An FDC is a combination of two or more active drugs in a single dosage form. In the case of antiretrovirals (ARVs) it is usually the three drugs that need to be taken daily. This means that a patient could end up taking one tablet daily instead of up to six or more tablets every day, making it easier for the patients to adhere to their treatment regimen ‘ especially in a massive treatment programme such as South Africa’s.
Dr Andrew Boulle, of the University of Cape Town, made an urgent appeal early last year for government to do everything in its power to ensure that FDCs are included in the tender.
Boulle said at the time that the tender offered South Africa ‘such an opportunity to get it right, given our enormous purchasing power’.
‘We should not allow this tender to go ahead unless we get it right. We need to ensure we get the one pill once a day regimen packaged in adherence-promoting 28-day blister packs with the days of the week indicated. Well-prepared treatment literacy material should be included in the pill packets,’ he said.
The Treatment Action Campaign also said at the time that the upcoming tender should include special provisions that allow for companies to submit tender bids in respect of drugs that have not yet been registered in South Africa but have already been approved by stringent drug regulatory authorities such as the US Food and Drug Administration (FDA).
The activists called on the health department to commit to procuring FDCs where available and for the MCC to fast track the registration of all crucial ARVs and combinations of ARVs so as to ensure a competitive tender.
However, there were no FDCs or blister packs included when the tender outcome was announced. This fact went virtually unnoticed as everyone celebrated the massive price reductions announced by health minister Dr Aaron Motsoaledi.
It has now emerged that the MCC refused to fast track the registration of the FDCs that could have made a massive difference, especially in settings with few doctors, nurses and pharmacists.
Speaking this week Boulle said a number of FDCs were excluded from the tender due to registration issues. ‘We were told that the intention was that provision should be made for these and a fast track MCC process should be pursued if one of these products was successful. From what I understand Treasury rejected it and the MCC did not like the idea of being bullied into fast tracking,’ said Boulle.
‘In my opinion we have missed a critical opportunity,’ he said.
A source, closely involved in the tender negotiations, confirmed that the reason for the absence of FDCs was largely due to the MCC. ‘The guidelines on how a regulatory authority evaluates an FDC has been established a long time ago. Despite this there are people in the MCC who do not subscribe to these guides and have ignored FDC dossiers. They only started looking at the dossiers very late in the year. Now that the tender has been awarded, the pressure is off the MCC to register these FDCs,’ he said.
There is agreement that South Africa needs a process whereby critical drugs that have already been registered by reputable regulatory in authorities in other countries be fast tracked.
It is understood that there are currently several bilaterals between the MCC and other authorities, which means that information exchange should not be a problem.
‘I am not sure whether they believe that they are somehow better than their overseas counterparts or they are scared that will earn less if the dossier is finished quicker,’ the source said.
Another source, who was also integral to the negotiations, confirmed that they had proposed that they include the bids of unregistered FDCs with a window of opportunity for it to be validated if included in the tender.
However, this proposal was rejected by Treasury with the MCC making it clear that it would not be pressurised.
Professor Francois Venter, President of the Southern African HIV Clinicians Society slammed the outcome this week: ‘We wrote to the Minister regarding the urgency of FDCs months ago, and we sent a copy of the letter to the MCC. We got acknowledgement of receipt of the letter but no follow-on correspondence. The MCC is a frustratingly opaque structure at present ‘ we desperately want it to work effectively and independently in ensuring safe and regulated medication, but currently it just seems to be an obstacle to getting access to decent treatment for people with HIV. FDCs are easier to dispense and easier to take, and this is a lost opportunity to improve the world’s largest ARV treatment programme.’
Medecins Sans Frontieres’ (MSF) medical director for South Africa and Lesotho, Dr Gilles van Cutsem said that the majority of ART programmes in resource-limited settings ‘ as well as the majority of MSF projects – were using the generic FDC of stavudine, lamivudine and nevirapine (Triomune).
‘South Africa’s choice of single dose combinations, which are more difficult to take but also more expensive, was an incomprehensible exception,’ said Van Cutsem.
He added now that the World Health Organisation has recommended a better first line regimen (less toxic and with a better resistance profile), containing tenofovir as opposed to stavudine, many countries have changed their protocols.
Dr Tom Boyles, who has worked on ARV programmes in some of the most rural areas of the South Africa said that in these settings there was typically a chronic shortage of pharmacy staff which could be the rate limiting step in improving ARV role out.
‘As a doctor in these settings I commonly took the place of a pharmacy assistant when no-one else was available and patients needed treatment. One thing I noticed was how much time it takes to count the pills from 3 containers that the patient brings back, then accurately dispense the correct number of pills and record what you dispensed. FDC’s and blister packs would dramatically speed up the process and allow much easier recording of adherence. Shortage of pharmacy staff is underestimated as a limiting factor in ART role out and the provision of FDC’s and blister packs would be a huge advantage,” he said.
Vishal Brijlal of the Clinton initiative said the cost of FDCs was expected to come down significantly and would in the long-term be much more affordable than the single dose combinations.
The use of FDCs has been found in studies to improve the likelihood for good adherence and maintenance of virological suppression, which ultimately leads to better treatment outcomes. FDCs are easier to take, reduce the number of pills, and simplify the regimen, and for these reasons have been shown to improve patients’ quality of life; in addition they decrease the risk of errors in taking as well as prescribing medication.
In addition to the advantages in terms of adherence, this reduces the risk of patients skipping some drugs which can lead to drug resistance. The same risk exists with ARVs, where for example some patients don’t take the efavirenz, because it can cause dizziness or vivid dreams.
Several attempts to get comment from the Medicines Control Council failed.