draft guidance document · 2019-05-15 · draft guidance document preparation of product monographs...

Draft Guidance Document

Preparation of Product Monographs in the Extensible Markup Language Format

This guidance document is being distributed for comment purposes only.

Draft date: 2019/05/15

Preparation of 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 : Préparation des monographies de produit en 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 1.5.2 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 XML Product Monograph structure, content and concepts ................................................. 8 15 2.1.1 Simplified metadata hierarchy ....................................................................................... 8 16 2.1.2 Output folder structure ............................................................................................... 11 17 2.1.3 Style sheet .................................................................................................................... 11 18 2.1.4 Derived content ........................................................................................................... 12 19 2.1.5 Validation ..................................................................................................................... 12 20 2.1.6 Controlled vocabularies ............................................................................................... 13 21 2.1.7 Object Identifiers (OID) ................................................................................................ 13 22

2.2 Template types .................................................................................................................... 13 23 2.2.1 2016 Templates ............................................................................................................ 13 24 2.2.2 Legacy template ........................................................................................................... 14 25

2.3 Submission process ............................................................................................................. 14 26 2.3.1 Step 1: Hold technical pre‐submission consultation ................................................... 14 27 2.3.2 Step 2: File a sample XML product monograph ........................................................... 15 28 2.3.3 Step 3: File the regulatory activity ............................................................................... 15 29

2.4 Lifecycle management ........................................................................................................ 15 30 2.4.1 Formats ........................................................................................................................ 15 31 2.4.2 Lifecycle for regulatory activities in the eCTD Format ................................................. 15 32 2.4.3 Lifecycle for regulatory activities in the non‐eCTD Electronic Format ........................ 17 33

2.5 Important considerations .................................................................................................... 18 34 2.6 Business conformance rules ................................................................................................ 18 35

2.6.1 XML prolog ................................................................................................................... 18 36 2.6.1.1 XML version and character encoding ................................................................... 18 37 2.6.1.2 Stylesheet location ................................................................................................ 18 38 2.6.1.3 Schema location .................................................................................................... 18 39

2.6.2 Document metadata .................................................................................................... 18 40 2.6.2.1 Regulatory activity (templateID OID .11) .............................................................. 18 41 2.6.2.2 Document ID (id root; OID .10) ............................................................................. 18 42 2.6.2.3 Document type (code; OID .10) ............................................................................ 19 43 2.6.2.4 Document title (title) ............................................................................................ 19 44


2.6.2.5 Date of initial approval (effective time low) and date of last revision (effective 45 time high) .......................................................................................................................... 19 46 2.6.2.6 Document language (language code; OID .29) ..................................................... 19 47 2.6.2.7 Document set ID (Set ID) ...................................................................................... 19 48 2.6.2.8 Document version number (version number) ...................................................... 19 49

2.6.3 Organization metadata ................................................................................................ 20 50 2.6.3.1 Market authorization holder (Represented Organization; OID .31) .................... 20 51 2.6.3.2 Canadian importer/distributor (Assigned Organization; OID .31) ........................ 20 52

2.6.4 Manufactured product metadata ................................................................................ 20 53 2.6.4.1 Manufactured product ......................................................................................... 20 54

2.6.4.1.1 Drug Identification Number (DIN) (template id extension; OID .42) ............ 20 55 2.6.4.1.2 Brand name (name) ....................................................................................... 20 56 2.6.4.1.3 Dosage form (form code; OID .3) ................................................................... 20 57 2.6.4.1.4 Nonproprietary name (name) ....................................................................... 21 58 2.6.4.1.5 Ingredients (ingredient substance; OID .14) .................................................. 21 59 2.6.4.1.6 Ingredient role ‐ cctive (ingredient class code; OID .39) ............................... 21 60 2.6.4.1.7 Ingredient role ‐ Adjuvant (ADJV) (ingredient class code; OID .39) .............. 21 61 2.6.4.1.8 Ingredient role ‐ Inactive (IACT) (ingredient class code; OID .39) ................. 21 62 2.6.4.1.9 Ingredient strength (quantity) ....................................................................... 21 63

2.6.4.2 Packaging .............................................................................................................. 22 64 2.6.4.2.1 Pack ID ........................................................................................................... 22 65 2.6.4.2.2 Pack type (container packaged product form code; OID .32) ....................... 22 66 2.6.4.2.3 Packaging quantity (quantity) ........................................................................ 22 67

2.6.4.3 Regulatory status of packaging ............................................................................. 22 68 2.6.4.3.1 Regulatory status (Marketing Act; OID .11) ................................................... 22 69 2.6.4.3.2 Regulatory activity and Control Number (Approval; OID .37) ....................... 22 70 2.6.4.3.3 Effective time low value ................................................................................ 23 71 2.6.4.3.4 Effective time high value ............................................................................... 23 72 2.6.4.3.5 Regulatory authority (territorialAuthority; OID 2.16.840.1.113883.2.20.6) . 23 73 2.6.4.3.6 Regulatory status of product ......................................................................... 23 74

2.6.4.4 Characteristics ....................................................................................................... 23 75 2.6.4.4.1 Product Class (template id extension; OID .53) ............................................. 23 76 2.6.4.4.2 Colour (OID .24) ............................................................................................. 23 77 2.6.4.4.3 Shape (OID .25) .............................................................................................. 23 78 2.6.4.4.4 Size ................................................................................................................. 23 79 2.6.4.4.5 Score .............................................................................................................. 23 80 2.6.4.4.6 Imprint ........................................................................................................... 23 81 2.6.4.4.7 Flavour (OID .26) ............................................................................................ 23 82 2.6.4.4.8 Image ............................................................................................................. 24 83 2.6.4.4.9 Combination product ..................................................................................... 24 84 2.6.4.4.10 Pharmaceutical standard ............................................................................. 24 85 2.6.4.4.11 Scheduling symbol ....................................................................................... 24 86 2.6.4.4.12 Therapeutic class ......................................................................................... 24 87

2.6.5 Narrative text ............................................................................................................... 24 88

3. Appendices ................................................................................................................................ 24 89


Appendix A ‐ Glossary................................................................................................................ 24 90 Appendix B ‐ References ........................................................................................................... 25 91 92


1. Introduction 93

1.1 Purpose/overview 94

To provide sponsors with guidance on the technical and business conformance rules needed to 95 prepare a product monograph using the Extensible Markup Language (XML) format and the 96 Health Level 7 (HL7) Structured Product Label (SPL) standard. 97

1.2 Scope and application 98

1.2.1 In‐scope 99

Human pharmaceutical drugs, biologic drugs and radiopharmaceuticals, regulatory activities 100 submitted in electronic format: Electronic Common Technical Document (eCTD) or non‐eCTD 101 format. 102

1.2.2 Out of scope 103

Over the counter (non‐prescription) drugs, self‐care products, natural health products, medical 104 devices, food and veterinary drugs. 105

1.3 Policy objectives 106

In recent years Health Canada announced a number of measures that will be taken to support 107 the health and safety of Canadian families, one of which is improving drug product labels. As 108 part of the HPFB’s strategic plan, the goal is to: 109

provide more relevant and easier to understand drug information on labels, in order to 110 help Canadians make better informed decisions about their medications, and 111

encourage the adoption of digital health technology to improve access, increase 112 efficiency, and improve outcomes for patients. 113

As part of this initiative, the HPFB recognized that unstructured formats, like Portable 114 Document Format (PDF), are not adequately positioned to support the objectives mentioned 115 above. We will therefore need to transition to more advanced technology formats. Particular 116 attention will be focused on formats that are open source and supported by international 117 standards. 118

One such format is XML; a markup language used to encode documents in a structured format 119 that is both human‐readable and machine‐readable. Since it is an open standard, XML is a 120 widely used format for exchanging electronic documents and data. 121

With respect to international standards, the HPFB aims to align its use of XML with other 122 international regulators, HL7 standards and the International Organization for Standardization 123 (ISO) standard for the Identification of Medicinal Product (IDMP). 124

1.4 Policy statements 125

This guidance document serves as the technical implementation guide for the Health Product 126 and Food Branch’s (HPFB) structured product monograph; which is based on XML, HL7’s SPL 127 standard and controlled vocabularies. 128


This guidance document is to be used in the preparation and filing of product monographs in 129 the XML format and is to be read in conjunction with the Guidance Document Product 130 Monograph. 131

1.5 Background 132

1.5.1 Extensible Markup Language (XML) 133

XML is a text‐based markup language used to encode electronic documents in a structured 134 format that is both human and machine‐readable. XML is used as a common format to facilitate 135 the interchange of data over the Internet. 136

XML is a free open standard maintained by the World Wide Web Consortium (W3C). 137

1.5.2 Health Level 7 (HL7) international 138

Founded in 1987, HL7 is a not‐for‐profit standards development organization dedicated to 139 providing standards for the exchange of electronic health information that supports clinical 140 practice and the management of health services. 141

Healthcare providers, government stakeholders, payers, pharmaceutical companies, 142 vendors/suppliers, and consulting firms support HL7. 143

Health Canada is contributing member of HL7. 144

1.5.3 Structured Product Label (SPL) standard 145

Structured Product Labeling (SPL) is a Health Level Seven International (HL7) standard which 146 defines the content of human prescription drug labeling in an XML format. In the Canadian 147 context, the product monograph is the ‘label’ or ‘the document’ that is being structured. 148

1.5.4 Structured document 149

In this context, structure refers to the fact that the product monographs content has been 150 encoded with XML; i.e., the content has been ‘markedup’ with XML to make it machine‐151 readable. As a result, the narrative text (e.g., section headings, all text and tables) and product 152 information (e.g., manufacturer, ingredients, dosage forms and packaging) are encoded and can 153 be found easily through search. 154

2. Guidance for implementation 155

2.1 XML Product Monograph structure, content and concepts 156

2.1.1 Simplified metadata hierarchy 157

Figure 1 is a simplified view of the XML product monographs metadata hierarchy. 158


Figure 1: Simplified view of the XML product monographs metadata hierarchy 159

160

161


Table 1 provides a summary of the six components that make up the XML product monograph. 162

163


Table 1: Summary of the six components that make up every XML product monograph 164

Component Description

1. XML Prologue Instructions to software programs; e.g., XML version, links to the style sheet and schema.

2. Document Metadata Identifies the type of document, its unique identifier, its version and its language (French or English).

3. Organization Metadata Information about the sponsor; e.g., company name, unique company identifier, address and role.

4. Manufactured Product Metadata

Brand name, dose form, proper/generic name, active ingredients, inactive ingredients, adjuvants, packaging, unit of presentation, marketing status, route of administration.

5. Narrative Text Product monograph content (excluding images); e.g., section headings, paragraphs, formatting, text and tables.

6. Images Encoded references to all accompanying images; e.g., figures, chemical structure, instructions for use.

2.1.2 Output folder structure 165

XML files end with a .xml file extension and only contain basic text. As a result, the XML product 166 monograph is made up of a single .xml file and separate image files as .jpg’s. 167

The .xml file contains all text based content, text formatting instructions (e.g., bold, underline, 168 bullets), metadata and references to the relevant image files. Since images are not text they 169 always accompany the .xml as separate files. This is also why the .xml only contains references 170 to images rather than the images themselves. 171

The .xml and the .jpg’s must always remain together in the same folder to avoid naming clashes 172 with other files and to ensure the .xml file can always find the corresponding .jpeg files. 173

Figure 2: Sample file and folder structured for a XML Product Monograph 174

175

2.1.3 Style sheet 176

A style sheet is a file or collection of files that describes how XML content should be displayed; 177 both in terms of appearance and structure. Style sheets do not change or modify the source 178 content in the XML document. The style sheet only modifies how the content is presented to 179 the end user. See Figure 3 for a simple example. 180


Figure 3: XML before and after the application of a style sheet 181

182

2.1.4 Derived content 183

Another unique aspect of XML documents and style sheets is derived content; i.e., content that 184 exists in the XML but not in the format that is displayed by the style sheet. E.g., the product 185 monograph Table of Contents and the Product Metadata Summary are automatically generated 186 from metadata and text pulled from throughout the XML. The style sheet collates these 187 disparate elements and presents them in a defined format and style. Schema 188

The purpose of the schema is to define the key rules and boundaries that the XML document 189 must adhere to. The metadata hierarchy in Figure 1 is a representative example of the structure 190 that is enforced by HL7’s SPL schema. 191

The schema goes further by defining how many of a given element the XML document can or 192 cannot have. E.g., there can only be one XML Prolog section; there must be one or more 193 manufactured products. 194

2.1.5 Validation 195

Validation is the process of checking a XML document against its schema to confirm that it is 196 both well‐formed and valid. 197


A XML document is considered well‐formed if it conforms to the W3C’s XML version 1.0 198 standard. 199

A XML document is considered valid if it conforms to the schema. In this context the XML 200 product monograph must comply with HL7’s SPL schema. 201

2.1.6 Controlled vocabularies 202

A controlled vocabulary is an established list of standardized, predefined and authorized terms 203 used for indexing and information retrieval. A controlled vocabulary ensures that a subject will 204 be described using the same term each time it is indexed, making it easier to find all 205 information about a specific topic during the search process. They are controlled using a 206 defined governance model, policies, guidance and change control procedures. 207

The XML product monograph is accompanied by a set of HPFB approved controlled 208 vocabularies. Use of these vocabularies is mandatory. 209

The HPFB’s controlled vocabulary list includes, but is not limited to: dosage‐form, route of 210 administration, pack type, units of presentation, units of measure, section id, ingredient id, 211 ingredient role. 212

Refer to the HPFB’s online registry for a full list of controlled vocabularies and their terms. 213

2.1.7 Object Identifiers (OID) 214

OIDs are identifiers based on the International Organization for Standardization (ISO). They are 215 used to name objects or concepts with a globally unique name. 216

Each of the HPFB’s vocabularies will be registered with HL7 international and assigned a unique 217 OID to facilitate identification, search and retrieval. 218

2.16.840.1.113883.2.20.6 is the root OID for the HPFB itself. All HPFB controlled vocabularies 219 will use extensions of this OID. E.g., 2.16.840.1.113883.2.20.6.3 (or OID 6.3) refers to the HPFB’s 220 approved list of dosage forms. 221

All of the HPFB’s controlled vocabularies, and their OID’s, will be posted online to the Health 222 Canada website. From there stakeholders will be able to view or download copies of the 223 approved terms and their attributes. 224

2.2 Template types 225

2.2.1 2016 Templates 226

The XML product monograph supports the following 2016 templates: 227

1. Product Monograph Template ‐ Standard 228 2. Product Monograph Template ‐ Notice of Compliance with Conditions 229 3. Product Monograph Template ‐ Subsequent Entry Product (except for Schedule C and D 230

products) 231 4. Product Monograph Template ‐ Schedule C 232 5. Product Monograph Template ‐ Schedule D 233 6. Product Monograph Template ‐ Schedule D ‐ Biosimilar Biologic Drug 234


2.2.2 Legacy template 235

The Legacy Template refers to any product monograph template that predates the 2016 236 templates. i.e., 2014 templates, 2004 templates, pre‐2004 templates or any combination 237 thereof. 238

Since the 2016 template is relatively new, most approved product monographs fall into the 239 legacy template category. The legacy template will allow sponsors to recreate their legacy 240 product monographs in the XML format without compromising the validation rules related to 241 section headings. 242

However, the Legacy Template cannot be used in lieu of the 2016 templates. The following 243 conditions must be met before being eligible to use the Legacy Template: 244

Condition #1: Pre‐existing approved products: New products are expected to begin their 245 lifecycles with the 2016 template. Therefore, only products approved with a legacy 246 template are eligible. 247

Condition #2: No content changes: The XML product monograph is a direct copy of the 248 approved product monograph; i.e., the content in the XML product monograph is 249 identical to the approved version and no content changes have been made. 250

Condition #3: Metadata reflects what is approved: The XML product monograph’s 251 metadata reflects only what is in the approved product monograph; e.g., the XML 252 product monograph metadata cannot include strengths or ingredients not in the 253 approved product monograph. 254

Condition #4: Compliant with the SPL schema: The XML product monograph is 255 compliant with the SPL schema. 256

2.3 Submission process 257

Sponsors filing a regulatory activity with an XML product monograph for the first time are 258 recommended to following this process. 259

Beyond the first filing, this process is not necessary for subsequent regulatory activities unless 260 there is a significant change. E.g., changes to HL7 specification; changes to the Health Canada 261 specification; sponsor switches to new tool to build the XML product monograph. 262

2.3.1 Step 1: Hold technical pre‐submission consultation 263

This consultation is for Health Canada to offer assistance and guidance on the technical, 264 scientific or regulatory aspects of the XML product monograph. This consultation does not need 265 to take place at the same time as the regulatory pre‐submission meeting. 266

Request a consultation by contacting the Office of Submissions and Intellectual Property (OSIP) 267 at OSIP‐BPPI@hc‐sc.gc.ca. Include the following information in the request: 268

1. the purpose of the meeting 269 2. a brief description of the product to be discussed at the meeting 270 3. three proposed dates for the meeting, including whether an afternoon or morning 271

meeting is being requested 272 4. type of meeting requested, in person, teleconference, or web conference 273

274


5. an agenda for the meeting 275 6. the names of sponsor representatives attending the meeting 276

2.3.2 Step 2: File a sample XML product monograph 277

Samples are validated by Health Canada to identify and help resolve any issues. Health Canada 278 will notify the sponsor via email if issues are identified; the sponsor corrects the errors and re‐279 submits the sample (this process continues until no issues are identified). If no issues are 280 identified the sponsors XML product monograph should be ready for filing. 281

This period is not part of and will not delay the review process. 282

Sponsors can submit sample XML product monographs to OSIP at OSIP‐BPPI@hc‐sc.gc.ca. 283

2.3.3 Step 3: File the regulatory activity 284

The Sponsor files the regulatory activity with the XML product monograph. 285

1. Validation: Health Canada validates the XML product monograph to identify any issues. 286 2. Issues identified: Health Canada will notify the sponsor via email if errors have been 287

identified. The sponsor will correct and re‐submit an updated transaction with the 288 corrected XML product monograph (this process will continue until all issues have been 289 resolved). 290

3. No issues identified: If no issues have been identified, the regulatory activity is 291 processed as per the relevant process. 292

2.4 Lifecycle management 293

2.4.1 Formats 294

For the initial regulatory activity (e.g., NDS, SNDS, ANDS, SANDS) product monographs shall be 295 provided in the following formats: 296

1. Product monograph (clean) – XML format (.xml file and associated .jpg files) 297 2. Product monograph (clean) – Word format (.docx file) 298 3. Product monograph (annotated) – Word format (.docx file) 299

For regulatory transactions submitted during review (e.g., response to request for clarification) 300 product monographs shall be provided in the following formats: 301

1. Product monograph (clean) – Word format (.docx file) 302 2. Product monograph (annotated) – Word format (.docx file) 303

Product monographs shall be provided in the following format within 20 calendar days of the 304 issuance of a Notice of Compliance (NOC): 305

1. Product monograph (clean) English – XML format (.xml and .jpg files) 306 2. Product monograph (clean) French – XML format (.xml and .jpg files) 307

2.4.2 Lifecycle for regulatory activities in the eCTD Format 308

Sponsors should use the following eCTD lifecycle attributes to manage Word and XML product 309 monographs under the following circumstances (Refer to Figure 5, Figure 6 and Figure 7 for 310 examples): 311


‘NEW’ when a clean or annotated product monograph is provided as part of the first 312 transaction of a regulatory activity (e.g., NDS, SNDS). 313

‘REPLACE’ when a clean or annotated product monograph is provided in response to 314 clarification request, screening deficiency notice (SDN), notice of deficiency (NOD), 315 notice of non‐compliance (NON). 316

‘NEW’ when a pristine product monograph is provided for the first time. The last clean 317 and annotated draft product monographs should be assigned the operation attribute 318 ‘DELETE’. 319

‘REPLACE’ when a pristine product monograph is provided to replace a previously 320 approved pristine product monograph. The last clean and annotated draft product 321 monographs should be assigned the operation attribute ‘DELETE’. 322

Figure 4: Example of an eCTD lifecycle for the first regulatory activity and its transactions 323 (e.g., NDS or ANDS) 324

325

326


Figure 5: Example of an eCTD lifecycle for a subsequent regulatory activity and its 327 transactions (e.g., SNDS, SANDS) 328

329

Figure 6: Example of an eCTD lifecycle for regulatory activities under simultaneous review 330

331

2.4.3 Lifecycle for regulatory activities in the non‐eCTD Electronic Format 332

Unlike eCTD lifecycles, non‐eCTD electronic submissions do not have XML backbones or XML 333 attributes. Therefore, there is no document lifecycle. 334

Sponsors are only required to submit product monograph files in the formats outlined under 335 section 0; i.e., Word and XML with the initial submission, Word only during review and XML 336 only for the final pristine submission. 337


2.5 Important considerations 338

The XML product monograph is the legal document. The Microsoft Word copies are 339 considered convenience copies to facilitate review. 340

Once a sponsor files a regulatory activity with a product monograph in the XML format, 341 all subsequent regulatory activities for the same product monograph must be filed in 342 XML format. 343

The HPFB will only provide validation reports for XML product monographs that fail 344 validation. Sponsors are expected to validate the XML product monograph and correct 345 any warning(s) and error(s) before submitting them to the HPFB. 346

2.6 Business conformance rules 347

The following section provides business, scientific and regulatory instructions for each of the 348 major sections of the XML product monograph (as depicted in Figure 1 and Table 1) and their 349 respective sub‐elements. 350

The heading names for this section use the following format: Health Canada term (SPL term; 351 controlled vocabulary OID). 352

2.6.1 XML prolog 353

This section provides technical data meant for software applications and developers. It is not 354 intended to be modified by sponsors. 355

2.6.1.1 XML version and character encoding 356

The version of XML in use and the standard for character encoding (i.e., UTF). 357

2.6.1.2 Stylesheet location 358

Link to the Health Canada stylesheet. 359

2.6.1.3 Schema location 360

Link to Health Canada’s copy of the HL7 SPL schema. 361

2.6.2 Document metadata 362

2.6.2.1 Regulatory activity (templateID OID .11) 363

The type of regulatory activity associated with this version of the product monograph; e.g., 364 NDS, SNDS, ANDS, SANDS. 365

Product monographs updated with a Level III Change are not submitted to Health Canada. 366 However, sponsors are expected to keep their XML product monograph up to date with Level III 367 Changes. Sponsors will select Level III Change as the regulatory activity if this version of the 368 product monograph is related to a Level III Change. 369

Regulatory Activity is specified from the appropriate Health Canada controlled vocabulary. 370

2.6.2.2 Document ID (id root; OID .10) 371

The Document ID is the unique identifier for this product monograph regardless of the version 372 number. 373


This Document ID is assigned with the first version of a given product monograph and does not 374 change. The purpose of this ID is to ensure all versions of a product monograph can be tied 375 back to a common parent ID. 376

Document ID is assigned using a globally unique identifier (GUID); e.g., 123e4567‐e89b‐12d3‐377 a456‐426655440000. 378

2.6.2.3 Document type (code; OID .10) 379

The type of document is specified; e.g., product monograph ‐ standard or product monograph – 380 schedule D. 381

The document type is specified from the appropriate Health Canada controlled vocabulary. 382

Refer to the Guidance Document ‐ Product Monograph for further details on the available 383 product monograph types. 384

2.6.2.4 Document title (title) 385

The title should include the following information in the following sequence as text: 386

<Scheduling Symbol> <BRAND NAME> (<common name>), <Dosage Form(s), Strength(s) and 387 Route(s) of Administration>, <Pharmaceutical Standard (if applicable)>, <Therapeutic 388 Classification>. 389

2.6.2.5 Date of initial approval (effective time low) and date of last revision (effective time high) 390

Use Date of Initial Approval for a new product monograph. The date is the original NOC date. 391

Use Date of Last Revision for subsequent revisions to any part of the product monograph. The 392 date is the NOC date from the most recent regulatory activity. 393

Since the Data of Initial Approval or Date of Last Revision is not known to the sponsor in 394 advance of filing it can be added to the XML product monograph when the pristine version is 395 filed following the issuance of a NOC. 396

Product monographs updated with a Level III Change are not submitted to Health Canada. 397 However, sponsors are expected to keep their XML product monograph up to date with Level III 398 Changes. In the case of a Level III Change, the Date of Last Revision is the date the Level III 399 Change was finalized by the sponsor. 400

2.6.2.6 Document language (language code; OID .29) 401

The language in which the content is based. 402

Language is specified from the appropriate Health Canada controlled vocabulary. 403

2.6.2.7 Document set ID (Set ID) 404

The unique identifier for this version of the product monograph. Unlike the Document ID, the 405 Document Version ID is unique for each version of the product monograph. 406

The Document Version ID is assigned using a GUID. 407

2.6.2.8 Document version number (version number) 408

The version number for this product monograph is specified as integers. 409


2.6.3 Organization metadata 410

2.6.3.1 Market authorization holder (Represented Organization; OID .31) 411

The full legal name, company ID, address and contact information for the sponsor in whose 412 name the Drug Identification Number (DIN) and NOC is to be registered. 413

The product monograph is a public document. Therefore, sponsors are advised not to include 414 contact information for an individual. Only include corporate contact information (company 415 website and 1‐800 number). 416

The legal name of the organization, and its corresponding company ID, are specified from the 417 appropriate Health Canada controlled vocabulary. 418

Company address and contact information are specified as text. 419

2.6.3.2 Canadian importer/distributor (Assigned Organization; OID .31) 420

If the address of the Market Authorization Holder is NOT located in Canada then the Canadian 421 organization responsible for the sale of this product in Canada must be specified. 422

The full legal name, company ID, address and contact information for organizations involved in 423 the import or distribution of the active ingredient(s) and drug product(s) associated with this 424 product monograph. 425

The product monograph is a public document. Therefore, sponsors are advised not to include 426 contact information for an individual. Only include corporate contact information (company 427 website and 1‐800 number). 428

The legal name of the organization, and its corresponding company ID, are specified from the 429 appropriate Health Canada controlled vocabulary. 430

Company address and contact information are specified as text. 431

2.6.4 Manufactured product metadata 432

This section captures details about the manufactured form of the drug product. 433

One manufactured product information section is required for each variation in strength, 434 dosage form and formulation. 435

2.6.4.1 Manufactured product 436

2.6.4.1.1 Drug Identification Number (DIN) (template id extension; OID .42) 437

The DIN assigned to this product by Health Canada can be specified as text. 438

Since the DIN is not known to the sponsor in advance of filing it can be added to the XML 439 product monograph when the pristine version is filed following the issuance of a NOC. 440

2.6.4.1.2 Brand name (name) 441

The brand name is specified as text. 442

2.6.4.1.3 Dosage form (form code; OID .3) 443

The manufactured dosage form is specified from the appropriate Health Canada controlled 444 vocabulary. 445


2.6.4.1.4 Nonproprietary name (name) 446

The non‐proprietary name is specified as text. 447

The International Non Proprietary Names (INN) is used as Health Canada's standard to assign 448 the preferred name to ingredients. 449

2.6.4.1.5 Ingredients (ingredient substance; OID .14) 450

The ingredient, ingredient identifier and role are specified from the appropriate Health Canada 451 controlled vocabulary. 452

The following sections describe how to manage ingredients, their role and strength/quantity. 453

2.6.4.1.6 Ingredient role ‐ cctive (ingredient class code; OID .39) 454

Active ingredients are specified using one of the following controlled vocabularies: 455

1. Active Ingredient ‐ Basis of Strength (ACTIB): The ingredient substance is itself the basis 456 of strength. The strength specifies the quantity of the substance in the formulation. 457

2. Active Ingredient ‐ Moiety is Basis of Strength (ACTIM): The ingredient’s therapeutic 458 moiety is the basis of strength. The strength specifies the quantity of the substance's 459 therapeutic moiety in the formulation. 460

3. Active ingredient ‐ Reference substance is basis of strength (ACTIR): In situations 461 where the active ingredient has undergone a change in chemical form the therapeutic 462 moiety may be in a different form; e.g., an in‐situ conversion of one salt to another salt 463 and the strength is expressed in terms of the active moiety (a base). In this case, 464 another reference substance with the same therapeutic moiety is the basis of strength. 465 The strength specifies the quantity of the reference substance present in the 466 formulation. 467

Quantity is mandatory for active ingredients 468

2.6.4.1.7 Ingredient role ‐ Adjuvant (ADJV) (ingredient class code; OID .39) 469

The role ADJV is selected from the Health Canada controlled vocabulary. 470

Quantity is optional for adjuvants 471

2.6.4.1.8 Ingredient role ‐ Inactive (IACT) (ingredient class code; OID .39) 472

The role IACTIV is selected from the Health Canada controlled vocabulary. 473

Quantity is optional for inactive ingredients. 474

2.6.4.1.9 Ingredient strength (quantity) 475

The strength/quantity is specified using a numerator (value and unit) and a denominator (value 476 and unit of presentation). 477

478


Table 2: Examples of how to present the strength of active ingredients 479

Numerator Value Numerator Unit (Unit of Measure)

Denominator Value

Denominator Unit (Unit of Measure/ Presentation)

10 mg per tablet 10 mg 1 Tablet

0.2 ml per syringe 0.2 ml 1 Syringe

2 mg per 5 ml 2 mg 5 ml

2.6.4.2 Packaging 480

2.6.4.2.1 Pack ID 481

The sponsor can specify a unique ID number for this package. 482

2.6.4.2.2 Pack type (container packaged product form code; OID .32) 483

The type of packaging is specified from the appropriate Health Canada controlled vocabulary. 484

2.6.4.2.3 Packaging quantity (quantity) 485

The quantity of the packaging is specified using a numerator (value and unit) and a 486 denominator (value and unit of presentation). The following table provides examples of how 487 packaging quantity is managed. 488

Table 3: Examples of how to present packaging quantity 489

Numerator Value

Numerator Unit (Unit of Presentation)

Denominator Value

Denominator Unit

Pack Type

10 tablets per bottle 10 Tablet 1 1 Bottle

1 ml per syringe 1 mL 1 1 Syringe

10 syringes per box 10 Syringe 1 1 Box

2.6.4.3 Regulatory status of packaging 490

2.6.4.3.1 Regulatory status (Marketing Act; OID .11) 491

The marketing act refers to the regulatory status of the manufactured product; e.g., approved, 492 cancelled, marketed, dormant. It is specified from the appropriate Health Canada controlled 493 vocabulary. 494

This regulatory status is equivalent to the status of the product’s DIN(s). 495

2.6.4.3.2 Regulatory activity and Control Number (Approval; OID .37) 496

The Health Canada Control Number for this regulatory activity is also listed. Since the Control 497 Number is not known to the sponsor in advance of filing it can be added to the XML product 498 monograph when the pristine version is filed following the issuance of a NOC. 499

The regulatory activity directly associated with the status; e.g., SNDS, SANDS. It is specified 500 from the appropriate Health Canada controlled vocabulary. 501


2.6.4.3.3 Effective time low value 502

The effective time low value is the date of initial approval and is specified as a date in the 503 YYYYMMDD format. 504

2.6.4.3.4 Effective time high value 505

The effective time low value is the date when the DIN was cancelled or package was cancelled 506 from the market. It is specified as a date in the YYYYMMDD format. 507

2.6.4.3.5 Regulatory authority (territorialAuthority; OID 2.16.840.1.113883.2.20.6) 508

The authority is always HPFB and is specified from the appropriate Health Canada controlled 509 vocabulary. 510

2.6.4.3.6 Regulatory status of product 511

The status of the product is described; e.g., Approved, Cancelled. The status is and is specified 512 from the appropriate Health Canada controlled vocabulary. 513

The effective time low value is the date of initial approval and is specified as a date in the 514 YYYYMMDD format. 515

The effective time low value is the date when the DIN was cancelled. It is specified as a date in 516 the YYYYMMDD format. 517

2.6.4.4 Characteristics 518

2.6.4.4.1 Product Class (template id extension; OID .53) 519

The type of manufactured drug product is specified from the appropriate Health Canada 520 controlled vocabulary; e.g., biologic, radiopharmaceutical, pharmaceutical, disinfectant. 521

2.6.4.4.2 Colour (OID .24) 522

Where applicable, the colour can be specified from the appropriate Health Canada controlled 523 vocabulary. 524

2.6.4.4.3 Shape (OID .25) 525

Where applicable, the shape can be specified using the terms in the appropriate Health Canada 526 controlled vocabulary. 527

2.6.4.4.4 Size 528

Where applicable, the size or dimensions of the product is specified as text. 529

2.6.4.4.5 Score 530

Where applicable, the imprint can be specified as text. 531

2.6.4.4.6 Imprint 532

Where applicable, the imprint can be specified as text. 533

2.6.4.4.7 Flavour (OID .26) 534

Where applicable, the flavour can be specified as text. 535


2.6.4.4.8 Image 536

Where applicable, a reference to an image can be provided. 537

2.6.4.4.9 Combination product 538

Where applicable, the type of combination product can be specified from the appropriate 539 Health Canada controlled vocabulary. 540

2.6.4.4.10 Pharmaceutical standard 541

The pharmaceutical standard is specified from the appropriate Health Canada controlled 542 vocabulary. 543

2.6.4.4.11 Scheduling symbol 544

The Scheduling Symbol is specified from the appropriate Health Canada controlled vocabulary. 545

2.6.4.4.12 Therapeutic class 546

The therapeutic classification is specified from the appropriate Health Canada controlled 547 vocabulary. 548

2.6.5 Narrative text 549

This component includes the narrative text of the product monograph. This includes text 550 (paragraphs, lists, tables); formatting instructions (bold, underline, italics); sections and 551 subsections. The major section headings are as follows: 552

1. Title Page 553 2. Recent Major Changes 554 3. Part I: Health Professional Information 555 4. Part II: Scientific Information 556 5. Part III: Patient Medication Information 557

3. Appendices 558

Appendix A ‐ Glossary 559

Acronyms 560

DIN Drug Identification Number

eCTD Electronic Common Technical Document

GUID Globally Unique Identifier

HL7 Health Level 7

HPFB Health Products and Food Branch

HTML Hypertext Markup Language


ID Identifier

IDMP Identification of Medicinal Product

ISO International Organization for Standardization

JFIF JPEG File Interchange Format

JPEG Joint Photographic Experts Group

OID Object Identifier

PDF Portable Document Format

SPL Structured Product Label

UTF Unicode Transformation Format

W3C World Wide Web Consortium

XML Extensible Markup Language

Appendix B ‐ References 561

1. Guidance Document: Validation Rules for Product Monographs in the Extensible Markup 562 Language Format 563

2. Guidance Document ‐ Product monograph 564 3. Guidance Document Questions and Answers: Plain Language Labelling Regulations 565 4. HL7 SPL Release 7 specification 566

draft guidance document · 2019-05-15 · draft guidance document preparation of product monographs...

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