How to access the bedaquiline donation program: step by step

This is a note for implementers providing a general overview and reviewing the steps they need to take in order to access the drug.

Bedaquiline (BDQ) is a powerful new tool for the treatment of patients with drug-resistant TB (DR-TB).

On April 1, USAID launched a Bedaquiline donation program for the treatment of patients with DR-TB. The program will provide 30,000 treatment courses of BDQ to patients in more than 100 countries over a period of four years. This will be a useful addition to country and program strategies for treating DR-TB.

As part of the donation program, countries and organizations can place an order for BDQ through the Stop TB Partnership’s Global Drug Facility. Information on the donation can be found here.

Most countries/programs treating patients for DR-TB meet the WHO recommendations for BDQ introduction but may need some additional support to refine the implementation process.

This note for implementers provides a general overview and reviews the five conditions with short, practical guidance in these areas. Countries and programs must certify they meet the five conditions specified below.

More specific questions can be addressed to [email protected] and [email protected] with a copy to [email protected].

Countries/programs wishing to access the drug should take the following steps from A to H:

A. Ensure you follow the five WHO recommendations for optimal introduction of BDQ

1)  Treatment is administered under closely monitored conditions. Countries/programs must have a program for managing drug-resistant TB and have guidelines and protocols for managing patients with DR-TB.

• Ideally, the guidelines would be a formalized document, but countries/programs without formal guidelines for managing DR-TB can still obtain BDQ and request assistance with development of formal guidelines. These guidelines do NOT need to specify or discuss the use of BDQ.

2) Proper patient inclusion: Countries/programs must have a mechanism for reviewing the patients who will receive BDQ. This can be a formal “clinical review committee”/consilium. This might even include a team of local experts to review patients being considered for BDQ use. Countries/programs without such a mechanism can still obtain BDQ and request assistance with the development of a review mechanism.

3) Patient informed consent is obtained: Countries/programs must have a process by which patients are given information about the treatment of DR-TB and sign a document stating they agree to receive treatment.

• For patients being considered for BDQ, information about this specific drug will need to be included in the consent process.
• Countries/programs without such a process can still obtain BDQ and request assistance with the development of a consent process.

4) Adherence to the principles of designing a WHO-recommended DR-TB regimen: Countries/programs must adhere to WHO recommendations on designing a DR-TB regimen, if they use BDQ in combination with other medications to treat DR-TB.

• In general, BDQ is recommended for patients with resistance or intolerance to an injectable, a fluoroquinolone or both drugs, although there are other conditions under which the drug can be given.  Examples of treatment regimens can be found http://www.who.int/tb/publications/pmdt_companionhandbook/en/.
• Countries/programs who require guidance on regimen design can still obtain BDQ and request assistance with the development of treatment regimen/design.

5) Pharmacovigilance and proper management of adverse drug reactions: Countries/programs must have a way to assess patients for adverse events, manage adverse events, and to document adverse events in the medical records.

• Ideally, there would be a formal mechanism for reporting serious adverse events to a nationally recognized pharmacovigilance body or a drug regulatory agency, but such mechanisms are not required to order BDQ, as long as there is a plan to identify an agency that can serve in this role.
• There are several types of active pharmacovigilance that can be developed in a country/program, and the ideal system will need to be chosen based on multiple factors, including the goal of the program, the available resources, and technical support.
• Countries SHOULD NOT WAIT for the development of this formal system before introducing BDQ, as these programs can take a long time to develop.
• Countries/programs can still obtain BDQ and request assistance with the development of an active pharmacovigilance system.

B. Review the background documentation on the program and the order form from the GDF (http://stoptb.org/gdf/drugsupply/procurement_forms.asp).

C. Estimate the number of patients who will benefit from the drug

• This can be done by reviewing data on rates of injectable or fluoroquinolone resistance and intolerance from cohorts treated in the previous years, and is usually between 25 and 30% of the patients treated for DR-TB. This estimate should take into account scale-up plans. The medication has a 24 month shelf-life.

D. Review the need for other second-line drugs that may be needed to treat patients   who will be receiving BDQ, especially other “group 5 drugs” such as linezolid and clofazimine.

E. Review Technical Assistance needs based on the above descriptions
As part of the donation program, USAID has committed to providing technical assistance to countries and programs as well. After reviewing these conditions, countries/programs can request TA in any or all of the areas by writing to [email protected] and [email protected] with a copy to [email protected].

F. Place order for BDQ and other second-line drugs as the turn-around time is likely to be several months, and TA activities can be carried out while awaiting drug arrival.

• Funding for the companion drugs and other activities can be sought from multiple sources, including re-programing of Global Fund moneys for introduction of new technologies.

G. Develop the mechanism for import of BDQ in the country if it is not registered yet

• This will usually be through an import waiver, although there may be different mechanisms depending on the country.  One helpful model for how to import BDQ is the model the country/program used for importing Xpert MTB/RIF® cartridges and supplies.

H. Review clinical cases and patient histories to see who would benefit from BDQ

• These would include patients who are failing current DR-TB therapy, those with resistance to a fluoroquinolone or injectable, those with adverse events (i.e. hearing loss), etc.

Please note: Although this is a donation program, countries might still need to account for operational costs that could be incurred, including but not limited to freight, insurance among others.

The BDQ Implementation Plan: The WHO recommends countries develop a BDQ implementation plan in which components of BDQ introduction are elaborated.  A guide to developing this plan can be found at: http://www.who.int/tb/publications/WHO_BDQimplementationplan.pdf.

Countries/programs can be assisted with development of these plans by contacting [email protected] and [email protected] with a copy to [email protected].