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guidance from the regulatory authorities (in essence through the licensing and inspection processes for the products), to provide the highest level of assurances both to the doctor using the product and the patient being treated. Most importantly, these assurances are for the patient receiving the product, in terms of safety, consistency and reproducibility of their products.

Assessment standards With the passing years, BoNT has been shown to be a highly effective and safe aesthetic, non-surgical treatment. There are reports, as with any pharmaceutical product (including those bought over-the- counter in pharmacies), of safety issues through adverse events that have occurred. These must be reported by the doctor giving the BoNT,

recorded by the

manufacturers and, again through legal requirements, reported to the regulatory authorities7

. Regular

updates (every 3 years for older products) on each product’s safety profile has to be provided by each manufacturer (Periodic Safety Update Report; PSUR), which is based on a detailed analysis of the adverse events received over the years, together with an overall analysis of product safety with time. The initial standards of quality for

the BoNT products were established in the 1980s with the original company involved in BoNT manufacture, Oculinum, Inc., in the custody of Dr Alan Scott, the Californian ophthalmologist who identified the potential of BoNT for therapeutic uses8

with his product Oculinum®, and with the US Food and Drug Administration (FDA), BoNT was made commercially available in the US late in 1989. Across the Atlantic, the company

Porton Products, through licensing arrangements with a UK government establishment called the Centre for Applied Microbiology and Research (CAMR), followed this path in parallel and obtained their first licence for the product Dysport®, still known today across the world by this name, and also as

58 ❚ November/December 2012 |

Azzalure® in Europe for aesthetic treatments. Oculinum was eventually bought by Allergan, Inc. and became Botox®, of course2,6 At that time, CAMR was already a


UK licensed manufacturer of biological products. Establishment of the required quality environment took no time, as this was already in existence. For Oculinum, Inc., this was somewhat different since manufacture of the active BoNT originally took place within a university in the US9

. The final

product vials were then made under contract in New Mexico. Over time, however, as the

regulatory standards improved and increased, all manufacturers have been obliged to continually upgrade and even replace their systems and processes used for BoNT product manufacture. This ever-changing situation has been excellent news for patients, even though companies have had to fulfil these increased requirements, often at great cost. The doctor and then the patient, by

default, have always been able to feel that the very best standards have been applied to products. Doctors should have confidence in these standards and should convey the safety messages to their patients.

Animal testing One of the most exceptional, yet unusual, aspects of BoNT safety has been that an animal test is used on every batch of product commercialised. There are generally two of these tests performed, one specifically for safety (called the General Safety Test in the US, or the Abnormal Toxicity test in Europe) and the other for potency10

. The use

of animals for the potency testing of BoNT has been a long-running issue for many, with much campaigning against the subject under the theme that animals should not be used for ‘cosmetic’ testing11–13

. Yet the

safety test that is performed is largely ignored. The safety aspects of the main animal potency test alone are

. Through the work

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