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Working document QAS/18.768

April 2018

Draft document for comment

PROPOSAL FOR REVISION OF THE WHO CERTIFICATION 1

SCHEME ON THE QUALITY OF PHARMACEUTICAL 2

PRODUCTS MOVING IN INTERNATIONAL COMMERCE 3

(April 2018) 4

DRAFT FOR COMMENT 5

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7

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© World Health Organization 2018 13

All rights reserved. 14

This draft is intended for a restricted audience only, i.e. the individuals and organizations having received this draft. The draft 15 may not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part or in whole, in any 16 form or by any means outside these individuals and organizations (including the organizations' concerned staff and member 17 organizations) without the permission of the World Health Organization. The draft should not be displayed on any website. 18 Please send any request for permission to: 19

Dr Sabine Kopp, Group Lead, Medicines Quality Assurance, Technologies Standards and Norms, Department of Essential 20 Medicines and Health Products, World Health Organization, CH-1211 Geneva 27, Switzerland. Fax: (41-22) 791 4730; email: 21 [email protected]. 22

The designations employed and the presentation of the material in this draft do not imply the expression of any opinion 23 whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its 24 authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines 25 for which there may not yet be full agreement. 26

The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended 27 by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions 28 excepted, the names of proprietary products are distinguished by initial capital letters. 29

All reasonable precautions have been taken by the World Health Organization to verify the information contained in this draft. 30 However, the printed material is being distributed without warranty of any kind, either expressed or implied. The responsibility 31 for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for 32 damages arising from its use. 33

This draft does not necessarily represent the decisions or the stated policy of the World Health Organization. 34

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Should you have any comments on the attached revision, please send these to Dr S. Kopp, Group Lead,

Medicines Quality Assurance, Technologies Standards and Norms ([email protected]), with a copy to

Mrs. Xenia Finnerty ([email protected]), by 15 May 2018.

Our working documents will be sent out electronically only and will also be placed on the Medicines

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mailto:[email protected]:[email protected]:[email protected]:[email protected]


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SCHEDULE FOR THE PROPOSED ADOPTION PROCESS OF DOCUMENT QAS/18.768: 36

PROPOSAL FOR REVISION OF THE WHO CERTIFICATION SCHEME ON THE 37

QUALITY OF PHARMACEUTICAL PRODUCTS MOVING IN INTERNATIONAL 38

COMMERCE 39

40

Recommendation by 52nd WHO Expert Committee on

Specifications for Pharmaceutical Preparations to prepare

a proposal for revision of the scheme for public

consultation

16–20 October 2018

Preparation of working document by WHO Secretariat February–March 2018

Circulation of working document for public comments April 2018

Consolidation of comments received May 2018

Discussion of working document and feedback received

during the informal consultation on regulatory tools for

medicines

19–20 May 2018

Circulation of revised working document for public

consultation June–July 2018

Consolidation of comments received and review of

feedback August 2018

Presentation to the 18th International Conference of Drug

Regulatory Authorities 3–7 September 2018

Presentation to the 53rd meeting of the WHO Expert

Committee on Specifications for Pharmaceutical

Preparations

22–26 October 2018

Any further action, as recommendation by the WHO

Expert Committee on Specifications for Pharmaceutical

Preparations

41


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PROPOSAL FOR IMPROVEMENT OF THE WHO CERTIFICATION SCHEME ON 42

THE QUALITY OF PHARMACEUTICAL PRODUCTS MOVING IN 43

INTERNATIONAL COMMERCE 44

1. INTRODUCTION 45

46

The WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in 47

International Commerce (the “Scheme”) is an international voluntary agreement to provide 48

assurance to countries participating in the Scheme, about the quality of pharmaceutical products 49

moving in international commerce. The primary document of the Scheme is the certificate of a 50

pharmaceutical product (CPP). 51

52

The fifty-second WHO Expert Committee on Specifications for Pharmaceutical Preparations 53

(ECSPP) in 2017 was informed about the current situation of the Scheme, including the fact that 54

the forty-third Expert Committee in 2008 had recommended that “the WHO Certification 55

Scheme on the Quality of Pharmaceutical Products Moving in International Commerce should 56

be revised” in line with recent developments. The Expert Committee in 2017 recommended that 57

the “WHO Secretariat should prepare a proposal for revision of the Scheme for public 58

consultation”. 59

60

The objective of this working document is to compile key issues on the Scheme and provide a 61

proposed revision of the Scheme for consideration during the upcoming fifty-third ECSPP 62

meeting in 2018. 63

64

2. BACKGROUND 65

66

The Scheme has been in operation since 1969 (World Health Assembly resolution WHA 22.50) 67

and was amended in 1975 (WHA 28.65), 1988 (WHA 41.18), 1992 (WHA 45.29) and 1997 68

(WHA 50.3) (1–5). The current Scheme provides following three types of certificate: 69

CPP; 70

statement of the licensing status of pharmaceutical product; 71

batch certificate. 72


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73

In 2007, the forty-second ECSPP discussed and identified a number of perceived problems with 74

the operation of the Scheme (6). 75

76

In 2008, a WHO consultation was held to make recommendations for consideration during the 77

forty-third ESPCC, taking account of the WHO working document QAS/07.240 which contains 78

key issues and possible action (7). The forty-third ECSPP in 2008 discussed the report of the 79

consultation (working document QAS/08.279) (8). In light of the changing environment, 80

including the rapid globalization of the pharmaceutical manufacturing sector, coupled with 81

changes in the make-up of both the regulators and the groups involved in procurement, the forty-82

third ECSPP endorsed the following recommendations (9): 83

84

“1. The WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in 85

International Commerce should be revised; 86

2. The proposal for revision of the Scheme and modification of the guidelines should be 87

discussed by the relevant WHO Governing Bodies – the Executive Board and the World 88

Health Assembly – and in consultation with WHO’s Legal Counsel. 89

3. In the interim a question and answer (Q&A) paper should be prepared on the function of 90

the Scheme.” 91

92

Based on the above recommendation, as an interim measure, a Q&A document on the function 93

of the Scheme was developed in 2010 and it was revised in 2015 (10, 11). However, the Scheme 94

has not been revised since 1997. 95

96

In 2017, the fifty-second ECSPP recommended that the “WHO Secretariat should prepare a 97

proposal for revision of the scheme for public consultation” (12). 98

99

The draft working document which includes the proposed revision of the Scheme was prepared 100

by the WHO Secretariat and it will be discussed during an informal consultation planned to be 101

held on 19 to 20 May 2018. In addition, the draft working document will be circulated, including 102


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to the Member States and other interested parties, for public consultation to prepare a version of 103

the working document for possible endorsement by the fifty-third ECSPP. 104

105

3. PROPOSED REVISION OF THE SCHEME 106

107

Since the last revision of the Scheme in1997 it has been discussed on various occasions and key 108

issues and possible actions have been identified. These are roughly classified into the following 109

two aspects: 110

(a) issues related to the revision of the Scheme; 111

(b) issues related to implementation/operational aspects of the Scheme. 112

113

The objective of this working document is to provide a proposed revision of the scheme for 114

consideration [endorsement/adoption] during the upcoming fifty-third ECSPP. Therefore, 115

possible action related to implementation and operational aspects of the Scheme (e.g. promotion 116

of the Scheme, making use of IT) would be considered after adoption of the revision of the 117

Scheme. 118

119

3.1 Summary of key issues and proposed actions related to the revision of the 120

Scheme 121

122

The table below outlines key issues and possible actions. These were prepared mainly based on 123

the report of the forty-third ECSPP and on working documents QAS/07.240 and QAS/08.279 124

and the Q&A document1 as well as comments from the Member States and interested parties 125

during public consultation (6, 7, 9, 12). 126

1 Q16 is “What are the main problem encountered in the application of the Scheme”


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Key issues Proposed actions

a The Scheme is formally at present

directed to individual Member States,

whereas regulatory and procurement

groupings of multistate organizations

also need to be able to operate within

the Scheme; this applies to both issuing

and receiving parties

The wordings in the Scheme should be changed so that regional organizations, such

as the European Union can formally

participate in the Scheme

[Note from Secretariat: Member State(s)”

=> “Member State(s) and/or regional

authority(ies)”.]

b The list of competent authorities is out

of date; details of some authorities have

changed. The current list of countries

that participate in the Scheme in its

present form is not readily available

Memberships as “certificate-issuing” countries should be renewed every five years

[Note from Secretariat: Added new para. as

section 2.5; See below for more detail.]

Member States should inform any update of the name and address of competent authorities

to the WHO secretariat

[Note from Secretariat: Added new

paragraph as section 2.7.]

c Exporting countries that do not fulfil the

prerequisites required by the Scheme

issue certificates to support export

Memberships as “certificate -issuing” countries should be renewed every five years.

Member States intending to continue to

participate in the Scheme as “certificate-

issuing” countries should resubmit

notification to the Director-General of the

World Health Organization (WHO) in the

same way as section 2.1



Member States intending to participate in the Scheme as certificate-–issuing countries

should declare that the competent authority

meets the requirements in the notification to

the WHO Director-General



In case that WHO does not receive the notification for renewal of membership for a

long time period, the Director-General may

delete such a Member State’s name from the

participant list in consultation with the

relevant Expert Committee


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d The CPP is no longer provided to

substitute the full dossier quality safety

and efficacy (QSE) review

CPPs should not be requested in countries that have the capability to conduct full QSE

reviews



e Information on who released the batch

for marketing is not disclosed in

certificates issued by exporting

countries

The certificate should include batch release site information in the CPP as a new option

(in section 2A.3, explanatory note 8 in model

certificate of the guidelines) (“option c” will

become the new “d” and a new “c” will be

created)

[Note from Secretariat: Added new words in

Appendix 1of the Annex.]

f There have been cases in which forged

certificates have been supplied to

competent authorities of importing

countries

Email address, telephone and fax numbers should be provided as contact information so

that the requesting authority can request

confirmation to the certifying authority

countries easily

[Note from Secretariat: Added new words in

section 2.4.]

g Lead times of the certifying authorities

can be very long, sometimes several

months

Certifying authority should provide a certificate without undue delay



h Importing countries require legalization

of certificates, additional stamps, etc. Unnecessary legalization should not be

requested



127

3.2 Proposed revision of the Scheme 128

129

The proposal for revision of the Scheme is attached as an annex. The amendments of the Scheme 130

in the annex are presented in track-change mode. Moreover, it should be noted that this revision 131

includes not only an amendment related to 3.1 in this working document but also editorial 132

changes such as: 133


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updating some definitions in “Glossary and index” in conformity with latest version of 134

relevant guidelines; 135

replacing some words (e.g. “license” by “market authorization”). 136

137

4. OTHER ISSUES RELATED TO OPERATION OF THE SCHEME 138

139

The table below outlines key issues not related to revision of the Scheme. As described in section 140

3 of this document, possible actions regarding implementation/operation of the Scheme (e.g. 141

promotion of the Scheme, making use of IT) should be considered after adoption of the revision 142

of the Scheme. 143

Key issues

a Countries not party to the Scheme issue certificates to support export of pharmaceutical

products.

b Not all of certificate-issuing countries adhere to the WHO template.

c Member States issue certificates for products not manufactured under their jurisdiction, e.g.

for products not authorized for marketing in their countries or not manufactured in their

country.

d Exporting countries issue other certificates such as free sale certificates.

e There are inconsistencies in listing the trade name of the product in the recipient country, if

different from the certifying country.

f The way of apply for a CPP is not harmonized, with each certifying authority having its

own system. (It would be helpful to work towards regional harmonization and a standard

electronic submission.)

144

5. REFERENCES 145

1. World Health Assembly resolution WHA22.50 (1969). 146





6. Forty-second WHO Expert Committee on Specifications for Pharmaceutical Preparations, 151

Geneva (WHO Technical Report Series, No. 948 (2008)). 152

7. Proposal for improvement of the WHO Certification Scheme on the Quality of 153


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Pharmaceutical Products Moving in International Commerce (working document 154

QAS/07.240). 155

8. Draft report to the forty-third WHO Expert Committee on Specifications for 156

Pharmaceutical Preparations. Recommendations for improvement of the WHO 157

Certification Scheme on the Quality of Pharmaceutical Products Moving in International 158

Commerce (QAS/08.279) (2008). 159

9. Forty-third WHO Expert Committee on Specifications for Pharmaceutical Preparations, 160

Geneva (WHO Technical Report Series, No. 953 (2009)). 161

10. WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in 162

International Commerce: Question and Answer (Q&A) (QAS/10.374, 2010) 163

11. WHO Certification Scheme on the quality of pharmaceutical products moving in 164

international commerce: Questions and Answers (Q & A) (WHO Drug Information Vol. 165

30, No. 3, 2016) 166

12. Fifty-second WHO Expert Committee on Specifications for Pharmaceutical Preparations 167

(WHO Technical Report Series, No. 1010 (2018)). 168

169

170


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ANNEX 171

[Note from Secretariat: Based on proposed action on pages 5–7; the new text is presented in 172

track-change mode.] 173

Guidelines on the implementation of the WHO Certification Scheme on the 174

Quality of Pharmaceutical Products Moving in International Commerce 175

1. PROVISIONS AND OBJECTIVES 176

1.1 A comprehensive system of quality assurance must be founded on a reliable system of 177

marketing authorizationlicensing and independent analysis of the finished pharmaceutical 178

product, as well as upon assurance obtained through independent inspection that all 179

manufacturing operations are carried out in conformity with accepted norms, referred to as "good 180

manufacturing practices" (GMP). 181

1.2 In 1969, the Twenty-second World Health Assembly, by resolution WHA22.50, endorsed 182

requirements for Good Practices in the Manufacture and Quality Control of Drugs (1) (referred 183

to henceforth as "GMP as recommended by WHO"). These comprise internationally- recognized 184

and respected standards that all Member States are urged to adopt and to apply. These 185

requirements have since been revised several timestwice. The first revision was adopted by the 186

Health Assembly in 1975 in resolution WHA28.65 (2). A second revision of the requirements is 187

included in the Thirty-second report of the WHO Expert Committee on Specifications for 188

Pharmaceutical Products (3). 189

1.3 These standards are fully consonant with those operative within the countries 190

participating in the Convention for the Mutual Recognition of Inspection in Respect of the 191

Manufacture of Pharmaceutical Products, and other major industrialized countries. They also 192

provide the basis for the WHO Certification Scheme on the Quality of Pharmaceutical Products 193

moving in International Commerce (referred to henceforth as "the Scheme") recommended 194

initially in resolution WHA22.50 (1). The Scheme is an administrative instrument that requires 195

each participating Member State or regional authority, upon application by a commercially 196

interested party, to attest to the competent authority of another participating Member State or 197

regional authority that: 198

a specific product is authorized to be placed on the market within its jurisdiction or, if it 199

is not thus authorized, the reason why that authorization has not been accorded; 200

the plant in which it is produced is subject to inspections at suitable intervals to establish 201

that the manufacturer conforms to GMP as recommended by the World Health 202

Organization ( WHO)); and 203

all submitted product information, including labelling, is currently authorized in the 204

certifying country. 205

1.4 The Scheme, as subsequently amended in 1975 (2), and 1988 (3), 1992 (4) and 1997 (5), 206

by resolutions WHA28.65, and WHA41.18, WHA45.29 and WHA50.3, is applicable to finished 207


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dosage forms of pharmaceutical products intended for administration to human beings or to 208

food-producing animals. 209

1.5 Provision for certification of active pharmaceutical ingredients (APIs) is also included 210

within the scope of the Scheme. This will be the subject of separate guidelines and certificates. 211

2. MEMBERSHIPELIGIBILITY FOR PARTICIPATION 212

[Note from Secretariat: the new text in section 2 includes rearrangement of the order of 213

paragraphs and such change is NOT presented in track-change mode except for the section 214

number.] 215

2.1 Any Member State as well as regional authority that has legal right to control the 216

regulation of pharmaceutical products are eligible to participate in the Scheme as a certifying 217

member and/or a requesting member if it complies with the requirements stipulated in section 2.2 218

or 2.3. 219

2.2 A Member State intending to becomeuse the Scheme a certifying memberto support the 220

export of pharmaceutical products should first satisfy itself that it possesses: 221

an effective marketing authorizationnational licensing system, not only for 222

pharmaceutical products, but also for the responsible manufacturers and distributors; 223

GMP requirements, consonant with those recommended by WHO, to which all 224

manufacturers of finished pharmaceutical products are required to conform; 225

effective controls to monitor the quality of pharmaceutical products registered or 226

manufactured within its country, including access to an independent quality control 227

laboratory; 228

a national pharmaceuticals inspectorate, operating as an arm of the national drug 229

regulatory authority, and having the technical competence, experience and resources to 230

assess whether GMP and other controls are being effectively implemented, and the legal 231

power to conduct appropriate investigations to ensure that manufacturers conform to 232

these requirements by, for example, examining premises and records and taking samples; 233

administrative capacity to issue the required certificates, to institute inquiries in the case 234

of complaint, and to notify expeditiously both WHO and the competent authority in any 235

Member State known to have imported a specific product that is subsequently associated 236

with a potentially serious quality defect or other hazard. 237

2.3 A regional authority intending to become a certifying member should possess by itself or 238

through its legal framework: 239

an effective marketing authorization system, not only for pharmaceutical products, but 240

also for the responsible manufacturers and distributors; 241

GMP requirements, consonant with those recommended by WHO, to which all 242

manufacturers of finished pharmaceutical products are required to conform; 243


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effective controls to monitor the quality of pharmaceutical products registered or 244

manufactured within its region, including access to an independent quality control 245

laboratory; 246

a pharmaceuticals inspectorate, operating as an arm of the drug regulatory authority, and 247

having the technical competence, experience and resources to assess whether GMP and 248

other controls are being effectively implemented, and the legal power to conduct 249

appropriate investigations to ensure that manufacturers conform to these requirements by, 250

for example, examining premises and records and taking samples; 251

administrative capacity to issue the required certificates, to institute inquiries in the case 252

of complaint, and to notify expeditiously both WHO and the competent authority in any 253

Member State and regional organization known to have imported a specific product that 254

is subsequently associated with a potentially serious quality defect or other hazard. 255

2.41 Membership as a certifying member and/or requesting member can be appliedAny 256

Member State intending to participate in the Scheme may do so by notifying in writing to the 257

WHO Director-General of: 258

its willingness to participate in the Scheme as a certifying member and/or a requesting 259

member (Member States and regional authorities may participate only as a certifying 260

member to control the import of pharmaceutical products and APIs); 261

any significant reservations it intends to observe relating to this participation; and 262

the name and address (including email address, telephone and fax numbers) of its 263

national drug regulatory authority or other competent authority; and 264

declaration to comply with the requirements for a certifying member stipulated in section 265 2.2 or 2.3, if applicable. 266

2.5 A Member State and regional authority that has a membership of a certifying member 267

should resubmit the notification in section 2.4 at least once every five years, in order to ensure 268

that it continues to comply with the requirement stipulated in section 2.2 or 2.3 and that contact 269

information keeps updated. 270

2.62 Consolidated list of information on the notification submitted by Member States and 271

regional authorities in accordance with provision in sections 2.4, 2.5 and 2.7 will be available 272

through WHO’s official website. (see also section 3.3).These notifications will be subsequently 273

announced in the monthly WHO Pharmaceutical Newsletter. An updated consolidated list will be 274

published annually in the Newsletter and will be available to governments at other times from: 275

the Division of Drug Management and Policies, WHO, 1211 Geneva 27, Switzerland. (See also 276

section 3.3) 277

2.3 A Member State may opt to participate solely to control the import of pharmaceutical 278

products and active substances. This intention should be stated explicitly in its notification to the 279

World Health Organization. 280

2.7 A Member State and regional authority should inform WHO of any change of 281

information notified to the WHO Director-General. 282


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2.8 Membership as a certifying member may be disqualified by the Director-General after 283

consultation with the ECSPP in the case that a Member State or regional authority would fail to 284

resubmit a notification in accordance with provision in section 2.5 for a long period. 285

2.95 Each Member State and regional authority assumes the responsibility to determine, 286

through a process of self-evaluation, whether it satisfies these prerequisites. The Scheme 287

contains no provision, under any circumstance, for external inspection or assessment, either of a 288

competent national authority or of a manufacturing facility. However, should a Member State or 289

regional organization so wish, it could approach WHO, or a well-recognized drug regulatory 290

authority, to occasionally delegate consultants to act as advisers in the course of national 291

inspections, and inspector training activities. 292

3. REQUESTING A CERTIFICATE 293

3.1 Three documents can be requested within the scope of the Sscheme: 294

a certificate of a pharmaceutical product (product certificate); 295

a statement of licensing status of pharmaceutical product(s); and 296

a batch certificate of a pharmaceutical product. 297

3.2 Proposed formats for these documents are provided in Appendices 1, 2 and 3 of these 298

guidelines. To facilitate their use, these documents are presented in forms suitable for generation 299

by computer. All participating Member States and regional authoritiescountries are henceforth 300

urged to adopt these formats to facilitate interpretation of certified information. Requests for the 301

provision of certificates offering more limited attestations, for instance, that the manufacturer 302

complies with GMP or that the product is authorized for "free sale" within the country of export 303

are discouraged. Similarly, requests should not be made for certification of information going 304

beyond the scope of this Scheme. When manufacture takes place in a country other than that 305

from which the product certificate is issued, an attestation relevant to compliance of the 306

manufacture with GMP may still be provided (as an attachment to the product certificate) on the 307

basis of inspections undertaken for registration purposes. 308

The Explanatory Notes attached to the three documents referred to above are very important. 309

Whilst they are not part of the document to be certified, they should always be attached to the 310

certificate. 311

3.3 A list of addresses of competent national regulatory authorities participating in the 312

Scheme that are responsible for the registration of pharmaceutical and/or veterinary products, 313

together with details of any reservations they have declared regarding their participation in the 314

Scheme will be available at the WHO official websitemay be obtained from WHO as indicated 315

in section 2.62. 316

3.4 Each competent authority in certifying members each country participating in the Scheme 317

should issue guidelines to all agents responsible for importing pharmaceutical products for 318

human and/or veterinary use that operate under its jurisdiction, including those responsible for 319


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public sector purchases, to explain the contribution of certification to the drug regulatory process 320

and the circumstances in which each of the three types of documents will be required. 321

Certificate of a pharmaceutical product 322

3.5 The Certificate of a pharmaceutical product (Appendix 1) issued by the competent 323

authority in the exporting country or regional authority (“the certifying authority”)exporting 324

country, is intended for use by the competent authority within an importing country and regional 325

organization in two situations: 326

when the product in question is under consideration for a product licencemarketing 327

authorization that will authorize its importation and sale; 328

when administrative action is required to renew, extend, vary or review such a marketing 329

authorization licence. 330

3.6 The Certificate of a pharmaceutical product should not be required by the Member States 331

or regulatory authorities where they undertake full quality, safety and efficacy review by 332

themselves. 333

3.76 All requests for certificates should be channeled through the agent in the importing 334

country (see section 3.4) and the product licencemarketing authorization holder or other 335

commercially-interested party in the exporting country ("the applicant"). The applicant should 336

submit the following information for each product to the authority issuing the certificate: 337

name and dosage form of product 338

name and amount of active ingredient(s) per unit dose (International Nonproprietary 339

Name(s) where such exist(s)), 340

name and address of product licencemarketing authorization holder and/or manufacturing 341

facility, 342

formula (complete composition including all excipients; also particularly when no 343

product licencemarketing authorization exists or when the formulation differs from that 344

of the authorizedlicensed product), 345

product information for health professionals and for the public (patient information 346

leaflets) as approved by the certifying authorityin the exporting country, 347

For product information to be attached to the certificate see section 4.7 348

3.87 The certificate is a confidential document. As such, it can be issued by the competent 349

authority in the exporting country ("the certifying authority") only with the permission of the 350

applicant and, if different, of the product-licencemarketing authorization holder. 351

3.98 The certificate is intended to be incorporated into a product-licencemarketing 352

authorization application in the competent authority in the importing country and regional 353

authority (“the requesting authority”). Once prepared, it is transmitted to the requesting authority 354

through the applicant and, when applicable, the agent in the importing country. 355


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3.109 When any doubt arises about the status or validity of a certificate, the 356

requestingcompetent authority in the importing country should request a copy directly from the 357

certifying authority, as provided for under section 4.9 of these guidelines. 358

3.110 In the absence of any specific agreement, each certificate will be prepared exclusively in 359

the working language(s) of the certifying authority. The applicant will be responsible for 360

providing any notarized translation that may be required by the requesting authority. 361

3.121 Since the preparation of certificates imposes a significant administrative load on 362

certifying authorities, the service may need to be financed by charges levied upon applicants. 363

3.132 Supplementary attestations are obtainable only at the discretion of the certifying authority 364

and with the permission of the applicant. The certifying authority is under no obligation to 365

supply additional information. Requests for supplementary information should consequently be 366

referred to the applicant, and only in exceptional circumstances to the certifying authority. 367

Statement of marketing authorizationlicensing status 368

3.143 Model statement of marketing authorizationStatement of Licensing Status (Appendix 2). 369

This attests only that a marketing authorizationlicence has been issued for a specified product, or 370

products, for use in the exporting country. It is intended for use by importing agents when 371

considering bids made in response to an international tender, in which case it should be requested 372

by the agent as a condition of bidding. It is intended only to facilitate the screening and 373

preparation of information. The importation of any product that is provisionally selected through 374

this procedure should be determined on the basis of a CPP. 375

Batch certificate 376

3.154 A batch certificate of a pharmaceutical product (Appendix 3) refers to an individual batch 377

of a pharmaceutical product and is a vital instrument in drug procurement. The provision of a 378

batch certificate is usually a mandatory element in tender and procurement documents. 379

3.165 A batch certificate is normally issued by the manufacturer and only exceptionally, as in 380

the case of vaccines, sera and some other biological products, by the competent authority inof the 381

exporting country or regional authority. The batch certificate is intended to accompany and 382

provide an attestation concerning the quality and expiry date of a specific batch or consignment 383

of a product that has already obtained market authorizationalready been licensed in the importing 384

country. The batch certificate should include the specifications of the final product at the time of 385

batch release and the results of a full analysis undertaken on the batch in question. In most 386

circumstances these certificates are issued by the manufacturer to the importing agent (i.e. the 387

product licencemarketing authorization holder in the importing country), but they must be made 388

available at the request of – or in the course of any inspection made on behalf of – the competent 389

national authority. 390

391


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4. ISSUING A CERTIFICATE 392

4.1 The certifying authority is responsible for assuring the authenticity of the certified data. 393

Certificates should not bear the WHO emblem, but a statement should always be included to 394

confirm whether or not the document is issued in the format recommended by WHO. 395

4.2 When the applicant is the manufacturer of the finished dosage form, the certifying 396

authority should satisfy itself, before attesting compliance with GMP, that the applicant: 397

applies identical GMP standards to the production of all batches of pharmaceutical 398

products manufactured within the facility, including those destined exclusively for 399

export.; 400

consents, in the event of identification of a quality defect consonant with the criteria set 401

out in section 5.1, to relevant inspection reports being released, in confidence, to the 402

requesting authoritycompetent authority in the country of import, should the latter so 403

require. 404

4.3 When the applicant is not the manufacturer of the finished dosage form, the certifying 405

authority should similarly satisfy itself – in so far as it has authority to inspect the records and 406

relevant activities of the applicant – that it has the applicant's consent to release relevant reports 407

on the same basis as described in section 4.2 (b) above. 408

4.4 GMP as recommended by WHO assigns to the manufacturer of the finished dosage form 409

responsibility for assuring the quality of APIs. National or regional regulations may require that 410

suppliers of APIs be identified in the product licencemarketing authorization, but the competent 411

authority may have no power to inspect them. 412

4.5 Notwithstanding this situation, a certifying authority may agree, on a discretionary and 413

voluntary basis, and at the request of a manufacturer, to undertake an inspection of a 414

manufacturer of APIs to satisfy specific requirements of a requesting authority. Alternatively, 415

pending the development of specific guidelines for APIs, the certifying authority may be able to 416

attest that the manufacturer is an established supplier of the substance in question to 417

manufacturers of finished dosage forms authorizedlicensed for marketing under its jurisdiction. 418

4.6 Whenever a product is purchased through a broker or another intermediary, or when more 419

than one set of premises has been involved in the manufacture and packaging of a product, the 420

certifying authority should consider whether it has received sufficient information to satisfy itself 421

that those aspects of the manufacture of the product for which the applicant is not directly 422

responsible have been undertake n in compliance with GMP as recommended by WHO. 423

4.7 The certifying authority should officially stamp and date all copies of product 424

information submitted to it in support of an application for a certificate and intended to be 425

appended to the certificate. 426

Every effort should be made to ensure that certificates and all annexed documentation are 427

consonant with the version of the product licencemarketing authorization operative on the date of 428


page 17

issue. Nevertheless, requesting authorities should not request unnecessary legalization procedure 429

that may cause undue delay of certificates. 430

When available, the certifying authority will add a summary basis of approval or any other 431

material the authority deems relevant. Translation by an applicant of these materials into a 432

widely used language, preferably English, shall be deemed to satisfy the provision of 3.110. 433

4.8 Any additional attachment to a certificate submitted by the applicant, such as price lists 434

of products for which bids are offered, should be clearly identified as not comprising part of the 435

attestation made by the certifying authority. 436

4.9 To avert potential abuse of the Scheme, to frustrate attempts at falsification, to render 437

routine authentication of certificates by an independent authority superfluous and to enable the 438

certifying authority to maintain comprehensive records of countries to which specific products 439

have been exported, each certificate should identify the importing country and be stamped on 440

each page with the official seal of the certifying authority. 441

If requested, an identical copy, clearly marked as duplicate, should be forwarded by the 442

certifying authority on demand directly to the requesting importing country authority. 443

4.10 The certifying authority should establish standard period of time for issue of certificates. 444

It should endeavor to make each issue of certificate completed within this period as far as the 445

applicant submits sufficient documents. 446

5. NOTIFYING AND INVESTIGATING A QUALITY DEFECT 447

5.1 Each certifying authority undertakes to institute enquiries into any quality defect reported 448

in a product exported in accordance with the provisions of the Scheme, on the understanding that: 449

the complaint is transmitted, together with the relevant facts, through the competent 450

requesting authority in the importing country; 451

the complaint is considered to be of a serious nature by the latter authority; and 452

the defect, if it appeared after delivery of the product into the importing country, is not 453

attributable to local conditions. 454

5.2 In the case of obvious doubt, a participating national authority may request WHO to 455

assist in identifying an independent quality control laboratory to carry out tests for the purposes 456

of quality control. 457

5.3 Each certifying authority undertakes to inform WHO and, as far as is possible, all 458

competent national authorities, of any serious hazard newly associated with a product exported 459

under the provisions of the Scheme or of any criminal abuse of the Scheme directed, in particular, 460

to the export of falsely labelled, spurious, counterfeited or substandard or falsified 461

pharmaceutical products. On receipt of such notification, WHO will transmit the message 462

immediately to the competent national authority in each Member State and regional organization. 463


page 18

5.4 WHO stands prepared to offer advice should difficulty arise in implementing any aspect 464

of the Scheme or in resolving a complaint, but it cannot be a party to any resulting litigation or 465

arbitration. 466

REFERENCES 467

1. Quality control of drugs. In: Twenty-second World Health Assembly, Boston, 468

Massachusetts, 8-25 July 1969. Part 1: Resolutions and decisions, annexes. Geneva, 469

World Health Organization, 1969: 99-105 (Official Records of the World Health 470

Organization, No. 176). 471

2. Certification Scheme on the Quality of Pharmaceutical Products Moving in International 472

Commerce. In: Twenty-eighth World Health Assembly, Geneva, 13-30 May 1975. Part 1: 473

Resolutions and decisions, annexes. Geneva, World Health Organization, 1975: 94-95 474

(Official Records of the World Health Organization, No. 226). 475

3. Good manufacturing practices for pharmaceutical products. In: WHO Expert Committee 476

on Specifications for Pharmaceutical Preparations. Thirty-second Report. Geneva, 477

World Health Organization, 1992: 14-79 (WHO Technical Report Series, No. 823). 478

34. WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in 479

International Commerce. In: Forty-first World Health Assembly, Geneva, 2-13 May 1988. 480

Resolutions and decisions, annexes. Geneva, World Health Organization, 1988: 53-55 481

(document WHA41/1988/REC/1). 482

4. Proposed guidelines for implementation of the WHO Certification Scheme on the Quality 483

of Pharmaceutical Products Moving in International Commerce. In: Forty-fifth World 484

Health Assembly, Geneva, 4-14 May 1992. Resolutions and decisions, annexes. Geneva, 485

World Health Organization, 1992: 155-165 (Document WHA41/1992/REC/1). 486

5. Guidelines for implementation of the WHO Certification Scheme on the Quality of 487

Pharmaceutical Products Moving in International Commerce. In: Forty-fifth World 488

Health Assembly, Geneva, 5-14 May 1997. Resolutions and decisions, annexes. Geneva, 489

World Health Organization, 1997: 2-3 (WHA50/1997/REC/1). 490


page 19

APPENDIX 1 491 492

MODEL CERTIFICATE OF A PHARMACEUTICAL PRODUCT 493

494

CERTIFICATE OF A PHARMACEUTICAL PRODUCT1 495

496

This certificate conforms to the format recommended by the World Health Organization (WHO) 497

(general instructions and explanatory notes attached) 498

499

No. of Certificate: ______________________________________________________________ 500

Certifying memberExporting (certifying) country): ___________________________________ 501

Requesting memberImporting (requesting) country): __________________________________ 502

503

1. Name and dosage form of the product: 504

_____________________________________________________________________________ 505

506

1.1. Active ingredient(s)2 and amount(s) per unit dose

3: 507

_____________________________________________________________________________ 508

_____________________________________________________________________________ 509

_____________________________________________________________________________ 510

For complete composition including excipients, see attached.4 511

512

1.2. Is this product authorizedlicensed to be placed on the market for use in the exporting 513

country?5

yes/no (key in as appropriate) 514

515

1.3 Is this product actually on the market in the exporting country? 516

yes/no/unknown (key in as appropriate) 517

If the answer to 1.2. is yes, continue with section 2A and omit section 2B. 518

If the answer to 1.2 is no, omit section 2A and continue with section 2B6: 519

520

2.A.1. Number of product licencemarketing authorization7 and date of issue: 521

_____________________________________________________________________________ 522

523

2.A.2. Product licenceMarketing authorization holder (name and address): ________________ 524

_____________________________________________________________________________ 525

_____________________________________________________________________________ 526

527

2.A.3. Status of product licencemarketing authorization holder8: a/b/c/d 528

(key in appropriate category as defined in note 8) 529

530

2.A.3.1. For categories b, c and dc, the name and address of the manufacturer producing the 531

dosage form is9: 532

_____________________________________________________________________________ 533

534


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2.A.3.2. For categories d, the name and address of the manufacturer certifying the finished 535

pharmaceutical product batch is:9 536

_____________________________________________________________________________ 537

538

2.A.4. Is a summary basis for approval appended? 10


540

2.A.5. Is the attached, officially approved product information complete and consonant with the 541

market authorizationlicence? 11

yes/no/not provided (key in as appropriate) 542

543

2.A.6. Applicant for certificate, if different from licence holder (name and address)12

: 544

_____________________________________________________________________________ 545

_____________________________________________________________________________ 546

547

2.B.1. Applicant for certificate (name and address): ___________________________________ 548

_____________________________________________________________________________ 549

_____________________________________________________________________________ 550

551

2.B.2. Status of applicant: a/b/c/d (key in appropriate category as defined in footnote 8) 552

553

2.B.2.1. For categories b, c and dc the name and address of the manufacturer producing the 554

dosage form is:9 555

_____________________________________________________________________________ 556

557

2.B.2.2. For categories d, the name and address of the manufacturer certifying the finished 558

pharmaceutical product batch is9 559

_____________________________________________________________________________ 560

561

2.B.3. Why is marketing authorization lacking? 562

not required/not requested/under consideration/refused (key in as appropriate) 563

564

2.B.4. Remarks13

: ______________________________________________________________ 565

_____________________________________________________________________________ 566

567

3. Does the certifying authority arrange for periodic inspection of the manufacturing plant in 568

which the dosage form is produced? yes/no/not applicable14

(key in as appropriate) 569

If not or not applicable, proceed to question 4. 570

571

3.1. Periodicity of routine inspections (years): ______ 572

573

3.2. Has the manufacture of this type of dosage form been inspected? 574


576

3.3 Do the facilities and operations conform to GMP as recommended by WHO? 15

577

yes/no/not applicable14

(key in as appropriate) 578

579


page 21

4. Does the information submitted by the applicant satisfy the certifying authority on all 580

aspects of the manufacture of the product? 16


582

If no, explain: _________________________________________________________________ 583

_____________________________________________________________________________ 584

585

Address of certifying authority: ___________________________________________________ 586

_____________________________________________________________________________ 587

588

Telephone number: _______________________ Fax number: _________________________ 589

E-mail address: __________________________ 590

591

Name of authorized person: ______________________________________________________ 592

593

Signature: ____________________________________________________________________ 594

595

Stamp and date: _______________________________________________________________ 596

597

General instructions 598

599 Please refer to the guidelines for full instructions on how to complete this form and information on the 600 implementation of the Scheme. 601 602 The forms are suitable for generation by computer. They should always be submitted as hard copy, with 603 responses printed in type rather handwritten. 604 605 Additional sheets should be appended, as necessary, to accommodate remarks and explanations. 606 607

Explanatory notes 608 609 1

This certificate, which is in the format recommended by WHO, establishes the status of the 610 pharmaceutical product and of the applicant for the certificate in the exporting country. It is for a 611 single product only since manufacturing arrangements and approved information for different dosage 612 forms and different strengths can vary. 613

614 2 Use, whenever possible, International Nonproprietary Names (INNs) or national nonproprietary 615

names. 616 617 3 The formula (complete composition) of the dosage form should be given on the certificate or be 618

appended. 619 620 4 Details of quantitative composition are preferred but their provision is subject to the agreement of the 621

product-licencemarketing authorization holder. 622 623 5 When applicable, append details of any restriction applied to the sale, distribution or administration of 624

the product that is specified in the product licencemarketing authorization. 625 626 6 Sections 2A and 2B are mutually exclusive. 627

628 7 Indicate, when applicable, if the licence is provisional, or the product has not yet been approved. 629


page 22

630 8 Specify whether the person responsible for placing the product on the market: 631

632 (a) manufactures the dosage form; 633 (b) packages and/or labels a dosage form manufactured by an independent company; 634 (c) certifies the finished pharmaceutical product batch; or 635 (dc) is involved in none of the above. 636

637 9 This information can only be provided with the consent of the product-licencemarketing authorization 638

holder or, in the case of non-registered products, the applicant. Non-completion of this section 639 indicates that the party concerned has not agreed to inclusion of this information. It should be noted 640 that information concerning the site of production is part of the product licencemarketing 641 authorization. If the production site is changed, the licencemarketing authorization has to be updated 642 or it is no longer valid. 643

644 10

This refers to the document, prepared by some national regulatory authorities, that summarizes the 645 technical basis on which the product has been licensed. 646

647 11

This refers to product information approved by the competent national drug regulatory authority, such 648 as summary product characteristics (SPC) 649

650 12

In this circumstance, permission for issuing the certificate is required from the product-651 licencemarketing authorization holder. This permission has to be provided to the authority by the 652 applicant. 653

654 13

Please indicate the reason that the applicant has provided for not requesting registration. 655 656

(a) the product has been developed exclusively for the treatment of conditions – particularly tropical 657

diseases – not endemic in the country of export; 658 (b) the product has been reformulated with a view to improving its stability under tropical conditions; 659 the product has been reformulated to exclude excipients not approved for use in pharmaceutical 660 products in the country of import; 661 (c) the product has been reformulated to meet a different maximum dosage limit for an active 662 ingredient; any other reason, please specify. 663

664 14

Not applicable means the manufacture is taking place in a country other than that issuing the product 665 certificate and inspection is conducted under the aegis of the country of manufacture. 666

667 15

The requirements for good practices in the manufacture and quality control of drugs referred to in the 668 certificate are those included in the thirty-second report of the Expert Committee on Specifications for 669 Pharmaceutical Preparations, WHO Technical Report Series, No. 823, 1992, Annex 1. 670 Recommendations specifically applicable to biological products have been formulated by the WHO 671 Expert Committee on Biological Standardization (WHO Technical Report Series, No. 822, 1992, 672 Annex 1). 673

674 16

This section is to be completed when the product-licencemarketing authorization holder or applicant 675 conforms to status (b) or (c) as described in note 8 above. It is of particular importance when foreign 676 contractors are involved in the manufacture of the product. In these circumstances the applicant should 677 supply the certifying authority with information to identify the contracting parties responsible for each 678 stage of manufacture of the finished dosage form, and the extent and nature of any controls exercised 679 over each of these parties. 680

681


page 23

The layout for this Model Certificate is available on diskette in WordPerfect from the Division of Drug 682 Management and Policies, World Health Organization, 1211 Geneva 27, Switzerland. 683


page 24

APPENDIX 2 684 685

MODEL STATEMENT OF MARKETING AUTHORIZATION 686

687

LICENSING STATUS OF PHARMACEUTICAL PRODUCT(S) 688 689

No. of Statement: ______________________________________________________________ 690

Certifying memberExporting (certifying) country): ___________________________________ 691

Requesting memberImporting (requesting) country): __________________________________ 692

693

Statement of marketing authorizationlicensing status of pharmaceutical 694

product(s) 1 695

696

This statement indicates only whether or not the following products are licensed to be put on the 697

market in the exporting country. 698

699

Applicant (name/address): _______________________________________________________ 700

701

Name of

product

Dosage

form

Active ingredient(s)2 and amount(s)

per unit dose:

Product-licenceMarketing

authorization no. and date

of issue3

702

The certifying authority undertakes to provide, at the request of the applicant (or, if different, the 703

product-licencemarketing authorization holder), a separate and complete certificate of a 704

pharmaceutical product (CPP) in the format recommended by the World Health Organization 705

(WHO), for each of the products listed above. 706

707

Address of certifying authority: ___________________________________________________ 708


Email address: __________________________ 710

711


713

Signature: ____________________________________________________________________ 714

715

Stamp and date: _______________________________________________________________ 716

717

This statement conforms to the format recommended by WHO. 718

719



page 25

721 Please refer to the guidelines for full instructions on how to complete this form and information on the 722 implementation of the Scheme. 723 724 The forms are suitable for generation by computer. They should always be submitted as hard copy, with 725 responses printed in type rather handwritten. 726 727 Additional sheets should be appended, as necessary, to accommodate remarks and explanations. 728 729

Explanatory notes 730

731 1 This statement is intended for use by importing agents who are required to screen bids made in 732

response to an international tender and should be requested by the agent as a condition of bidding. The 733 statement indicates that the listed products are authorized to be placed on the market for use in the 734 exporting country. A Certificate of a Pharmaceutical ProductCPP in the format recommended by 735 WHO will be provided, at the request of the applicant and, if different, the product-licencemarketing 736 authorization holder, for each of the listed products. 737


names. 740 741 3 If no product licencemarketing authorization has been granted, enter "not required", "not requested", 742

"under consideration" or "refused" as appropriate. 743 744 The layout for this Model Certificate is available on diskette in WordPerfect from the Division of Drug 745 Management and Policies, World Health Organization, 1211 Geneva 27, Switzerland. 746


page 26

APPENDIX 3 747 748

MODEL BATCH CERTIFICATE OF A PHARMACEUTICAL PRODUCTS 749

750

MANUFACTURERS/OFFICIAL1 BATCH CERTIFICATE OF A 751

PHARMACEUTICAL PRODUCT 752 753

This certificate conforms to the format recommended by the World Health Organization (WHO) 754

(general instructions and explanatory notes attached). 755

756

1. No. of Certificate: _______________________________________________________ 757

758

2. Importing (requesting) authority: ___________________________________________ 759

760

3. Name of product: _______________________________________________________ 761

762

3.1. Dosage form: __________________________________________________________ 763

764

3.2 Active ingredient(s)2 and amount(s) per unit dose: _____________________________ 765

____________________________________________________________________________ 766

____________________________________________________________________________ 767

768

3.2.1 Is the composition of the product identical to that registered in the country of export? 769

(yes/no/not applicable)3 770

If no: please attach formula (including excipients) of both products. 771

4. Product-licenceMarketing authorization holder4 (name and address): _________________ 772

___________________________________________________________________________ 773

___________________________________________________________________________ 774

775

4.1 Product-licenceMarketing authorization number4: _____________________________ 776

777

4.2 Date of issue4: _________________________________________________________ 778

779

4.3 Product licenceMarketing authorization issued by4: ____________________________ 780

781

4.4 Product certificate number4,5

: _____________________________________________ 782

783

5.1 Batch number: _________________________________________________________ 784

785

5.2 Date of manufacture: ____________________________________________________ 786

787

5.3 Shelf life (years): _______________________________________________________ 788

789

5.4 Contents of container: ___________________________________________________ 790

791


page 27

5.5 Nature of primary container: ______________________________________________ 792

793

5.6 Nature of secondary container/wrapping: ____________________________________ 794

795

5.7 Specific storage conditions: ______________________________________________ 796

797

5.8 Temperature range: _____________________________________________________ 798

799

6. Remarks6: ____________________________________________________________ 800

___________________________________________________________________________ 801

802

7. Quality analysis: 803

804

7.1 What specifications apply to this dosage form. Either specify the pharmacopoeia or 805

append company specifications.7 806

___________________________________________________________________________ 807

808

7.1.1 In the case of a product registered in the exporting country, have these company 809

specifications7 been accepted by the competent authority? (yes/no) 810

811

7.2 Does the batch comply with all parts of the above specifications? 812


814

7.3 Append certificate of analysis8

815

816

It is hereby certified that the above declarations are correct and that the results of the analyses 817

and assays on which they are based will be provided on request to the competent authorities in 818

both the importing and exporting countries. 819

820

Name and address of authorized person: _____________________________________________ 821

______________________________________________________________________________ 822

823


E-mail address: __________________________ 825

826


828

Signature: ____________________________________________________________________ 829

830

Stamp and date: _______________________________________________________________ 831

832


834 Please refer to the guidelines for full instructions on how to complete this form and information on the 835 implementation of the Scheme. 836 837


page 28

The forms are suitable for generation by computer. They should always be submitted as hard copy, with 838 responses printed in type rather handwritten. 839 840 Additional sheets should be appended, as necessary, to accommodate remarks and explanations. 841

842

Explanatory notes 843

844 Certification of individual batches of a pharmaceutical product is only undertaken exceptionally by the 845 competent authority of the exporting country. Even then, it is rarely applied other than to vaccines, sera and 846 biologicals. For other products, the responsibility for any requirement to provide batch certificates rests with 847 the product-licencemarketing authorization holder in the exporting country. The responsibility to forward 848 certificates to the competent authority in the importing country is most conveniently assigned to the importing 849 agent. 850 851 Any inquiries or complaints regarding a batch certificate should always be addressed to the competent 852 authority in the exporting country. A copy should be sent to the product- licencemarketing authorization 853 holder. 854 855 1 Strike out whichever does not apply. 856


names. 859 860 3 "Not applicable" means that the product is not registered in the country of export. 861 862 4 All items under 4 refer to the product licencemarketing authorization or the certificate of a 863

pharmaceutical product (CPP) issued in the exporting country. 864 865 5 This refers to the Certificate of a Pharmaceutical ProductCPP as recommended by WHO. 866 867 6 Indicate any special storage conditions recommended for the product as supplied. 868 869 7 For each of the parameters to be measured, specifications give the values that have been accepted for 870

batch release at the time of product registration. 871 872 8 Identify and explain any discrepancies from specifications. Government batch release certificates 873

issued by certain governmental authorities for specific biological products provide additional 874 confirmation that a given batch has been released, without necessarily giving the results of testing. 875 The latter are contained in the manufacturer's certificate of analysis. 876

877 The layout for this Model Certificate is available on diskette in WordPerfect from the Division of Drug 878 Management and Policies, World Health Organization, 1211 Geneva 27, Switzerland. 879


page 29

APPENDIX 4 880 881

GLOSSARY AND INDEX 882 883

In order to facilitate understanding, this glossary explains terms in the guidelines and/or refers to 884

relevant sections. It is considered as supplementary information and not as being a formal part of 885

the Scheme. 886

For clarity, all definitions that have been taken from the glossary of the WHO Technical Report 887

Series No. 823, 1992 are preceded by an asterisk. 888

889

abuse of Scheme. 890

See section 4.9 and 5.2 of the guidelines. 891

892

active pharmaceutical ingredients. 893

Any substance or mixture of substances intended to be used in the manufacture of a 894

pharmaceutical dosage form and that, when so used, becomes an active ingredient of that 895

pharmaceutical dosage form. Such substances are intended to furnish pharmacological activity or 896

other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to 897

affect the structure and function of the body. See section l.5, 4.4 and 4.5 of the guidelines 898

899

addresses of competent authorities. : 900

See item 2.62 and 3.3 of the guidelines. 901

902

applicant. 903

The party applying for a product certificate. This is normally the product 904

licencemarketing authorization holder. In all instances, having regard to commercial 905

confidentiality of certain data, the competent authority in the exporting country must obtain 906

permission to release these data from the product licencemarketing authorization holder, or, in 907

the absence of a product licencemarketing authorization, from the manufacturer. 908

909

authentication of certificates. 910

See section 4.9 of the guidelines. 911

912

*batch (or lot). 913

A defined quantity of a starting material, packaging material, or product processed in a 914

single process or series of processes so that it can be expected to be homogeneous. It may 915

sometimes be necessary to divide a batch into a number of sub-batches, which are later brought 916

together to form a final homogeneous batch. In the case of terminal sterilization, the batch size is 917

determined by the capacity of the autoclave. In the case of continuous manufacture, the batch 918

must correspond to a defined fraction of the production, characterized by its intended 919

homogeneity. The batch size can be defined either as a fixed quality or as the amount produced 920

in a final time interval.It may sometimes be necessary to divide a batch into a number of sub-921

batches, which are later brought together to form a final homogeneous batch. 922

923

*Bbatch certificate. 924


page 30

A document containing information, as set out in Annex 3 of the guidelines for use, will 925

normally be issued for each batch by the manufacturer. Furthermore, exceptionally a batch 926

certificate may be validated or issued by the competent authority of the exporting country, 927

particularly for vaccines, sera and other biological products. The batch certificate travels with 928

every major consignment (see also section 3.14 of the guidelines). 929

930

*batch number (or lot number). 931

A distinctive combination of numbers and/or letters which uniquelyspecifically identifies 932

a batch on the labels, itsthe batch records, and correspondingthe certificates of analysis, etc. 933

934

*bulk product. 935 Any product that has completed all processing stages up to, but not including, final 936

packaging. 937

938

certifying authority. 939

This is the competent authority that issues product certificates. It shall ensure that it 940

possesses the capacities listed in section 2.2 and 2.32.4 of the guidelines. 941

942

charges for product certificates. 943


945

competence and evaluation of national authority. See sections 2.2, 2.3, 2.9 and 4.2 of 946

the guidelines. 947

948

competent authority. 949

This is the national or regional authority as identified in the formal letter of acceptance in 950

which each Member State or regional authority informs WHO of its intention to participate in the 951

Scheme. The competent authority can issue or receive certificates. The extent of participation 952

should be indicated in the letter of acceptance. (see section 2.1 of the guidelines) 953

WHO makes available upon request a continuously updated list of addresses of competent 954

authorities and, when applicable, the specific conditions for participation (see section 2.6 of the 955

guideline). 956

957

dosage form. 958

The form of the completed pharmaceutical productpreparation, e.g. tablet, capsule, elixir, 959

suppository. 960

961

drug regulatory authority. 962

An national or regional authority responsible for the registration of and other regulatory 963

activities connecting pharmaceutical products. appointed by the government of a Member State 964

to administer the granting of Marketing Authorizations for pharmaceutical products in that 965

country. 966

967

expiry date. 968


page 31

The date given on the individual container (usually on the label) of a product up to and 969

including which the product is expected to remain within specifications, if stored correctly. It is 970

established for each batch by adding the shelf life to the date of manufacture. 971

972

*finished pharmaceutical product. 973

A finished dosage form of a pharmaceutical product that has undergone all stages of 974

manufactureproduction, including packaging in its final container and labelling. 975

976

free sale certificate. 977


979

good manufacturing practices. 980

That part of quality assurance which ensures that products are consistently produced and 981

controlled to the quality standards appropriate to their intended use and as required by the 982

marketing authorization. 983

984

good manufacturibng practices certificate. 985


987

importing agents, guidelines for. 988


990

International Nonproprietary Name (INN). 991

The shortened scientific name based on the active ingredient. WHO is responsible for 992

assigning INNs to pharmaceutical substances. 993

994

language of product certificates. 995


997

Licence holder 998

An individual or a corporate entity being in the possession of a marketing authorization of a 999

pharmaceutical product. 1000

1001

Licensee 1002

An individual, or corporate entity responsible for the information, the publicity, the 1003

pharmacovigilance, the surveillance of batches, and if applicable of their withdrawal, for a 1004

pharmaceutical product, whether or not it be the holder of the marketing authorization. 1005

1006

limits of certification by competent authority. 1007


1009

Lot 1010

See batch 1011

1012

*manufacture. 1013


page 32

All operations of purchase of materials and products, production, quality control, release, 1014

storage, distributionshipment of pharmaceuticalfinished products, and related controls. 1015

1016

*manufacturer. 1017

A company that carries out operations such as production, packaging, repackaging, 1018

labelling and relabelling of pharmaceuticals.at least one step of manufacture. (for categories of 1019

manufacturer, see Appendix 1, Explanatory Note No. 7). 1020

1021

marketing authorization. 1022

A legal document issued by the competent drug regulatory authority for the purpose of 1023

marketing or free distribution of a product after evaluation for safety, efficacy and quality. It 1024

must set out, inter alia, the name of the product, the pharmaceutical dosage form, the quantitative 1025

formula (including excipients) per unit dose (using INNs or national generic names where they 1026

exist), the shelf -life and storage conditions and packaging characteristics. It specifies the 1027

information on which authorization is based (e.g. “The product(s) must conform to all the details 1028

provided in your application and as modified in subsequent correspondence.”). It also contains 1029

the product information approved for health professionals and the public, the sales category, the 1030

name and address of the holder of the authorization and the period of validity of the 1031

authorization. Once a product has been given marketing authorization, it is included on a list of 1032

authorized products – the register – and is often said to be “registered” or to “have registration”. 1033

Market authorization may occasionally also be referred to as a “licence” or “product licence”. 1034

See product licence 1035

1036

marketing authorization holder. 1037

An individual or a corporate entity being in the possession of a marketing authorization 1038

of a pharmaceutical product. 1039

1040

*pharmaceutical product. 1041

Any material and productmedicine intended for human use or veterinary useproduct 1042

administered to food-producing animals, presented in its finished dosage form or as a starting 1043

materialan active ingredient for use in such a dosage form, that is subject to control by 1044

pharmaceutical legislation in both the exporting state and/or the importing state. 1045

1046

product. 1047

See pharmaceutical product. 1048

1049

product certificate. 1050

A document containing the information as set out in Appendix 1 of the guidelines that is 1051

validated and issued for a specific product by the competent authority of the exporting country 1052

or regional authority and intended for use by the competent authority in the importing country or 1053

– in the absence of such an authority – by the drug procurement authority (see also section 3.5 of 1054

the guidelines). 1055

1056

product information. 1057

This is the approved product information referred to in section 4.7 of the guidelines and 1058

item 2.A.5 of the product certificate. It normally consists of information for health professionals 1059


page 33

and the public (patient information leaflets) as approved in the exporting country, and when 1060

available, a data sheet or a summary of product characteristics approved by the drug regulatory 1061

authority. 1062

1063

Product licence 1064

A legal document issued by the competent drug regulatory authority for the purpose of marketing 1065

or free distribution of a product after evaluation for safety, efficacy and quality. It must set out, 1066 inter alia, the name of the product, the pharmaceutical dosage form, the quantitative formula 1067

(including excipients) per unit dose (using INNs or national generic names where they exist), the 1068

shelf-life and storage conditions and packaging characteristics. It specifies the information on 1069

which authorization is based (e.g. “The product(s) must conform to all the details provided in 1070

your application and as modified in subsequent correspondence.”). It also contains the product 1071

information approved for health professionals and the public, the sales category, the name and 1072

address of the holder of the authorization, and the period of validity of the authorization. Once a 1073

product has been given marketing authorization, it is included on a list of authorized products – 1074

the register – and is often said to be “registered” or to “have registration”. Market authorization 1075

may occasionally also be referred to as a “licence” or “product licence”. 1076

1077

Product licence holder 1078

See licence holder 1079

1080

*production. 1081

All operations involved in the preparation of a pharmaceutical product, from receipt of 1082

materials, through processing, and packaging, and repackaging, labelling and relabelling, to 1083

completion of the finished product. 1084

1085

registration. 1086

Any statutory system of approval required at national or regional level as a precondition 1087

for introducing a pharmaceutical product onto the market. 1088

1089

Registration certificate 1090

See product licence 1091

1092

specifications. 1093

A list of detailed requirements with which the products or materials used or obtained 1094

during manufacture have to conform. They serve as a basis for quality evaluation.See Appendix 1095

3, Batch Certificate, explanatory note 7. 1096

1097

Sstatement of licensing status. 1098

See section 3.13 of the guidelines and Annex 2 1099

1100

summary basis of approval. 1101

This refers to the document prepared by some national regulatory authorities, that 1102

summarizes the technical basis on which the product has been licensed (see section 4.7 of the 1103

guidelines and explanatory note 9 of the product certificate contained in Annex 1). 1104

1105


page 34

Summary product characteristics (SPC). 1106

Product information as approved by the drug regulatory authority. The SPC serves as the 1107

basis for production of information for health personnel as well as for consumer information on 1108

labels and leaflets of medicinal products and for control of advertising. (see also product 1109

information). 1110

1111

tenders and brokers. 1112


1114

transmission of product certificate. 1115


1117

validity of product certificate. 1118


1120

when to request a product certificate. 1121

See item 3.5 of the guidelines. 1122

1123

WHO responsibility. 1124

See item 5.4 of the guidelines. 1125

1126

1127

REFERENCES 1128

1129

1. WHO Expert Committee on Specification for Pharmaceutical Preparations. Thirty-second 1130

report. Geneva, World Health Organization, 1992:18-22 (WHO Technical Report Series, 1131

No. 823) 1132

1. WHO good distribution practices for pharmaceutical products. In: WHO Expert 1133

Committee on Specifications for Pharmaceutical Preparations. Forty-fourth report. 1134

Geneva, World Health Organization, 2010, Annex 5 (WHO Technical Report Series, No. 1135

957). 1136

2. WHO guidelines on quality risk management. In: WHO Expert Committee on 1137

Specifications for Pharmaceutical Preparations. Forty-seventh report. Geneva, World 1138

Health Organization, 2013, Annex 2 (WHO Technical Report Series, No. 981). 1139

3. WHO good manufacturing practices for pharmaceutical products: main principles. In: 1140

WHO Expert Committee on Specifications for Pharmaceutical Preparations. Forty-eighth 1141

report. Geneva, World Health Organization, 2014, Annex 2 (WHO Technical Report 1142

Series, No. 986). 1143


page 35

4. Model quality assurance system for procurement agencies. In: WHO Expert Committee 1144

on Specifications for Pharmaceutical Preparations. Forty-eighth report. Geneva, World 1145

Health Organization, 2014, Annex 3 (WHO Technical Report Series, No. 986). 1146

1147

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proposal for revision of the who certification … · working document qas/18.768 page 2 36...

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