicines regulator in a pre-packaged form and includes both136

innovator and generic products.137

Apart from those products, drugs prescription, preparation and dispensation138

processes may be related to a larger class of products for which the product139

identification and description is also required. In this particular deliverable an analysis140

of the different types of products will be conducted in order to identify which products141

may be included in WP3. Then, for a selection of them the appropriateness of the142

WP2 solution will be verified, identifying possible gaps and any additional needs.143

The following types of products are in scope of this deliverable:144

non-pre-packaged medicinal products, branded as well as not branded145

pre-packaged medicinal products towards which there might occur additional146

identification needs (e.g. additionally regulated).147

The following types of products are not in scope of this deliverable and will be148

addressed in WP4:149

openMedicine – D3.1

Page 9 of 52 24/06/2016

products obtained via a compounding process (e.g. cytostatics, parenteral150

foods for special medical purposes),151

clusters (group of medicinal products which have been preselected by a152

Regulatory Agency or by the Health Ministry or other similar organization,153

following predefined criteria).154

1.2. Goal of D3.1155

Deliverable D3.1 “Assessment of the WP2 solution for ‘other’ medicinal products” has156

two goals to achieve:157

list ‘other’ medicinal products including non-pre-packaged branded medicinal158

products or pre-packaged medicinal products towards which there might occur159

additional identification needs,160

identify any potential gaps in the WP2 model.161

The goal of the deliverable is NOT to develop a classification of medicinal products162

but to analyse various references in order to spot any possible medicinal product163

types that might need additional identifiers, not foreseen in WP2 or new attributes not164

included in the ISO IDMP standards.165

1.3. Adopted approach and methodology166

In order to achieve the goals of the task and deliver the final material the following167

approach and methodology has been adopted; WP3 is divided into two major steps:168

Step 1 (corresponding to deliverable D3.1):169

a) identification of EU regulatory requirements and other relevant documents170

regarding identification and description of other medicinal product types,171

b) analysis of relevant EU regulatory aspects in order to highlight the reason for172

additional or separate regulations towards these products and in order to173

determine whether there is a potential need for any identifiers1 or identifying174

attributes2 not foreseen in WP2 or in the IDMP,175

c) listing of ‘other’ medicinal product types,176

1 an attribute that unequivocally specifies an entity - in this case a product. Each unique identifier identifies one unique product2 identifying or descriptive attributes; identifying attributes are attributes whose unique combination of values enables to identify

a unique product; descriptive attributes are attributes that describe certain aspects of the product

openMedicine – D3.1

Page 10 of 52 24/06/2016

d) confirmation of identifying concepts out of WP2 as applicable for ‘other’177

medicinal products,178

e) identification of gaps and any limitations that might occur.179

Step 2 (corresponding to deliverable D3.2):180

a) modification of the WP2 model so that ‘other’ medicinal products can be181

identified and described in a cross-border environment182

b) examples of a prescription for each of these products as well as an extract of183

an Electronic Health Record documenting a treatment with these products.184

Step 2 will be undertaken in Task 3.2 and the two tasks are closely related to each185

other D3.1 and D3.2 shall therefore be treated and analysed as complementary186

deliverables.187

openMedicine – D3.1

Page 11 of 52 24/06/2016

2. References188

In order to develop the D3.1 the following materials and documents have been189

analysed and are referenced to:190

project deliverables:191

D.2.1192

D.2.2193

ISO standards:194

Standard ISO11615:2012(E)195

Standard ISO11238:2012(E)196

EU legal framework:197

REGULATION (EC) No 726/2004 OF THE EUROPEAN PARLIAMENT198

AND OF THE COUNCIL of 31 March 2004 laying down Community199

procedures for the authorisation and supervision of medicinal products for200

human and veterinary use and establishing a European Medicines Agency:201

http://ec.europa.eu/health/files/eudralex/vol-202

/reg_2004_726/reg_2004_726_en.pdf203

DIRECTIVE 2001/83/EC OF THE EUROPEAN PARLIAMENT AND OF204

THE COUNCIL of 6 November 2001 on the Community code relating to205

medicinal products for human use:206

http://ec.europa.eu/health/files/eudralex/vol-207

1/dir_2001_83_cons2009/2001_83_cons2009_en.pdf208

REGULATION (EC) No 1394/2007 OF THE EUROPEAN PARLIAMENT209

AND OF THE COUNCIL of 13 November 2007 on advanced therapy210

medicinal products and amending Directive 2001/83/EC and Regulation211

(EC) No 726/2004: http://ec.europa.eu/health/files/eudralex/vol-212

1/reg_2007_1394/reg_2007_1394_en.pdf213

COMMISSION DIRECTIVE 1999/21/EC of 25 March 1999 on dietary foods214

for special medical purposes:215

https://www.fsai.ie/uploadedFiles/Consol_Dir1999_21.pdf216

COMMISSION REGULATION (EC) No 953/2009 of 13 October 2009 on217

substances that may be added for specific nutritional purposes in foods for218

openMedicine – D3.1

Page 12 of 52 24/06/2016

particular nutritional uses: http://eur-lex.europa.eu/legal-219

content/EN/TXT/PDF/?uri=CELEX:32009R0953&from=EN220

JUDGMENT OF THE COURT (Third Chamber) 16 July 2015:221

http://curia.europa.eu/juris/document/document.jsf;jsessionid=9ea7d2dc30222

d544b0894445c44c8a9230ebfa9d15c6e0.e34KaxiLc3qMb40Rch0SaxuQb223

Nj0?text=&docid=165910&pageIndex=0&doclang=EN&mode=lst&dir=&occ224

=first&part=1&cid=387522225

other sources:226

‘Boundary for the “Pharmaceutical and Biological Products” Hierarchy in227

the International Release of SNOMED CT® vs. National Extension228

Content’, SNOMED CT, www.snomed.org/doc229

‘International Non-proprietary Names (INN) for Pharmaceutical230

Substances’, WHO:231

http://www.who.int/medicines/services/inn/Radical_Book_2012.pdf232

233

234

openMedicine – D3.1

Page 13 of 52 24/06/2016

3. Terms and definitions235

The definitions in this document are derived from, and maintained in, the online236

glossary:237

http://www.openmedicine.ramit.be/dictionary/238

The glossary will be completed progressively and intends to list the medication239

related concepts and their definitions in different EN/ISO standards as well as in240

European Directives and Guidelines.241

openMedicine – D3.1

Page 14 of 52 24/06/2016

4. Current and future identification and242

description methods243

Medicinal products identification and description methods vary between countries in the244

European Union and also globally. This is mainly due to different legal, economic and245

organizational issues. Countries do store data in an electronic format in national databases246

but as in the majority of instances product identifiers and identifying attributes are understood247

nationally, data matching between countries is cumbersome and not always successful, even248

when implementing the full epSOS approach.249

However, some steps are being taken in order to make medicinal products data available250

centrally for specific reasons. As an example, it is worth mentioning that all marketing-251

authorisation holders (MAHs) of medicines authorised in the European Union (EU) and252

European Economic Area (EEA) must submit information on these medicines to the253

European Medicines Agency (EMA) and must keep this information up-to-date. MAHs are254

also required to submit information concerning all medicinal products for which they hold a255

marketing authorisation in EEA countries outside the EU (i.e. Iceland, Liechtenstein and256

Norway). This is done mainly in response to the pharmacovigilance legislation. The257

programme is aimed at providing robust, high quality and sustainable systems and services258

to gather and analyse data and information for pharmacovigilance. The Article 57 project259

deliverables have been achieved in different phases over the past four years and the260

ongoing collaboration of MAHs will be vital to maximise the utility of this information for261

pharmacovigilance.262

The EMA is in the process of implementing the standards developed by the International263

Organization for Standardization (ISO) for the identification of medicinal products (IDMP).264

The move to ISO IDMP is to standardize data formats outside EU and to improve the265

common format. ISO IDMP includes a set of common global standards for data elements,266

formats and terminologies for the unique identification of and the exchange of information on267

medicines. Following a phased implementation process, pharmaceutical companies will be268

required to submit data on medicines to EMA in accordance with these formats and269

terminologies. With the development and adoption of the ISO IDMP standards by the270

European Medicines Regulatory Network (EMRN), there is an opportunity to bring together271

common terminologies and data structures to provide a single source of European medicinal272

product information.273

WP2 solution was built upon the ISO IDMP standards and in accordance with the EMA274

implementation activities regarding this particular concept of standardized medicinal products275

identification as well as legal basis with respect to ISO IDMP. It is therefore important to276

underline that in the proposed solution it is assumed that the ISO IDMP approach is277

implemented in order to streamline e-prescribing and e-dispensing processes in the cross-278

border context. WP3 work, being a continuation of the WP2 achievements, is based on the279

same foundation and the same assumption. Whenever WP2 identification concepts are280

found to be applicable for ‘other’ medicinal products in D.3.1, it means that there is281

a theoretical possibility to use them in practice. However, some additional guidance might be282

needed with reference of selected medicinal products or even the extension of the EMA283

scope of activities. This guidance and recommendations will be provided in D3.2.284

openMedicine – D3.1

5. Summary of approach and model285

developed in WP2286

As defined in D2.1, the foremost goal is to enable safe dispensation of a medicinal287

product by correctly identifying the product prescribed. The main focus of D2.1 is the288

identification of a medicinal product, as defined in ISO IDMP. IDMP uses the289

concepts of Medicinal Product, Pha290

levels within these concepts. These concepts are recommended for identification of291

medicinal products and constitute the basis for the identification model developed in292

WP2. These concepts can be illustrated in t293

294

Figure 1. IDMP-based identification concepts295

The main characteristics that are associated with the MPID, PCID, BAID_1 and296

BAID_2 are:297

name of the Medicinal Product;298

Page 15 of 52

Summary of approach and model

developed in WP2

remost goal is to enable safe dispensation of a medicinal

product by correctly identifying the product prescribed. The main focus of D2.1 is the

identification of a medicinal product, as defined in ISO IDMP. IDMP uses the

concepts of Medicinal Product, Pharmaceutical Product, and Package, including

levels within these concepts. These concepts are recommended for identification of

medicinal products and constitute the basis for the identification model developed in

WP2. These concepts can be illustrated in the way shown in figure 1.

based identification concepts

The main characteristics that are associated with the MPID, PCID, BAID_1 and

name of the Medicinal Product;

24/06/2016

Summary of approach and model

remost goal is to enable safe dispensation of a medicinal

product by correctly identifying the product prescribed. The main focus of D2.1 is the

identification of a medicinal product, as defined in ISO IDMP. IDMP uses the

rmaceutical Product, and Package, including

levels within these concepts. These concepts are recommended for identification of

medicinal products and constitute the basis for the identification model developed in

he way shown in figure 1.

The main characteristics that are associated with the MPID, PCID, BAID_1 and

openMedicine – D3.1

Page 16 of 52 24/06/2016

legal status of supply;299

terms of the marketing authorization;300

marketing authorization (licence) holder;301

manufacturer(s);302

authorizing Medicines Regulatory Agency;303

qualitative and quantitative composition;304

ingredients, strength, pharmaceutical form, route of administration;305

device(s) as part of a Medicinal Product;306

clinical particulars;307

product classification(s);308

package description [e.g. container, administration device(s) and package309

quantity];310

regulated product information and documentation.311

The main characteristics that are associated with the PHPID are:312

Administrable Dose Form313

Unit of Measurement314

Strength315

Sample Core Dataset regarding Substance includes the following descriptive attribute316

elements deriving from the ISO IDMP:317

Substance Name (ISO 11238 3.4 Naming of substances)318

Substance ID (ISO 11238 3.5 Requirements for unique identifiers)319

Substance Type (ISO 11238 3.6 Types of substances)320

Sample Core Dataset regarding Clinical Particulars includes the following attribute321

elements deriving from the ISO IDMP:322

Therapeutic Indication323

Contra-Indication324

Population specifics325

Other therapy specifics326

Interactions327

Interactant328

openMedicine – D3.1

Page 17 of 52 24/06/2016

Sample Core Dataset regarding Authoriztion includes the following attribute elements329

deriving from the ISO IDMP:330

Marketing Authorisation Number331

Country332

Legal Status of Supply333

Authorisation Status334

Authorisation Status Date335

Validity Period336

Procedure Identifier/Number (e.g. MRP number)337

Marketing Authorisation Holder Identifier338

Medicines Regulatory Agency339

Marketing authorization procedure340

Procedure identifier/number341

Procedure type342

The following standards are part of IDMP and are used for the description of343

Pharmaceutical Products and Medicinal Product:344

EN/ISO 11238:2012(E), Health Informatics, Identification of Medicinal345

Products (IDMP) standard Data elements and structures for unique346

identification and exchange of regulated information on substances347

EN/ISO 11239:2012(E), Health Informatics, Identification of Medicinal348

Products (IDMP) standard Data elements and structures for unique349

identification and exchange of regulated information on pharmaceutical dose350

forms, units of presentation, routes of administration and packaging351

EN/ISO 11240:2012(E), Health Informatics, Identification of Medicinal352

Products (IDMP) standard Data elements and structures for unique353

identification and exchange of units of measurement354

The above enumerated product attributes have been analysed in D2.2 and grouped355

into the three sections, presented in table 2. Additionally, the attributes that are in the356

clinical documents (e.g. prescriptions) are also analysed and listed in table 3.357

358

openMedicine – D3.1

Page 18 of 52 24/06/2016

Table 2. openMedicine Collection of identifiers - Product characteristics359

360

Source: D2.2361

362

Concept

PhPID

PhP Stratum

Substance(s)

Route of Administration

Administrable Dose Form

Strength

Quantity

Units

Reference Strength

Quantity

Units

Medical Device

Unit of Presentation

MPID

Medicinal Product Name

Marketing Authorization

Country

Holder

Number

Procedure ID

Indication

Pharmaceutical Dose form

Legal Status of Supply

Classification

PCID

Package Item Container

Type

Quantity

Material

Alternate Material

Package Component

Component Type

Material

Alternate Material

Manufactured Item

Manufactured Dose Form

Unit of Presentation

Manufactured Item Quantity

Pro

du

ctA

ttri

bu

tes

Ph

arm

aceu

tica

lPro

du

ct

PhP

ID

Med

icin

alP

rod

uct

MPI

D

Pac

kage

PC

ID

openMedicine – D3.1

Page 19 of 52 24/06/2016

Table 3. openMedicine Collection of identifiers - information in care context363

364

365

Source: D2.2366

At the product characteristics level it is expected that all the products will have367

a unique ID. In order to identify in an unequivocal way it is needed to know the368

identifier; it might also be useful to dispose of a sufficient set of identifying attributes.369

Identifications have always to be considered in their context. If the context is unclear,370

the use of an ID may not be sufficient as it is essential to know what the ID refers to.371

Use of any coded term (for example the product specified in a prescription) is372

understood only if both parties (in the example, the prescribing and dispensing373

systems) understand what the code refers to and can find the code value itself.374

A number of requirements to be met have been identified in T2.2 in order to enable375

cross-border e-prescription and dispensation. They include the following elements:376

a central repository of common medicinal product information exists, but yet377

not sufficiently structured to be interactive,378

the prescription must specify the medicinal product but is not expected to379

convey all the product characteristics,380

openMedicine – D3.1

Page 20 of 52 24/06/2016

the identifying information in the prescription must be sufficient by itself or381

complemented by additional data to identify the product,382

besides the specification of the product the receiving system must have the383

information available to retrieve the product to be dispensed,384

the product information may be checked by the prescribing and dispensing385

systems,386

it happens that the dispenser needs additional information about a product387

outside their local range of dispensable products,388

the substitution rules are typically built in the prescribing and dispensing389

systems so they are considered harmonized within the scope of prescription390

and dispense in the same country,391

the marketing authorization holders submit information updates to the392

regulators to keep the product information accurate and up to date,393

local product characteristics (e.g. local classification) may also be needed to394

be shared.395

The overall recommendations include specifying a product by referring to one or396

more of the possible identifiers, namely: PhPID, MPID and PCID. The prerequisite for397

such recommendations is as follows: both sending and receiving party understand398

the concepts by using harmonised Object Identifiers (OIDs). Detailed information399

regarding the concept is included in WP2 deliverables.400

In order to have a clear overview over the types of identifiers and differences401

between them, the following concepts should be borne in mind:402

PhPID – Pharmaceutical Product Identifier, unique identifier and uniform403

representation of the pharmaceutical product using the substance(s)/specified404

substance(s), their (reference) strength(s), the administrable dose form and,405

where applicable, the integral device3,406

MPID – Medicinal Product Identifier, unique identifier allocated to407

a medicinal product supplementary to any existing authorisation number as408

ascribed by a Medicines Regulatory Agency in a jurisdiction4,409

PCID – Package Identifier, unique identifier for the packaged Medicinal410

Product5.411

3 ISO IDMP, Standard ISO11615:2012(E)4 ibid.5 ibid. and ISO IDMP, Standard ISO11238:2012(E)

openMedicine – D3.1

Page 21 of 52 24/06/2016

Another pivotal role in the whole identification process is played by the central EMA412

database, the Article 57 database or the future database which is going to be ISO413

IDMP Compliant. The database will be held for all possible regulatory processes414

related to medicinal products. In order to enter product data into the database, the415

MAH is asked to provide comprehensive product information by using a standard416

reporting form. This medicinal product information should be made available by the417

EMA, and become the important central source of information to be used across418

Europe.419

openMedicine – D3.1

Page 22 of 52 24/06/2016

6. Inventory of ‘other’ medicinal products420

In article 1 of Directive 2001/83/EC a medicine is defined as “Any substance or421

combination of substances being presented as having properties for treating or422

preventing disease in human beings; Any substance or combination of substances423

which may be used in or administered to human beings either with a view to424

restoring, correcting or modifying physiological functions by exerting425

a pharmacological, immunological or metabolic action, or to making a medical426

diagnosis.”427

Medicinal products can be divided into many groups with regards to various criteria.428

The approach that has been adopted in the project led to dividing medicinal products429

into: ‘pre-packaged branded medicinal products’ and ‘‘other’ medicinal products’.430

WP2 deals with pre-packaged medicinal products to which Directive 2001/83/EC431

refers to.432

The aim of the analysis undertaken for the sake of this particular deliverable is to433

determine:434

if there are any other examples of products that might occur in a435

different form from a pre-packaged branded form as this might mean that436

some other identifiers and attributes might be needed in order to identify437

and describe the product,438

if there are any other examples of products that ARE pre-packaged and439

branded but require special identifiers and attributes due to additional440

regulations,441

and442

if the attributes available in the EMA database (Article 57 now, and ISO443

IDMP database later on) cover additional information that might be444

needed to describe ‘other’ medicinal products.445

As a starting point for the development of an inventory to be considered for the WP3,446

WP2 references have been analysed, namely:447

REGULATION (EC) No 726/2004 OF THE EUROPEAN PARLIAMENT AND448

OF THE COUNCIL of 31 March 2004 laying down Community procedures for449

the authorisation and supervision of medicinal products for human and450

veterinary use and establishing a European Medicines Agency and451

DIRECTIVE 2001/83/EC OF THE EUROPEAN PARLIAMENT AND OF THE452

COUNCIL of 6 November 2001 on the Community code relating to medicinal453

products for human use.454

openMedicine – D3.1

Page 23 of 52 24/06/2016

6.1. Products mentioned in Directive 2001/83455

by name and products included in456

Regulation (EC) No 726/2004457

Directive 2001/83 refers to a number of products that are either in scope of this458

directive or administrative data is that of this directive. Such as:459

advanced therapy medicinal products,460

biologic medicinal products,461

investigational medicinal products,462

radiopharmaceuticals,463

medicinal products that are designated as orphan medicinal products pursuant464

to Regulation (EC) No 141/2000.465

Regulation (EC) No 726/2004, among many other information, includes an Annex in466

which medicinal products to be authorised by the community are included. This is the467

list of products that have to be authorised in a central procedure by the EMA and it468

embraces the following examples:469

1. “Medicinal products developed by means of one of the following470

biotechnological processes:471

recombinant DNA technology,472

controlled expression of genes coding for biologically active proteins in473

prokaryotes and eukaryotes including474

transformed mammalian cells,475

hybridoma and monoclonal antibody methods.476

2. Medicinal products for veterinary use intended primarily for use as477

performance enhancers in order to promote the growth of treated animals or to478

increase yields from treated animals6.479

3. Medicinal products for human use containing a new active substance which,480

on the date of entry into force of this Regulation, was not authorised in the481

Community482

4. Medicinal products that are designated as orphan medicinal products pursuant483

to Regulation (EC) No 141/2000.”484

The list includes among others:485

6 which are out of scope of the project as it concentrates on products for human use only

openMedicine – D3.1

Page 24 of 52 24/06/2016

products whose manufacturing or development process is special (e.g.486

medicinal products developed by means of particular biotechnological487

processes),488

products of innovative character (e.g. medicinal products with a new active489

substance that has not been referred to in any prior application whose490

exceptional qualities justify a ‘fast track’ procedure for authorisation),491

products for rare diseases.492

The above mentioned products characteristics does not require any special attributes493

or identifiers not foreseen in the WP2 solution as all information regarding these494

medicinal products is contained in Art. 57 (a mandatory requirement towards all495

medicinal products authorised in Europe). Attributes, such as special manufacturing496

processes, development stage of the product or substance origin are products497

attributes that are covered with the ISO IDMP standards. These products do not need498

any additional identifiers either. These special pieces of data are not explicitly499

included either in a prescription in country A nor in an IT pharmacy system in country500

B because these are attributes linked to identifiers, e.g. PhPID, MPID and PCID. On501

that basis the matching can be done (one way or another as described in various502

scenarios in D2.2).503

6.2. Products excluded from Directive 2001/83504

Directive 2001/83 applies to medicinal products for human use intended to be505

placed on the market in Member States and either prepared industrially or506

manufactured by a method involving an industrial process.507

Among other information, the directive includes a list of products that are excluded508

from the document. Among these products there is a subgroup that will be analysed509

furtherly for the sake of the WP3, e.g.:510

magistral formula,511

officinal formula,512

any radionuclides in the form of sealed sources,513

whole blood, plasma or blood cells of human origin,514

any advanced therapy medicinal product, as defined in Regulation (EC) No515

1394/2007, which is prepared on a nonroutine basis according to specific516

quality standards, and used within the same Member State in a hospital under517

the exclusive professional responsibility of a medical practitioner, in order to518

comply with an individual medical prescription for a custom-made product for519

an individual patient.520

openMedicine – D3.1

Page 25 of 52 24/06/2016

These products will be included in the inventory of ‘other’ medicinal products and521

analysed furtherly. However, whole blood, plasma or blood cells of human origin are522

not reprocessed products and will not be analysed, being out of scope of the project.523

6.3. Products in scope of Directive 2001/83524

and additionally regulated525

The analysis of relevant documents has shown that there is a subgroup of products526

that are in scope of Directive 2001/83 but are additionally regulated. This subgroup527

includes the following products:528

homoeopathic medicines,529

herbal products,530

orphan products,531

products for paediatric use.532

These products will be included in the inventory of ‘other’ medicinal products and533

analysed furtherly.534

6.4. Other sources of information535

Another source of information, e.g. the document: ‘Boundary for the “Pharmaceutical536

and Biological Products” Hierarchy in the International Release of SNOMED CT® vs.537

National Extension Content’, revealed other possibilities regarding the extension of538

the list, including some other types of products not mentioned in previous chapters.539

They include:540

Food Supplements and OTC Medicines,541

nutritional Products,542

medical devices,543

nanotechnology products.544

545

6.4.1. Health Supplements546

Food Supplements – as a rule – are not considered as medicinal products. They are547

regulated separately and are included in DIRECTIVE 2002/46/EC OF THE548

EUROPEAN PARLIAMENT AND OF THE COUNCIL of 10 June 2002 on the549

approximation of the laws of the Member States relating to food supplements. Food550

supplements means foodstuffs the purpose of which is to supplement the normal diet551

and which are concentrated sources of nutrients or other substances with a552

nutritional or physiological effect, alone or in combination, marketed in dose form,553

namely forms such as capsules, pastilles, tablets, pills and other similar forms,554

sachets of powder, ampoules of liquids, drop dispensing bottles, and other similar555

forms of liquids and powders designed to be taken in measured small unit quantities.556

openMedicine – D3.1

Page 26 of 52 24/06/2016

Food supplements that are used for special medical purpose are regulated557

separately and are treated as medicinal products.558

6.4.2. Over The Counter products559

Over The Counter products are pre-packaged medicinal products and are included560

in the WP2 solution as the majority of OTC products are pre-packed branded561

medicinal products. OTC is a merely regulatory attribute. However, OTC medicinal562

products includes products that are not always pre-packed and branded, e.g.563

magistral formulas. It that case, they might have different identification needs as564

explained in chapter 7.565

6.4.3. Medical devices566

Medical devices are articles intended to diagnose, cure, treat, prevent, or mitigate a567

disease or condition, or to affect a function or structure of the body, that do not568

achieve their primary effect through a chemical action and are not metabolized.569

Medical devices are separately regulated and are in scope of COUNCIL DIRECTIVE570

93/42/EEC of 14 June 1993 concerning medical devices. These products can be571

divided into reusable drug delivery systems or non-reusable devices with an572

active substance. The first type of medical devices is out of scope of the project.573

The other type is treated as a pre-packaged branded medicinal product and is574

handled within WP2.575

6.4.4. Rx dental products576

As far as Rx dental products are concerned, they are regulated differently in577

different European countries. In some countries there are no Rx dental products (e.g.578

products that needs a prescription and are only applicable for dental treatment) in579

some other countries dental products are not considered as medicinal products but580

as cosmetics (e.g. in Spain). For that reason, these products will not be separately581

analysed.582

6.4.5. Leeches583

As far as leeches are concerned, in Europe there are no regulations regarding them.584

However, in the U.S. the Food and Drug Administration has approved medicinal585

leeches for commercial marketing, not as drugs, but as medical devices. According to586

an FDA Talk Paper, the agency announced that leeches meet the definition of587

a device because they are considered to be articles intended to diagnose, cure, treat,588

prevent, or mitigate a disease or condition, or to affect a function or structure of the589

body, that do not achieve their primary effect through a chemical action and are not590

metabolized. Leeches' primary mode of action is the eating of blood, which is591

a mechanical process. Being classified as medical devices, leeches are out of scope592

of the project.593

Taking into the consideration the above mentioned legal context, the following594

products will be furtherly analysed:595

openMedicine – D3.1

Page 27 of 52 24/06/2016

foods for special medical purpose,596

nanotechnology medicinal products.597

6.5. Inventory of ‘other’ medicinal products598

The analysis of the above included sources and the conclusions formulated in599

sections 5.1, 5.2 and 5.3, led to the development of the inventory included in table 4:600

openMedicine – D3.1

Page 28 of 52 24/06/2016

Table 4. Identified products with respect to WP in which they are discussed601

Informationsource

In scope of WP2 In scope of WP3 In scope of WP4 Out of scope of theproject

Mentioned byname in theDirective2001/83 andincluded inRegulation726/2004

biologic medicinal products

none none

medicinal productsfor veterinary useintended primarily foruse as performanceenhancers in order topromote the growth oftreated animals or toincrease yields fromtreated animals

investigational medicinalproducts

radiopharmaceuticals

medicinal products forhuman use containing a newactive substance which, onthe date of entry into force ofthis

medicinal products that aredesignated as orphanmedicinal products pursuantto Regulation (EC) No141/2000

reprocessed plasma

Excludedfrom theDirective2001/83 none

magistral formula

none

whole blood, plasmaor blood cells ofhuman originofficinal formula

radionuclides in the form ofsealed sources

openMedicine – D3.1

Page 29 of 52 24/06/2016

advanced therapy medicinalproduct, which is prepared on anonroutine basis according tospecific quality standards, andused within the same MemberState in a hospital under theexclusive professionalresponsibility of a medicalpractitioner, in order to complywith an individual medicalprescription for a custom-madeproduct for an individual patient

Mentioned byname in theDirective2001/83 andRegulation726/2004ANDadditionallyregulated

none

advanced therapy medicinalproducts

none

Not applicable

homoeopathic products

herbal medicinal products

orphan medicinal products

product for paediatric use

Mentioned inotherreferences

non-reusable drug deliverysystems

nanotechnology medicinalproducts

parenteral foods forspecial medical purposes

leeches

OTC products enteral foods for special medicalpurposes

cytotoxic compoundings Rx dental products

allergen diagnostic products health supplements

reusable drugdelivery systems

Source: own602

openMedicine – D3.1

Page 30 of 52 24/06/2016

603

openMedicine – D3.1

Page 31 of 52 24/06/2016

Table 5 includes products appropriate for WP3.604

Table 5. Inventory of ‘other’ medicinal products in scope of WP3605

Non-pre-packaged medicinal products Pre-packaged medicinal products

magistral formula

officinal formula

radionuclides in the form of sealedsources

advanced therapy MP preparedon a nonroutine basis

advanced therapy medicinal

products

foods for special medical

purposes

homoeopathic medicines

herbal medicinal products

orphan medicinal products

medicinal products for paediatric

use

nanotechnology medicinalproducts

Source: own606

The list above includes both products that can be prescribed and dispensed in607

hospital environment only and products that are also available in community608

pharmacies. The overall goal of the project is to enable cross-border identification of609

products. E-prescription aspects are key for the analysis. However, identification610

issues occur also in many other uses-cases, e.g. keeping record of medicinal611

products dispensed to a patient in his or her patient summary is also very important.612

That is why all products listed above will be analysed with respect to any possible613

identification concepts that go beyond the WP2 solution.614

The developed inventory includes both products that are pre-packaged and non-pre-615

packaged. As the overall recommendations deriving from WP2 include specifying616

a product by referring to one or more of the possible identifiers, namely: PhPID,617

MPID or PCID. The analysis will be focused on determining product618

identification level to be referred to in order to identify and describe a product619

belonging to ‘other’ medicinal products in cross-border settings no matter620

what the aim is, e.g. prescribing and dispending, developing patient summary,621

patient safety issues, etc.622

623

openMedicine – D3.1

Page 32 of 52 24/06/2016

Table 6. List of products to be considered for D3.1 and legal conditionings624

Name of product Definition (or explanation) Legal aspects Links

a) magistral formula

A pharmaceutical compound,

prepared by the pharmacist or

someone under his direction, for a

given patient according to a

prescription and following the

technical and scientific standards of

the pharmaceutical art. The product

is sold at the pharmacy to the

patient who is given the appropriate

information about the product

Judgment of the Court (Third

Chamber), 16 July 2015, in Joined

Cases C‑544/13 and C‑545/13,

ECLI:EU:C:2015:481.

http://curia.europa.eu/juris/document/docu

ment.jsf;jsessionid=9ea7d2dc30d544b0894

445c44c8a9230ebfa9d15c6e0.e34KaxiLc3

qMb40Rch0SaxuQbNj0?text=&docid=1659

10&pageIndex=0&doclang=EN&mode=lst&

dir=&occ=first&part=1&cid=387522

b) officinal formula

A pharmaceutical compound,

developed or prepared by a

pharmacist or someone under his

direction, which is listed and

described by the national formulary,

sold at the pharmacy directly to its

patients

Judgment of the Court (Third

Chamber), 16 July 2015, in Joined

Cases C‑544/13 and C‑545/13,

ECLI:EU:C:2015:481.

http://curia.europa.eu/juris/document/docu

ment.jsf;jsessionid=9ea7d2dc30d544b0894

445c44c8a9230ebfa9d15c6e0.e34KaxiLc3

qMb40Rch0SaxuQbNj0?text=&docid=1659

10&pageIndex=0&doclang=EN&mode=lst&

dir=&occ=first&part=1&cid=387522

c) radionuclides in the

form of sealed

sources

Radioactive isotopes for medical

purposes that is permanently

sealed in a capsule or closely

bonded and in a solid form.

Good Radiopharmaceutical Practice http://www.eanm.org/publications/guideline

s/index.php?navId=37

d) advanced therapy

medicinal products

Any of the following medicinal

products for human use:

-a gene therapy medicinal product

Regulation (EC) No 1394/2007 http://ec.europa.eu/health/files/eudralex/vol-

1/reg_2007_1394/reg_2007_1394_en.pdf

openMedicine – D3.1

Page 33 of 52 24/06/2016

as defined in Part IV of Annex I to

Directive 2001/83/EC,

-a somatic cell therapy medicinal

product as defined in Part IV of

Annex I to Directive 2001/83/EC,

-a tissue engineered product as

defined in point (b) of Reg (EC)

e) foods for special

medical purposes

Product intended to provide

nutrients that may otherwise not be

consumed in sufficient quantities

COMMISSION REGULATION (EC)

No 953/2009 of 13 October 2009 on

substances that may be added for

specific nutritional purposes in foods

for particular nutritional uses

and

COMMISSION DIRECTIVE

1999/21/EC of 25 March 1999 on

dietary foods for special medical

purposes

http://eur-lex.europa.eu/legal-

content/EN/TXT/HTML/?uri=CELEX:32009

R0953&from=EN

http://eur-lex.europa.eu/legal-

content/EN/TXT/PDF/?uri=CELEX:31999L0

021&from=EN

f) homoeopathic

products

Medicinal product prepared from

products, substances or

compositions called homeopathic

stocks in accordance with a

homeopathic manufacturing

procedure described by the

European Pharmacopoeia or, in

absence thereof, by the

pharmacopoeias currently used

officially in the Member States.

Directive 2001/83/EC

and

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

http://eur-lex.europa.eu/legal-

content/EN/TXT/PDF/?uri=CELEX:31992L0

073&from=EN

openMedicine – D3.1

Page 34 of 52 24/06/2016

relating to medicinal products and

laying down additional provisions on

homeopathic medicinal products

g) herbal medicinal

products

Any medicinal product, exclusively

containing as active ingredients one

or more herbal substances or one

or more herbal preparations, or one

or more such herbal substances in

combination with one or more such

herbal preparations.

Directive 2001/83/EC

and

Directive 2004/24/EC of the

European Parliament and of the

Council, amending, as regards

Traditional Herbal Medicinal

Products, Directive 2001/83/EC on

the European Union Code relating to

Medicinal Products for Human Use

h) orphan medicinal

products

A pharmaceutical agent that has

been developed specifically to treat

a rare medical condition

.

Directive 2001/83/EC

and

REGULATION (EC) No 141/2000 OF

THE EUROPEAN PARLIAMENT

AND OF THE COUNCIL of 16

December 1999 on orphan medicinal

products

http://eur-

lex.europa.eu/LexUriServ/LexUriServ.do?ur

i=OJ:L:2000:018:0001:0005:en:PDF

i) medicinal products

for paediatric use

Medicinal products for medical care

of infants, children, and

adolescents

Directive 2001/83/EC

and

REGULATION (EC) No 1901/2006

OF THE EUROPEAN PARLIAMENT

AND OF THE COUNCIL of 12

http://ec.europa.eu/health/files/eudralex/vol-

1/reg_2006_1901/reg_2006_1901_en.pdf

openMedicine – D3.1

Page 35 of 52 24/06/2016

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

Source: own625

626

openMedicine – D3.1

Page 36 of 52 24/06/2016

7. Analysis of chosen products with627

reference to the WP2 solution628

In order to validate the WP2 ISO IDMP-based solution for the identification and629

description needs of other products the following approach has been adopted. All630

available legal documents and other relevant materials included in Table 4 have631

been analysed in order to find out which identification concepts developed in the632

WP2 are applicable and if there are any other attributes / identifiers missing to633

uniquely identify and describe ‘other’ medicinal products.634

7.1. Non-pre-packaged medicinal products635

a) magistral formula636

Magistral formula is a pharmaceutical compound, prepared by the pharmacist or637

someone under his/her direction, for a given patient according to a prescription and638

following the technical and scientific standards of the pharmaceutical art. The product639

is prepared and sold at the pharmacy to the patient who is given the appropriate640

information about the product. A doctor may prescribe a medication that the641

pharmacist must prepare in-pharmacy. It is a medicine aimed at an individual patient642

and responds to the requirements of a medical prescription which includes the643

specifications of the active substances to use. It will be prepared according to the644

scientific and technical requirements of the pharmaceutical good practice. Magistral645

formulas will be prepared following the good manufacturing practices and quality646

control. They will also include the name of the pharmacist who prepared them and all647

the necessary information to allow the correct identification, correct storage, as well648

as safe use. It could be of an authorised or not authorised active substance or649

medicinal product.650

The pharmacist, along with his/her team of technicians, combines, according to651

precise instructions, the necessary ingredients to obtain the medication. This may652

consist of creams, ointments, liquids, capsules, etc. The magistral preparation of653

products is a practical way for a doctor to personalize patient treatment according to654

his/her needs. It also makes medications available in formulations that do not exist655

commercially. The magistral preparation of products complies with strict rules to656

ensure the quality of the product the patient will receive.657

Magistral formulas are dispensed on the basis of compounded prescriptions. A658

compounded prescription is an order that requires mixing of one or more ingredients659

(active medicaments) with one or more pharmaceutical necessities (vehicle,660

suspending agent). The physician selects ingredients that he/she desires and the661

pharmacist prepares the medication accordingly. The name of each drug may be662

placed on a separate line right under the preceding one.663

openMedicine – D3.1

Page 37 of 52 24/06/2016

Remedium cardinale (basis). The basis is the principal drug and gives the664

prescription its chief action.665

Remedium adjuvans (adjuvant). As the name suggests, the adjuvant is a drug666

that aids or increases the action of the principal ingredient.667

Remedium corrigens (corrective). The corrective modifies or corrects668

undesirable effects of the basic or adjuvant.669

Remedium constituens (vehicle). The vehicle is the agent used as a solvent in670

the solution, to increase the size and volume, or to dilute the mixture.671

The most potent or principal drug is written first, the other ingredient second, and the672

vehicle last, as shown in the example.673

Since the formulas are uniquely defined by the composition, the availability of one or674

the other is equivalent: Either the components, or the identifier675

Example:676

Natrii bromati (bromatis) 6,0 Rem. basis677

Phenobarbitali 0,6 Rem. adjuvans678

Sirupi Menthae 60,0 Rem. corrigens679

Aquae destillatae ad 300,0 Rem. constituens680

Misce fiat mixture (Mix to obtain mixture)681

Identification and description needs:682

This formula is described with the following attributes:683

1. Identification (Name) of the substance or product684

2. Quantity of the substance or product that MAY be stated in the prescription itself685

(already covered) or perhaps a new attribute (to be analysed in D3.2)686

3. Role of the substance or product that requires a new attribute687

4. Instructions for preparation that can be present in the prescription or perhaps a688

new attribute (to be analysed in D3.2)689

WP2 identification concept applicable: PhP and Substance dataset690

New identification concept applicable, not yet in the WP2 solution: Formulary691

ID to be added to the list of identifiers and role of the substance or products as692

a new attribute693

b) officinal formula694

openMedicine – D3.1

Page 38 of 52 24/06/2016

Officinal formula is a pharmaceutical compound, developed or prepared by695

a pharmacist or someone under his/her direction, which is listed and described by a696

formulary, sold at the pharmacy directly to its patients. The main difference between697

magistral and officinal formula is the fact that the latter is not a personalized698

treatment method and may be sold to any patient. Moreover, an officinal formula is699

a formula contained in the Pharmacopeia. They must be numbered and described by700

the national formulary. They have to be prescribed under the generic name but never701

under commercial name. They must also include the name of the pharmacist who702

prepared them and all the necessary information to allow correct identification,703

correct storage, as well as safe use.704

Noncompounded prescription or formula officinalis (officina is the Latin word for705

workshop) does not require mixing of two or more ingredients to obtain a finished706

product. A precompounded order consists of a drug or a mixture of drugs that can be707

supplied by a pharmaceutical company by its official or proprietary name and, if it708

contains more than one substance, the specific ingredients do not have to be listed.709

Whenever it happens that the formula is modified by a pharmacist due to certain710

reasons, then such medicinal products shall be treated and identified as magistral711

formula.712

Example and explanation:713

Siropus simplex (Saccharum 64,0, Aqua purificata 36,0)714

Identification and description needs:715

This formula is described with the following attributes:716

1. Identification (Name) of the substance or product717

2. Quantity of the substance or product that MAY be stated in the prescription itself718

(already covered) or perhaps a new attribute (to be analysed in D3.2)719

3. Role of the substance or product that requires a new attribute720

4. Instructions for preparation that can be present in the prescription or perhaps721

a new attribute (to be analysed in D3.2)722

5. (local / regional / global) formula ID: analysed in D3.2723

WP2 identification concept applicable: PhP and substance dataset can be used724

to identify the substance or product725

New identification concept applicable, not yet in the WP2 solution: national726

formula ID and role of the substance or products as a new attribute727

c) radionuclides in the form of sealed sources728

A radiopharmaceutical product is any medicinal product which, when ready for use,729

contains one or more radionuclides (radioactive isotopes) included for a medicinal730

purpose. Radioactive materials can be permanently sealed in a capsule or is closely731

openMedicine – D3.1

Page 39 of 52 24/06/2016

bonded and in a solid form. The capsule or material of a sealed source shall be732

strong enough to maintain leak tightness under the conditions of use and wear for733

which the source was designed, also under foreseeable mishaps. Sealed-source734

therapy, in which the radioisotope remains in a capsule or metal wire during therapy735

and is never allowed to dissolve in fluids, is usually referred to as brachytherapy.736

Brachytherapy contrasts with unsealed source radiotherapy in which a therapeutic737

radionuclide (radioisotope) is injected into the body to chemically localize to the738

tissue requiring destruction. Brachytherapy instead involves the precise placement of739

short-range radiation-sources (radioisotopes) directly at the site of the cancerous740

tumour. These are enclosed in a protective capsule or wire, which allows the ionizing741

radiation to escape to treat and kill surrounding tissue but prevents the charge of742

radioisotope from moving or dissolving in body fluids. The capsule may be removed743

later, or (with some radioisotopes) it may be allowed to remain in place744

Example:745

Commonly used radiation sources (radionuclides) for brachytherapy include:746

Radionuclide Type

Cesium-131 (131Cs) Electron Capture, ε

Cesium-137 (137Cs) β−- particles

Cobalt-60 (60Co) β−- particles

Iridium-192 (192Ir) γ-rays

Iodine-125 (125I) Electron Capture, ε

Palladium-103 (103Pd) Electron Capture, ε

Ruthenium-106 (106Ru) β−- particles

Identification and description needs:747

Both capsule (or any other material used) and the radionuclide itself should be748

identified in a unique way. For this purpose, both the name and an identifier of749

a particular radionuclide and its type shall be used. Currently, these identifiers are not750

available and are not foreseen in the WP2 solution.751

WP2 identification concept applicable: PhP dataset752

New identification concept applicable, not yet in the WP2 solution: PhP for753

radionuclides in the form of sealed sources754

7.2. Pre-packaged medicinal products755

additionally regulated756

a) advanced therapy medicinal products757

openMedicine – D3.1

Page 40 of 52 24/06/2016

As a rule, advanced therapy medicinal products are in scope of the Directive758

2001/83/EC. These products are additionally regulated by Regulation (EC) No759

1394/2007. In addition to the particulars mentioned in Article 55(2) and (3) of760

Directive 2001/83/EC, the following particulars shall appear on the immediate761

packaging of advanced therapy medicinal products:762

(a) the unique donation and product codes, as referred to in Article 8(2) of Directive763

2004/23/EC;764

(b) in the case of advanced therapy medicinal products for autologous use, the765

unique patient identifier and the statement ‘For autologous use only’.766

This requirement refers to products deriving from the same individual. In other words,767

one individual is both a donor and a recipient. It means that these products are not768

subject to the analysis as they cannot be substituted in any way and no equivalents769

can be found.770

There are also advanced therapy medicinal products which are prepared on771

a nonroutine basis according to specific quality standards, and used within the same772

Member State in a hospital under the exclusive professional responsibility of773

a medical practitioner, in order to comply with an individual medical prescription for774

a custom-made product for an individual patient. In that case, the approach is similar775

to the one used with reference to magistral formulas regarding identification issues.776

Example:777

ChondroCelect is a suspension for implantation that contains cartilage cells and is778

a type of advanced therapy medicine called a ‘tissue-engineered product’, containing779

cells or tissues that have been manipulated so that they can be used to repair,780

regenerate or replace tissue.781

Identification and description issues:782

Whenever advanced therapy medicinal products are pre-packaged branded products783

such products should have all pre-defined identifiers appropriate for products784

included in the WP2 solution in order to meet identification needs in a cross-border785

setting.786

Advanced therapy medicinal products produced on nonroutine basis dispensed in787

hospitals shall be identified by means of PhP dataset.788

WP2 identification concept applicable: PhP, MP and PC datasets (pre-packaged789

products) or PhP dataset (when subject to magistral rules).790

b) foods for special medical purposes791

The term “foods for special medical purposes” means dietary foods intended to meet792

the particular nutritional requirements of persons affected by or malnourished793

because of a specific disease, disorder or medical condition. For this reason these794

products must be used under medical supervision which may be applied with the795

assistance of other competent health professionals. In other words, dietary foods for796

openMedicine – D3.1

Page 41 of 52 24/06/2016

special medical purposes means a category of foods for particular nutritional uses797

specially processed or formulated and intended for the dietary management of798

patients and to be used under medical supervision.799

Foods for special medical purposes can be divided into enteral and parenteral800

nutrition.801

PARENTERAL - Parenteral nutrition will be dealt with in WP4802

ENTERAL - With reference to enteral nutrition products that are pre-803

packaged branded products such products the WP2 solution should be804

applicable in order to meet identification needs in a cross-border setting.805

Example:806

CARNATION® INSTANT BREAKFAST® LACTOSE FREE PLUS, Chocolate Splash,807

250 mL808

Identification and description needs:809

Foods for special medical purposes are pre-packaged branded products. It means810

that in order to meet identification needs in a cross-border setting such products811

should have all pre-defined identifiers appropriate for products included in the WP2812

solution.813

WP2 identification concept applicable: PhP, MP and PC datasets814

c) homoeopathic products815

Homoeopathic medicines are medicinal products prepared from products,816

substances or compositions called homeopathic stocks in accordance with a817

homeopathic manufacturing procedure described by the European Pharmacopoeia818

or, in absence thereof, by the pharmacopoeias currently used officially in the Member819

States. They are regulated by Directive 2001/83/EC. However, additionally, they are820

regulated by COUNCIL DIRECTIVE 92 / 73 /EEC of 22 September 1992 widening821

the scope of Directives 65 /65 /EEC and 75 /319/EEC on the approximation of822

provisions laid down by law, regulation or administrative action relating to medicinal823

products and laying down additional provisions on homeopathic medicinal products.824

The latter does not include any additional identification needs but rather explains the825

nature of homoeopathic medicines. Directive 2001/83/EC underlines that826

homoeopathic medicines must be registered and approached in a similar manner as827

‘other’ medicinal products in scope of that directive.828

Example:829

Avenoc is a homoeopathic medicine that is used to relieve minor symptoms of830

hemorrhoids and similar venous conditions due to dilated blood vessels in the rectal831

area.832

Identification and description needs:833

openMedicine – D3.1

Page 42 of 52 24/06/2016

Whenever homoeopathic medicines are pre-packaged branded products such834

products should have all pre-defined identifiers appropriate for products included in835

the WP2 solution in order to meet identification needs in a cross-border setting.836

WP2 identification concept applicable: PhP, MP and PC datasets837

Whenever homoeopathic medicines are preparations made in a pharmacy, they838

should be approached as magistral formulas (see point a) of this chapter).839

d) herbal medicinal products840

Herbal products include any medicinal product, exclusively containing as active841

ingredients one or more herbal substances or one or more herbal preparations, or842

one or more such herbal substances in combination with one or more such herbal843

preparations. Herbal products are regulated by Directive 2001/83/EC. However,844

additionally, they are regulated by Directive 2004/24/EC of the European Parliament845

and of the Council, amending, as regards Traditional Herbal Medicinal Products,846

Directive 2001/83/EC on the European Union Code relating to Medicinal Products for847

Human Use. The latter does not include any additional identification needs but rather848

refers to registration procedures that are simpler in case of herbal medicinal products849

(e.g. clinical trials are not required, etc.). This simplified registration procedure is850

intended for herbal medicinal products with a long tradition, which do not fulfil the851

requirements for a marketing authorisation, in particular those requirements whereby852

an applicant can demonstrate by detailed references to published scientific literature853

that the constituent or the constituents of the medicinal products has or have a well-854

established medicinal use with recognised efficacy and level of safety (so-called "well855

established use"). With regard to the manufacturing of these products and their856

quality, applications for registration of traditional herbal medicinal products have to857

fulfil the same requirements as applications for a marketing authorisation.858

Example:859

Peppermint oil is an essential oil obtained by steam distillation from the fresh aerial860

parts of the flowering plant.861

Identification and description needs:862

Whenever herbal medicines are pre-packaged branded products such products863

should have all pre-defined identifiers appropriate for products included in the WP2864

solution in order to meet identification needs in a cross-border setting.865

WP2 identification concept applicable: PhP, MP and PC datasets866

Whenever herbal medicines are preparations made in a pharmacy, they should be867

approached as magistral formulas (see point a) of this chapter).868

e) orphan medicinal products869

Orphan medicinal products are products including a pharmaceutical agent that has870

been developed specifically to treat a rare medical condition or valuable medicinal871

openMedicine – D3.1

Page 43 of 52 24/06/2016

products at risk to disappear from the market. These products are in scope of872

Directive 2001/83/EC. Moreover, they are additionally regulated by REGULATION873

(EC) No 141/2000 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of874

16 December 1999 on orphan medicinal products. The purpose of this Regulation is875

to lay down a Community procedure for the designation of medicinal products as876

orphan medicinal products and to provide incentives for the research, development877

and placing on the market of designated orphan medicinal products. In particular, the878

regulation refers to the procedure regarding the process of obtaining the designation879

of a medicinal product and the procedure of handling application forms by the880

Agency where the application for marketing authorisation is made. The regulation881

does not reveal any additional identification needs with respect to these products.882

Example:883

Dacogen (active substance: decitabine) is an oprhan medicinal product used in884

treatment of adult patients aged 65 years and above with newly diagnosed de novo885

or secondary acute myeloid leukaemia (AML), according to the World Health886

Organization (WHO) classification, who are not candidates for standard induction887

chemotherapy888

Identification and description needs:889

Orphan medicinal products are pre-packaged branded products such products890

should have all pre-defined identifiers appropriate for products included in the WP2891

solution in order to meet identification needs in a cross-border setting.892

WP2 identification concept applicable: PhP, MP and PC datasets893

f) products for paediatric use894

Products for paediatric use include medicinal products for medical care of infants,895

children, and adolescents. They are regulated by Directive 2001/83/EC. However,896

they are additionally regulated by REGULATION (EC) No 1901/2006 OF THE897

EUROPEAN PARLIAMENT AND OF THE COUNCIL of 12 December 2006 on898

medicinal products for paediatric use and amending Regulation (EEC) No 1768/92,899

Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004. This900

Regulation lays down rules concerning the development of medicinal products for901

human use in order to meet the specific therapeutic needs of the paediatric902

population. The regulations says that a ‘medicinal product authorised for a paediatric903

indication’ means a medicinal product which is authorised for use in part or all of the904

paediatric population and in respect of which the details of the authorised indication905

are specified in the summary of the product characteristics drawn up in accordance906

with Article 11 of Directive 2001/83/EC. The regulations refer to the procedure of907

qualifying medicinal products as products for paediatric use. However, the regulation908

does not reveal any additional identification needs with respect to these products.909

Example:910

openMedicine – D3.1

Page 44 of 52 24/06/2016

Movicol (active substances: Macrogol 3350, Sodium chloride, Sodium bicarbonate,911

Potassium chloride) is a medicinal product for paediatric use used in treatment of912

chronic constipation with children.913

Identification and description needs:914

Products for paediatric use are pre-packaged branded products such products915

should have all pre-defined identifiers appropriate for products included in the WP2916

solution in order to meet identification needs in a cross-border setting.917

WP2 identification concept applicable: PhP, MP and PC datasets918

g) narcotics919

Some products may be considered as narcotics in one country or another, or globally920

considered narcotics. These products are regulated and as such have an identifier921

that is globally recognized. They can be treated as packaged products.922

The constraints that exist on narcotics are not impacting identification, but rather923

permissions to prescribe and dispense924

Example:925

Product X (must see D1.1) is a product that is considered a narcotic in country B926

(must see D1.1). In the prescription, the physician identifies the product from its ID in927

the formulary. The dispenser identifies the product and, from his local product DB,928

realizes that the product is a narcotic, and must check with the patient or in the929

prescription if additional data is provided to justify the dispense.930

Identification and description needs:931

Narcotics are pre-packaged branded products. Such products should have all pre-932

defined identifiers appropriate for products included in the WP2 solution in order to933

meet identification needs in a cross-border setting.934

WP2 identification concept applicable: PhP, MP and PC datasets935

7.3. Identification of substances936

In some instances it is the substance that differentiates one product from another.937

A common approach including all types of substances will be included in the ISO938

IDMP solution, currently under development. It means that no matter what kind of939

product is taken into consideration, being it a herbal, homoeopathic, nanotechnology940

or advanced therapy medicinal products, the solution will provide substance941

identification. The Agency is currently developing an EMA roadmap to implement942

Substance, Products, Organisations and Referentials (SPOR) master data943

management services, which will also support the implementation of the ISO IDMP944

standards in consultation with the EU regulatory network and European945

pharmaceutical-industry associations. These include data management services for:946

openMedicine – D3.1

Page 45 of 52 24/06/2016

substance data, describing the ingredients of a medicine,947

product data, describing the marketing and medicinal information relating to a948

product,949

organisation data, providing the contact details of organisations and950

individuals responsible for various aspects of a medicine,951

referential data, providing controlled vocabularies (e.g. dosage,952

pharmaceutical forms, country codes, package codes, weight codes) for a953

medicine, which are explicitly defined for use in Europe.954

The EMA will create in collaboration with the EU Regulatory Network a target955

operating model that will ensure the unique identification of substances is in956

compliance with the ISO IDMP 11238 standard. This approach has the following957

goals:958

To develop and deploy an information system that can serve as a global959

repository for definitional, regulatory and scientific information on substances;960

To develop and distribute a global identifier for every substance in medicinal961

products and clinical trials;962

To distribute an information system for both regulators, companies and other963

interested parties to facilitate registration into the global repository.964

7.4. Gap analysis regarding ‘other’ medicinal965

products966

In the course of the analysis, it has been found that the WP2 solution is applicable for967

the majority of ‘other’ medicinal products groups identified for the sake of WP3 and968

especially D3.1. The aim of the analysis was to verify what identification concepts969

that have been developed in the WP2 solution are applicable for ‘other’ medicinal970

products. Table 7 includes the gap-analysis by showing which attributes are and / or971

will be available in future when the ISO IDMP approach is fully implemented and972

which will not be available. For the latter, the WP2 model will have to be modified in973

order to enable medicinal product cross-border identification.974

All the cases identified so far are assuming that:975

the regulators have assigned the identifiers for the products and value sets for976

the attributes.977

the different national databases have incorporated these identifiers978

the clinical documents (prescriptions, patient summaries) are able to transport979

those identifiers and attributes (all, or a subset - that remains to be decided).980

However, if a transition phase is needed between pre- and post-IDMP adoption at the981

European level, these assumptions may not apply, e.g.:982

the cross-border identifiers may not be available983

openMedicine – D3.1

Page 46 of 52 24/06/2016

the identifiers conveyed in a prescription (or other document) may not be the984

global ones.985

the attributes may not share a value set (e.g. substance codes)986

987

In T3.2 the impact of this situation will be analysed and various scenarios will be988

presented in D3.2.989

990

openMedicine – D3.1

Page 47 of 52 24/06/2016

Table 7. Gap-analysis regarding ‘other’ medicinal products in scope of WP3991

ISO IDMPPre-

packagedbrandedproducts

(WP2products)

*

WP3 products

Pro

du

ctA

ttri

bu

tes

Concept

Magistralformulas

Officinalformulas

Radionuclides in the

form ofsealedsources

Homoeopathic

medicinalproducts

Herbalmedicinalproducts

Orphanmedicinalproducts

Medicinalproducts for

paediatricuse

Nanotechnology medicinal

products

Enteral foods forspecial medical

purposes

Ph

arm

aceu

tica

lPro

du

ct

Ph

PID

PhPID Y N N N Y Y Y Y Y Y

PhP Stratum Y Y Y Y Y Y Y Y Y Y

Substance(s) Y Y Y Y Y Y Y Y Y Y

Route of Administration Y Y Y Y Y Y Y Y Y Y

Administrable Dose Form Y Y Y Y Y Y Y Y Y Y

Strength Y Y Y Y Y Y Y Y Y Y

Quantity Y Y Y Y Y Y Y Y Y Y

Units Y Y Y Y Y Y Y Y Y Y

Reference Strength Y Y Y Y Y Y Y Y Y Y

Quantity Y Y Y Y Y Y Y Y Y Y

Units Y Y Y Y Y Y Y Y Y Y

Medical Device Y Y Y Y Y Y Y Y Y Y

Unit of Presentation Y Y Y Y Y Y Y Y Y Y

Med

icin

alP

rod

uct

MP

ID

MPID Y n/a n/a n/a Y Y Y Y Y Y

Medicinal Product Name Y n/a n/a n/a Y Y Y Y Y Y

Marketing Authorization Y n/a n/a n/a Y Y Y Y Y Y

Country Y n/a n/a n/a Y Y Y Y Y Y

Holder Y n/a n/a n/a Y Y Y Y Y Y

Number Y n/a n/a n/a Y Y Y Y Y Y

Procedure ID Y n/a n/a n/a Y Y Y Y Y Y

Indication Y n/a n/a n/a Y Y Y Y Y Y

Pharmaceutical Dose form Y n/a n/a n/a Y Y Y Y Y Y

openMedicine – D3.1

Page 48 of 52 24/06/2016

Legal Status of Supply Y n/a n/a n/a Y Y Y Y Y Y

Classification Y n/a n/a n/a Y Y Y Y Y Y

Pac

kage

PC

ID

PCID Y n/a n/a n/a Y Y Y Y Y Y

Package ItemContainer Y n/a n/a n/a Y Y Y Y Y Y

Type Y n/a n/a n/a Y Y Y Y Y Y

Quantity Y n/a n/a n/a Y Y Y Y Y Y

Material Y n/a n/a n/a Y Y Y Y Y Y

AlternateMaterial Y n/a n/a n/a Y Y Y Y Y Y

Manufactured Item Y Y Y Y Y Y Y Y Y Y

ManufacturedDose Form Y Y Y Y Y Y Y Y Y Y

Unit ofPresentation Y Y Y Y Y Y Y Y Y Y

ManufacturedItem Quantity Y Y Y Y Y Y Y Y Y Y

Att

rib

ute

sin

Car

eC

on

text

Pre

scri

pti

on

Pro

du

ct

Product identification Y Y7* Y* Y* Y Y Y Y Y Y

Identifier Y Y* Y*/L Y* Y Y Y Y Y Y

Codeset Y N N/L8 N Y Y Y Y Y Y

Product Name Y N Y Y Y Y Y Y Y Y

Strength Y Y Y Y Y Y Y Y Y Y

Pharmaceutical Dose Form Y Y Y Y Y Y Y Y Y Y

Trea

tmen

t

Posology Y Y Y Y Y Y Y Y Y Y

Quantity toadminister perintake Y Y Y Y Y Y Y Y Y Y

Frequency ofintakes Y Y Y Y Y Y Y Y Y Y

Duration oftreatment Y Y Y Y Y Y Y Y Y Y

7 the field is available in the prescription and it will be shown in D3.2 what is the identifier used8 the field is available in the prescription and if here is an identifier it can be put there, but it is a local identifier

openMedicine – D3.1

Page 49 of 52 24/06/2016

TreatmentStart Y Y Y Y Y Y Y Y Y Y

Quantity to administer Y Y Y Y Y Y Y Y Y Y

Indication Y Y Y Y N Y Y Y Y Y

Route Y Y Y Y Y Y Y Y Y Y

Substitution handling Y Y Y Y Y Y Y Y Y Y

Pat

ien

tSu

mm

ary

Pro

du

ct

Active ingredient Y Y Y Y Y Y Y Y Y Y

Name Y Y Y Y Y Y Y Y Y Y

Code Y N N N Y Y Y Y Y Y

Exemption: brand name Y N N N Y Y Y Y Y Y

Strength Y Y Y Y Y Y Y Y Y Y

Pharmaceutical Dose Form Y Y Y Y Y Y Y Y Y Y

Trea

tmen

t Number of units per intake Y Y Y Y Y Y Y Y Y Y

Frequency of intakes Y Y Y Y Y Y Y Y Y Y

Duration of treatment Y Y Y Y Y Y Y Y Y Y

Treatment Start Y Y Y Y Y Y Y Y Y Y

992

993

openMedicine – D3.1

Page 50 of 52 24/06/2016

Table 8 presents the summary of the analysis of chosen products with reference to994

the WP2 solution.995

Table 8. Results of the analysis of chosen products with reference to the WP2996

solution997

Subgroup of

products

Name of the product WP2 identification

concept

applicable

Need for

extension of

WP2 model

(Yes or No)

Non-pre-

packaged

medicinal

products

a) magistral formulaSusbtance ID Yes – guidance

needed

b) officinal formulaPhPID Yes – guidance

needed

c) radionuclides in the

form of sealed sources

PhPID Yes – guidance

needed

d) advanced therapy

medicinal products

prepared in a hospital

on a nonroutine basis

PhPID Yes – guidance

needed

Pre-packaged

medicinal

products

additionally

regulated

a) advanced therapymedicinal product9

PhPID, MPID,PCID

No

b) foods for special

medical purposes

PhPID, MPID,

PCID

No

c) homoeopathicmedicines

PhPID, MPID,PCID

No

d) herbal products PhPID, MPID,

PCID

No

e) orphan products PhPID, MPID,

PCID

No

f) medicinal products for

paediatric use

PhPID, MPID,

PCID

No

Source: own998

The results of the gap analysis show that there is a need to extend the WP2 model999

with reference to the following types of products:1000

magistral formulas,1001

9 excluding the ones prepared on nonroutine basis in a hospital

openMedicine – D3.1

Page 51 of 52 24/06/2016

officinal formulas (including advanced therapy medicinal products prepared on1002

nonroutine basis in a hospital),1003

radionuclides in the form of sealed sources.1004

Other products included in the table shall be approached in the same way as1005

described in D2.2, chapter 10. Various scenarios can be taken into consideration.1006

They include both products prescribed by brand name and products prescribed by1007

generic name or INN. Due to the fact that additional legal requirements towards1008

these products does not influence their identification process and also because all1009

products attributes are included in ISO IDMP, no additional identification needs exist1010

with reference to these products. WP2 solution is fully applicable.1011

The prerequisite for the solution developed in WP2 to be working with reference to1012

the above included ‘other’ medicinal products, is meeting the requirements1013

formulated in section 4. That means, among others, that a central repository of1014

common product information must exist and that central repository should include1015

identification concepts developed in WP2. Some guidance may be needed for the1016

clinical domain, i.e. an explanation on how the clinical documents may use the1017

attributes in WP2 to convey the necessary information. For example conveying a1018

magistral formula in a prescription, not using the formula's identifier but rather the1019

components. Moreover, there should be a possibility to include other product1020

information if needed or if new types of products appear. The logic adopted regarding1021

data type, format and aggregation methods, should be similar to the one adopted in1022

the WP2 solution.1023

7.5. Conclusions1024

The conducted analysis led to formulation of the following conclusions:1025

according to the results of the gap analysis there is a need to extend the WP21026

solution with reference to products mentioned in 7.4 which will be presented in1027

D3.2,1028

if the same approach is adopted with reference to ‘other’ medicinal products1029

identified for the sake of D3.1, then the WP2 solution meets their identification1030

needs,1031

if other products determined, described and analysed in T3.1 have appropriate1032

identifiers depending on identification needs of each product and all product1033

additional data is included in the database, then the WP2 solution meets the1034

identification needs of ‘other’ medicinal products,1035

openMedicine – D3.1

Page 52 of 52 24/06/2016

product additional information, e.g. attributes should cover all specific1036

identification needs enabling distinguishing products and determining1037

individual differences between them,1038

whenever there is an attribute type missing in the product description, the1039

database should be extended in order to meet other products’ identification1040

needs.1041

Examples of various scenarios will be analysed in T3.2 and included in D3.2.1042