12 Jul 2006

MSF Qualification Scheme

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1. General Commitment

As a medical organization, MSF regularly dispenses drugs to patients in the programmes it runs all over the world.

MSF attaches the utmost importance to the quality of the medicines that are given/dispensed to patients.

MSF strongly considers that any patient wherever he/she lives has a right to be treated with effective and safe drugs.

2. MSF drugs procurement chain

The organization has set up its own Procurement Centres (MSF Logistique, Bordeaux, France in 1986, and MSF Supply (formerly Transfer), Merchtem, Belgium, in 1989). The objective is double:

Operational: to supply medical and non-medical relief goods to MSF teams at the shortest possible notice

Qualitative: to keep a strict control on the quality of supply and make sure that it is compliant with our technical requirements.

In the specific field of drugs supply, the general policy of the organization is to select sources and dispatch drugs to wherever MSF is running programmes

When drugs are supplied by the MSF Procurement Centres, MSF considers that it is the moral responsibility of the organization to guarantee their quality. The MSF Executive Committee has consequently asked MSF pharmacists to develop a qualification procedure in order to achieve this objective.

In some countries however, MSF is not authorized to import medicines. In that case, the MSF qualification procedure cannot apply and the responsibility to assure the quality of the drugs rests with National Drug Authorities.

3. Definition

"The qualification of the medicines is an essential part of the quality assurance. It verifies that the products meet at least the norms and standards set by international organizations"

WHO Pre Qualification Project: link

4. Objective

To identify and qualify pharmaceutical products that are compliant with the MSF quality standards.

5. The Evaluators

The evaluation work is essentially carried out by MSF Headquarters Pharmacists MSF HQ pharmacists are:

The Operational Section Pharmacists.
OSPs are based in the head offices of the 5 main operational sections of MSF in Europe (Belgium, France, Holland, Spain, and Switzerland).

They regularly visit MSF missions in the field and verify that supply channels and products dispensed to patients are in line with the standards defined at HQ level

The Procurement Centre Pharmacists
MSF Procurement Centres are licensed by the Belgian and French Drug Authorities respectively.

Procurement Centre Pharmacists are legally responsible for the compliance of their agency with E.U. Good Distribution Practices. The PCPs are also in charge of market investigations.

The Access Campaign Pharmacists. In 1999, MSF launched a Campaign aiming to improve access to quality essential medicines for all (www.accessmed-msf.org)

The Access Campaign Pharmacists mainly work on pharmaceutical products for which access is problematic (patents barriers, lack of R & D, drugs for neglected diseases, ...).

The International Pharmacists Coordinator is in charge of coordinating these three groups of pharmacists. He/she is the head of Quality Assurance for the organization and directly reports to MSF Directors.

External experts are consulted and/or used for specific parts of the evaluation (e.g. GMP audits, Active Pharmaceutical Ingredients specifications, bio equivalence studies, ...)

6. Principles

The MSF qualification procedure is based on a principle of mutual trust. We therefore assume that all information communicated by the manufacturer is true and correct.

The manufacturer is asked to certify the veracity and accuracy of the information and documents submitted to MSF.

Any mistake or omission (intentional or not) may lead to the disqualification of the product and/or the manufacturer.

The MSF Qualification Scheme is neither intended to interfere with the WHO pre-qualification initiative, nor to duplicate any existing work (GMP inspections, product evaluations) carried out by stringent Drug Regulatory Authorities

Therefore,

Any WHO pre-qualified product included in the MSF List of Medicines is automatically qualified by MSF

Any product registered in a highly regulated country, AND that is included in the MSF List of Medicines, is automatically qualified by MSF

MSF is not a Drug Regulatory Agency.

The MSF Qualification Scheme has been exclusively designed for the organization and the decisions taken are only valid for MSF.

The MSF Qualification Scheme, is based on internationally recognized principles and built on two pillars:

the manufacturing site assessment

the product dossier assessment

The norms and standards that underlie the MSF QS are:

those published by the WHO (GMP guidelines, Technical Report Series)

the WHO International Pharmacopoeia, the European Pharmacopoeia, The British Pharmacopoeia and the United States Pharmacopoeia

the MSF specifications for pharmaceutical products MSF_specificationsMay2007.doc  

The MSF qualification procedure is open to any manufacturer regardless of the country where it operates.

7. Steps of the qualification procedure

1. Expression of interest
2. Screening of Manufacturer Information File
3. Evaluation of the Manufacturer Information File
4. Assessment of the manufacturing site
5. Result of the evaluation of the manufacturing site(s)
6. Request for information on products
7. Submission of product questionnaires
8. Evaluation of questionnaire
9. Result of the evaluation of the product dossier
10. Monitoring and follow-up

7.1. Expression of interest

Any manufacturer who wishes to participate to the MSF qualification procedure is invited to express his interest by filling in the "Manufacturer Information File" (MIF). MSF_Qualification_Scheme_MIF_May_2007.doc   

The manufacturer should send the MIF and requested annexes to the MSF International Office, by electronic mail or by post (add e-mail and post addresses) An acknowledgement of receipt will be sent in return to the manufacturer.

7.2. Screening of the Manufacturer Information File

Each file submitted by a manufacturer is first screened for completeness.

MIFs that are not complete will not be considered for evaluation.

In that case, the manufacturer will be informed that the file is incomplete and will be given a deadline to complete it.

If the manufacturer is not able to submit the complementary information within the given schedule, the MIF will be rejected.

Special attention will be paid to the list of products submitted by the manufacturer as an annex to the MIF. The evaluation procedure will only be initiated for manufacturers who produce pharmaceuticals that match with MSF interests.

7.3. Evaluation of the Manufacturer Information File

Complete MIFs will be evaluated by MSF pharmacists and, if need be, by external experts. The manufacturer will be informed in writing of the outcome of the evaluation of the MIF.

7.4. Assessment of the manufacturing site

7.4.1. Technical visit to the manufacturing site

GMP inspections carried out by the WHO PQ inspectors, by a PIC/S or an ICH member inspectorate are taken into consideration by MSF.

However, the sites that were found GMP compliant after a WHO PQ/PIC/S/ICH inspection are visited by a MSF HQ pharmacist (= technical visit).

A "technical visit" is not a full GMP audit. It is usually shorter and designed to make sure that the products of potential interest for MSF are actually manufactured on the approved premises.

7.4.2. Audit of the manufacturing site

NON PIC/S/WHO PQ/ICH inspected facilities are eligible for a MSF approval provided they successfully pass an audit conducted by a MSF mandated GMP expert The decision to audit a site is taken by the MSF International Pharmacists Coordinator on the basis of the evaluation of the "MIF". Audits are carried out against the WHO GMP guidelines.

7.4.3. Schedule of audits and technical visits

The MSF International Pharmacists Coordinator will inform the manufacturer whenever an audit or a technical visit of the plant is needed. Taking into account the constraints of the manufacturer and those of MSF, the audit or technical visit will be scheduled at the shortest possible notice.

7.4.4. Reporting

The auditor writes a report on the findings of the audit that is sent to the manufacturer.

If any additional information is required or corrective action has to be taken by the manufacturer, MSF pharmacists will postpone their final conclusions until the additional information and corrective actions have been evaluated by the auditor and the MSF pharmacists.

In the event of a disagreement between the manufacturer and the MSF pharmacists and auditor, the manufacturer will be asked to express his position clearly.

The manufacturer’s appeal will be evaluated by the auditor and the MSF pharmacists and an appropriate feedback will be given to the manufacturer.

The outcome of the technical visits is given orally at the end of the visit.

7.5. Result of the evaluation of the manufacturing site

On the basis of the evaluation of the Manufacturer Information File and, if need be, the conclusions of the technical visit or audit, the MSF International Pharmacists Coordinator will inform the manufacturer in writing of the outcome of the evaluation of his dossier which can be :

The site is approved by MSF

The site is NOT approved by MSF

A new audit is needed In this case, a tentative schedule is proposed to the manufacturer. The decision to approve (or not) the manufacturing site is postponed until the outcome of the re-audit has been evaluated by the MSF pharmacists.

7.6. Request for information on products

Manufacturers with at least one MSF approved manufacturing site will be asked to submit detailed technical information on the products that present an interest for the organization. The MSF pharmacists will provide the approved manufacturer with an electronic format of the Inter Agency Product Questionnaire (IAPQ).

The IAPQ is a tool that has been developed by the MSF pharmacists in collaboration with the UNICEF Supply Division, the WHO Procurement Department and the International Committee of the Red Cross.

7.7. Submission of product questionnaire

The approved manufacturer will submit the questionnaire to MSF together with the requested annexes and a sample of the product he intends to sell to MSF.

Questionnaires that are not complete will not be considered for evaluation. In this case, the manufacturer will be informed that that the questionnaire is incomplete and will be given a deadline to complete it. If the manufacturer is not able to submit the complementary information within the given schedule, the product dossier will be rejected

7.8. Evaluation of the product questionnaire

Key indicators of the quality assurance of a product are assessed

Countries of registration National Drug Regulatory Authority (NDRA) in the country of origin

Stability studies on the finished products

Finished Product (FP) specifications

Active Pharmaceutical Ingredient (API) Quality Assurance

Sample (dosage form packaging labelling possibly analysis)

Manufacturing site WHO GMP level of compliance

Therapeutic equivalence (if needed)

A rating is given for the first six indicators.

This rating reflects the level of compliance (1 = poorly compliant, 6 = fully compliant) of each indicator with the MSF standards and specifications.


Click table for large view

Any rating lower than three means that the product cannot be qualified for MSF.

Therapeutic equivalence

A similar rating is not applicable to this important indicator.

The WHO clearly states that "reasonable assurance must be provided that the multi source product is therapeutically equivalent and interchangeable with the comparator product" (WHO Technical Report Series 937, annex 7)

In the same document, WHO experts add that "bioequivalence is significant only if compliance with Good Manufacturing Practices and sourcing of Active Pharmaceutical Ingredients are well controlled".

MSF also considers that an evaluation of the therapeutic equivalence only makes sense if and only if the other parts of the product file have already been satisfactorily assessed by the MSF pharmacists.

The need for in vivo equivalence studies or the qualification for a biowaiver is evaluated for each product on the basis on the following WHO documents

"Guidelines on registration requirements to establish interchangeability"

"Proposal to waive in vivo bioequivalence requirements for WHO Model List of Essential Medicines immediate release, solid oral dosage forms"

(WHO Technical Report Series 937, annexes 7and 8)

At the time of the submission of the product file, the MSF pharmacists inform the manufacturer upon the need to provide (or not) a proof of therapeutic equivalence.

7.9. Result of the evaluation of the product questionnaire

The pharmacist in charge of the evaluation of the product dossier will communicate the results of his/her evaluation to the International Pharmacists Coordinator.

The outcome of the evaluation can be:

The product is compliant with the MSF requirements and specifications

The product is not compliant

In the first case

The pharmacist in charge of the dossier informs the manufacturer in writing that the product is approved by MSF,

The details of the approved product dossier are summarized in a Product Specification Sheet that is sent for signature to the manufacturer.

It is only after reception of the signed PSS that the product is considered to be "MSF qualified".

The qualification of a product does not imply that the product will be purchased by MSF. It is the necessary green light to start the commercial negotiations.

In the second case The manufacturer is informed that its product does not meet the MSF requirements and specifications and therefore cannot be approved.

7.10. Monitoring and follow up

MSF site approvals are granted for a period of 3 years.

Periodic re-audits or new technical visits are scheduled accordingly. Intermediate visits can also be planned in order to trace back the records of batches that have been delivered to MSF Procurement Centres.

Recent satisfactory WHO PQ/PIC/S/ICH inspections can be taken into consideration for the renewal of a GMP approval.

The MSF qualification of a product is valid for a period of 3 years.

During the period of validity of a qualification, the manufacturer is asked to undertake to advise MSF promptly of any changes in the manufacture or specifications of the product.

The implementation of the changes is subject to prior formal approval by MSF. If MSF accepts the proposed changes, a new PSS will be sent for signature to the manufacturer.

If MSF does not accept the proposed changes, the product will be disqualified.

The implementation of a change (in the manufacturing process or the specifications of a MSF qualified product) that has not been approved beforehand by MSF will be considered as a breach of contract.

Only products that are conforming to the signed PSS can be supplied to MSF Procurement Centres.

Random samples of products supplied to our Procurement Centres may be taken for independent testing as appropriate. In the event of failure to meet the requirements, the MSF pharmacists will inform the manufacturer and will further investigate the problem.

8. Confidentiality commitment

As a principle, all the information communicated to MSF in the context of the qualification process is considered confidential and will be treated as such.

Any person involved in the assessment process is asked to sign a confidentiality agreement by which he/she ensures that:

The confidential information is not used for any purpose other than the evaluation activities conducted for MSF

Confidential information is not disclosed or provided to any person who is not bound by similar obligations of confidentiality

All information collected, submitted or observed during the evaluation process is the property of MSF.

Manufacturers are reminded that all information contained in the Inter Agency Product Questionnaire may be shared with the UNICEF Supply Division, the WHO Procurement Department and the ICRC.

9. Commercial negotiation

Only manufacturers with at least one MSF approved manufacturing site will be allowed to participate to commercial negotiations. Only MSF qualified products will be purchased by MSF Procurement Centres.

10. Conflict of interest

All personnel involved in the MSF qualification procedure are asked to sign a "Declaration of Interest" by which they confirm that no situation of real, potential or apparent conflict of interest is known to them, including that they have no financial or other interest in, and/or relationship with a party, which:

May have vested commercial interest in obtaining access to any Confidential Information disclosed to them in the course of the evaluation activities, and/or

May have vested interest in the outcome of the evaluation activities including parties such as the manufacturers whose products are subject to evaluation or manufacturers of competing products