Appendix 18. Compassionate use of TB drugs

Update: October 2023

18.1 Definition

"Compassionate use" (also called "expanded access") is a regulatory framework [1] Citation 1. European Medical Agency. Human Regulatory. Compassionate use [Accessed 19 April 2023].
https://www.ema.europa.eu/en/human-regulatory/research-development/compassionate-use [2] Citation 2. World Health Organization. (‎2008)‎. Guidelines for the programmatic management of drug-resistant tuberculosis: emergency update 2008. World Health Organization. 
https://apps.who.int/iris/handle/10665/43965 that allows the use of an investigational new drug (IND) for patients:

• who have a life-threatening disease, and
• no satisfactory treatment registered by national regulatory authorities (NRA), and
• who cannot enter clinical trials.

18.2 National regulations

In most countries, only drugs for which a marketing authorisation has been granted by the NRA can be used in humans.

Some NRAs have developed mechanisms to facilitate access to IND at different stages of development prior to marketing authorisation.

In this case, a clinician or an institution can apply for approval of the use of an IND under compassionate use conditions and seek permission to import it. Approval may be given for a patient or a group of patients, generally after review by a dedicated medical committee.

18.3 Indications

Compassionate use may be considered for patients with drug-resistant tuberculosis (DR-TB) when therapeutic regimens composed of drugs with marketing authorisation have failed, or are very likely to fail, and no surgical option is appropriate.

The IND should always be used with other likely effective drug(s), see Chapter 10, Section 10.1.2, to avoid the emergence of resistance to the IND. The number of likely effective drug(s) given with the IND should be, as a minimum, one bactericidal drug or two bacteriostatic drugs.

Possible interactions and overlapping toxicities between the IND and other TB drugs should be taken into consideration. The use of an IND should not result in the discontinuation of an essential likely effective drug.

The use of two INDs should follow the same principles.

18.4 Minimal requirements

The minimal requirements for compassionate use of an IND include:

• Adequate patient management (including clinical, bacteriological and biological monitoring, adherence support, etc.).
• Monitoring and management of potential adverse effects specific to the IND.
• A pharmacovigilance system (aDSM) a Citation a. For more information see: World Health Organization. Active tuberculosis drug-safety monitoring and management (aDSM). Framework for implementation. WHO, Geneva, 2015.
  https://apps.who.int/iris/bitstream/handle/10665/204465/WHO_HTM_TB_2015.28_eng.pdf;jsessionid=97A194C2FA7D78CF2E18BD60C8C6E3F7?sequence=1 .
• A patient-informed consent process:
  • inform the patient that the safety and efficacy of the IND have not been proven,
  • explain the potential benefits and risks.
• Approval by an ethics review board and by the Ministry of Health.
• Approval by the manufacturer of the IND.

The support of a regulatory affairs pharmacist is necessary regardless of whether the country has a regulatory framework authorising compassionate use.