Medicinal products for HIV and related diseases

WHO
Medicinal products for HIV and related diseases Not set

Reference:
Beneficiary countries or territories:
Published on: 15-Aug-2007
Deadline on: 02-Dec-2007 23:59 (GMT 0.00)

Description

7th Invitation

to manufacturers of medicinal products

for HIV and related diseases

to submit an Expression of Interest (EOI) for product evaluation to the WHO Prequalification Programme

(May 2007)

To support national and global efforts to increase access to and the affordability of HIV/AIDS-related care and treatment, WHO, together with UNICEF, UNAIDS and UNITAID, invite manufacturers of selected pharmaceutical products to submit Expressions of Interest (EOIs) for product evaluation. The first EOI for products for HIV/AIDS-related care and treatment was published in 2000 and the 6th EOI was published in October 2005.

Article 1. Procedure for this EOI

The current EOI is published in accordance with the Procedure for assessing the acceptability, in principle, of pharmaceutical products for purchase by United Nations agencies, adopted in 2001 by the 37th WHO Expert Committee on Specifications for Pharmaceutical Preparations, published as part of the 37th report of the Committee (no. 908 of the WHO Technical Report Series) in 2003, and amended subsequently as part of the 41st report of the Committee, published as No. 943 of the WHO Technical Report Series in 2007.

Assessment of product(s) submitted under this EOI will include evaluation of :

• product dossiers, which must include product data and information as specified in the guidelines for submission

• manufacturing sites, which must adhere to good manufacturing practices (GMP)

• clinical sites (if applicable), which must adhere to good clinical practices (GCP).

If evaluation demonstrates that a product and its corresponding manufacturing (and clinical) site(s) meet WHO recommended standards, it will be included in the list of medicinal products that are considered to be acceptable for procurement by UN organizations and others.

Article 2. Medicinal products included on the 7th EOI

The ultimate aim of this 7th EOI is to increase the range of selected products and sources available in relation to treatment for HIV/AIDS. The medicines listed in the 7th EOI have been identified by WHO Department of HIV/AIDS as vital to effective treatment for people living with HIV/AIDS. These products are included either in the WHO Model List of Essential Medicines and/or in the WHO treatment guidelines relating to antiretroviral therapy for HIV infection in adults and adolescents, and in infants and children.

Products included in the WHO Model List of Essential Medicines are those satisfy the priority health care needs of a population. They are selected on the basis of disease prevalence, evidence on efficacy and safety, and comparative cost-effectiveness. Products

included in WHO treatment guidelines are selected on the basis of an assessment of the quality of evidence for benefits, harms, costs, and appropriateness for use in a variety of situations, taking onto account needs of special populations, and the values and preferences of the groups (professional and patient) using them.

Interested manufacturers are encouraged to submit documentation for recommended dosage forms and strengths, as specified below, of medicinal products in the following categories. Products of special interest under current Invitation are highlighted italic in the text. Appropriate solid dosage formulations for adults should be scored for pediatric use purposes.

1. Antiretrovirals as single-ingredient formulations for use in adults and adolescents:

1.1. Nucleoside/Nucleotide Reverse Transcriptase Inhibitors

- Abacavir, tablet 300 mg; 600 mg

- Didanosine, capsule (enteric-coated) 200 mg; 250 mg; 400 mg,

tablet (buffered) 100 mg; 150 mg; 200 mg

- Emtricitabine, capsule 200 mg

- Lamivudine, tablet 150 mg; 300 mg

- Stavudine, capsule 30 mg

- Tenofovir disoproxil fumarate, tablet 300 mg

- Zidovudine, tablet 300 mg, capsule 250 mg, solution (i/v) 10 mg/ml

1.2. Non-Nucleoside Reverse Transcriptase Inhibitors

- Efavirenz, capsule 200 mg, tablet 600 mg

- Nevirapine, tablet 200 mg

1.3. Protease Inhibitors

- Atazanavir, capsule 300 mg

- Indinavir, capsule 200 mg; 400 mg

- Nelfinavir, tablet 250 mg; 625 mg

- Ritonavir, capsule 100 mg, tablet (heat-stable) 100 mg

- Saquinavir, capsule 200 mg; 500 mg

2. Antiretrovirals as single-ingredient formulations for use in children:

2.1. Solid dosage formulations of

- Abacavir, tablet (scored) 60 mg; 300 mg

- Didanosine, capsule (enteric-coated) 125 mg

- Efavirenz, capsule 50 mg; 100 mg

- Lamivudine, tablet (scored) 30 mg

- Nevirapine, tablet (scored) 100 mg

- Ritonavir, tablet (heat-stable) 100 mg

- Zidovudine, tablet (scored) 60 mg; 100 mg

2.2. Solutions or dissolvable formulations of

- Abacavir, oral liquid 100 mg/5ml

- Emtricitabine, oral liquid 50 mg/5ml

- Lamivudine, oral liquid 50 mg/5ml

- Nevirapine, oral liquid 50 mg/5ml, granules 6 mg

- Zidovudine, oral liquid 50 mg/5ml, granules 12 mg

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3. Anti-retrovirals as fixed-dose combinations (FDC) for adults and adolescents:

3.1. Reverse Transcriptase Inhibitors

- Lamivudine + Zidovudine, tablet (scored) 150 mg + 300 mg

- Lamivudine + Stavudine + Nevirapine, tablet (scored) 150 mg + 30 mg + 200 mg

- Lamivudine + Zidovudine + Nevirapine, tablet (scored) 150 mg + 300 mg + 200 mg

- Tenofovir + Emtricitabine, tablet 300 mg + 200 mg

- Tenofovir + Lamivudine, tablet 300 mg + 300 mg

- Tenofovir + Efavirenz + Emtricitabine, tablet 300 mg + 600 mg + 200 mg

- Tenofovir + Efavirenz + Lamivudine, tablet 300 mg + 600 mg + 300 mg

3.2. Protease Inhibitors

- Atazanavir + Ritonavir, capsule (heat stable) 300 mg + 100 mg

- Lopinavir + Ritonavir, capsule 133,3 mg + 33,3 mg;

tablet (heat-stable) 200 mg + 50 mg

4. Anti-retrovirals as fixed-dose combinations for paediatric use:

4.1. Reverse Transcriptase Inhibitors

- Lamivudine + Abacavir, tablet (scored) 30 mg + 60 mg

- Lamivudine + Zidovudine, tablet (scored) 30 mg + 60 mg

- Lamivudine + Zidovudine+ Abacavir, tablet (scored) 30 mg + 60 mg+ 60 mg

- Lamivudine + Stavudine + Nevirapine

- Lamivudine + Zidovudine + Nevirapine

4.2. Protease Inhibitors

- Lopinavir + Ritonavir, tablet (heat-stable) 100 mg + 25 mg

5. Medicines to treat HIV/AIDS related conditions:

5.1. Antibacterial agents: 5.2. Antiprotozoal, antifungal and

- Azithromycin antimycobacterial agents:

- Benzylpenicillin - Amphotericin B

- Cefixime - Dapsone

- Ceftriaxone - Fluconazole

- Ciprofloxacin - Folinic acid

- Clarithromycin - Itraconazole

- Clindamycin - Pentamidine

- Spectinomycin - Pyrimethamine

- Sulfadiazine - Rifabutin

- Sulfamethoxazole + Trimethoprim

5.3. Antiviral agents 5.4. Anti-cancer drugs

- Aciclovir - Bleomycin

- Ganciclovir - Etoposide

- Vinblastine

- Vincristine

5.5. Palliative care drugs

- Amitriptyline - Ibuprofen

- Chlorphenamine - Loperamide

- Codeine - Morphine (oral formulation)

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Article 3. How to submit an expression of interest

In order to submit an expression of interest for product evaluation, the manufacturer send the following to the WHO Prequalification Programme:

1. Covering letter, in English, expressing interest in participating in the WHO Prequalification Programme and confirming that the information submitted in the product dossiers is complete and correct.

2. Product dossier, in English, in the format as specified in the guidelines for submitting product data and information.

3. A product sample, for example e.g. 1 x 100 tablets, to enable chemical and pharmaceutical analysis.

4. A site master file, for each manufacturing site listed in the product dossier, in the requisite format.

Items 1-3 (i.e. the covering letter, product dossier and product sample) should be sent by surface mail to Dr Matthias Stahl of the WHO Prequalification Programme, addressed as follows:

CONFIDENTIAL

Attention: Dr Matthias Stahl

WHO Prequalification Programme

Product Name:

UNICEF Supply Division

UNICEF Plads – Freeport

2100 Copenhagen

Denmark

Items 4 (i.e. the site master file) should be sent by surface mail to Ms Laura Oakes of the WHO Prequalification Programme, addressed as follows:

Attention: Ms Laura Oakes

World Health Organization

HTP/PSM/QSM

WHO Prequalification Programme

20 Avenue Appia

1211 Geneva 27

Switzerland.

Deadline for submission: December 1, 2007

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Article 4. Quality assessment procedure following submission of an expression of interest by a manufacturer

The quality assessment is undertaken to evaluate whether the pharmaceutical product being evaluated meets the requirements recommended by WHO, and is manufactured in compliance with good manufacturing practices (GMP).

The procedure established by WHO for quality assessment incorporates:

• general understanding of the production and quality control activities of the manufacturer;

• assessment of product data and information on safety, efficacy and quality submitted by the manufacturer, including product formulation, manufacture and test data and results;

• assessment of the manufacturing site's adherence to GMP, and its consistency in production and quality control of starting materials, with specific emphasis on active pharmaceutical ingredients, and finished product;

• assessment of clinical testing units or organizations (i.e. parties performing one or more clinical trials with the product) for compliance with good clinical practices and good laboratory practices, as appropriate;

• random sampling and testing of medicines supplied.

Previous evaluation conducted by the relevant National Drug Regulatory Authority (NDRA) may be taken into account during the evaluation conducted by WHO, provided that NDRA has expertise in the product area. If appropriate, the relevant NDRA may be invited to collaborate with WHO on the quality assessment. Any manufacturer who submits a product for evaluation, is therefore encouraged to authorize its NDRA to discuss relevant product files with WHO representatives, during assessments and inspections, if required (subject to appropriate confidentiality provisions, if necessary).

Once WHO is satisfied that quality assessment has been completed for the manufacturer of the relevant starting materials, the finished pharmaceutical product, and the clinical testing units, and that the product meets WHO recommended standards, the product (as produced at the specified manufacturing site) is added to the WHO List of Prequalified Products.

Article 5. References and further information

For further information on the WHO Prequalification Programme, please visit the Programme's web-site at: www.who.int/prequal. If you have any questions relating to the procedure for responding to an EOI, please write to the WHO Prequalification Programme at its email address: prequal@who.int. Your question(s) will be directed to the prequalification team member who can best advise you.

For further information on WHO treatment guidelines, please consult:

1. WHO guidelines on "Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for public health approach", WHO, Geneva 2006; available at:

http://www.who.int/entity/hiv/pub/guidelines/artadultguidelines.pdf

2. WHO guidelines on "Antiretroviral therapy for HIV infection in infants and children: recommendations for public health approach", WHO, Geneva 2006 available at:

http://www.who.int/hiv/pub/guidelines/paediatric020907.pdf

3. Report of meetings on paediatric ARV medicines; available at:

http://www.who.int/hiv/events/paediatricmeetingreport.pdf

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Attention: Ms Laura Oakes World Health Organization HTP/PSM/QSM WHO Prequalification Programme 20 Avenue Appia 1211 Geneva 27 Switzerland.