assessment tool based on the model quality … · working document qas/13.555 august 2013...

Working document QAS/13.555

August 2013

RESTRICTED

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ASSESSMENT TOOL 3

BASED ON THE MODEL QUALITY ASSURANCE SYSTEM 4

FOR PROCUREMENT AGENCIES 5

AIDE-MEMOIRE FOR INSPECTION 6

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DRAFT FOR COMMENT 9

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© World Health Organization 2013 14

All rights reserved. 15

This draft is intended for a restricted audience only, i.e. the individuals and organizations having received this draft. The draft 16 may not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part or in whole, in 17 any form or by any means outside these individuals and organizations (including the organizations' concerned staff and 18 member organizations) without the permission of the World Health Organization. The draft should not be displayed on any 19 web site. 20

Please send any request for permission to: 21

Dr Sabine Kopp, Manager, Medicines Quality Assurance Programme, Quality Assurance & Safety: Medicines, Department 22 of Essential Medicines and Health Products, World Health Organization, CH-1211 Geneva 27, Switzerland; e-mail: 23 [email protected]. 24

The designations employed and the presentation of the material in this draft do not imply the expression of any opinion 25 whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or 26 of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate 27 border lines for which there may not yet be full agreement. 28

The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or 29 recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors 30 and omissions excepted, the names of proprietary products are distinguished by initial capital letters. 31

All reasonable precautions have been taken by the World Health Organization to verify the information contained in this 32 draft. However, the printed material is being distributed without warranty of any kind, either expressed or implied. The 33 responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health 34 Organization be liable for damages arising from its use. 35

This draft does not necessarily represent the decisions or the stated policy of the World Health Organization. 36 37

Should you have any comments on the attached text, please send these to

Dr Sabine Kopp, Manager, Medicines Quality Assurance Programme, Quality

Assurance and Safety: Medicines, World Health Organization, 1211 Geneva 27,

Switzerland; e-mail: [email protected]; fax: (+41 22) 791 4730 ([email protected]) and to

Ms Marie Gaspard ([email protected]), by 23 September 2013.

Working documents are sent out electronically and they will also be placed on the

Medicines web site for comment. If you do not already receive directly our draft

guidelines please let us have your e-mail address (to [email protected]) and we will

add it to our electronic mailing list.


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SCHEDULE FOR THE PROPOSED ADOPTION PROCESS OF DOCUMENT QAS/13.555: 39

ASSESSMENT TOOL 40

BASED ON THE MODEL QUALITY ASSURANCE SYSTEM FOR PROCUREMENT 41

AGENCIES 42


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Need for a Model Quality Assurance System Assessment

Tool identified in a WHO-Global Fund to Fight Aids,

Tuberculosis and Malaria (GFATM) joint stakeholders

meeting

August 2011

Working group, consisting of representatives from:

CHMP, Crown Agents, GDF, GFATM, ICRC, IDA,

MSF, MSH, PFSC, QUAMED, UNICEF, UNION,

UNOPS, USAID and WHO, created to develop a

harmonized assessment tool

Several meetings were held, along

with communications via email

Outcome: Model Quality Assurance System Assessment

Tool – inspection of a procurement agency circulated for

comments

August 2013

Compilation of comments

September 2013

Presentation to 48th meeting of the WHO Expert

Committee on Specifications for Pharmaceutical

Preparations

14-18 October 2013

Any further action as required, as recommended by the

WHO Expert Committee on Specifications for

Pharmaceutical Preparations


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ASSESSMENT TOOL 49

BASED ON THE MODEL QUALITY ASSURANCE SYSTEM FOR PROCUREMENT 50

AGENCIES 51


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CONTENTS 56

page 57

58

1. Introduction ………………………………………………………………………... 59

2. Purpose …………………………………………………………………………….. 60

3. Scope ………………………………………………………………………………. 61

4. Assessment tool ……………………………………………………………………. 62

5. Revision history ……………………………………………………………………. 63 64

65

1. INTRODUCTION 66

67

The Expert Committee on Specifications for Pharmaceutical Preparations of the World 68

Health Organization (WHO) adopted a Model Quality Assurance System for Procurement 69

Agencies (MQAS) during a meeting in Geneva, Switzerland in 2005. This was subsequently 70

published as Annex 6 in the Technical Report Series, No. 937 in 2006. 71

72

The Global Fund to Fight Aids, Tuberculosis and Malaria (GFATM) Secretariat coordinated 73

this project with the aim to prepare a harmonized assessment tool based on the WHO 74

document: Model quality assurance system for procurement agencies (MQAS); WHO 75

guidelines on good storage practices (GSP) and WHO Guidelines on good distribution 76

practices (GDP). (For current versions, see www.who.int/medicines.) 77

78

This harmonized tool was developed by a working group consisting of representatives from 79

the following organizations: CHMP, Crown Agents, GDF, ICRC, IDA, MSF, MSH, PFSCM, 80

QUAMED, UNICEF, UNION, UNOPS and USAID. 81

82

2. PURPOSE 83

84

This harmonized tool was developed by the working group with the objective that it could be 85

utilized with the aim of better use of resources by coordinating procurement agency (PA) 86

assessments; and working towards mutual recognition of PA assessment findings. 87


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3. SCOPE 89

90

The assessment tool is based on the six modules in the MQAS: 91

92

Module I General requirements for procurement agencies 93

Module II Prequalification 94

Module III Purchasing 95

Module IV Receiving and storage 96

Module V Distribution 97

Module VI Reassessment 98

99

The tool covers these topics in different modules below. The logical flow considered is the 100

quality system and infrastructure of the PA under assessment, how the PA performed 101

prequalification, then purchasing of the products followed by the receiving and storage 102

thereof. The last two modules then focus on the receiving of orders and dispatch of products 103

followed by the reevaluation concept. 104

105

4. ASSESSMENT TOOL 106

107

The tool should be used by qualified, experienced persons when assessing PA (including 108

wholesalers, distributors) for compliance with recommended international standards. It can 109

also be useful for a PA when doing a self-assessment. 110

111

The tool is not checklist, but serves as a document to help and remind inspectors as to what 112

should be assessed during inspections of PAs. 113

114

Module I: General requirements for procurement agencies 115

116

This Module covers general requirements for procurement agencies including premises, 117

equipment, transport and documentation (such as SOPs, confidentiality, code of conduct and 118

complaint handling). It should be used in all cases of assessment of a procurement agency. 119

(Modules 2 to 6 may be used depending on the activities performed by the procurement 120

agency.) 121


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122

Area of

operation

Note Critical aspects

Premises,

Equipment,

Furniture,

Transport

General

• Licensed to operate

• Sufficient space (offices for

personnel, products, documents,

samples, etc.)

• Suitable conditions

• Necessary furniture

• Working office equipment

• Stationery and consumables

• Telephone and email access

• Appropriate transport available

Compliance with legislation

(licence)

There must be a sufficient and

functional infrastructure to enable

the PA to perform its activities

Human

resources

Personnel

• Compliance with national

legislation (e.g. responsible

person)

• Sufficient number of people

• Key personnel – quality

assurance, prequalification,

purchasing, storage and

distribution

• Quality assurance/

prequalification and purchasing

independent of one another

• Support staff

• Contracted personnel and

agreements

Training, education and

experience


Quality assurance/prequalification

and purchasing independent of one

another (personnel – and reporting

structure)


page 6

Organization Organization chart

• Authorized and current

• In line with the job descriptions

Job descriptions

• Written job descriptions

• Signed and dated

Ethical

considerations

Conflict of interest

• Policy on conflict of interest is

observed

• Signed declaration of interest.

No vested interests

Code of conduct

• Written, authorized and

implemented

• Covers conduct of personnel

• All personnel to comply with a

code of conduct

Confidentiality

• Relevant product information

kept confidential

• Confidentiality agreements exist

Declaration and management of

conflict of interest

Computers Appropriate hardware and software

• Sufficient capacity and memory

• Access control

• Data transfer procedures

• Reliable and accurate quality

and management of data and

information

• Data storage (e.g. hard copies)

If used, reliable data management

(including access control)


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• Back-up at defined intervals,

storage, access, readable

• Virus protection programme

and firewall

• Technical support

• Maintenance

• Trained personnel

Financial

systems

• Adequate banking facilities

• Signatories of bank accounts

appointed

• Accounting system in place

• National and international

financial transactions

• Financial transactions

performed without delay

• Funds available

• Regular financial audits are

performed.

Documentation Comprehensive documented system

• Covers policies, guidelines,

norms, standards, manuals,

procedures, records and related

documents

• SOPs for activities

Quality manual (QM)

• Contains a quality policy

• Evidence of QM

implementation, QM

maintained, reviewed and

amended as necessary

Activities and responsibilities

described in standard operating

procedures (SOPs) which are

implemented and followed;

Records reflecting activities


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Standard operating procedures

• SOP for writing an SOP

followed

• Written, clear, detailed SOPs for

activities

• Controlled, distributed and

retrieved when required

• Available for use

• SOPs are reviewed periodically

• Quality risk management

(QRM) principles applied

Style and layout

• SOPs in defined format

• Signed and dated

Activities to be

covered by

SOPs

All activities should be covered by

SOPs and include:

• prequalification

• purchasing

• receiving and storage

• distribution

• training

• handling of complaints

• handling of recalls

• document/record control

including distribution and

retrieval of SOPs

• self-inspection

• monitoring of environmental

conditions (e.g. temperature)

• monitoring supplier

performance

Written SOPs followed for

prequalification, purchasing,

storage, distribution, complaints,

recalls, identifying and reporting

substandard/spurious/falsely-

labelled/falsified/counterfeit

(SSFFC) medical products;

Change control


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• identifying and reporting

SSFFC medical products

• evaluating offers received

• ordering product(s) from

supplier or manufacturer

• change control

• variations

• corrective and preventive action

(CAPA)

List of

prequalified

products,

manufacturers

and suppliers

• Current, authorized, access-

controlled list

• Based on the outcome of

evaluation

• Contains required information

• Product-, manufacturing site-

and supplier-specific (where

relevant)

• A key person responsible

A controlled list is maintained

Maintenance

of records

• Records of all operations kept

• Sufficient space for archiving

• Access controlled

• Retention period appropriate

Records are available for review

Contract

arrangements

• Written contracts for delegated

activities

Written, valid agreements in place

123

124

125


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126

Module II: Prequalification 127

128

Prequalification is one of the key elements in ensuring purchase and supply of 129

pharmaceutical products of acceptable quality. The prequalification process can be 130

subdivided into two major parts, i.e. product-related assessment and manufacturer-related 131

inspection. 132

133

Area of

operation


Principles • Documented policy and

procedures for

prequalification

• Include assessment of

product and manufacturers/

suppliers

• If delegated – written

agreement in place

Key persons

and

responsibilities

• Responsible personnel

identified

• Independent from the

purchasing personnel

• Job descriptions

• Communication between

evaluation and inspections

Evaluation of product information

(Evaluators)

• List of evaluators

• Suitable qualifications and

experience


• Contracted external

Qualified, trained personnel perform

prequalification activities (including

assessment and inspections)

Quality assurance/prequalification and

purchasing independent of one another

(personnel and reporting)


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evaluators used

(confidentiality, conflicts of

interest and financial

resources, references)

Inspection of manufacturing sites

(Inspectors)

• List of inspectors


• Qualified, trained,

experienced

• Contracted inspectors –

confidentiality and no

conflict of interest

Key steps in

prequalification

defined

Step 1. Soliciting information

• Procedures for preparation of

detailed, clear specifications;

soliciting information;

receiving and processing of

the information

• Policy and procedure for

handling late submissions

• Recording of data received

• Procedure for submitting

product information publicly

available and accessible

• Product information to be

submitted defined (as a

minimum, see product

questionnaire)

Step 2: Receive product information

• Written procedures for

Evaluation of product data and

information as well as the criteria used

to approve or reject a product

Ensuring compliance with GMP


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receiving, identification,

marking files, containers and

samples, and sufficient space

for unpacking and storage

• Procedure to ensure

traceability of the product

information

• Personnel available

Step 3: Screen product information

• SOP: screen for completeness

• A screening form used

• Record of screening kept

• Outcome communicated to

manufacturer/supplier

Step 4: Evaluate product information

• Follow SOP to evaluate

against requirement

• Time frames

• Evaluation report for each

product exists

• Outcome communicated to

the manufacturer/supplier

• Response invited where

needed

• Outcome accepted or rejected

• Evaluation report kept as

record

• Samples analysed if needed

(see also monitoring below)


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Step 5: Plan, prepare and perform

inspections

General points

• Evidence of GMP

compliance

• Site of manufacture known

• Site inspection policy

• Contract manufacturing sites

known

Control over active

pharmaceutical ingredients

(APIs) (inspection risk based)

Plan

• SOP and recording system

for inspection planning

• Procedure and data reviewed

as part of preparation for

inspection (e.g. site master

file)

Conduct

• SOP: how to perform an

inspection

• Scope: data and information

verified and WHO GMP

compliance assessed

• If not done – conditions for

waiving on-site inspections

Inspection report

• Inspection report for each site

inspected

• Outcome communicated

• CAPA requested, received


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and reviewed

• Conclusion or outcome

• Copy of report kept

Step 6: Finalize assessment process

• Written procedure followed

• Covers product evaluation

plus laboratory results and

inspection outcome

• Responsible persons

(decision-taking) and reasons

for decision

• Outcome communicated

• List of prequalified products,

manufacturers and suppliers

• Agreement between PA and

supplier/manufacturer

• List reviewed and updated at

regular intervals

Cost recovery

• If used, transparent procedure

• Fee-for-services structure

134

Module III: Purchasing 135

136

Procurement should be done with the aim of purchasing effective, quality assured products, 137

and not be focused on price alone. The term “procurement” in this Module relates specifically 138

to the purchase of health sector goods from manufacturers or suppliers. The module goes on 139

to describe the key activities in purchasing pharmaceutical products, as well as the 140

recommended organizational structure of the procurement agencies which carry out these key 141

activities. 142

143

144


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Area of operation Note Critical aspects

Procurement strategies • Policy: suppliers are selected

and monitored through a

process that takes into account

product quality, service

reliability and performance,

delivery time, ethics, legal

status, financial viability and

minimum order quantities;

Purchase prequalified products (from

manufacturers/suppliers)

• Efficient and transparent

management

• Financial management

procedures

• Competitive procurement

methods

• Procedure to calculate lowest

possible total cost

• Procurement and purchasing

procedures are transparent

• Independent contract review

• Purchasing and tender

documents list all

pharmaceutical products by

their international

nonproprietary name (INN)

or national generic names

• Intellectual property rights are

respected in accordance with

best practice and national law

Purchasing prequalified

products


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Procurement methods • Responses are responsive to

the defined terms and

conditions and are examined

from invited suppliers

• Adjudication procedure

• Explicit criteria for awarding

contracts

• Informed of the outcome

• Restricted tender

• Prequalified products and

suppliers

• Competitive negotiation

• Direct procurement

Adjudication procedure and

related records

Use a defined, transparent

procurement method

Key activities • Develop a list or catalogue of

products (INN)

• Develop specifications for the

products

Quantification

• Methods of product

quantification

• Quantities purchased based on

reliable estimate

Procurement method

• According to their policy and

procedures

Organization and

responsibilities

• Personnel with appropriate

qualifications and training


• Independent from those

responsible for

prequalification and quality

assurance

• Procurement planned


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Monitoring of the

performance or

prequalified products,

manufacturers/suppliers

• Procedure for continuous

monitoring of the

performance of products,

manufacturers and suppliers

Monitoring may include:

• review of quality control

results

• verification that the product

batches supplied have been

manufactured in compliance

with standards and

specifications accepted in the

product information through

inspection;

• adverse events

• random samples of batches

supplied analyzed (risk-based

approach)

• independent testing – reliable

quality control laboratory (see

selection criteria for quality

control laboratory)

• certificates of analysis

available where appropriate

• status of the laboratory (e.g.

authorized, accredited)

• handling of out-of-

specification results

• monitoring of complaints

• outcome of inspection of

manufacturing sites

• outcome of reassessment of

product information

Handling out of specification

results

Monitoring performance of

products, manufacturers and

suppliers and action taken by

the PA in case of non-

compliance


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• monitoring of direct and

indirect product costs

• monitoring of adherence to

delivery schedules

• contract terms and conditions

• tracking system (values of

contracts awarded, total

purchases, performance)

Donations • Written procedure

145

Module IV: Receiving and storage 146

147

The procurement agency should ensure that the pharmaceutical products purchased are 148

received and stored correctly and in compliance with applicable legislation and regulations. 149

Products should be received and stored in such a way that their quality and integrity is 150

preserved, batch traceability is maintained and stock can be rotated. 151

152

Area of

operation


General

arrangements

• Received and stored correctly

• Quality and integrity is

maintained

• Batch traceability

• Stock rotation

• Unidirectional flow

• Security of materials and

products

• Subcontracting

Procedures followed for receiving

and storage

Batch traceability

Pre-shipment

quality control

• Batches released by the

manufacturer (certificate of

analysis (CoA))

• Batches additionally tested

(risk-based approach) prior to

Batch release with CoA (meeting

specifications)


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shipment to PA

• Selection criteria for quality

control laboratory

Receiving of

stock

• Receiving and dispatch bays

• Incoming containers cleaned,

quarantined

• Review of CoAs

• Released for use or

distribution (responsible

person involved)

Checks on receipt:

• order, delivery note, labels and

transport conditions, integrity

of packages and seals and for

uniformity of the containers

Visual inspection for:

• contamination; tampering and

damage; expiry date,

compliance with labelling,

packaging instructions

• suspect containers and

damaged containers – recorded

and investigated

Goods received and checked

according to an appropriate SOP –

supported by records

Products released by responsible

person

Post-

procurement

control

• Random sampling for

independent laboratory

analysis

• Selection criteria for quality

control laboratory

• SOP and national legislation

• Representative samples –

sampling plans and

instructions (risk assessment)

Action taken in case of non-

conforming product


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• Appropriately trained and

qualified personnel

Rejected

materials

• SOP for rejected products

• Separate storage or validated

computerized system

• Action approved by authorized

personnel and recorded

Rejected materials kept separately,

access controlled and handled

appropriately

Storage of

materials/

products

Personnel

• Trained

• Personal hygiene and

sanitation

• Appropriate garments

Storage areas

• No unauthorized access

• Sufficient space

• Adequate ventilation,

temperature and relative

humidity

• Conditions checked,

monitored and recorded

• Segregation of rejected,

expired, recalled or returned

stock

• Toilet and washing facilities

separated from storage areas

• Narcotics/psychotropic

medicines as per national

legislation

• SOP for fire control

• No smoking and eating

• SOP and records for cleaning

• Waste management

• Pest-control

Access controlled and sufficient

space

Appropriate conditions for storage


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• SOP for handling spillages

Storage conditions

• As established by the

manufacturer

• Orderly, batch segregation,

stock rotation, first expired-

first out (FEFO)

• Stored off the floor

• Space to permit cleaning and

inspection

• Pallets in a good state of

cleanliness and repair

• Stacking of products without

damage

• Freeze-sensitive products –

use monitoring devices

• Cold rooms (qualification,

temperature mapping, alarm,

monitoring, records, back-up

system in case of failure)

Monitoring of storage conditions

• Temperature mapping protocol

and report

• Calibrated sensors/devices

• Ongoing monitoring with

records

• Out-of-limit and out-of-trend

results investigated, action

taken

Miscellaneous and hazardous

materials

• Rodenticides, insecticides,

fumigating agents and


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sanitizing materials

• Toxic substances and

flammable materials

Re-packaging

and re-labelling

• If performed – in compliance

with national legislation and

WHO GMP

Compliance with national legislation

and WHO GMP

Stock control

• Validated stock control system

• Batch number control and

expiry dating

• Periodic stock reconciliation

• Significant stock discrepancies

investigated

• Records maintained

• Damaged containers handled

Control of obsolete and outdated

materials and products

• SOP

• Regular checks

Recalled materials and products

• SOP

• Written records of actions with

signatures

• Products identified, recorded,

reconciled and stored

separately

• Decision by appropriately

qualified and experienced

member of staff

Returned goods

• SOP

• Quarantined and assessed

• Resale conditions

• Destruction in compliance

Stock control in place (e.g.

reconciliation, obsolete materials,

recalled products, returned goods,

FEFO and waste)


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with national requirements

• Records

Waste materials

• SOP

• Safe storage while awaiting

disposal

• Toxic substances and

flammable materials

• No accumulation

• Safe disposal, national

regulations

Documentation:

written

instructions and

records

• SOPs for activities

• Handling of expired stock

• Ensuring batch traceability

• Records for storage

conditions, precautions

• National regulations

concerning labels and

containers

• Comprehensive records of all

activities

• Retention of records

Record keeping ensuring traceability

(e.g. receiving, issuing, expired

goods)

153

Module V: Distribution 154

155

The PA (or contracted party) should have a well-managed distribution system meeting the 156

objectives of ensuring constant supply of quality medicines. Distribution should be done in 157

accordance with general principles of GMP. 158

159


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160

Area of

operation


General • Constant supply of

medicines

• Minimize medicines losses

(spoilage and expiry)

• Accurate inventory records

• Prevent theft and fraud

Transport

conditions

• Transport process has no

negative impact on product

• Required storage conditions

maintained

• Temperature excursions –

risk assessment

Appropriate transport conditions

Cold chain • Validated process

• Applied where needed

• Appropriate containers

• Packaging procedure

• Cooling agents used

• Calibrated monitoring

devices

• Monitoring records reviewed,

maintained

Cold chain validated, maintained and

monitored

Dispatch

procedures

• Compliance with legislation

• Authorized recipients

• Procedures in place

• Special packaging

requirements observed where

needed

• Dispatch and transport after

receipt of a delivery order


Authorized recipients


page 25

Dispatch

containers

• Provide protection

• Appropriately labelled

• Prevent theft (e.g.

locked/wrapped)

Dispatch

records

• Detailed records kept (e.g.

date, customer name and

address; product name and

batch number and quantity)

• Products and batches

traceable

• Discrepancies investigated

Records ensure traceability of goods

Port of entry • Storage conditions met

• Temperature-sensitive

products handled

appropriately

• Security measures in place

(e.g. prevent theft, fraud and

bribery)

161

Module VI: Reassessment 162

163

Quality of products and services should be continuously monitored. This process includes 164

reassessment. 165

166

Area of

operation


Reevaluation

of

manufacturers

• Reinspection frequency based

on risk assessment

• Within five-year cycle

• Change control

• Mechanism for suspension

and withdrawal

Reinspection policy and procedure

followed


page 26

Reevaluation

of products

• Reevaluation procedure

• Within five-ear cycle

• Variations procedure

Reevaluation of product policy and

procedure followed

Monitoring

performance of

contractors

• Written procedure

• Covers continuous

monitoring, periodic review

and renewal of contracts

• System for documenting

service problems

Procedure followed for monitoring

performance

167

5. REVISION HISTORY 168

169

Date Version number Reasons for revision

February 2013 1.2013 Original

June 2013 2.2013 Editing in line with revisions proposed in

MQAS

170

171

172


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ANNEX 1 173

INTER-AGENCY FINISHED PHARMACEUTICAL PRODUCT QUESTIONNAIRE V2 174

175

176

Please fill out one form separately for each pharmaceutical product 177

Section 1: Administrative section 178

179

1.1 Product Identification 180

181 1.1.1 Active pharmaceutical ingredient(s) (use INN if any):_____________________ 182

183

1.1.2 Generic name of the product:______________________________________ 184

185

1.1.3 Trade (proprietary) name (if any):___________________________________ 186

187

1.1.4 Dosage form: 188

� Tablets � Capsules � Injectable � Syrups/oral liquids 189

190

� Other: (Please specify) 191

192

1.1.5 Strength per dosage unit: ______________________________________ 193

194

1.1.6 Route of administration: 195

�Oral � I.M. � I.V. � S.C. � Other (Please specify) 196

197

1.1.7 Please provide the formulation of the product (complete qualitative and quantitative 198

composition including active ingredient(s), overages if any and excipients). Mention 199

specifically if the product is a fixed-dose combination (FDC) or Copackaged 200

(Annex A) 201

_________________________________________________________ 202

203

_________________________________________________________ 204

205

_________________________________________________________ 206

207

1.2 Packaging 208 209

1.2.1 Description and materials used for primary packaging1 and pack size (quantity of 210

dosage-form units per pack): Annex B 211

212

1.2.2 Pack size and Description of secondary packaging materials: Annex C 213

214

1 For example, HDPE bottle, Alu-Alu strip, neutral glass vial.


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Contact details 215

216

1.3 Manufacturer identification 217 218

Name, address and activities of the manufacturer and manufacturing site(s) (or contract 219

manufacturer(s): 220

221

Name of

manufacturer,

contract

manufacturer if

any

Reference of

manufacturing

licence, date and

expiry date, if

any

Physical address.

Please specify

units, block if

existing

Telephone

number,

facsimile

number and

email contact

details

Activity (e.g.

packaging)

222

1.4 Supplier identification 223

(to be filled in if not identical to that indicated in 1.3) 224

225

Name of company:_________________________________________ 226

227

Physical address (complete details required):_____________________________ 228

_____________________________________________________________ 229

230

Telephone number:__________________ 231

232

Fax:_____________________________ 233

234

Website:___________________________________________________________ 235

236

Email:___________________________________ 237

238

Link with the product 239 240

Marketing licence holder Manufacturer 241

Distributor/wholesaler Other 242

243

1.5 Note for the applicant 244 245

Please note that the information in this questionnaire can be shared confidentially among 246

ICRC, MSF, WHO and UNICEF for procurement purposes. If you have any objection, please 247

indicate to the relevant agency that you are dealing with. 248

249

Has the dossier been submitted to any of the following agencies (ERP, ICRC, MSF, The 250

Union, WHO procurement centre, UNICEF)? 251


page 29

252

Please precise the date of the submission: ______________________________________ 253

254

1.6 Regulatory (Licencing) status 255

256

1.6.1 In the country of manufacture 257

258

� Product registered and currently marketed – Licence no.:________________________ 259

Provide a copy in Annex D 260

261

� Product registered for marketing in the country of manufacturing but not currently 262

marketed – Licence no.:_________________________________________________ 263

264

265

� Product registered for export only – Licence no.:_____________________________ 266

267

� Product not registered (please clarify):_____________________________________ 268

269

270

� Please attach a certificate of pharmaceutical product (CPP) according to the WHO 271

Certification Scheme (WHO Technical Report Series, No. 863 in Annex E. An earlier 272

version is not acceptable). 273

274

� If a CPP cannot be obtained from the national drug regulatory authority (NDRA), 275

please state the reason and send equivalent document if any. 276

277

� Submit recent as well as historical deficiency/acceptance letters issued by the WHO 278

Prequalification Programme (PQP)/SRA in relation to the specific product dossier in 279

Annex F. 280

281

1.6.2 In other countries 282

283 List other countries where the product is registered and is currently marketed (please provide 284

registration number) 285

________________________________________________________________ 286

287

________________________________________________________________ 288

289

1.6.3 WHO prequalification status, if applicable 290

291 This product is prequalified by WHO/PQP.

2 292

293

� Yes � No 294

295

If yes, please attach a copy of the relevant WHO/PQP approval letter signed by your 296

company (Annex G) 297

298

299

2 WHO Prequalification website link: http://apps.who.int/prequal/.


page 30

1.6.4 Submitted for prequalification: indicate date of submission, WHO acceptance letter 300

for product dossier review mentioning the WHO reference number assigned by 301

WHO for this specific product (Annex H) 302

_____________________________________________________________ 303

304

1.7 Samples for technical evaluation 305

306 1.7.1 Samples of finished product and insert information 307

308

You are required to please provide a sample of the finished product(s) offered, and relevant 309

inserts/leaflets. (If you cannot submit any of the above with the questionnaire, please state 310

why not and when you will do so.) (Annex I) 311

312

313

1.7.2 Label language (attach a copy): primary packaging 314

315

� Bilingual English/French � English � French � Other(specify) 316

317

1.7.3 Label language (attach a copy): secondary packaging 318

319

� Bilingual English/French � English � French � Other (specify) 320

321

For oral powder for suspension and powder for injection, in-use periods and storage 322

conditions after reconstitution should be stated on the product label 323

324

1.7.4 Patient information leaflet (Annex J) 325

326

� Yes (attach a copy) � No 327

Section 2. Active pharmaceutical ingredients 328

329

(In case of more than one active ingredient or more than one manufacturer is used, please 330

replicate this section) 331

2.1. Details of API used (INN if any): 332

333

……………………………………………………………………………………………… 334

335

2.1.1 Manufacturer 336

337 Manufacturer (name, physical address + country)/manufacturing site (please list all 338

alternative sources): 339

___________________________________________________________ 340

__________________________________________________________________ 341

__________________________________________________________________ 342

343

GMP certificate from the country of origin: attach a copy of the GMP certificate if available 344

in Annex K 345


page 31

Last inspection of API manufacturing sites performed when available 346

(please attached GMP certificate or relevant letter) by: 347

348

� Finished product manufacturer 349

� WHO Prequalification Programme, Geneva 350

� EDQM 351

� US FDA 352

� PIC/S members 353

� Others (specify) 354

� None of above 355

Outcomes and date: ___________________________________________ 356

357

____________________________________________________________ 358 359

Is the API(s) used to manufacture this product is/are WHO-prequalified? 360

361

Yes No 362

363

2.1.2 API specifications 364

365

Specifications and standard test methods exist for this API: 366

367

� Yes � No 368

� Attach a copy of the internal API(s ) specifications in Annex L 369

370

API specifications: 371

372

� BP (Edition/Year): 373

� USP (Edition/Year): 374

� The International Pharmacopoeia (Ph.Int.) (Edition/Year) 375

� Others (specify): 376

� Specifications additional to those in the pharmacopoeia referred to above if available. 377

378

379

� If specifications are in-house specifications, different from BP, USP and Ph.Int., 380

attach also validated analytical methods in Annex M 381

382

2.1.3 Certificate of analysis 383

384

Please provide a copy of the certificate of analysis of the API from the API manufacturer as 385

well as from the finished pharmaceutical product (FPP) manufacturer in Annex N 386

387

388

389


page 32

2.1.4 Suitability of monograph for API 390

391

Are you in a possession of the following information for APIs? 392

393

Certificate of suitability to the European Pharmacopoeia (CEP): please attach a copy of the 394

CEP and its annexes (Annex O) 395

396

397

Certificate No.: ______________________________________________________ 398

399

Open part of drug master file (DMF) registered in (country): 400

401

____________________________________________________________________ 402

403

Technical file (please attach): 404

405

� Yes � No 406

407

Section 3: Finished product 408

3.1 Manufacturing site GMP status 409

410

GMP inspections carried out by a NDRA 411

412

NRA of country of origin

Any other inspection of PIC/s member

GMP certificate no.

Valid until

Country

413

Please attach the recent/valid GMP certificates/letter (Annex P) 414

415

Other GMP inspections carried out by (tick all that apply): 416

417

Agency Date of audit Outcome

WHO Prequalification Programme

UNICEF Supply Division

MSF International

ICRC

Other (specify)


page 33

3.2 Finished product specification 418

419 3.2.1 Non-sterile products or sterile products 420

421

422

Standard Edition Year published

BP

USP

Ph.Int.

In-house Year documented

Specifications additional to those in the

pharmacopoeia referred to above (e.g. dissolution,

syringeability): explain

Other ( specify)

423

� If specifications are in house specifications, different from BP, USP and Ph.Int., attach 424

copy of the in-house finished product specifications and also validated analytical methods 425

in Annex Q 426

427

� Please attach a copy of the certificate of analysis for the three last batches released in 428

Annex R 429

430

� Have the manufacturing methods for each standard batch size been validated? 431

432

� Yes � No 433

434

If no, please clarify:____________________________________________ 435

436

___________________________________________________________ 437

438

If yes, please provide details of validation status in the table below: 439

440

The batch size of the validated batches

The batch numbers of the validated batches

Manufacturing dates of the validated batches

Reference number for the process validation report

If processes are yet to be validated then reference number

for the process validation protocol should be indicated.

441

Provide batch formulae for all proposed batch sizes: 442

_______________________________________________________________ 443

444


page 34

________________________________________________________________ 445

446

3.2.2 Additional information for sterile products 447

448

Provide the data on validation of the sterile aspects of the product including recent media fill 449

validation data as applicable in Annex S 450

451

Describe the method of sterilization used when applicable 452

________________________________________________________________ 453

454

455

3.2.3 Inactive ingredients (excipients) of medical/pharmaceutical relevance, amount in 456

dosage form or per dosage unit (e.g. contains alcohol 10%, paraben) 457

458

Specifications:_________________________________________________________ 459

460

Justification of specifications:______________________________________________ 461

___________________________________________________________________ 462

___________________________________________________________________ 463

464

3.3 Stability of finished product 465

466

3.3.1 Is stability testing data available? 467

468

� Yes � No 469

470

Please provide the protocol and the report for accelerated and real-time stability testing, 471

including: type and material of container; conditions (temperature/relative humidity/duration 472

of stability study); number of batches involved in the study (minimum three); batch sizes for 473

each lot tested; date of beginning of the study; and study conclusions. (These can be provided 474

in Annex T.) 475

476

3.3.2 Was the stability testing done on a product of the same formula, same API source, 477

manufactured on the same site and packed in the same packaging material as the 478

product that will be supplied? 479

480

� Yes � No 481

482

483

If no, describe the differences:_______________________________________________ 484

485

_________________________________________________________________ 486

487

488

489


page 35

3.3.3 Please specify whether stability studies have been done or are on-going with all 490

declared API sources 491

492

� Yes � No 493

494

Submit a declaration in Annex U that stability studies have been done or are being done with 495

all declared API sources 496

497

If no, explain why: ________________________________________________________ 498

499

__________________________________________________________________ 500

501

502

3.3.4 Do you have on going stability data for this product? 503

504

� Yes � No 505

506

Attach status report of any ongoing stability studies in Annex V 507

508

3.3.5 Shelf-life as it appears on packaging 509

510

� 2 years � 3 years � 4 years � 5 years 511

512

Other: (specify) 513

514

515

3.3.6 Specific storage conditions for this product as they appear on the packaging and based 516

on stability studies (e.g. «Do not store above 30 °C – Protect from light»): 517

518

Temperature

Light

Humidity

Other (specify)

519

3.3.7 Product suitable for use in: 520

521

Zone I 522

Zone II 523

Zone III 524

Zone IVa 525

Zone IVb 526

Other (specify): 527

3.3.8 For oral powder for suspension and powder for injection, provide in-use 528

stability data and storage condition after reconstitution in Annex W 529


page 36

530

Indicate the period until which the product is stable after reconstitution based on the 531

available in-use stability data: 532

533

Section 4: Safety/efficacy and or therapeutic equivalence (WHO Technical Report Series, 534

No. 902 Annex 11) 535

4.1 For innovator products 536

537

Please attach a summary of pharmacology, toxicology and efficacy of the product 538

539

4.2 For generic products: THERAPEUTIC EQUIVALENCE 540

541

� Demonstrated 542

543

� Not demonstrated 544

545

Not relevant, please explain why:_____________________________ 546

547

_______________________________________________________ 548 549

550

If demonstrated, 551 552

4.2.1 By in vivo bioequivalence studies 553

554

Indicate Biopharmaceutics Classification System (BCS) classification: 555

_________________________________________________________________ 556

557

_________________________________________________________________ 558

559

Justify above classification:______________________________________________ 560

561

____________________________________________________________ 562

563

Study period (dd/mm/yyyy): from to 564

565

Reference product 566

Generic name:

Dosage form:

Strength:

Brand/trade name:

Manufacturer:

Manufacture site:

Batch number:

Expiry date:

567


page 37

Study protocol 568

Contract research organization

(CRO) name:

Country of study:

Number of volunteers:

Study design (describe in detail):

569

Bio batch size:

Bio batch number:

Bio batch API(s) source(s):

Study conclusion:

570

Attach graphic/pictorial representation of summary study results 571

572

Study results 573 F2 (similarity factor) value: (Standard 50–100%) 574

575

___________________________________________________________ 576

F1 (difference factor) value: 577

___________________________________________________________ 578

579

Study conclusion: 580 ____________________________________________________________ 581

582

____________________________________________________________ 583

584

Attach graphic/pictorial representation of summary study results 585

586

� Provide a copy of the report of the proof of therapeutic equivalence (BE study) 587

comparative dissolution profile, dissolution tests, others if any in Annex X 588

� For bioequivalence studies indicate the stringent regulatory authority 589

(SRA)/WHO/PIC(S) inspection status of the CRO (if the CRO has ever received 590

inspections in relation to the current or other studies). 591

592

� Attach schematic representation of study design 593

594

� Attach study protocol summary 595

596

4.2.2 By comparative in vitro dissolution tests according to conditions described in WHO 597

BCS classification document (WHO Technical Report Series, No. 937, or later) 598

599 Yes 600

601

No (explain):________________________________________________ 602

603

___________________________________________________________ 604

605

606

607


page 38

Reference product 608

Generic name

Dosage form

Strength

Brand/trade name

Manufacturer

Manufacture site

Batch number

Expiry date

609 610

Name and contact details of laboratory performing tests: 611

______________________________________________________________ 612

613

614

4.2.3 By another method (please describe study conclusion briefly): 615

616

________________________________________________________ 617

618 Attach graphic/pictorial representation of summary study results in Annex Y 619

620

4.3 The product used in the therapeutic equivalence study is essentially the same as 621

the one that will be supplied (same materials from the same suppliers, same 622

formula and same manufacturing method) 623 624

Yes 625

626

No (explain what the differences are and justify that the differences do not have any 627

impact on the bioavailability):__________________________________________ 628

629

______________________________________________________________________ 630

631

� Please provide in Annex Z a flow diagram describing the manufacturing and control 632

process of this product with relevant parameters. 633

Section 5: Commitment and authorization 634

635

5.1 Commitment 636 637

I, the undersigned, 638

………………………………….………………………………………………… ................... …., 639

(position in the company, e.g. General Manager, Authorized Person, Responsible 640

Pharmacist), acting as responsible for the company……………………………………(name 641

of the company), certify that the information provided (above) is correct and true, 642

643

(if the product is marketed in the country of origin, select the appropriate box below) 644

645


page 39

� and I certify that the product offered is identical in all aspects of manufacturing and 646

quality to that marketed in ……………………………………..(country of 647

origin),including formulation, method and site of manufacture, sources of active and 648

excipient starting materials, quality control of the product and starting material, 649

packaging, shelf-life and product information. 650

651

� and I certify that the product offered is identical to that marketed in 652

………………………………………………………………….(name of country),except: 653

……………………………………………………………………………… .................. …….. 654

…………………………………………………………………………………… . …………… 655

(e.g. formulation, method and site of manufacture, sources of active and excipient starting 656

materials, quality control of the finished product and starting material, packaging, shelf-657

life, indications, product information) 658

If any changes occur to the information after the submission of this product questionnaire, the 659

manufacturer/supplier undertakes to provide the relevant update as soon as possible. 660

661

662

Date: …………..…………………………… Signature: 663

664

……………………………………………… 665

666

5.2 Power of attorney 667

668

The manufacturer authorizes a distributor to submit the questionnaire 669

670 [SIGNATURE] 671

672 Distributor (Signed by Distributor for Manufacturer under power of attorney ) 673

674

Please provide a copy of the power of attorney (Annex AA) 675

676

677

5.3 Authorization for sharing information with other agency 678

679 I, the undersigned confirm that the company has no objection to the information contained 680

herein being shared with the agencies listed on page 2 (1.4) except: 681

682

___________________________________________________________________ 683

684

___________________________________________________________________ 685

686

687

688

689


page 40

I, the undersigned, certify that the information provided above is accurate, correct, complete, 690

up-to-date and true at the time of submission 691

692

Full name:__________________________________________________________ 693

___________________________________________________________________ 694

695

Full title/position in company:____________________________________________ 696

697

____________________________________________________________________ 698

699

Company name:_______________________________________________________ 700

701

____________________________________________________________________ 702

703

704

705

Signature Date

706

707

Company seal/stamp: 708

709

710

711


page 41

712

713

714

Section 6: Attachments/annexes 715

716

Attachments or Annexes to the questionnaire should be in PDF format and should be 717

well indexed to facilitate review 718 719

Please ensure that all documents necessary to enable objective evaluation of your product are 720

attached. This checklist may not be exhaustive. 721

722

A. Formulation of the product (complete qualitative and quantitative composition 723

including active ingredient(s) and excipients (1.1.7) 724

725

B. Description and composition of primary packing materials (1.2.1) 726

727

C. Description and composition of secondary packaging materials (1.2.2) 728

729

D. Copy of product registered and currently marketed – Licence no. (1.6.1) 730

731

E. Certificate of pharmaceutical product (CPP) according to the WHO Certification 732

Scheme (WHO Technical Report Series, No. 863 in the Annex. Earlier version is not 733

acceptable) (1.6.1) 734

735

F. Submit recent as well as historical deficiency/acceptance letters issued by PQP/SRA 736

in relation to the specific product dossier.(1.6.1) 737

738

G. Copy of the relevant WHO Prequalification approval letter signed by your company 739

(1.6.3) 740

741

H. WHO acceptance letter for product dossier review mentioning the WHO reference 742

number assigned by WHO for this specific product (1.6.4) 743

744

I. Package insert/leaflet (1.7.1) 745

746

J. Patient Information Leaflet (1.7.4) 747

748

K. GMP certificate from the country of origin (2.1.1) 749

750

L. Attach a copy of the internal API(s) specifications (2.1.2) 751

752

M. Validated analytical methods if specifications for finished product are in-house 753

specifications, different from BP, USP and Ph.Int. (2.1.2) 754

755

N. Copy of the certificate(s) of analysis of the API from the API manufacturer as well as 756

from the FP manufacturer (2.1.3) 757

758

O. Copy of the certificate of suitability to the European Pharmacopoeia CEP and its 759

annexes (2.1.4) 760


page 42

761

P. Recent/valid GMP certificates/letter (3.1) 762

763

Q. If specifications are in house specifications, different from BP, USP and Ph.Int., 764

attach copy of the in-house finished product specifications and also validated 765

analytical methods (3.2.1) 766

767

R. Copy of the certificate of analysis for the three last batches released (3.2.1) 768

769

S. Data on validation of the sterile aspects of the product including recent media fill 770

validation data as applicable (3.2.2) 771

772

T. Protocol and report for accelerated and real time stability testing (3.3.1) 773

774

U. Submit a declaration that stability studies have been done or being done with all 775

declared API source (3.3.3) 776

777

V. Attach status report of any ongoing stability studies (3.3.4) 778

779

W. For oral powder for suspension and powder for injection, provide in-use stability data 780

and storage condition after reconstitution (3.3.8) 781

782

X. Provide a copy of the report of the proof of therapeutic equivalence (BE study) 783

comparative dissolution profile, dissolution tests, others if any (4.2.1) 784

785

Y. Attach graphic/pictorial representation of summary study results (4.2.3) 786

787

Z. Flow diagram describing the manufacturing and control process of this product with 788

relevant parameters (4.3) 789

790

AA. Copy of the power of attorney (5.2) 791

792


page 43

793

ANNEX 2 794

INSPECTION REPORT: PROCUREMENT AGENCY 795

796

Section 1. General information 797

798

Name of organization:

Website reference:

Physical address:

Postal address:

Tel.:

Fax:

Contact person:

Email address:

Activities: Prequalification

Purchasing

Receiving and storage

Distribution

Reassessment

Date of assessment/inspection:

Products and/or product category

(e.g. pharmaceuticals, diagnostics,

medical devices)

Inspector:

799


page 44

800

Section 2. Summary 801

General information about the procurement agent and site

___________________________________________________________________________

___________________________________________________________________________

History of inspections

___________________________________________________________________________

___________________________________________________________________________

Focus of the inspection and inspected areas

___________________________________________________________________________

___________________________________________________________________________

Summary of findings

General activities:

___________________________________________________________________________


page 45

___________________________________________________________________________

Prequalification:

___________________________________________________________________________

___________________________________________________________________________

Purchasing:

___________________________________________________________________________

___________________________________________________________________________

Receiving and storage:

___________________________________________________________________________

___________________________________________________________________________

Distribution (including the ability to supply the needed products in quantities required):

___________________________________________________________________________

___________________________________________________________________________

Reassessment:

___________________________________________________________________________


page 46

___________________________________________________________________________

802

Section 3. Observations and deficiencies/non-compliance 803

(Note: Module I should be used in all cases of assessment of a procurement agency. Modules 804

2 to 6 may be used depending on the activities performed by the procurement agency) 805

806

Module I: General requirements Classification

(C, M, O)*

1.

2.

3.

4.

5.

Module II: Prequalification

6.

7.

8.

9.

10.

Module III: Purchasing

11.

12.

13.

14.

Module IV: Receiving and Storage

15.


page 47

16.

17.

18.

Module V: Distribution

19.

20.

21.

22.

Module VI: Reassessment

23.

24.

25.

26.

807

* 808

Critical Observation (C) 809

An observation relating to any activity, action or omission thereof, by the procurement 810

agency, in relation to product(s), that may result in a significant risk to the user. 811

812 Major Observation (M) 813

A non-critical observation that: 814

• may have a negative impact on a product in relation to prequalification, purchasing, 815

storage, distribution or requalification; and/or 816

• indicates a major deviation from the MQAS; and/or 817

• consists of several other deficiencies, none of which on its own may be major, but 818

which may together represent a major deficiency and should be explained and 819

reported as such. 820

821 Other Observation (O) 822

An observation that cannot be classified as either critical or major, but indicates a departure 823

from the recommendations in the MQAS (including GSP and GDP). 824

825

826


page 48

Section 4. Outcome of the inspection (select one of the following options) 827

Based on the areas inspected, the personnel met and the documents reviewed, and considering

the findings of the inspection, including the observations listed above – the agency was

considered to be operating in compliance with the MQAS for the following activities (select

the appropriate one(s)) prequalification, purchasing, storage, distribution, requalification).

Or



considered not yet to be operating at an acceptable level of compliance with the MQAS for

the following activities (select the appropriate one(s)) prequalification, purchasing, storage,

distribution, requalification). The CAPAs will be reviewed after which a conclusion will be

made whether the procurement agency is operating in compliance with the MQAS. (A

reinspection may be considered before the conclusion is reached.)

Or



considered to be operating at an unacceptable level of compliance with the MQAS for the

following activities (select the appropriate one(s)): prequalification, purchasing, storage,

distribution, requalification).

828

829

830

_____________________________ _________________________ 831

Signature: Date: 832

833


page 49

(Name):______________________ 834

(Print) 835

836

History of changes 837

Version 1. Initial format

Version 2. Additions Add under section 3

(Note: Module I should be used in all cases

of assessment of a procurement agency.

Modules 2 to 6 may be used depending on the

activities performed by the procurement

agency)

Add classification of observations as critical,

major and minor and definitions

Edit wording in section 4 for the outcome

838

839

*** 840

assessment tool based on the model quality … · working document qas/13.555 august 2013...

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