The FDA OTC Acne Monograph – stifling the development of better treatments?
30 July 2010
By Dr Anne Eady
In my personal view the biggest single barrier to the development of better therapies for acne is the 20 year old FDA OTC Acne Monograph. Here I’ll explain why I believe this regulatory document is stifling much needed innovation in the management of this very common skin condition. Acne is unusual in that remedies fall into two regulatory classes, medicines and cosmetics (although these cannot be sold as acne remedies but rather as products to manage ‘breakouts’). Teenagers and their parents aren’t generally aware of this and find it hard to discriminate between product intended to manage a few pimples and those required to treat more severe disease. In most countries including the US and the UK, the OTC segment is the first port of call for acne sufferers for whom cosmetic products haven’t worked. Here I will use the term ‘acne’ to refer both to the disease and to the cosmetic indication of ‘spots’.
Acne is easily self-diagnosable and therefore amenable to self-selection of treatment. Moreover pressure in the US, UK and elsewhere on healthcare budgets, means that OTC route is likely to become even more important in the future than it is now as the main conduit via which acne sufferers access treatment. The emerging role of pharmacists in the management of easily diagnosed conditions like acne further focuses attention on the OTC route. Seeking help from a medical practitioner could and should become a strategy of last resort.
So where is the problem? There is an urgent need for innovative treatments for acne that can be made available via non-prescription routes. People with acne don’t want to take antibiotics for months or years at a time and antibiotics are not a suitable therapy for a chronic condition like acne. In the community, antibiotics for acne are a significant driver of antibiotic resistance which is a communicable adverse treatment effect. Benzoyl peroxide (BPO) and topical retinoids offer alternatives to antibiotics but neither is problem free. BPO is the oldest topical treatment for acne and has been around for over 50 years. It works well but it bleaches everything with which it comes into contact. Modern formulations have done much to reduce irritancy in all but highly susceptible individuals or those who tend to be over-zealous in the amounts they apply. Topical retinoids are still underused and offer an equally effective alternative to BPO. Whilst BPO is available without a prescription, topical retinoids are not. In the future, they might be re-classified as long as regulators can be persuaded that the risk of teratogenicity is infinitely small.
In the US, over-the-counter acne medicines are regulated by the FDA via the monograph system. So, what else is permitted in the OTC space? The answer is very little that anyone nowadays would choose to use – would you want to put sulphur or resorcinol on your skin? The FDA monograph is backward looking and yet it still influences OTC availability of acne treatments within and beyond the US. Apart from BPO, the only other OTC listed active that can be said to demonstrate efficacy is salicylic acid, another very old remedy. Salicylic acid, in the concentrations permitted, is not a very effective treatment for those with anything other than mild, ‘cosmetic’ acne. Unlike BPO, for which evidence of efficacy is overwhelming, published reports of its efficacy are few and far between and not very convincing.
I’m sure these criticisms apply across the FDA Monograph system and don’t just apply to acne. The OTC sector should drive not stifle innovation. It is the obvious regulatory space for new products to treat diseases like acne. Cosmetic companies are much more innovative than big pharma and yet can only go so far given that cosmetics cannot be seen to treat disease and acne is a disease. However, the spectrum of severity of acne is wide, onset is typically slow and prevention is surely better than cure. So if a cosmetic product can be said to enhance the appearance of skin by keeping it blemish-free then, in theory at least, it could work as well as any medicine. Assuming that there will always be a big demand for treatments as well as prophylactics, new medicinal products containing new actives will be required. Most existing topical acne therapies produce at best a 50-60% reduction in lesions after weeks or months. There is still much room for improvement despite the advances in formulation technology that have allowed the development of combinations products based on BPO and an antibiotic, a retinoid and an antibiotic or more recently BPO and a retinoid. This is still just playing around with old molecules when what are urgently required are entirely new actives that can be sold OTC. If we really want to relieve the burden on physicians, reduce reliance on antibiotics and put control in patients’/consumers’ hands, we have to give them choice and we have to provide effective new remedies that overcome the disadvantages of the older ones.
I’d like to see either a complete overhaul of the FDA OTC Acne Monograph or preferably its abandonment and I’d like to see it sooner rather than later. It is worth mentioning that the final FDA rule on BPO was only published in March of this year. This is hardly indicative of a responsive regulatory process. The FDA has led the way with tighter controls on the availability of oral isotretinoin and yet none of the available alternatives come even close to the power of this agent. Isn’t it about time that regulators facilitated the development of safer, more effective treatments? Without the constraints imposed by the monograph, I’m sure big pharma and major healthcare companies will respond rapidly to the challenge of overcoming conservatism and competing successfully with the more innovative cosmetic sector.
References
1. Food and Drug Administration. Topical Acne Drug Products for Over-The-Counter Human Use: Final Monograph. Federal Register 1991; 56 (159): 41008 – 41020.
2. Food and Drug Administration. Classification of Benzoyl Peroxide as Safe and Effective and Revision of Labeling to Drug Facts Format; Topical Acne Drug Products for Over-The-Counter Human Use; Final Rule. Federal Register 2010; 75 942): 9767-9777.
3. Patel M, Bowe WP, Heughebaert C, Shalita AR. The development of antimicrobial resistance due to the antibiotic treatment of acne vulgaris: a review. J Drugs Dermatol 2010; 9(6): 655-664.
4. Seidler EM, Kimball AB. Meta-analysis comparing efficacy of benzoyl peroxide, clindamycin, benzoyl peroxide with salicylic acid, and combination benzoyl peroxide/clindamycin in acne. J Am Acad Dermatol 2010; 63 (1): 52-62.
Acne is easily self-diagnosable and therefore amenable to self-selection of treatment. Moreover pressure in the US, UK and elsewhere on healthcare budgets, means that OTC route is likely to become even more important in the future than it is now as the main conduit via which acne sufferers access treatment. The emerging role of pharmacists in the management of easily diagnosed conditions like acne further focuses attention on the OTC route. Seeking help from a medical practitioner could and should become a strategy of last resort.
So where is the problem? There is an urgent need for innovative treatments for acne that can be made available via non-prescription routes. People with acne don’t want to take antibiotics for months or years at a time and antibiotics are not a suitable therapy for a chronic condition like acne. In the community, antibiotics for acne are a significant driver of antibiotic resistance which is a communicable adverse treatment effect. Benzoyl peroxide (BPO) and topical retinoids offer alternatives to antibiotics but neither is problem free. BPO is the oldest topical treatment for acne and has been around for over 50 years. It works well but it bleaches everything with which it comes into contact. Modern formulations have done much to reduce irritancy in all but highly susceptible individuals or those who tend to be over-zealous in the amounts they apply. Topical retinoids are still underused and offer an equally effective alternative to BPO. Whilst BPO is available without a prescription, topical retinoids are not. In the future, they might be re-classified as long as regulators can be persuaded that the risk of teratogenicity is infinitely small.
In the US, over-the-counter acne medicines are regulated by the FDA via the monograph system. So, what else is permitted in the OTC space? The answer is very little that anyone nowadays would choose to use – would you want to put sulphur or resorcinol on your skin? The FDA monograph is backward looking and yet it still influences OTC availability of acne treatments within and beyond the US. Apart from BPO, the only other OTC listed active that can be said to demonstrate efficacy is salicylic acid, another very old remedy. Salicylic acid, in the concentrations permitted, is not a very effective treatment for those with anything other than mild, ‘cosmetic’ acne. Unlike BPO, for which evidence of efficacy is overwhelming, published reports of its efficacy are few and far between and not very convincing.
I’m sure these criticisms apply across the FDA Monograph system and don’t just apply to acne. The OTC sector should drive not stifle innovation. It is the obvious regulatory space for new products to treat diseases like acne. Cosmetic companies are much more innovative than big pharma and yet can only go so far given that cosmetics cannot be seen to treat disease and acne is a disease. However, the spectrum of severity of acne is wide, onset is typically slow and prevention is surely better than cure. So if a cosmetic product can be said to enhance the appearance of skin by keeping it blemish-free then, in theory at least, it could work as well as any medicine. Assuming that there will always be a big demand for treatments as well as prophylactics, new medicinal products containing new actives will be required. Most existing topical acne therapies produce at best a 50-60% reduction in lesions after weeks or months. There is still much room for improvement despite the advances in formulation technology that have allowed the development of combinations products based on BPO and an antibiotic, a retinoid and an antibiotic or more recently BPO and a retinoid. This is still just playing around with old molecules when what are urgently required are entirely new actives that can be sold OTC. If we really want to relieve the burden on physicians, reduce reliance on antibiotics and put control in patients’/consumers’ hands, we have to give them choice and we have to provide effective new remedies that overcome the disadvantages of the older ones.
I’d like to see either a complete overhaul of the FDA OTC Acne Monograph or preferably its abandonment and I’d like to see it sooner rather than later. It is worth mentioning that the final FDA rule on BPO was only published in March of this year. This is hardly indicative of a responsive regulatory process. The FDA has led the way with tighter controls on the availability of oral isotretinoin and yet none of the available alternatives come even close to the power of this agent. Isn’t it about time that regulators facilitated the development of safer, more effective treatments? Without the constraints imposed by the monograph, I’m sure big pharma and major healthcare companies will respond rapidly to the challenge of overcoming conservatism and competing successfully with the more innovative cosmetic sector.
References
1. Food and Drug Administration. Topical Acne Drug Products for Over-The-Counter Human Use: Final Monograph. Federal Register 1991; 56 (159): 41008 – 41020.
2. Food and Drug Administration. Classification of Benzoyl Peroxide as Safe and Effective and Revision of Labeling to Drug Facts Format; Topical Acne Drug Products for Over-The-Counter Human Use; Final Rule. Federal Register 2010; 75 942): 9767-9777.
3. Patel M, Bowe WP, Heughebaert C, Shalita AR. The development of antimicrobial resistance due to the antibiotic treatment of acne vulgaris: a review. J Drugs Dermatol 2010; 9(6): 655-664.
4. Seidler EM, Kimball AB. Meta-analysis comparing efficacy of benzoyl peroxide, clindamycin, benzoyl peroxide with salicylic acid, and combination benzoyl peroxide/clindamycin in acne. J Am Acad Dermatol 2010; 63 (1): 52-62.
