Draft Guidance Document · 161 Structured Product Labeling (SPL) is a Health Level Seven International (HL7) standard which 162 defines the content of human prescription drug labeling

Draft Guidance Document

Validation Rules for Product Monographs in the Extensible Markup Language Format

This guidance document is being distributed for comment purposes only.

Draft date: 2019/05/15

Validation Rules for Product Monographs in the Extensible Markup Language Format | 2

Health Canada is responsible for helping Canadians maintain and improve their health. It ensures that high‐quality health services are accessible, and works to reduce health risks.

Également disponible en français sous le titre : Ébauche de la ligne directrice : Règles de validation des monographies de produit dans le format Extensible Markup Language

© Her Majesty the Queen in Right of Canada, as represented by the Minister of Health, 2019

Publication date: May 2019

This publication may be reproduced for personal or internal use only without permission provided the source is fully acknowledged.


Foreword Guidance documents are meant to provide assistance to industry and health care professionals on how to comply with governing statutes and regulations. Guidance documents also provide assistance to staff on how Health Canada mandates and objectives should be implemented in a manner that is fair, consistent, and effective.

Guidance documents are administrative instruments not having force of law and, as such, allow for flexibility in approach. Alternate approaches to the principles and practices described in this document may be acceptable provided they are supported by adequate justification. Alternate approaches should be discussed in advance with the relevant programme area to avoid the possible finding that applicable statutory or regulatory requirements have not been met.

As a corollary to the above, it is equally important to note that Health Canada reserves the right to request information or material, or define conditions not specifically described in this document, in order to allow the Department to adequately assess the safety, efficacy, or quality of a therapeutic product. Health Canada is committed to ensuring that such requests are justifiable and that decisions are clearly documented.

This document should be read in conjunction with the accompanying notice and the relevant sections of other applicable Guidance documents.


Table of contents 1 1. Introduction ................................................................................................................................ 7 2

1.1 Purpose/overview ................................................................................................................. 7 3 1.2 Scope and application ........................................................................................................... 7 4

1.2.1 In‐scope .................................................................................................................................... 7 5 1.2.2 Out of scope ............................................................................................................................ 7 6

1.3 Policy objectives .................................................................................................................... 7 7 1.4 Policy statements .................................................................................................................. 7 8 1.5 Background ............................................................................................................................ 8 9

1.5.1 Extensible Markup Language (XML) ..................................................................................... 8 10 1.52 Health Level 7 (HL7) international ......................................................................................... 8 11 1.5.3 Structured Product Label (SPL) standard ............................................................................ 8 12 1.5.4 Structured document ............................................................................................................. 8 13

2. Guidance for implementation ..................................................................................................... 8 14

2.1 General technical conformance requirements ..................................................................... 8 15 2.1.1 Identifiers ................................................................................................................................. 8 16 2.1.2 Content changes ..................................................................................................................... 9 17 2.1.3 File type .................................................................................................................................... 9 18 2.1.4 SPL file name ........................................................................................................................... 9 19 2.1.5 External file references .......................................................................................................... 9 20 2.1.6 Codes ........................................................................................................................................ 9 21 2.1 7 Case sensitivity ........................................................................................................................ 9 22 2.1.8 Display name ........................................................................................................................... 9 23 2.1.9 Image quality ........................................................................................................................... 9 24 2.1.10 Date and time ...................................................................................................................... 10 25 2.1.11 Narrative text ...................................................................................................................... 10 26 2.1.12 General validation rules ..................................................................................................... 10 27

2.2 XML prolog .......................................................................................................................... 11 28 2.2.1 Description ............................................................................................................................. 11 29 2.2.2 XML sample ........................................................................................................................... 11 30 2.2.3 Validation rules ..................................................................................................................... 11 31

2.3 Document ............................................................................................................................ 11 32 2.3.1 Description ............................................................................................................................. 11 33 2.3.2 XML sample ........................................................................................................................... 12 34 2.3.3 Validation rules ..................................................................................................................... 12 35

2.4 Market authorization holder and importer or distributor .................................................. 13 36 2.4.1 Description ............................................................................................................................. 13 37 2.4.2 XML sample ........................................................................................................................... 13 38 2.4.3 Validation rules ..................................................................................................................... 14 39

2.5 SPL body .............................................................................................................................. 15 40 2.5.1 Description ............................................................................................................................. 15 41 2.5.2 XML sample – manufactured product section.................................................................. 16 42 2.5.3 XML sample – narrative text section.................................................................................. 16 43 2.5.4 Validation rules ..................................................................................................................... 16 44


2.6 Manufactured product ........................................................................................................ 17 45 2.6.1 Description – manufactured product code and name .................................................... 17 46

2.6.1.1 XML sample – manufactured product ............................................................... 17 47 2.6.1.2 Validation rules .................................................................................................. 22 48

2.6.2 Description – manufactured product ingredients ............................................................ 22 49 2.6.2.1 XML sample – Active Ingredient Base (ACTIB) ................................................... 22 50 2.6.2.2 XML sample – Active Ingredient Moiety (ACTIM) ............................................. 23 51 2.6.2.3 XML sample – Active Ingredient Reference (ACTIR) .......................................... 23 52 2.6.2.4 XML sample – Inactive Ingredient (IACT) ........................................................... 24 53 2.6.2.5 XML sample – Adjuvant (ADJV) .......................................................................... 24 54 2.6.2.6 Validation rules .................................................................................................. 24 55

2.6.3 Packaging ............................................................................................................................... 24 56 2.6.3.1 Description – general packaging ........................................................................ 24 57 2.6.3.2 XML sample – general packaging ....................................................................... 25 58 2.6.3.3 Validation rules – general packaging ................................................................. 25 59 2.6.3.4 Description ‐ kit .................................................................................................. 26 60 2.6.3.5 XML sample – kit ................................................................................................ 26 61 2.6.3.6 Validation rules – kit .......................................................................................... 27 62

2.6.4 Regulatory status of packaging ........................................................................................... 27 63 2.6.4.1 Description ......................................................................................................... 27 64 2.6.4.2 XML sample ........................................................................................................ 28 65 2.6.4.3 Validation rules .................................................................................................. 28 66

2.6.5 Regulatory activity and control number ............................................................................ 28 67 2.6.5.1 Description ......................................................................................................... 28 68 2.6.5.2 XML sample ........................................................................................................ 28 69 2.6.5.3 Validation rules .................................................................................................. 29 70

2.6.6 Regulatory status of the manufactured product .............................................................. 29 71 2.6.6.1 Description ......................................................................................................... 29 72 2.6.6.2 XML sample ........................................................................................................ 29 73 2.6.6.3 Validation ........................................................................................................... 30 74

2.6.7 Product characteristics ........................................................................................................ 30 75 2.6.7.1 XML sample – characteristics ............................................................................ 31 76 2.6.7.2 Validation ........................................................................................................... 33 77

2.6.8 Route of administration ....................................................................................................... 33 78 2.6.8.1 Description ......................................................................................................... 33 79 2.6.8.2 XML sample ........................................................................................................ 33 80 2.6.8.3 Validation ........................................................................................................... 33 81

2.7 Narrative text sections ........................................................................................................ 33 82 2.7.1 General ................................................................................................................................... 33 83

2.7.1.1 Formatting ......................................................................................................... 34 84 2.7.1.2 Symbols and special characters ......................................................................... 34 85


2.7.1.3 Footnotes ........................................................................................................... 35 86 2.7.1.4 Lists .................................................................................................................... 35 87 2.7.1.5 Tables ................................................................................................................. 36 88 2.7.1.6 Hypertext links ................................................................................................... 37 89 2.7.1.7 Recent major label changes ............................................................................... 37 90 2.7.1.8 XML sample ........................................................................................................ 38 91 2.7.1.9 Validation rules – narrative text ........................................................................ 38 92

2.7.2 Images .................................................................................................................................... 39 93 2.7.2.1 Description ......................................................................................................... 39 94 2.7.2.2 Validation rules .................................................................................................. 40 95

2.7.3 Title page ................................................................................................................................ 40 96 2.7.3.1 Description ......................................................................................................... 40 97 2.7.3.2 XML sample ........................................................................................................ 40 98 2.7.3.3 Validation rules .................................................................................................. 42 99

2.7.4 Recent major changes .......................................................................................................... 42 100 2.7.4.1 Description ......................................................................................................... 42 101 2.7.4.2 XML sample ........................................................................................................ 42 102 2.7.4.3 Validation rules .................................................................................................. 42 103

3. Appendices ................................................................................................................................ 43 104

3.1 Appendix A – glossary ......................................................................................................... 43 105 3.2 Appendix B – references ..................................................................................................... 43 106

107


1. Introduction 108 1.1 Purpose/overview 109 To provide sponsors with detailed technical guidance on the XML hierarchy, technical 110 conformance rules and technical validation rules needed to prepare a valid XML product 111 monograph in compliance with the HL7 SPL standard. 112

1.2 Scope and application 113 1.2.1 In‐scope 114

Human pharmaceutical drugs, biologic drugs and radiopharmaceuticals, regulatory activities 115 submitted in electronic format: Electronic Common Technical Document (eCTD) or non‐eCTD 116 format. 117

1.2.2 Out of scope 118

Over the counter (non‐prescription) drugs, self‐care products, natural health products, medical 119 devices, food and veterinary drugs. 120

1.3 Policy objectives 121 In recent years Health Canada announced a number of measures that will be taken to support 122 the health and safety of Canadian families, one of which is improving drug product labels. As 123 part of the HPFB’s strategic plan, the goal is to: 124

Provide more relevant and easier to understand drug information on labels, in order to 125 help Canadians make better informed decisions about their medications; and 126

Encourage the adoption of digital health technology to improve access, increase 127 efficiency, and improve outcomes for patients. 128

As part of this initiative, the HPFB recognized that unstructured formats, like Portable 129 Document Format (PDF), are not adequately positioned to support the objectives mentioned 130 above. We will therefore need to transition to more advanced technology formats. Particular 131 attention will be focused on formats that are open source and supported by international 132 standards. 133

One such format is XML; a markup language used to encode documents in a structured format 134 that is both human‐readable and machine‐readable. Since it is an open standard, XML is a 135 widely used format for exchanging electronic documents and data. 136

With respect to international standards, the HPFB aims to align its use of XML with other 137 international regulators, HL7 standards and the International Organization for Standardization 138 (ISO) standard for the Identification of Medicinal Product (IDMP). 139

1.4 Policy statements 140 This guidance document defines the validation rules for the Health Product and Food Branch’s 141 (HPFB) structured product monograph; which is based on XML, HL7’s SPL standard and 142 controlled vocabularies. 143


This guidance document is to be used in the preparation and filing of product monographs in 144 the XML format and is to be read in conjunction with the Guidance Document Preparation of 145 Product Monographs in the Extensible Markup Language Format. 146

1.5 Background 147 1.5.1 Extensible Markup Language (XML) 148

XML is a text‐based markup language used to encode electronic documents in a structured 149 format that is both human and machine‐readable. XML is used as a common format to facilitate 150 the interchange of data over the Internet. 151

XML is a free open standard maintained by the World Wide Web Consortium (W3C). 152

1.52 Health Level 7 (HL7) international 153

Founded in 1987, HL7 is a not‐for‐profit standards development organization dedicated to 154 providing standards for the exchange of electronic health information that supports clinical 155 practice and the management of health services. 156

Healthcare providers, government stakeholders, payers, pharmaceutical companies, 157 vendors/suppliers, and consulting firms support HL7. 158

Health Canada is contributing member of HL7. 159

1.5.3 Structured Product Label (SPL) standard 160

Structured Product Labeling (SPL) is a Health Level Seven International (HL7) standard which 161 defines the content of human prescription drug labeling in an XML format. In the Canadian 162 context, the product monograph is the ‘label’ or ‘the document’ that is being structured. 163

1.5.4 Structured document 164

In this context, structure refers to the fact that the product monographs content has been 165 encoded with XML; i.e., the content has been ‘marked up’ with XML to make it machine‐166 readable. As a result, the narrative text (e.g., section headings, all text and tables) and product 167 information (e.g., manufacturer, ingredients, dosage forms and packaging) are encoded and can 168 be found easily through search. 169

2. Guidance for implementation 170 2.1 General technical conformance requirements 171 2.1.1 Identifiers 172

Unless stated otherwise (e.g., Hyperlink Identifier (ID) or Observation Media ID), identifiers shall 173 be Globally Unique Identifiers (GUID). This includes but is not limited to the following: 174

• Document Root ID 175 • ID 176 • SetId 177 • Section ID 178


GUID’s should follow the canonical structure, content and formatting rules; e.g., displayed in 179 five groups separated by hyphens, in the form 8‐4‐4‐4‐12 for a total of 36 characters (32 180 alphanumeric characters and four hyphens). 181

It is the sponsor’s responsibility to ensure that there are no collisions between identifiers. 182

2.1.2 Content changes 183

Changing the content of a subsection requires both the section@ID and the 184 effectiveTime@value of the subsection to be updated. The effectiveTime and the section@ID of 185 any ancestor sections must also be updated. 186

2.1.3 File type 187

Only file formats detailed in the table below are permitted in the SPL output: 188

Table 1: List of acceptable file types 189

File Format Description Specifications Extension JPEG/JFIF Joint Photographic Experts Group (JPEG) / JPEG File

Interchange Format (JFIF) is a compression standard for encoding and exchanging still digital raster files.

ISO 10918‐1 jpg

XML Extensible Markup Language (XML) is a markup language that defines document encoding rules.

W3C XML 1.0 xml

2.1.4 SPL file name 190

The SPL content (e.g., xml and images) must always be placed in a single SPL folder. 191

The .xml file must be named with GUID from the documentID. 192

It is the sponsor’s responsibility to ensure there are no content naming collisions between any 193 of the files in the SPL folder. 194

2.1.5 External file references 195

All files associated with the SPL document are referenced in the .xml. 196

2.1.6 Codes 197

There are no spaces in codes. 198

2.1 7 Case sensitivity 199

There is no general case sensitivity rule. 200

2.1.8 Display name 201

All display names are language specific. When derived from a controlled vocabulary the display 202 name shall match the language of the document; e.g., French display name for a French 203 document and English display names for English documents. 204

2.1.9 Image quality 205

All images will be displayed as is without transformation or modification. Therefore, images 206 shall be of sufficient quality and size to be legible by end users. 207


2.1.10 Date and time 208

Time values (such as effectiveTime@value, effectiveTime.low@value and 209 effectiveTime.high@value) are based on ISO‐8601. They use the following format 210 YYYYMMDDHHMMSS+”GMT offset”. 211

All values other than the + symbol are integers; the time aspect is based on a 24hr notation; 212 and, unless specified otherwise, use the Time Zone offset assumed to be GMT time. 213

YYYY represents the year and is 4 digits; MM represents the month and is 2 digits; DD 214 represents the day and is 2 digits; HH represents the hour and is 2 digits; MM represents the 215 minutes and is 2 digits; SS represents the seconds and is 2 digits. 216

The time may be followed by a + (plus) or a ‐ (minus) symbol and a Time Zone offset from GMT 217 expressed as 4 digits. While the ISO standard provides many options the HPFB only allows for 218 the following three permutations on time values: 219

1. Date Only: in this model the string is limited to YYYYMMDD. 220 2. Date and GMT Time: in this model the string is limited to YYYYMMDDHHMMSS. 221 3. Date and Local Time: in this model the GMT offset is added as an example 222

YYYYMMDDHHMMSS‐0500 represents EST. The offset is static and therefore must be 223 manually adjusted for Daylight Saving Time as appropriate. 224

2.1.11 Narrative text 225

No text (i.e., ) is to appear immediately under the 226 following major section headings. 227

• Title Page 228 • Part I: Health Professional Information 229 • Part II: Scientific Information 230 • Part III: Patient Medication Information 231

With respect to the above mentioned section headings, text can only appear under the sub‐232 headings; e.g., text cannot appear immediately under Part I but text is meant to appear under 233 section 1 Indications. 234

Text is meant to appear directly under the Recent Major Changes section heading. 235

2.1.12 General validation rules 236

1. XML is well formed and valid against the schema 237 2. There are no data elements and attributes in addition to those described in this 238

document 239 3. There are no spaces in codes 240 4. Codes must have a codeSystem name attribute 241 5. Display names are case insensitive 242 6. There are no spaces in id extensions 243 7. Letters in Globally Unique Identifiers (GUID) are lower case 244 8. There are no empty or incomplete elements 245 9. Characteristics have no class code at all 246 10. There are no confidentiality codes 247


2.2 XML prolog 248 2.2.1 Description 249

The XML version, character encoding, the schema and the location of the schema. 250

2.2.2 XML sample 251

252 255 258 262

2.2.3 Validation rules 263

1. XML reference is for version 1.0 and encoding “UTF‐8”. 264 2. There is an xml‐stylesheet reference to 265

https://github.com/HealthCanada/HPFB/blob/master/Structured‐Product‐Labeling‐266 (SPL)/Style‐Sheets/current/hpfb‐spm.xsl 267

3. The schemaLocation of the urn:hl7‐org:v3 namespace is provided as 268 “https://github.com/HealthCanada/HPFB/blob/master/Structured‐Product‐Labeling‐269 (SPL)/Schema/current/SPL.xsd” 270

4. There are no processing instructions other than the xml and xml‐stylesheet declarations. 271 5. There are no comments. 272 6. SPL file name is the document id GUID followed by “.xml”. 273 7. A submission contains only the SPL file whose name ends in ‘.xml’ and, if appropriate, 274

associated image files whose names end in '.jpg'. 275 8. All image files associated with the SPL document are referenced in the .xml. 276

2.3 Document 277 2.3.1 Description 278

Provides general information about the overall document: 279

• The templateId extension specifies the regulatory activity associated with this version of 280 the product monograph. 281

• The is a GUID and is unique for each version of the document. Letters used in a 282 GUID are lower case. 283

• The is the HPFB code that specifies the document type. 284 • The data element is used for the title for the product monograph. 285


• Images are not included in the title. 286 o Multiple lines may be used in the title with each line separated by a line break 287

tag. 288 • The specifies the Date of Last Revision for this version. 289 • The specifies the Date of Initial Approval. 290 • The is the HPFB code that specifies the language of the document. 291 • The is a GUID and is a unique identifier for the document that remains constant 292

through all versions/revisions of the document. 293 • The is an integer greater than zero that specifies the version of the 294

document. 295


297 298 299 302

"Scheduling Symbol" "Brand Name" "Proper name" "Dosage Form(s), 303 Strength(s) and Route(s) of Administration" "Pharmaceutical Standard, "Pharmaceutical 304 Standard, "Pharmaceutical Standard" "Therapeutic Classification" 305

306 307 20170101 308 309 311 312 313


1. There is a document id. 315 2. id root is a Globally Unique Identifier (GUID). 316 3. id does not have an extension. 317 4. id does not match any other id in the document. 318 5. There is a code for document type from the code system is 2.16.840.1.113883.2.20.6.10 and 319

the display name matches the code. 320 6. There are no images in the title. 321 7. There is an effective time with at least the precision of day in the format YYYYMMDD. 322 8. There is an original text description with at least the precision of day in the format 323

YYYYMMDD. 324 9. There is a code for language from the code system 2.16.840.1.113883.2.20.6.29 and the 325

display name matches the code. 326 10. There is a set id. 327


11. The set id is a GUID. 328 12. There is a version number. 329 13. Value of version number is a whole number > 0. 330

2.4 Market authorization holder and importer or distributor 331 2.4.1 Description 332

Provides the company name, address and contact information for the market authorization 333 holder associated with this document. If applicable, the company name, address and contact 334 information for the Canadian importer or distributor will be specified as well. 335

• The is the HPFB code that specifies the company ID for the 336 market authorization holder. 337

• is the HPFB code that specifies the company ID for the Canadian 338 importer or distributor. 339


341 … 342 343 344 345 346 347 Market Authorization Holder Inc 348 349 350 256 Lanark Drive 351 Ottawa 352 Ontario 353 a1a 2a2 354 356 357 358 359 360 Market Authorization Holder Inc 361 362 363 364 365 366 Importer Inc 367 368 369


257 Lanark Ave 370 Ottawa 371 Ontario 372 a2a 1a1 373 374 375 376 377 378 Importer Inc 379 380 381 382 383 384 385 386


1. One id is a company code from the code system 2.16.840.1.113883.2.20.6.31 and the 388 display name matches the code. 389

2. There is a name. 390 3. There is an address with street address line, city, province and country. 391 4. The country code is from the code system 2.16.840.1.113883.2.20.6.17 and the display 392

name matches the code. Country is a full country name. 393 5. If the country is “Canada”, then the contact party’s address has a province (2‐letter 394

abbreviation) and has a postal code. 395 6. If the country is “Canada”, then there is a postal code as a 6 digit alpha numeric number in 396

the format “A1A 1A1” with a space separating the third and fourth characters. There is no 397 hyphen. 398

7. There is a postal code. 399 8. There are two elements. 400 9. One telecom value begins with “tel:” and is a telephone number based on the following 401

rules: 402 a. telephone numbers are global telephone numbers; 403 b. telephone numbers contain no letters or spaces; 404 c. telephone numbers begin with “+”; 405 d. include hyphens to separate the country code, area codes and subscriber number; 406 e. have any telephone number extensions separated by “;ext=”; 407 f. If there is a semicolon in the telephone number, then it is followed by ext. 408

10. One telecom value begins with “mailto:” and encodes an email address in the format 409 @. 410


11. The value matches the value; i.e., the contact person value and 411 the company name value are the same. 412

2.5 SPL body 413 2.5.1 Description 414

The body of the SPL document includes structured components for the manufactured 415 product(s) and the narrative text sections of the product monograph (e.g., Title Page, Part I: 416 Health Professional Information, Part II: Scientific Information and Part III: Patient Medication 417 Information). 418

Sections and subsections have id, title, and code. HPFB codes are used for sections and 419 subsections codes. 420

The of the sections and subsections and order of the sections and subsections in the SPL 421 are used to render the product monograph contents. The numbering for the sections and 422 subsections are included in the display name of each section or subsection. 423

In the SPL schema, the element contains multiple s, and each 424 contains a . 425

Sections are used to aggregate paragraphs into logical groupings. The order in which sections 426 appear in an SPL document is the order the sections will appear when displayed (rendered) 427 using the standard HPFB stylesheet. Major sections are defined by the Guidance Document 428 Product Monograph and the product monograph templates associated with the relevant 429 product type; e.g., the 2016 Product Monograph Template – Schedule D defines the major 430 product monograph section headings for a biologic. 431

Sections that have not been assigned a specific HPFB code are assigned the HPFB code for “SPL 432 Unclassified Section”. 433

Each section has a unique identifier (), an , and a HPFB code (i.e., the 434 element). A section may or may not contain a . 435

The human readable content of the product monograph is contained within the element 436 in the . The can be nested to form sub‐sections. The schema for subsections 437 in SPL requires that the nested tag first be nested inside a tag. Use 438 nested sections to relate paragraphs. The section tag applies to all of the nested sections. By 439 nesting sections, computer systems can use the section tags in SPL to display information useful 440 for the care of patients. If information is not associated with the tag, it will not be displayed. 441

Using the following principles for markup of text information improves access to information in 442 the product monograph: 443

• Capture the section heading using the element rather than placing the text of the 444 title within the element. This allows computer systems to use and display this 445 information properly. 446

• Link different parts of the product monograph using the ID attribute to the 447 element. For example,


'reference' the section entirely, e.g., for retrieval of a whole section in a non‐browser 450 interface. 451

• Separate the text and images for each concept using tags. 452

2.5.2 XML sample – manufactured product section 453

454 … 455 456 457 458 459 460 463

464 465

2.5.3 XML sample – narrative text section 466

467 … 468 469 470 471 472 Title Page 473 474 "Scheduling Symbol" "Brand Name" "Proper name" "Dosage 475 Form(s), 476 Strength(s) and Route(s) of Administration" "Pharmaceutical Standard, "Pharmaceutical 477 Standard, "Pharmaceutical Standard" "Therapeutic Classification" 478 479 480 481 482 483


1. Each section has zero to many subsections. 485 2. Each section and subsection has an id root and no extension. 486 3. id root (section id) is a GUID. 487 4. id does not match any other id in the document. 488 5. id (section id) does not match any other id across all sections. 489


6. Each section and subsection has a code from the code system 2.16.840.1.113883.2.20.6.8 490 and the display name matches the code. 491

7. Each section has an effective time with at least the precision of day in the format 492 YYYYMMDD. 493

8. There are no figures in the title for a section or subsection. 494

2.6 Manufactured product 495 2.6.1 Description – manufactured product code and name 496

Provides information about the manufactured product(s) associated with this product 497 monograph. This includes: 498

• The is the Drug Identification Number (DIN) for this manufactured product. 499 • The is the proprietary name or brand name for this manufactured product. 500 • The is the manufactured dosage form of the manufactured product. 501 • The is the non‐proprietary name for 502

this manufactured product. 503

2.6.1.1 XML sample – manufactured product 504

505 506 507 508 509 510 512 513 514 515 516 518 Product#1 519 522

523 524 International Nonproprietary Name 525 526 527 528 529 530


531 532 533 535 ingredient#1 ‐ base 536 537 538 540 ingredient#2 ‐ moiety 541 542 543 544 545 547 ingredient#3 ‐ referenced as basis of strength 548 549 550 551 552 553 554 556 ingredient#4 557 558 559 560 561 562 563 564 565 567 569 570 571 572 574 575


576 577 578 579 580 581 582 583 584 585 587 588 589 P 590 591 593 594 595 596 597 598 599 600 602 603 604 605 606 607 608 609 610 611 613 616 biologic 617 618 619 620


621 622 624 627 light blue 628 629 630 631 632 633 635 638 shape 639 640 641 642 643 644 645 646 647 648 649 650 652 653 654 655 656 657 659 value 660 661 662 663 664


666 667 new almond 668 669 670 671 672 673 675 676 677 678 679 680 681 682 684 686 687 688 689 690 692 694 695 696 697 698 700 703 704 705 706 707 709


710 711 712 713 714 715

2.6.1.2 Validation rules 716

1. There is a code representing the DIN with the code system 2.16.840.1.113883.2.20.6.42. 717 2. There is a proprietary name. 718 3. There is a formCode with the code system 2.16.840.1.113883.2.20.6.3. Display name 719

matches the code. 720 4. There is a non‐proprietary name. 721 5. There is a approval with the code system 2.16.840.1.113883.2.20.6.11. Display name 722

matches the code. 723

2.6.2 Description – manufactured product ingredients 724

Information about the ingredients in this manufactured product. 725

• is the ingredient information based on role (active, inactive or adjuvant), 726 strength, ingredient code and ingredient name. 727

• The is the packaging information based on pack code, quantity, pack type 728 and regulatory status of the packaging. 729

• The is the regulatory activity associated with this manufactured 730 product based on the control number, regulatory activity type and country. 731

• The is the regulatory status for this manufactured product 732 • The are the characteristics of this manufactured product; 733

i.e., Shape, size, score, imprint, flavour, image, pharmaceutical standard, scheduling 734 symbol, therapeutic class. 735

• The is the route of 736 administration for this product. 737

2.6.2.1 XML sample – Active Ingredient Base (ACTIB) 738

739 740 741 742 743 744 745 ingredient#1 ‐ base 746 747 748 750


ingredient#2 ‐ moiety 751 752 753 754 755

2.6.2.2 XML sample – Active Ingredient Moiety (ACTIM) 756

757 758 759 760 761 762 763 ingredient#1 ‐ base 764 765 766 768 ingredient#2 ‐ moiety 769 770 771 772 773

2.6.2.3 XML sample – Active Ingredient Reference (ACTIR) 774

775 776 777 778 779 780 782 ingredient#1 ‐ base 783 784 785 787 ingredient#2 ‐ moiety 788 789 790 791 792 793


ingredient#3 ‐ referenced as basis of strength 794 795 796 797 798

2.6.2.4 XML sample – Inactive Ingredient (IACT) 799

800 801 803 ingredient#4 804 805 806

2.6.2.5 XML sample – Adjuvant (ADJV) 807

808 809 810 ingredient#1 ‐ base 811 812 813


1. There is a class code with the code system 2.16.840.1.113883.2.20.6.39 (ingredient role). 815 Display name matches the code. 816

2. There is a strength with a numerator and denominator if the ingredient role is ACTIB, ACTIM 817 or ACTIR. 818

3. Numerator and denominator have a value greater than zero and a unit. 819 4. Unit comes from the code system 2.16.840.1.113883.2.20.6.15 (units of measure). 820 5. For percentages numerator unit is not 1, instead use a volume unit for volume fractions and 821

a mass unit for mass fractions. 822 6. The denominators values and units for all ingredients in this product are the same. 823 7. There is an ingredient code from the code system 2.16.840.1.113883.2.20.6.14 (ingredient 824

id). 825 8. The same ingredient code is not used more than once per product. 826 9. There is an ingredient name. Name matches the code display name. 827

2.6.3 Packaging 828

2.6.3.1 Description – general packaging 829

The packaging includes the quantity of product in the package and the package type, along with 830 all packaging aspect that make up the package (such as inner packages). 831


Packaging is represented as a quantity, a product ID if applicable and a package type. The 832 quantity aspect is represented as a numerator and denominator along with a unit of measure 833 and packaging type. The Units of Presentation code (the numerator) is derived from OID: 834 2.16.840.1.113883.2.20.6.15, while the Packaging Type code (the denominator) is derived from 835 OID: 2.16.840.1.113883.2.20.6.32. 836

2.6.3.2 XML sample – general packaging 837

838 839 840 841 842 843 845 846 847 848 849 850 851 852 853 854 855 856 857 858

2.6.3.3 Validation rules – general packaging 859

1. A product may have an “as content” (package information) element. 860 2. Quantity (for package information) includes a numerator and denominator. 861 3. Numerator (for package amount) has a value greater than zero and a unit. 862 4. If the product has parts, then the initial numerator value and unit is “1”. 863 5. Unit of the numerator (for package amount) of the initial package is the same as the units 864

for the denominators of all the ingredient quantities (strengths). 865 6. Unit of the numerator (for package amount) of an outer package is the same as the unit for 866

the denominator of the quantity of the inner package. 867 7. Denominator has value 1 and either no unit or unit “1”. 868 8. There is a pack type code from the code system 2.16.840.1.113883.2.20.6.32 and the 869

display name matches the code. 870 9. There is a package item code with code and code system 2.16.840.1.113883.2.20.6.56. 871


10. If the package item code is mentioned elsewhere in the document, then the package type 872 code and quantity value and unit are the same. 873

11. Package type code does not match any other package item code in the same package 874 hierarchy. 875

2.6.3.4 Description ‐ kit 876

When products have more than one part, each part is described under . 877 Currently, when a drug product has parts, it is considered a Kit indicated by the formCode for 878 KIT. Products may be combined in various ways such as: 879

• Drug kit with a device part. 880 • Drug in a delivery device. 881

2.6.3.5 XML sample – kit 882

883 884 885 name of kit 886 887 888 889

890 891 892

893 894

895 name of drug part 896 898 899 900

901 902 903

904 905

907

909

910 911

912 913


914 915

916 917

918 919

921

name of part 922 description of device part 923 924

925 927 928

929 930 931

2.6.3.6 Validation rules – kit 932

1. If the pack type is Kit, then there is one or more parts. 933 2. Each part has an overall quantity. 934 3. If there is an “as content” (packaging) data element in the part, then the numerator unit is 935

the same as the numerator unit for the “as content” data element. 936 4. If there is no “as content” (packaging) data element in the part, then the numerator unit is 937

1. 938 5. There is a code and code system is 2.16.840.1.113883.2.20.6.56. 939 6. There is a name. 940 7. Procedures for ingredients, characteristics and packaging are the same as for products 941

without parts. 942

2.6.4 Regulatory status of packaging 943

2.6.4.1 Description 944

The marketing status provides information on when the product is on or off the market. 945

The indicates the regulatory status. The status of the product is described in the 946 using the appropriate HPFB status code. The status specifies when the product is 947 available on the market or no longer available on the market. 948

The is used to capture the Date of Initial Approval and the date the DIN was 949 cancelled. Effective time low value is the date when the original Notice of Compliance was 950 issued. Effective time high is the date when the DIN was cancelled. 951


2.6.4.2 XML sample 952

953 954 955 956 957 958 960 961 962 963 964 965 966 967 968 969 970 971 972 973


1. There is not more than one regulatory status on any one item. 975 2. Regulatory status code is from the code system 2.16.840.1.113883.2.20.6.37 and the display 976

name matches the code. 977 3. If the status code is Approved, then there is a low value (marketing start date) and no high 978

value (marketing end date). 979 4. If the marketing status code is Cancelled, then there is a low and high value. 980 5. The effective time low and effective time high have at least the precision of day in the 981

format YYYYMMDD. 982 6. If there is an effective time high value, then it is not less than the low value. 983

2.6.5 Regulatory activity and control number 984


The structure specifies the regulatory activity and, if applicable, the control number 986 under which the product is approved. The control number is captured in the . 987

2.6.5.2 XML sample 988

989 990 991


992 993 P 994 995 996 997 998 999 1000 1001


1. There is one marketing category for every product and product part. 1003 2. There is a regulatory activity code from the code system 2.16.840.1.113883.2.20.6.11 and 1004

the display name matches the code. 1005 3. Territorial authority is the code for Canada from the code system 1006

2.16.840.1.113883.2.20.6.17 and the display name matches the code. 1007

2.6.6 Regulatory status of the manufactured product 1008


The indicates the activity of “marketing” (or in cases of some packages as “marketing of 1010 sample packages not for sale”). The status of the product is described in the as 1011 either “active” for being on the market or “completed” when marketing is done the product is 1012 no longer going to be available on the market. The date when the product is on or off the 1013 market is included in the . The date when the product is on the market is 1014 characterized by the . 1015

The date off the market such as the expiration date of the last lot released to the market is 1016 characterized by the . 1017

2.6.6.2 XML sample 1018

1019 1020 1021 1022 1023 1024 1025 1026 1027 1028


2.6.6.3 Validation 1029

1. There is not more than one regulatory status on any one item. 1030 2. Regulatory status code is from the code system 2.16.840.1.113883.2.20.6.37 and the display 1031

name matches the code. 1032 3. If the status code is active or new, then there is a low value (marketing start date) and no 1033

high value (marketing end date). 1034 4. The effective time low value (Notice of Compliance date) and high value (DIN Cancellation 1035

date) have at least the precision of day in the format YYYYMMDD. 1036 5. If the regulatory status code is approved, dormant or marketed, there is only a low value. 1037 6. If the regulatory status code is cancelled, then there is a low and high value. 1038

2.6.7 Product characteristics 1039

Product characteristics include a range of items that includes: the scheduling symbol, the 1040 therapeutic class, pharmaceutical standard, colour, score, shape, size, imprint and image 1041 flavour. 1042

Characteristic value types are as follows: 1043

• Physical Quantity (PQ): A dimensioned quantity expressing the result of measuring. 1044 • Integer Number (INT): Integer numbers (‐1,0,1,2, 100, 3398129, etc.) are precise 1045

numbers that are results of counting and enumerating. Integer numbers are discrete, 1046 the set of integers is infinite but countable. No arbitrary limit is imposed on the range of 1047 integer numbers. Two NULL flavors are defined for the positive and negative infinity. 1048

• Interval (IVL): A set of consecutive values of an ordered base data type. 1049 • Interval of Physical Quantities (IVL_PQ): A range of physical quantity can either be 1050

expressed using "low" and "high" child elements to define the bounds of the interval (if 1051 only one of these is sent, then the other is assumed to be unbounded), or by sending 1052 the "center" element to express a single quantity instead of a range. The IVL_PQ flavour 1053 is used when there is a single value in an attribute that is able to contain an interval of 1054 quantity values. This is equivalent to Quantity in Standard Units. 1055

• Coded Value (CV): Coded data, specifying only a code, code system, and optionally 1056 display name and original text. Used only as the type of properties of other data types. 1057

• Coded with Equivalents (CE): Coded data that consists of a coded value and, optionally, 1058 coded value(s) from other coding systems that identify the same concept. Used when 1059 alternative codes may exist. 1060

• Character String (ST): The character string data type stands for text data, primarily 1061 intended for machine processing (e.g., sorting, querying, indexing, etc.) Used for names, 1062 symbols, and formal expressions. 1063

• Encapsulated Data (ED): Data that is primarily intended for human interpretation or for 1064 further machine processing outside the scope of HL7. This includes unformatted or 1065 formatted written language, multimedia data, or structured information in as defined by 1066 a different standard (e.g., XML‐signatures.) Instead of the data itself, an ED may contain 1067 only a reference (see TEL.) Note that ST is a specialization of the ED where the 1068 mediaType is fixed to text/plain. 1069


• Boolean (BL): BL stands for the values of two‐valued logic. A BL value can be either true 1070 or false, or, as any other value may be NULL. 1071

2.6.7.1 XML sample – characteristics 1072

1073 1074 1075 1078 biologic 1079 1080 1081 1082 1083 1084 1085 1088 light blue 1089 1090 1091 1092 1093 1094 1095 1098 shape 1099 1100 1101 1102 1103 1104 1105 1106 1107 1108 1109 1110 1111 1112 1113


1114 1115 1116 1117 value 1118 1119 1120 1121 1122 1123 1124 new almond 1125 1126 1127 1128 1129 1130 1131 1132 1133 1134 1135 1136 1137 1138 1140 1142 1143 1144 1145 1146 1148 1150 1151 1152 1153 1154 1156 1158


1159 1160


1. There is a characteristic code from the code system 2.16.840.1.113883.2.20.6.23 and the 1162 display name matches the code. 1163

2. There is a characteristic value code from the corresponding code system and the display 1164 name matches the code. 1165

3. The characteristic value code is compliant with the specified value typev. 1166 4. Value type is PQ, INT, IVL_PQ, CV, CE, ST, ED, or BL. 1167

2.6.8 Route of administration 1168


The route of administration for the product. 1170

2.6.8.2 XML sample 1171

1172 1173 1174 1175 1176


1. There is a route of administration code from the code system 1178 2.16.840.1.113883.2.20.6.7 and the display name matches the code. 1179

2.7 Narrative text sections 1180 2.7.1 General 1181

The narrative text that makes up the Title Page, Part I: Health Professional Information, Part II: 1182 Scientific Information and Part III: Patient Medication Information. 1183

The human readable text content of the document is contained within the element. The 1184 actual content is contained within a , , and/or . 1185

• If a section consists only of nested sections, the tag is not included. 1186 • Elements that can be used within the element to capture the human readable 1187

content include paragraphs (), lists (), tables () and images 1188 (). 1189

• Elements permitted as children of the element, used as children of the 1190 element or within and include superscripts (), 1191 subscripts (), links (), line breaks (
), footnotes (), 1192 footnote references (). 1193

• Images may be included in the content of labeling using the tag. 1194 This tag may be used as a direct child of for ‘block’ images or as a child of 1195 for inline images. 1196


2.7.1.1 Formatting 1197

There are certain aspects of the content that must be specified in the source to insure that the 1198 content of labeling is formatted correctly when rendered, as an example: 1199

1200 1201

The next snippet will appear as bold italics in the 1202 rendering. 1203

1204

1205

Will be rendered as: The next snippet will appear as bold italics in the rendering. 1206

The can be nested, for example: 1207

1208 1209 bold italics 1210 1211 But it can also be represented as: 1212 1213 1214 bold italics. 1216 1217

Both of the above will appear as bold italics 1218

The values for for font effect are bold, italics and underline. To assist people who 1219 are visually impaired, the is used to prompt computer screen reader 1220 programs to emphasize text such as a box warning. The bold, italics and underline font effects 1221 may be used together with each other and the emphasis styleCode. For example: 1222

1223 1224 1225 1226

Will appear as bold and be emphasized by screen reader programs. 1227

2.7.1.2 Symbols and special characters 1228

Special characters can be included in the text. Superscripts and subscripts are accomplished 1229 using the and tags. 1230

Since the SPL encoding is UTF‐8, any Unicode character can be included as is. Unicode 1231 references may also be inserted as either dddd; where dddd is the Unicode value in decimal 1232 notation or where dddd is the Unicode value in hexadecimal notation. The font used 1233 in the standard HPFB stylesheet is a Unicode font assuring that most Unicode characters will be 1234 rendered correctly if viewed by a browser supporting this font. 1235


The only prohibited characters in XML that cannot be directly used are less‐than “


• Circle (List bullets are hollow discs: ○) 1273 • Square (List bullets are solid squares: ■) 1274

For example: 1275

In addition to the standard specialized lists, user‐defined characters are also permitted as 1276 markers by nesting within the tag. Note that any character, XML entity, or 1277 Unicode symbol, may be used in the , and that the for each are not 1278 restricted to the same character. For example: * the asterisk is used 1279 as item marker here.. 1280

2.7.1.5 Tables 1281

Tables can be created with the full structure (header (e.g. for column names), body (e.g. for the 1282 rows of the table) and footer e.g. for table footnotes)). The element is required for an 1283 SPL table while the elements and are optional in the SPL schema. The structure 1284 will display a standard typographical table with rules between the caption (table title) and 1285 head, the head and body, and the body and . If a element is included and 1286 footnotes are present in a table, then footnotes are rendered after the existing content of the 1287 element. 1288

It is recommended to always start with a standard table (i.e. and elements) 1289 and test to see whether the rendering is unambiguous and interpretable. In the unusual 1290 situation where additional formatting is needed, the rule styleCode specified or certain 1291 attributes may be used to modify the table. 1292

The rule codes are as follows (note that the control names are case sensitive): 1293

• Rule on left side of cell is Lrule 1294 • Rule on right side of cell is Rrule 1295 • Rule on top of cell is Toprule 1296 • Rule on bottom of cell is Botrule 1297

Note: More than one rule control may be used in a cell, e.g., Cell content. 1299

Rule control codes should be used only when necessary for the interpretability of the table. Use 1300 of these codes may result in overriding the default rules for tables. Rather than setting the rule 1301 for each cell, table rules may also be controlled according to entire rows or columns by use of 1302 the styleCode attributes with , , , , and elements. 1303

To make rowgroups appear with horizontal rules, use the styleCode attribute "Botrule" with the 1304 appropriate element. The Botrule value is rarely needed on the element. 1305

The preferred method for using vertical rules is to define colgroup with styleCode="Lrule” or 1306 “Rrule" (or both). Only if this does not yield the desired vertical rule should the Lrule or Rrule 1307 code value with styleCode attributes on the or element itself be used. Note: In 1308 general, vertical rules should not be used. Good typography for tables means using few vertical 1309 rules. 1310

To merge cells vertically and horizontally, the rowspan and colspan attributes should be used 1311 on the element. 1312


To determine the width of a table, the width attribute may be used on the element and 1313 to determine the width of a table column, the width attribute may be used on the and 1314 elements. Note: best practice is to omit the width aspect. This ensures the 1315 rendering is done to the width. The only time the width should be specified is when the 1316 information is to be smaller than the standard width and in those cases a relative size (%) 1317 should be used. 1318

For horizontal alignment, the preferred method for aligning cell content within the margins is to 1319 use in the element, though this can be used in the 1320 element as well. Valid values for align are “left”, “center”, “right”, “justify” (for full justification 1321 of contents within the cells), and “char” (for character alignment within the cells). Using the 1322 markup ensures that the contents for all cells in the column share the same 1323 alignment. 1324

For vertical alignment, the valign attribute can be used within cells. For cases in which the cell 1325 alignment must be different from other cells in the column, align is also available as an attribute 1326 on the other table elements, including . 1327

Markup for table footnote is rendered in the tag. This element does not need to be 1328 included in SPL; the standard stylesheet will include a tag if a element is 1329 present within either the or sections. A section should be included in 1330 SPL only if there is additional information other than footnotes that needs to be rendered in 1331 this section. 1332

For table text spacing, in some instances, the use of a “tab” or text indentation is desirable in a 1333 given table cell. In an SPL document, this effect is achieved by using the nonbreaking space 1334 ( ) as if it were a “tab” space. As the following snippet of XML shows, two nonbreaking 1335 spaces were used to offset the word “Male” from the margin: Male. 1336 The nonbreaking space can also be used to keep text in a table from breaking inappropriately 1337 due to browser resizing. 1338

2.7.1.6 Hypertext links 1339

SPL offers hypertext linking capabilities generally similar to those found in the HTML 1340 specification. 1341

Links are specified by the construct, where the value for the href attribute of 1342 (the target of the link) is the ID attribute value of a , , , 1343 , , element. The stylesheet does not support the styleCode 1344 attribute of the element; if a styleCode is needed for a link, this should be coded via 1345 the element within the link as with other text. 1346

2.7.1.7 Recent major label changes 1347

SPL offers a notation to identify recent major changes in the product monograph text including 1348 table elements and table data . The recent major text is tagged using the , for example: 1350

This is an example of text that is not changed. 1351 1352

This is an example of text that is a recent major change 1353


1354 This is an example of changed text that is not considered a recent major change 1355

1356

2.7.1.8 XML sample 1357

1358 1359 1360 1362 Part I: Health Professional Information 1363 1364 1365 1366 1367 1369 1 Indications 1370 1371 1372 sample text 1373 1374 1375 1376 1377 1378 1379 1381 1.1 Pediatrics 1382 1383 1384 sample text 1385 1386 1387 1388 1389 1390

2.7.1.9 Validation rules – narrative text 1391

1. Text is enclosed under , , or elements. 1392


2.7.2 Images 1393


The SPL schema uses elements to identify graphic files to be rendered at 1395 the locations where they are referenced by elements in the . An 1396 image in a SPL will be rendered wherever it is referenced by the renderMultimedia markup, no 1397 matter where the observationMedia markup appears. 1398

The referencedObject attribute of the renderMultiMedia element identifies the corresponding 1399 observationMedia instance by means of its ID identifier such as . For example, 1401

1402 1403

... 1404 1405 ... 1406

1407 1408

1409 descriptive text 1410 1411

1412 1413

1414 1415

1416

The element does not contain the graphics file, but instead points at the 1417 file. 1418

For image placement, if an image is a block image (i.e., should appear in its own space), insert 1419 the renderMultimedia tag between elements. If an image is inline (i.e., should 1420 appear alongside text), insert the renderMultimedia tag in the text of a as 1421 appropriate. Inline images are expected to be uncommon and basically represent symbols that 1422 cannot be represented by Unicode characters. In addition, are not applicable for 1423 inline images since these are not offset from the surrounding text. 1424

The standard HPFB stylesheet does not perform any resizing of graphics or changing the 1425 resolution of graphics files. Thus, all images are rendered in the browser as‐is, with all 1426 characteristics of the actual graphic file itself. To ensure that a graphic will appear as desired, it 1427 is important that the graphic file is edited to a dimension appropriate for its presentation within 1428 the browser. If this is not done, the appearance of the graphic may reduce the readability of the 1429 file. JPEG image file type using appropriate pixels per inch for images for viewing in a browser 1430 using the standard HPFB style sheet. 1431

Only file formats detailed in Error! Reference source not found. are permitted 1432

1433



1. There is text. 1435 2. Value xsi:type is as above. 1436 3. Media type is image/jpeg. 1437 4. Reference value is the file name for a valid image. 1438 5. Size of image file is less than 1 MB. 1439 6. File is a JPEG image and the name has the extension “.jpg”. 1440 7. Image components are referenced at least once in the text of any section. 1441 8. Image reference in text has an image “observationMedia” element with a matching ID in 1442

the same document. 1443

2.7.3 Title page 1444


The title page of the product monograph which includes the title, company name and address, 1446 control number, date of initial approval and date of last revision. 1447

2.7.3.2 XML sample 1448

1449 1450 1451 1452 Title Page 1453 1454 1455 1456 1457 14

Draft Guidance Document · 161 Structured Product Labeling (SPL) is a Health Level Seven International (HL7) standard which 162 defines the content of human prescription drug labeling

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