1. The PQS Secretariat - WHO · xISO 7886-1:1993 - Sterile hypodermic syringes for single use - Part 1: Syringes for manual use. xISO 7886-3:2005 - Sterile hypodermic syringes for

SOP No FCH/ IVB/QSS/PQS/014 Date of issue: 30/06/2005 Revision Date: 06/01/2007 Version: 01.05 Effective date: 30/06/2005 Page: 2 of 29Title: How to evaluate applications for the pre-qualification of single-use injection devices

Table of Content 1.0 Purpose.......................................................................................................................... 3 2.0 Scope............................................................................................................................. 3 3.0 Responsibility ............................................................................................................... 3 4.0 Documentation required................................................................................................ 3 5.0 Procedure ...................................................................................................................... 5

5.1 Pre-qualification Register ................................................................................... 6 5.2 Cost recovery ...................................................................................................... 6 5.3 Confidentiality .................................................................................................... 6 5.4 Obtain applications ............................................................................................. 6 5.5 Pre-qualification information pack ..................................................................... 7 5.6 Product dossier.................................................................................................... 7 5.7 Evaluation ........................................................................................................... 7 5.7.1 Acceptable standards:..................................................................................... 8 5.7.2 Licensing requirements:.................................................................................. 9 5.7.3 Manufacturer’s declaration:......................................................................... 10 5.8 Evaluation results.............................................................................................. 10 5.9 Approval process .............................................................................................. 10 5.10 Publication ........................................................................................................ 11 5.11 Complaint monitoring....................................................................................... 11

6.0 Distribution ................................................................................................................. 11 Annex 1 – Definitions....................................................................................................... 12 Annex 2 – Provisions for evaluators of product dossiers within the scope of the evaluation procedure for single-use injection devices ...................................................... 13 Annex 3 – Standard letter A: Invitation to apply for pre-qualification............................. 14 Annex 4 – Standard letter B: Rejection of a preliminary application............................... 15 Annex 5 – Standard letter C: Pre-qualification information pack .................................... 16 Annex 6 – Standard letter D: Request for missing information........................................ 21 Annex 7 – Standard letter E: Evaluation notification ....................................................... 22 Annex 8 – Standard letter F - Deleted: ............................................................................. 23

Omitted in revision 01.05 ............................................................................................. 23 Annex 9 – Standard letter G: Rejection ............................................................................ 24 Annex 10 – Standard letter H: Acceptance....................................................................... 25 Annex 11 - Product Summary Sheet questionnaire for single-use injection devices ....... 26 Annex 12 – Dossier submission checklist ........................................................................ 28 REVISION HISTORY FORM ......................................................................................... 29


1.0 Purpose Before a single-use injection device can be added to the PQS database, it must be pre-qualified. A device can only be pre-qualified if it complies with the relevant ISO standards and complies with the requirements of Pre-qualification of single-use injection devices under the PQS system: A guideline for manufacturers. (January 2007 edition). Note that this SOP describes the procedure for reviewing pre-qualification applications for single-use injection devices only. SOP No: FCH/ IVB/QSS/PQS/009 - How to evaluate applications for the pre-qualification of PQS products is the relevant reference document for all other PQS products.

The procedures set out in this SOP will be followed by the PQS Secretariat (Secretariat) and by the PQS Steering Group (PQS-SG).

2.0 Scope Applicable to all single-use injection devices offered for pre-qualification through the PQS initiative.

3.0 Responsibility Responsibilities and tasks will be assigned as follows:

1. The PQS Secretariat (Secretariat) will establish and maintain a register recording details of all applications for the pre-qualification of single-use injection devices.

2. The Secretariat can recommend that a single-use injection device on the register should be pre-qualified. The PQS Steering Group (PQS-SG) may confirm this recommendation and will then direct the Secretariat to add the product to the PQS database.

3. The Secretariat will amend the PQS website and may otherwise circulate the decision to add the device.

4.0 Documentation required Associated documents: Refer to the following:

PQS Standard Operating Procedures:WHO. Pre-qualification of single-use injection devices under the PQS system: A guideline for manufacturers. (January 2007 edition)1

SOP No FCH/ IVB/QSS/PQS/001: How to develop and publish a PQS product performance specification.

1 Referred to in this document as the Guideline for manufacturers.


SOP No FCH/ IVB/QSS/PQS/002: How to review and revise a PQS product performance specification. SOP No FCH/ IVB/QSS/PQS/003: How to withdraw a PQS product performance specification. SOP No FCH/ IVB/QSS/PQS/004: How to develop and publish a PQS product verification protocol. SOP No FCH/ IVB/QSS/PQS/005: How to review and revise a PQS product verification protocol. SOP No FCH/ IVB/QSS/PQS/006: How to withdraw a PQS product performance specification.SOP No: FCH/ IVB/QSS/PQS/009: How to evaluate applications for the pre-qualification of PQS products SOP No FCH/ IVB/QSS/PQS/010: How to re-evaluate a pre-qualified PQS product.SOP No FCH/ IVB/QSS/PQS/011: How to remove a pre-qualified product from the PQS database. SOP No FCH/ IVB/QSS/PQS/015: How to re-evaluate a pre-qualified single-use injection device. SOP No FCH/ IVB/QSS/PQS/016: How to remove a pre-qualified single-use injection device from the PQS database.

ISO standards and WHO performance specifications:ISO 7864:1993 - Sterile hypodermic needles for single use.ISO 7886-1:1993 - Sterile hypodermic syringes for single use - Part 1: Syringes for manual use.ISO 7886-3:2005 - Sterile hypodermic syringes for single use - Part 3: Auto-disable syringes for fixed-dose immunization.ISO 7886-4: 2006 - Sterile hypodermic syringes for single use - Part 4: Syringes with re-use prevention feature.ISO 8537:1991 - Sterile single-use syringes, with or without needle, for insulin.

Other references:WHO. Guiding principles to ensure injection device security. WHO/BCT/03.12.WHO. Best infection control practices for intradermal, subcutaneous and intramuscular needle injections. WHO/BCT/DCT/01.02.WHO. Bundling principles. WHO/V&B/99.25.WHO. A guide for the quality assurance of single-use injection equipment. WHO/BCT/03.02.WHO. Medical device regulations, global overview and guiding principles. Geneva: World Health Organization, 2003.


5.0 Procedure Each of the task headings below includes (in brackets) a description of the person or group responsible for the task. Figure 1 summarizes the pre-qualification process. The Product Evaluation stage is shown in more detail in Figure 2. Refer to Annex 1 for the definitions of certain critical terms used in this SOP.

Figure 1 – Procedure for pre-qualifying injection devices

DOSSIER EXAMINATION

PRODUCT EVALUATION

Product cleared by Regulatory Authority of

a GHTF founding member?

Product conforms withapproved quality system standards

yes

no

Product cleared by Regulatory Authority of

a GHTF founding member?

Product conforms withapproved quality system standards

yes

no

yes

no

yes

Manufacturer submits product

dossier

Dossier complete?

yes no

yes

no

one cycle only - one month maximum time to respond

Missing inforeceived?

Manufacturer appliesto Secretariat to pre-qualify

Start

either/or

Secretariat invitesmanufacturer to

pre-qualify (Letter A)

PRELIMINARY PQS PRE-QUALIFICATION APLICATION

Device obviouslyunsuitable?

SendLetter B

Send Letter C

Pre-qualificationinformation pack

yesno

SendLetter D

Send Letter E

Product conforms withrelevant ISO standard?

no

yes

no

Productsatisfactory?

no

Productsatisfactory?

yes Pre-qualify product

(Letter H)

Reject product

(Letter G)


5.1 Pre-qualification Register (Secretariat): The Secretariat will establish and maintain a register which records details of every application for product pre-qualification, including single-use injection devices. Copies of all correspondence with manufacturers will be kept in the register. The register section relating to single-use injection devices will be organized according to the following hierarchy:

PQS-E08:<manufacturer>:<product>

5.2 Cost recovery (Secretariat): WHO will charge manufacturers of single-use injection devices for the dossier assessment; charges will be on a cost recovery basis. In addition, and where relevant, manufacturers may be required to pay a WHO-accredited testing laboratory directly for independent testing of their devices. The Secretariat will prepare and will maintain an up-to-date schedule of charges, which will be sent out to all applicant manufacturers with the pre-qualification information pack.

5.3 Confidentiality Secretariat, PQS-SG, evaluators): WHO will treat, and will require evaluators of product dossiers to treat all information to which they will gain access during the evaluation, or otherwise in connection with the discharge of their responsibilities in regard to the pre-qualification of single-use injection equipment as confidential. In addition, the evaluators of product dossiers will be required to sign a Declaration of Interest. A sample of the confidentiality and declaration of interest undertaking for evaluators of product dossiers is attached in Annex 2. If, based on this Declaration of Interest, it is felt that there is no risk of real or perceived conflict of interest and it is thus deemed appropriate for evaluators to undertake this work, they will discharge their functions exclusively as advisers to WHO.

5.4 Obtain applications (Secretariat): The Secretariat is responsible for obtaining pre-qualification applications for single-use injection devices. There are two basic ways in which this can be done:

1. The manufacturer can make a preliminary PQS pre-qualification application. This application should take the form described in paragraph 3.7 of the Guideline for manufacturers.

2. The Secretariat may approach a potentially suitable manufacturer, in writing or by email, and formally invite him to apply for pre-qualification for a specific device or devices. Standard letter A will be used as the basis for this approach (Annex 3).

If the information or samples received at this stage clearly show that a device is unsuitable for pre-qualification, the manufacturer should be informed in writing using Standard Letter B (Annex 4).


5.5 Pre-qualification information pack (Secretariat): Provided a device passes the preliminary filtering process described in paragraph 5.4, a manufacturer who seeks pre-qualification will receive a pre-qualification information pack by the Secretariat. The pack will contain, as a minimum, the following information:

two copies2 of a covering letter outlining the requirement for a product dossier, the details of the pre-qualification process and details of the initial dossier assessment fee. If the device in question is to comply with one of the three WHO performance specifications, the letter will include details of the laboratory testing requirements. In addition the letter will include an annex setting out standard disclaimers, formal terms and conditions and definitions. Standard letter C will be used as the basis for this correspondence (Annex 5); the current version of the Guideline for manufacturers;the Product Summary Sheet questionnaire for single-use injection devices (Annex 11);

5.6 Product dossier (Manufacturer): All manufacturers who seek pre-qualification will submit a product dossier to the Secretariat. This must contain all the required information and samples that are requested in Standard Letter C, together with the dossier examination fee in US$ as defined in the latest Guideline for manufacturers per device3.The Secretariat will screen the dossier for completeness and will clear the fee payment before the dossier is evaluated. If the dossier is incomplete the manufacturer will be contacted in writing and will be given a single opportunity to provide the missing information or material; Standard letter D will be used for this purpose (Annex 6). If, after one month has elapsed, the manufacturer has failed to supply the missing information, fee or samples, the dossier will be rejected and returned to the manufacturer. Under these circumstances any dossier examination fee that has been received will be retained by WHO. Standard letter E (Annex 7) will be used to inform the manufacturer that the dossier is complete (Option 1), or to return an incomplete dossier (Option 2) after the one month period of grace has expired.

5.7 Evaluation (Secretariat): The completed Product Summary Sheet shown in Annex 11, together with the supporting paperwork provided by the manufacturer, should contain all the basic information needed to carry out the dossier evaluation. The dossier checklist4 in Annex 12 should be used to ensure that all items required have been received and are acceptable.

Figure 2 illustrates the logical steps of the product evaluation stage in more detail.

2 One copy is to be signed by the manufacturer and returned with his submission as an acknowledgement that he has read and accepted the standard Terms and Conditions. 3 The fee scale is fixed for a certain period as defined in Guideline for manufacturers.4 Checklist derived from Guideline for manufacturers.


Figure 2 – Product evaluation stage Start of ProductEvaluation stage

no

no

OPTION 1: device clearedby the Regulatory Authority

of a GHTF founding member?

yes

no

yesDoes the dossier include evidence of ISO compliance?

yes

OPTION 2: current certificate of conformity with one of the TABLE 2 quality

system standards?

yes

Does the evaluation ofthe dossier justify pre-qualification?

no

Reject device(Standard letter G)

Pre-qualify device(Standard letter H)

5.7.1 Acceptable standards: Devices that conform to one of the two categories described in this section are potentially eligible for pre-qualification. Compliance with one of the two listed ISO standards is mandatory. Devices that only conform to national or regional standards are not eligible even if they do comply with the licensing and/or quality system standards set out in section 3.6. These are the three categories: Category 1: Syringes for therapeutic use:

Syringes for general purpose use with a reuse-prevention feature must satisfy the requirements of ISO 7886-4: 2006 - Sterile hypodermic syringes for single use - Part 4: Syringes with re-use prevention feature.


Syringes for general purpose use without a reuse-prevention feature must satisfy the requirements of ISO 7886-1:1993 - Sterile hypodermic syringes for single use - Part 1: Syringes for manual use.

Category 2: Syringes for fixed-dose immunization:

Auto-disable syringes for fixed dose immunization must satisfy the requirements of ISO 7886-3:2005 - Sterile hypodermic syringes for single use - Part 3: Auto-disable syringes for fixed-dose immunization.

Category 3: Syringes for insulin injection: Syringes for insulin injection must comply with ISO 8537:1991 - Sterile single-use syringes, with or without needle, for insulin.Hypodermic Needles: The needles for all ISO-compliant devices must conform to ISO 7864:1993 - Sterile hypodermic needles for single use.

Generally: You should be aware that the individual UN procurement agencies reserve the right to impose additional conditions when seeking offers for the supply of pre-qualified syringes. The technical specifications shall not be in contradiction to established ISO standards. Note: at this stage, this pre-qualification procedure is geared towards syringes, there is no separate category covering hypodermic needles. This may be covered at a later stage.

5.7.2 Licensing requirements: If a device is licensed in the territory of one of the founding members of the Global Harmonization Task Force (GHTF)5, it meets the minimum quality criteria required under the PQS pre-qualification procedure (Option 1 below). If the device is not licensed, the manufacturer must be able to demonstrate that his manufacturing process meets one or more of the quality system standards listed below (Option 2).

1. Option 1: License in a GHTF founding member country: Domestic market clearance in any one of the five countries will indicate that the manufacturer has an acceptable quality system in place, although WHO will still need to see evidence of compliance with one or more of the quality system standards listed in Table 2. The manufacture must submit a certified copy of his domestic market license(s) in accordance with Table 1.

Table 1 – Licensing requirements in the five GHTF founding member countries

Australia 6 Canada European

UnionJapan United States

Marketing permit/ condition

GMPALS License

or CE Mark

Device license CE mark Device license 510k device

letter

5 The founding members of the GHTF are Australia, Canada, the European Union, Japan and the United States.6 New, proposed legislation.


Table 2 - Acceptable quality system standards in the five GHTF founding member countries

Country Quality system standards for

medical devices Certification body

Australia ISO13485 or ISO13488 Government or third party accredited by the government

Canada ISO13485 or ISO13488 Third party accredited by the government

European Union ISO13485 or ISO13488 Notified Bodies

Japan GMP (QS Standard for medical devices #1128) Government

United States QS (21 CFR part 820) Government

2. Option 2: No license in a GHTF founding member country: If the device does not have Option 1 market clearance then the manufacturing process must meet one or more of the quality system standards listed in Table 2. The manufacture must submit documentary evidence of his conformity to these standards from a certification body accredited by the regulatory authorities in one of the GHTF founding member countries. The documentary evidence must take the form of certified copies of the relevant paperwork.

5.7.3 Manufacturer’s declaration: No device should be pre-qualified unless and until the manufacturer has signed and returned the Manufacturer’s declaration attached to Standard Letter C.

5.8 Evaluation results (Secretariat): The Secretariat will monitor the evaluation process and will receive the evaluation results and, where relevant, the laboratory test results. If the results are unsatisfactory the manufacturer will be notified in writing of the outcome of the evaluation and will be informed that the product is not suitable in its current form. Standard letter G will be used as the basis for this (Annex 9). A copy will also be sent to UNICEF-SD. If the results are satisfactory the Secretariat will prepare a pre-qualification recommendation for approval by the PQS-SG.

5.9 Approval process (PQS-SG): The PQS-SG will review the pre-qualification recommendation and will direct the Secretariat either to add or to reject the product. The pre-qualification recommendation can only be rejected by the PQS-SG in cases where there has been a discrepancy or mistake in the pre-qualification process.


5.10 Publication (Secretariat): If the PQS-SG rejects pre-qualification, the manufacturer will be notified as outlined in 5.8 above. If the PQS-SG approves pre-qualification the manufacturer will be notified in writing of the outcome of the evaluation and will be informed that the product has been granted PQS pre-qualification status and will be listed on the PQS database. A copy will also be sent to UNICEF-SD and a copy will be filed in the Prequalification Register, with another copy in the Product Performance Register. Standard letter H will be used for this (Annex 10).

A new PQS website entry will then be created for the product, overwritten with the words:

NEW PRODUCT AS AT <DD.MM.YY>.

The overwriting will remain on the website for a minimum period of six months, after which it will be deleted. Notification of the addition will be posted on the TechNet21 and SIGN e-forums.

5.11 Complaint monitoring (Secretariat): By signing the Manufacturer’s declaration, the manufacturer of a pre-qualified single-use injection device agrees to collaborate with WHO and, where relevant with other UN agencies, in the investigation of complaints regarding device failure and adverse events relating to his injection devices. Such complaints may come to light in one or both of the following ways:

The complaint may be reported directly to the manufacturer; in this situation the manufacturer will provide WHO with full details of the complaint. The complaint may be reported directly to WHO or to another UN agency; in this situation WHO will provide the manufacturer with the details.

If circumstances justify it, the complaint is to be reported to the national regulatory authority where the device was used and to the national regulatory authority where the manufacturing site is located.

The Secretariat will monitor and record such complaints and make the necessary arrangements for their investigation.

6.0 Distribution (Secretariat): This SOP is to be distributed to the following organizations, groups and individuals:

PQS Secretariat and other WHO departments involved in prequalification; UNICEF-SD and other interested UN agencies; all members of the PQS Steering Group; all members of the PQS Injection Equipment Specification Working Group; all evaluators appointed to carry out work that lies within the scope of this SOP.


Annex 1 – Definitions Correspondence Includes mail, fax and email. Device A medical device, including a syringe. Evaluator An individual or organization (including a testing laboratory)

responsible for evaluating or assessing any aspect of a product as described in this SOP.

in writing Where the phrase in writing is used this means correspondence must be transmitted by mail, fax or email. A hard copy will be kept on file.

Manufacturer In the context of this SOP the word manufacturer means the Legal Manufacturer.

Legal Manufacturer Legal Manufacturer means the natural or legal person with responsibility for the design, manufacture, packaging and labelling of a product or device before it is placed on the market under his own name, regardless of whether these operations are carried out by that person himself or on his behalf by a third party7.Note that a Legal Manufacturer may commonly contract another company to manufacture products or devices sold under the Legal Manufacturer’s name. Such a contracted manufacturer is typically known as an Original Equipment Manufacturer or OEM.

Primary container8 The primary container comprises a single self-contained syringe unit housed within a sterile unit container.

Product In this document, where the word product is used on its own, it includes device.

QA Quality Assurance. Secondary container4

The secondary container is the packaging which contains more than one unit containers.

Storage container4 The storage container is a carton or other form of packaging containing a specific number of secondary containers.

Unit container4 The unit container is the sterile enclosure which encloses a single self-contained syringe unit.

7 Definition derived from Article 1 2.(f) of the EU Medical Device Directives. 8 Definition derived from draft ISO DIS 7886-3


Annex 2 – Provisions for evaluators of product dossiers within the scope of the evaluation procedure for single-use injection devices In the course of discharging your functions as an expert adviser to WHO under the attached Agreement for the Performance of Work (APW), you will gain access to certain information, which is proprietary to WHO or entities collaborating with WHO, including the manufacturers of the product(s) which need to be assessed as part of the pre-qualification evaluation procedure by WHO. You undertake to treat such information (hereinafter referred to as “the Information”) as confidential and proprietary to WHO or the aforesaid parties collaborating with WHO. In this connection, you agree: (a) not to use the Information for any other purpose than discharging your obligations under the

above-mentioned APW; and (b) not to disclose or provide the Information to any person who is not bound by similar obligations of

confidentiality and non-use as contained herein.

However, you will not be bound by any obligations of confidentiality and non-use to the extent that you are clearly able to demonstrate that any part of the Information: (i) was known to you prior to any disclosure by or on behalf of WHO (including by the

manufacturer(s)); or (ii) was in the public domain at the time of disclosure by or on behalf of WHO (including the

manufacturer(s)); or (iii) becomes part of the public domain through no fault of your own; or (iv) becomes available to you from a third party not in breach of any legal obligations of

confidentiality. You also undertake not to communicate your deliberations and findings and/or those of the team(s) of experts in which you will participate, as well as any resulting recommendations to, and/or decisions of, WHO to any third party, except as explicitly agreed by WHO.

You will discharge your responsibilities hereunder exclusively in your capacity as an expert adviser to WHO. In this connection, you confirm that the information disclosed by you in the Declaration of Interest is correct and that no situation of real, potential or apparent conflict of interest is known to you, including that you have no financial or other interest in, and/or other relationship with, a party, which: (i) may have a vested commercial interest in obtaining access to any part of the Information referred

to above; and/or (ii) may have a vested interest in the outcome of the evaluation of the injection device(s), in which

you will participate (such as the manufacturers of the medical device(s) that is (are) being assessed or manufacturers of competing injection devices).

In connection with the above, it is noted that the manufacturer(s) of the injection device(s) under assessment has (have) the right to object to your participation in the team(s) of experts which will evaluate its (their) injection device(s). If such objection cannot be resolved in consultation with the manufacturer(s), WHO shall be entitled to terminate this Agreement or cancel parts of the activities to be undertaken by you hereunder. In such event, any amount payable to you under the APW will be adjusted accordingly.

I hereby accept and agree with the conditions and provisions contained in this document.

Signed _______________________________ Name (typewritten)__________________________

Institute ________________________________________

Place ________________ Date _____________________


Annex 3 – Standard letter A: Invitation to apply for pre-qualification

Dear Sirs,

Expression of interest for pre-qualification of a single-use injection device under the PQS system.

WHO and UNICEF maintain a database of single-use injection devices pre-qualified for procurement by United Nations agencies. This database can be found at http://www.who.int/vaccines-access/vacman/pis/new%20sheets%20intro.htm

We are writing to you concerning <product description> which we believe may comply with the requirements of the relevant WHO performance specification for single-use injection devices <reference and web address>. If you are interested in offering this product for evaluation under the terms of the PQS system, please confirm this in writing and we will send you a pre-qualification information pack.

Yours faithfully,


Annex 4 – Standard letter B: Rejection of a preliminary application Dear Sirs,

Preliminary application for pre-qualification of a single-use injection device under the PQS system. Your reference:

We refer to your letter dated <dd.mm.yyyy>.

We have carefully reviewed your preliminary application and have inspected the samples which you provided. We regret to inform you that we do not consider the following single-use device(s) is/are likely to meet minimum WHO requirements for pre-qualification. The reasons are as follows:

Device <ref> <list reasons>.

Device <ref> <list reasons>.

OPTION: We consider that the following devices may be suitable; please find attached a pre-qualification information packs for each of these:

Device <ref> Device <ref>

We regret that we are unable to enter into any further correspondence on this matter.

Yours faithfully,

Note: A manufacturer may submit several devices with his preliminary application. Some of these may be suitable and some not; the optional paragraph covers this eventuality.


Annex 5 – Standard letter C: Pre-qualification information pack

Dear Sirs,

Application for pre-qualification of a single-use injection device under the PQS system: Pre-qualification information pack.

We refer to your letter dated <dd.mm.yyyy> in which you expressed an interest in offering single-use injection devices for evaluation under the terms of the PQS system.

We now enclose a pre-qualification information pack containing the following: Pre-qualification of single-use injection devices under the PQS system – A guideline for manufacturers.Product Summary Sheet questionnaire for single-use injection devices.

If, after reading this material, you still wish your device to be evaluated, please supply us with a complete Product Dossier which contains all the information requested below. If your application is successful, your product will be pre-qualified under the PQS system for procurement by United Nations Agencies. Details of the product will be published on the PQS website and on other UN websites as appropriate.

You must submit a separate and complete Product Dossier for every type of device that you wish to be evaluated. One dossier is required for each volume of syringe (for example, if you submit 1 ml, 2 ml and 5 ml syringes we will require three dossiers) and for each manufacturing site. Each dossier must be contained in a separate sealed package, clearly labelled: PQS PRE-QUALIFICATION DOSSIER, addressed to: PQS Secretariat Department of Immunization, Vaccines & Biologicals/QSS World Health Organization CH-1211 Geneva 27 Switzerland The package must also to be labelled with the applicant’s name and address. Formal electronic submissions in PDF or JPEG format are also accepted.

Each dossier must include the following information: 1. A covering letter. 2. A countersigned copy of this letter. By countersigning the letter you confirm that you

have read and agreed to abide by WHO’s standard Terms and Conditions for pre-qualification.

3. The non-refundable Dossier Examination Fee of US$ <enter amount from the latest Guideline for manufacturers> per device made payable to WHO as per invoice details.


4. A completed Product Summary Sheet Questionnaire supported by the following material:

Confirmation that you are the Legal Manufacturer of the device. General information about the manufacturer, including name and address. Confirmation of the brand name of the device. Product specifications, including details of product marking and traceability. A manufacturer's certificate specifying the needle size and the needle length supplied with the device. Details of the regulatory situation in the country of origin, including certified photocopies of the original assessment report issued by the relevant national regulatory authority. Where applicable, details of the regulatory approval for the device in other countries, including certified photocopies of original documents. Documentary evidence that the device conforms to the relevant ISO standard. Full product license details, including certified photocopies of current license(s). Certified photocopies of your current quality system certification issued by one of the certification bodies listed in Table 2. Post-market surveillance report(s) (if any). Other evaluation report(s) (if any).

5. A minimum of twenty samples of the injection device, in sealed unit containers, all taken from the same lot and packed within unopened secondary container(s).

6. Indicative cost of the product per unit, Incoterm EXW, for 100,000 units, 1 million units and 10 million units.

In conclusion we remind you that you must countersign the Manufacturer’s declaration attached to this letter and must return the signed copy with your dossier; this will confirm your acceptance of the Terms and Conditions for pre-qualification set out below. We cannot accept your dossier unless this has been done.

Yours faithfully,

Manufacturer’s declaration: We confirm that we have read and agree to abide by all the Terms and Conditions for pre-qualification of single use injection devices attached to this letter.

Signed: ……………………………………………………………………………………..

For and on behalf of: ……………………………………………………………………….

Date: …………………………………


TERMS AND CONDITIONS FOR THE PRE-QUALIFICATION OF SINGLE-USE INJECTION DEVICES 1. Examination of dossier: The Product Dossier will be screened by WHO for completeness prior to the

evaluation of the dossier. The dossier can be rejected on grounds of incompleteness and returned to the manufacturer. Complete dossiers will be retained for evaluation purposes.

2. Dossier Examination Fee: The Dossier Examination Fee is non-refundable and must be paid in full, in US$, before the dossier can be formally examined by WHO.

3. Laboratory Testing Fee: Omitted in revision 01.05 4. Evaluation: The WHO unit responsible for the evaluation will be independent from all UN agency

procurement units. Every single-use injection device will be evaluated against the relevant PQS performance specification and product verification protocol, current at the time of the evaluation. The manufacturer will receive a letter from WHO advising on the outcome of the evaluation process with regard to the specific product(s) of that particular manufacturer.

5. Laboratory testing: Omitted in revision 01.056. Meaning of pre-qualification: The grant of pre-qualification status following the evaluation process

indicates that the single-use injection device is technically satisfactory for procurement by United Nations Agencies for the purpose for which the device is intended, subject to any limitations set out in the PQS website or catalogue. However, the grant of pre-qualification status does not guarantee that an acceptable commercial arrangement can be reached between the supplier of the single-use injection device and the purchaser; nor does it guarantee that the quality of the delivered single-use injection device will be acceptable to the purchaser. In this context the word, ‘purchaser’, could cover more than one of the UN agency procurement units, including UNICEF, IAPSO, UNFPA, and WHO.

7. Publication: Following satisfactory evaluation, the single-use injection device, as manufactured at the specified manufacturing site, will be included in the list of ‘pre-qualified’ PQS products and WHO will inform the interested UN agency procurement unit(s) accordingly. Details of the product will then be posted on the PQS website and may also be published in a hard copy catalogue

8. Re-evaluation: The product will be subjected to review once a year, unless major changes occur in the meantime.

Manufacturers are required to ensure that all relevant time-expiring licenses and certificates remain valid and must provide WHO with evidence of the periodic renewal of such documents in the form of certified copies. Manufacturers must advise WHO in writing of any changes that may have an impact on the safety, performance, efficacy or quality of the product. Manufacturers must also advise WHO in writing of any contemplated changes to the product, to the manufacturing process or to the manufacturing site. If there is a change in manufacturing site WHO will require the manufacturer to make a new pre-qualification submission.

Re-evaluation may also be carried out in the following situations: If any omission by the manufacturer in the initial evaluation procedure, or during the follow-up activities, is evident in relation to the requirements, including compliance with quality system standards and failure to notify complaints. If any batch or batches of supplied product(s) are documented by WHO, or one or more of the UN agencies or organizations, not to be in compliance with the agreed specifications of the product or to reveal failure(s) regarding safety, performance or quality of the device; If the investigation of a complaint considered leads to the conclusion that the quality and/or safety of the product is in question.


9. Monitoring of complaints: The manufacturer of a pre-qualified single-use injection device must agree to collaborate with WHO and, where relevant with other UN agencies, in the investigation of complaints regarding device failure and adverse events relating to the device. Upon request, WHO or other relevant UN agencies will investigate reported complaints concerning the device, in collaboration with the manufacturer. WHO will maintain a database of complaints. Following investigation, WHO will provide UN agencies with a written report of the problem with recommendations for action, if any. If circumstances justify it, the complaint is also to be reported to the national regulatory authority where the device was used and to the national regulatory authority where the manufacturing site is located.

10. Confidentiality undertaking: WHO will treat, and will require evaluators of product dossiers to treat all information to which they will gain access during the evaluation, or otherwise in connection with the discharge of their responsibilities in regard to the pre-qualification of PQS products as confidential. In addition, the evaluators of product dossiers will be required to sign a Declaration of Interest. If based on this Declaration of Interest, it is felt that there is no risk of real or perceived conflict of interest and it is thus deemed appropriate for evaluators to undertake this work, they will discharge their functions exclusively as advisers to WHO. A sample of the confidentiality and declaration of interest undertaking for evaluators of product dossiers can be obtained on request.

11. The following disclaimer applies to all products that are accepted for inclusion on the PQS database.Disclaimer: Inclusion in the PQS database does not constitute an endorsement, or warranty of fitness, of any product for a particular purpose, including in regard to its safe and appropriate use in immunization programmes. WHO does not furthermore warrant or represent that: 1) the database is complete or error free and/or that 2) the products that have been found to meet the standards recommended by WHO, will continue to do so and/or that 3) the products listed have obtained regulatory approval for use in every country of the world or that its use is otherwise in accordance with the national laws and regulations of any country, including but not limited to patent laws. In addition, WHO wishes to alert procuring UN agencies that the improper storage, handling and transportation of products may affect their quality, efficacy and safety. WHO disclaims any and all liability and responsibility for any injury, death, loss, damage or other prejudice of any kind whatsoever that may arise as a result of, or in connection with the procurement, distribution and use of products included in the list.

DEFINITIONS: 1. Adverse event means an incident resulting in permanent impairment, hospitalization, congenital

malformation, injury or death to patients or users of a single-use injection device.2. Wherever a certified photocopy is requested, the photocopy must be certified as a true copy of the

original document by a person registered to practice law in the Legal Manufacturer’s country of origin and must be endorsed with the legal practitioner’s official stamp and signature.

3. Device failure means the failure of a single-use injection device to meet or exceed the specifications issued by the manufacturer.

4. In the context of these terms and conditions the word manufacturer means the Legal Manufacturer.5. Legal Manufacturer means the natural or legal person with responsibility for the design, manufacture,

packaging and labelling of a product or device before it is placed on the market under his own name, regardless of whether these operations are carried out by that person himself or on his behalf by a third party.

6. The primary container comprises a single self-contained syringe unit housed within a sterile unit container.

7. In the context of these terms and conditions, where the word product is used on its own, it means single-use injection device.

8. The secondary container is the packaging which contains more than one unit containers.9. Single-use injection device includes single-use syringes used in conjunction with single-use needles,


auto-disable (AD) syringes designed specifically for immunization and syringes with a reuse-prevention feature for general purpose.

10. The storage container is a carton or other form of packaging containing a specific number of secondarycontainers.

11. The unit container is the sterile enclosure which encloses a single self-contained syringe unit.


Annex 6 – Standard letter D: Request for missing information

Dear Sirs,

Application for pre-qualification of a single-use injection device under the PQS system. Your reference:

We refer to your letter dated <dd.mm.yyyy> with regard to <product/device description>, which accompanied the Product Dossier requested in our letter dated <dd.mm.yy>.

We have now made a preliminary examination of the Product Dossier and find that the following material is missing:

<list missing information, fee, samples, etc.>

If we do not receive the missing items within one month of the date of this letter we will have to reject your application. The Dossier will then be returned to you but we will not be able to return the Dossier Examination fee.

If you have any queries, please contact us as soon as possible.

Yours faithfully,


Annex 7 – Standard letter E: Evaluation notification

Dear Sirs,


We refer to your letter dated <dd.mm.yyyy> with regard to < device description>, which accompanied the Product Dossier requested in our letter dated <dd.mm.yyyy>.

EITHER: We have now made a full examination of your Product Dossier and confirm that the dossier is complete; it will now be formally evaluated in accordance with PQS procedures.

ORSince you have failed to respond to the request for missing information contained in our letter dated <dd.mm.yyyy> we are returning your dossier.


Yours faithfully,


Annex 8 – Standard letter F - Deleted:

Omitted in revision 01.05


Annex 9 – Standard letter G: Rejection

Dear Sirs,


We refer to your application dated <dd.mm.yyyy> with regard to < device description>.

We have now received the results of the formal evaluation and regret to inform you that we are unable to recommend the device for inclusion on the database of pre-qualified products, for the following reasons:

<briefly list principle reasons>

We thank you for your application and enclose a copy of the evaluation report. You are free to re-submit a new or modified device at any time in the future provided it complies fully with the requirements set out in the edition of the Guideline for manufacturerscurrent at the time of re-submission.


Yours faithfully,


Annex 10 – Standard letter H: Acceptance

Dear Sirs,


We refer to your application for pre-qualification dated <dd.mm.yyyy> concerning < device description>.

We have now received the results of the device evaluation and are pleased to inform you that < device description> has been recommended for inclusion on the PQS database of single-use injection devices pre-qualified for procurement by United Nations Agencies.

We enclose a copy of the evaluation report for you information. You will note that there are a certain matters about which the evaluator(s) had concerns. These are as follows:

<list any items that need to be drawn to the manufacturer’s attention>

We hope that you will be able to deal with these matters by the time the device is re-evaluated in one year’s time.

Finally, we draw your attention again to the terms and conditions and definitions set out in the pre-qualification information pack sent to you on <dd.mm.yyyy>. Note particularly the requirement that you inform us of any future changes to the device specification or changes to the manufacturing site, and that you notify us of any complaints, product recalls, component defects and other events that may affect the device.

.

Yours faithfully,

SOP

No

FCH

/ IV

B/Q

SS/P

QS/

014

Dat

e of

issu

e: 3

0/06

/200

5 R

evis

ion

Dat

e: 0

6/01

/200

7 V

ersi

on: 0

1.05

Ef

fect

ive

date

: 30/

06/2

005

Page

: 26

of 2

9T

itle

: H

ow t

o ev

alua

te a

pplic

atio

ns f

or t

he p

re-q

ualif

icat

ion

of s

ingl

e-us

e in

ject

ion

devi

ces

Ann

ex 1

1 -

Pro

duct

Sum

mar

y Sh

eet

ques

tion

nair

e fo

r si

ngle

-use

inje

ctio

n de

vice

s In

form

atio

n it

em

INJE

CT

ION

DE

VIC

E P

RO

DU

CT

SU

MM

AR

Y S

HE

ET

(C

ompl

ete

one

ques

tion

nair

e pe

r pr

oduc

t an

d pe

r m

anuf

actu

ring

sit

e)

1D

evic

e de

scri

ptio

n

2

Bra

nd n

ame

Rem

arks

3

Ven

dor s

tatu

s M

anuf

actu

rer

W

hole

sale

r

Dis

tribu

tor

O

ther

(spe

cify

)

Nam

e A

ddre

ssP

hone

and

Fax

C

onta

ct p

erso

n fo

r qu

alit

y as

sura

nce

Web

-sit

e, e

-mai

l

4V

endo

r

M

anuf

actu

rer

5

Man

ufac

turin

g Si

te

6

Pare

nt c

ompa

ny (i

f any

)

Reg

ulat

ory

auth

orit

y (c

heck

all

appl

icab

le)

Num

ber

Dev

ice

nam

e as

sub

mit

ted

to a

utho

riti

es

Aus

tralia

Li

cens

e nu

mbe

r:

Can

ada

Li

cens

e nu

mbe

r:

Euro

pean

Uni

on

CE

mar

k nu

mbe

r:

Japa

n

Lice

nse

num

ber:

U

nite

d St

ates

51

0(k)

num

ber:

7

Com

plia

nce

with

regu

latio

ns

Oth

er (s

peci

fy):

Stan

dard

s us

ed (

chec

k ap

plic

able

) C

erti

fica

tion

bod

y. S

peci

fy n

ame

& c

ount

ry

& a

ttach

cop

y of

the

certi

ficat

e. (S

ee n

ote

1)L

ast

audi

t da

te

Exp

irat

ion

date

ISO

1348

5 or

ISO

1348

8

Japa

n Q

S St

anda

rd #

1128

Uni

ted

Stat

es Q

S (2

1 C

FR p

art 8

20)

8C

onfo

rmity

with

qua

lity

syst

em st

anda

rds

Oth

er (s

peci

fy, e

.g. I

SO90

01:2

000)

Stan

dard

s us

ed (

chec

k ap

plic

able

) T

est

labo

rato

ry. S

peci

fy n

ame

& c

ount

ry &

at

tach

a c

opy

of th

e ce

rtific

ate.

(Se

e no

te 3

) L

abor

ator

y ac

cred

itat

ion

body

ISO

786

4: 1

993

for n

eedl

es

ISO

788

6-1:

1993

Syr

inge

s for

sing

le-u

se

ISO

788

6-3:

200

5 A

D sy

ringe

s for

imm

uniz

atio

n

IS

O 7

886-

4: 2

006

Syrin

ges w

ith re

-use

pre

vent

ion

feat

ure

ISO

853

7: 1

991

for i

nsul

in

Oth

er st

anda

rds i

n ad

ditio

n to

ISO

(spe

cify

):

9C

onfo

rmity

with

pro

duct

st

anda

rds

Yes

(If y

es, p

leas

e pr

ovid

e va

lidat

ed re

ports

incl

udin

g so

urce

s)

10Po

st-m

arke

t sur

veill

ance

re

ports

Y

es (I

f yes

, ple

ase

prov

ide

all r

epor

ts in

clud

ing

sour

ces)

N

o 11

Oth

er e

valu

atio

n re

ports

(G

ive

deta

ils a

nd p

rovi

de a

ll re

ports

incl

udin

g so

urce

s)

Not

es: 1

) For

exa

mpl

e: N

otifi

ed b

odie

s in

the

Euro

pean

Uni

on; Q

ualit

y Sy

stem

s Reg

istra

rs in

Nor

th A

mer

ica.

3)

Pro

duct

test

ing

mus

t inc

lude

ster

ility

, pac

kagi

ng a

nd la

belli

ng re

quire

men

ts.

SOP

No

FCH

/ IV

B/Q

SS/P

QS/

014

Dat

e of

issu

e: 3

0/06

/200

5 R

evis

ion

Dat

e: 0

6/01

/200

7 V

ersi

on: 0

1.05

Ef

fect

ive

date

: 30/

06/2

005

Page

: 27

of 2

9T

itle

: H

ow t

o ev

alua

te a

pplic

atio

ns f

or t

he p

re-q

ualif

icat

ion

of s

ingl

e-us

e in

ject

ion

devi

ces

Inst

ruct

ions

for

com

plet

ing

the

Pro

duct

Sum

mar

y Sh

eet

Que

stio

nnai

re

Gen

eral

not

e: A

ll ap

plic

ants

mus

t com

plet

e ite

ms 1

, 2, 3

, 4, 5

, 6, 8

, 9, 1

0 an

d 11

. Com

plet

e ite

m 7

onl

y if

the

devi

ce h

as a

lice

nse/

clea

ranc

e in

one

of

the

GH

TF fo

undi

ng m

embe

r cou

ntrie

s.

Item

1:

Giv

e a

brie

f des

crip

tion

of th

e de

vice

.

Item

2:

Giv

e th

e br

and

nam

e th

at is

use

d on

the

mar

ket.

If m

ore

than

one

nam

e is

use

d, p

leas

e lis

t all

nam

es.

Item

3:

Che

ck th

e ap

prop

riate

box

to in

dica

te th

e st

atus

of t

he V

endo

r.

Item

4 a

nd it

em 5

: In

som

e ca

ses t

he v

endo

r may

als

o be

the

man

ufac

ture

r. In

such

cas

es, p

rovi

de a

ll th

e re

ques

ted

info

rmat

ion

unde

r bot

h he

adin

gs, e

ven

if th

e de

tails

are

iden

tical

.

Item

6:

If th

e m

anuf

actu

rer i

s a su

bsid

iary

of a

par

ent c

ompa

ny, o

r is u

nder

con

tract

to a

noth

er c

ompa

ny, p

leas

e su

pply

the

nece

ssar

y in

form

atio

n.

Trac

eabi

lity

of th

e de

vice

to th

e Le

gal M

anuf

actu

rer m

ust b

e cl

early

stat

ed o

n al

l pac

kagi

ng. T

he L

egal

Man

ufac

ture

r’s d

ocum

enta

tion

syst

em m

ust

also

incl

ude

trace

abili

ty o

f the

dev

ice

to th

e or

igin

al m

anuf

actu

ring

site

.

Item

7:

Che

ck e

ach

GH

TF fo

undi

ng m

embe

r cou

ntry

in w

hich

the

regu

lato

ry a

utho

rity

has l

icen

sed/

clea

red

the

devi

ce.

In e

ach

case

, giv

e th

e lic

ense

or c

lear

ance

num

ber a

nd st

ate

the

devi

ce n

ame

that

was

subm

itted

to th

e au

thor

ity. N

ote

that

the

subm

itted

dev

ice

nam

e m

ay b

e di

ffere

nt

from

the

bran

d na

me;

we

requ

ire th

is in

form

atio

n so

that

we

can

verif

y yo

ur m

arke

t cle

aran

ce w

ith e

ach

of th

e re

gula

tory

aut

horit

ies.

Item

8:

Che

ck a

ll qu

ality

syst

em st

anda

rds a

pplic

able

to th

e m

anuf

actu

ring

site

. Aga

inst

eac

h ch

ecke

d st

anda

rd st

ate

the

nam

e an

d co

untry

of

orig

in o

f the

Cer

tific

atio

n B

ody

whi

ch v

erifi

ed c

ompl

ianc

e w

ith th

e st

anda

rd a

nd p

rovi

de a

cer

tifie

d co

py o

f the

qua

lity

syst

em c

ertif

icat

ion.

Sta

te

the

date

of t

he la

st c

ertif

icat

ion

audi

t and

the

date

of e

xpiry

. The

max

imum

per

iod

betw

een

audi

ts m

ust n

ot e

xcee

d th

ree

year

s.

Item

9:

Che

ck a

ll pr

oduc

t sta

ndar

ds a

pplic

able

to th

e de

vice

. A

gain

st e

ach

of th

e ch

ecke

d st

anda

rds s

tate

the

nam

e of

the

test

labo

rato

ry

whi

ch

carr

ied

out t

he te

st a

nd st

ate

the

nam

e of

the

body

whi

ch a

ccre

dite

d th

e la

bora

tory

. Pr

oduc

t tes

ting

mus

t inc

lude

ster

ility

, pac

kagi

ng a

nd la

belli

ng

requ

irem

ents

. W

e re

quire

a c

opy

of th

e te

st c

ertif

icat

e fo

r ISO

-com

plia

nt d

evic

es.

Item

10:

Pro

vide

all

post

-mar

ket s

urve

illan

ce re

ports

issu

ed b

y re

gula

tory

aut

horit

ies,

user

s or o

ther

par

ties a

nd st

ate

the

sour

ce o

f eac

h.

Item

11:

If a

vaila

ble,

pro

vide

any

oth

er th

ird p

arty

eva

luat

ion

repo

rts.


Annex 12 – Dossier submission checklist

Each dossier should contain the following: Rec’d Check

1. A covering letter.

2. A countersigned copy of the letter of invitation received from WHO

3. The correct Dossier Examination Fee, in US dollars.

4. Completed Product Summary Sheet Questionnaire supported by the following:

Confirmation that applicant is the Legal Manufacturer of the device.

General information about the manufacturer, including name and address.

Confirmation of the brand name of the device.

Product specifications, including details of product marking and traceability.

A manufacturer's certificate specifying the needle size and the needle length supplied with the device.

Certified photocopy of the regulatory approval for the device in the country of origin issued by the relevant national regulatory authority. Evaluator to check with Regulatory Authority.

Where applicable, details of the regulatory approval for the device in other countries, including certified photocopies of original documents. Evaluator to check with Regulatory Authority(s).

Documentary evidence that the device conforms to the relevant ISO standard.

Full product license details, including certified photocopies of current license(s). Evaluator to check with Regulatory Authority(s).

Certified photocopies of your current quality system certification issued by one of the certification bodies listed in Table 2. Evaluator to check with certification body.

Post-market surveillance report(s) (if any).

Other evaluation report(s) (if any).

5. A minimum of twenty samples of the injection device, in sealed unit containers, all taken from the same lot and packed within unopened secondary container(s).

6. Indicative cost of the product per unit, EXW, for 100,000 units, 1 million units and 10 million units.

7. A correctly labelled and addressed envelope/package.

Documents

1. The PQS Secretariat - WHO · xISO 7886-1:1993 - Sterile hypodermic syringes for single use - Part 1: Syringes for manual use. xISO 7886-3:2005 - Sterile hypodermic syringes for