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simple. By including the test, the manufacturers have clear information that the product batches they want to sell are the correct potency, not under- or—more-importantly—over-potent. The test is able to detect, with great sensitivity, whether anything is wrong. The additional safety test is a regulatory requirement imposed for exactly that: it cannot detect potency itself, but looks for anything else within a product batch that might give abnormal results if the product is administered in vivo. Much has been written with


regard to the potency tests for BoNT. Some commentators hate even the thought of animal use in such ways11–13


. However, since the


very beginning of BoNT products, over 20 years ago, alternatives have been looked for. Certainly, in the first 15 years,


technology was not able to deliver a sensitive, robust equivalent. Many commentators have simply refused to recognise this, focusing only on the ‘animal rights’ issues. Writers have latched onto unguarded comments from a few scientists that alternative test methods exist, but the reality was far from a few words on a page13


.


Reassurances In the last 5 years, the science of BoNT has brought us much more knowledge on many aspects of how the molecule works. One of those aspects has been to show new ways in which to substitute the animal test, and perhaps achieve alternative ways of demonstrating and measuring the product potency within the normal quality environment of a BoNT manufacturer. This last aspect is absolutely paramount. Many test methods can now be used in the laboratory to examine BoNT potency without animals, but just about all of them will not or cannot translate to the manufacturing and testing environment needed. Again, this is largely ignored by many commentators. One company has recently


succeeded and publicly announced that they have the regulatory


References


1. Pickett A. Issues in aesthetic uses of botulinum toxins. PRIME 2012; 2(2): 88–91


2. Pickett A. Characteristics, properties and applications of botulinum toxins in therapeutic use today in the NHS. British Journal of Medicines Procurement 2012; 4(1): 16–23


3. Pickett A. Botulinum toxin as a clinical product: manufacture and pharmacology. In: Foster K. ed, Botulinum neurotoxin — molecular understanding and its application. London: Springer Science, 2012 [in press]


4. Good Manufacturing Practice: Guidance and legislation. Medicines and Healthcare products Regulatory Agency. London: MHRA, 2012. http://tinyurl.com/bvqcakv (accessed 12 November 2012)


5. Good Manufacturing Practice: The inspection process. Medicines and Healthcare products Regulatory Agency. London: MHRA, 2012. http://tinyurl.com/cyg42mk (accessed 12 November 2012)


6. Pickett A. Documented research reveals evolution of BoNT for aesthetics. The European Aesthetic Guide 2012; Spring: 39–46


authority’s permission, in some countries, to minimise the animal potency assay for testing of BoNT product batches in favour of an alternative test method not using animals14


. In at least one country in


Europe, a promotional brochure highlighting this has been produced. Not every country, by any means, has agreed as yet. I have recently tried to bring some perspective to the situation14


.


The most difficult problem has been the over-interpretation by many that the company has completely eliminated animal testing from all BoNT manufacture. That cannot


7. Reporting safety problems. Medicines and Healthcare products Regulatory Agency. London: MHRA, 2012. http://tinyurl.com/c5ogqdd (accessed 12November 2012)


8. Scott AB. Development of botulinum toxin. Disability and Rehabilitation 2007; 29(23): 1757–8


9. Schantz EJ, Johnson EA. Botulinum toxin: the story of its development for the treatment of human disease. Perspect Biol Med 1997; 40(3): 317–27


10. Botulinum toxin type A for injection: European Pharmacopoeia monograph 01/2005: 2113.


11. Bottrill K. Growing old disgracefully: the cosmetic use of botulinum toxin. Altern Lab Anim 2003; 31(4): 381–91


12. Bitz S. The botulinum neurotoxin LD50 test — problems and solutions. ALTEX 2010; 27(2): 114–6


13. Pickett A. Comment on ‘The botulinum neurotoxin LD50 test — problems and solutions’. ALTEX 2011; 28(1/11): 60–1


14. Pickett A. The botulinum toxin LD50 potency assay — another chapter, another mystery. Altern Lab Anim 2012; 40(4): 221–3


of safety and efficacy for the product. As the methods used have not been published as yet, the BoNT scientific community can give no commentary at present.


Conclusions This article is headed ‘promotion’ as it has been sponsored for publication. I am very pleased to be able to promote quality. Quality means safety, efficacy, reliability. Whatever happens, we must not


let quality become a marketing tool. Doctors need to be clearly assured that the quality of BoNT products is of the highest standards, and always


labor“Many test methods can now be used in the


animals, but just about all of them will not or cannot translate to the manufacturing and testing environment needed.





happen. Certainly, a large part of animal use can be eliminated and the company has achieved much to get to that point. But regulatory requirements do not permit every single animal to be removed from the production and quality processes. This is an exceptionally important


change to one of the major tests carried out on every batch of BoNT released to the marketplace. The doctors who use that BoNT product and the patients who receive it need reassurances about this change. They need to be assured and re-assured that the new test brings at least equivalent guarantees


present for the products that they use. The use of reliable products with the history that exists and the standards they bring provides those assurances.


 Declaration of interest Andy Pickett is also Head of Development at Q-Med, a Galderma division. The opinions and comments expressed are those of the author and Toxin Science Limited only.


 Citations given here for the reader are to UK legislation, as examples only. Equivalent legislation, rules and regulations exist throughout Europe.


prime-journal.com | November/December 2012 atory to examine BoNT potency without





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