Subtopic 4: Claims must not be inconsistent with the details of the marketing authorization
This is always the case, even if new data can contradict data present in the SmPC. For example if the side effect of ‘pancreatitis’ was listed for a product and a large safety trial demonstrated that there was no increased risk, a claim that there was no risk would not be approvable as it would be inconsistent with the SmPC.
Likewise if there are limitations to the licensed population and you subsequently generate positive data in a slightly different population, your claims must still reflect the licensed population cited in the SmPC. For instance the product bendamustine is licensed as follows:
Front line treatment of multiple myeloma (Durie-Salmon stage II with progress or stage III) in combination with prednisone for patients older than 65 years who are not eligible for autologous stem cell transplantation and who have clinical neuropathy at time of diagnosis precluding the use of thalidomide or bortezomib containing treatment.
In clinical practice this population represents a tiny subset of myeloma patients. There are numerous studies that have shown efficacy in patients who did not have neuropathy at diagnosis and who were treated with thalidomide and/or bortezomib. However because of the restricted licensed population bendamustine cannot be promoted for use in these patients.
Consider these examples
Consistent claims?
Consider the following claims that were made in the US for Abilify (aripiprazole)
“Unique pharmacology sets Abilify apart”
Abilify
- is thought to increase neuronal activity in hypoactive conditions
- Is thought to decrease neuronal activity in hyperactive conditions
- Has a high affinity for both dopamine and serotonin receptors
These claims were presented in conjunction with the image of a light dimmer switch set halfway between ‘high’ and ‘low’ presented against a well lit background wallpaper, with clearly defined graphics of human brains.
Now take a look at the US PI – in particular what is said in the Clinical Pharmacology section. Do you think the claims are consistent or inconsistent with the PI?
This was the subject of an FDA warning letter. The FDA stated that the sum of the claims and the way it was presented misleadingly implied a greater degree of certainty about the mechanism of action of Abilify in humans than is currently known and referred to the PI which states that the mechanism of action of this agent is unknown.
Consistent with licensed indication?
Below are some claims in a sales aid for Tindamax in the US. This agent is licensed in the US as follows:
Tindamax is also indicated for the treatment of bacterial vaginosis (BV) in non-pregnant women; pathogens such as Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, Candida albicans, and Herpes simplex virus should be ruled out.
There is also a boxed warning for the product for the potential risk for carcinogenicity, as well as contraindications for use in your patients with previous hypersensitivity to tinidazole or other nitroimidazole derivatives, during the first trimester of pregnancy, and in nursing mothers.
Which of the following statements do you agree with?
- The claims are not inconsistent with the licensed indication
- The claims are inconsistent with the licensed indication
- The claims are misleading
- The claims are not approvable as they could compromise patient safety
Ruling
These claims miss out an important part of the licensed indication – it is licensed in non-pregnant women. Moreover there is a boxed warning about use in early pregnancy. They misleadingly imply that TINDAMAX can be used in any patients with BV and therefore the claims are inconsistent with the marketing authorization. The claims were the subject of an FDA warning letter because of this, and the company was told to cease use of the claims.
Claims:
"TINDAMAX (tinidazole tablets) is the one and only treatment for BV that gives you patients..."
"For short, affordable treatment of bacterial vaginosis (BV)..."
