MARLOW, England--(BUSINESS WIRE)--Allergan is pleased to announce the company has received two positive opinions regarding its fully in vitro, cell-based assay for use in the stability and potency testing of BOTOX® and VISTABEL® (Allergan’s botulinum toxin type A products). Upon approval, the new assay will be implemented as quickly as possible for the release of product for sale in the relevant countries. Allergan estimates that use of the new assay will reduce the use of animal-based assay testing for BOTOX® and VISTABEL® by 95 percent or more over the next three years, as other regulatory agencies around the world approve this new assay. The result of years of research and development commitment, this new assay is the first to be developed and approved for any botulinum toxin currently available worldwide and is specific to Allergan’s botulinum toxin type A products, BOTOX® and VISTABEL®. This approval does not extend to botulinum toxins made by other manufacturers, who will continue to use their animal-based release assays.
The first positive opinion, from Agence Française de Sécurité Sanitaire des Produits de Santé (AFSSAPS), relates to VISTABEL® and paves the way for approval in 29 countries in the European Union. The second positive opinion was granted by the Irish Medicines Board (IMB) for BOTOX® and covers 14 European Union countries involved in the Mutual Recognition Process. The Medicines and Healthcare products Regulatory Agency (MHRA) have already approved the assay for BOTOX® vials sold in the UK.
“We are pleased that Allergan has achieved these significant milestones with the European regulators for the first non-animal based assay for the potency and stability testing of BOTOX® and VISTABEL®. This represents a significant scientific breakthrough in the manufacturing of neurotoxins and is the right and necessary step forward in eliminating the use of animals for release of the product. Allergan’s cell-based assay now sets the standard for all other botulinum toxin manufacturers and demonstrates that with commitment and perseverance, it is possible to find validated, robust alternative methods of testing medicines while maintaining the highest level of patient safety. We now call on other companies manufacturing botulinum toxin products, including Ipsen and Merz, to follow Allergan's ethical lead,” said Michelle Thew, Chief Executive of the British Union for the Abolition of Vivisection (BUAV).
These approvals follow more than a decade of Allergan research and development and an investment of approximately $65 million directed toward minimizing to the greatest degree possible the need for animal-based assays in the manufacture of BOTOX® and VISTABEL®. Until Allergan’s cell-based assay, the mouse LD50 potency assay has been the standard for potency and stability testing for all botulinum toxin products and was required by regulatory agencies around the world for testing final product for release to assure its safety and efficacy. Limitations associated with the mouse LD50 assay include the necessary involvement of animals due to the current structure of the assay, the complexity of the procedures involved, lack of specificity to botulinum toxin type A, as well as variability between assays and laboratories.
“We are proud to have achieved this major scientific milestone demonstrating how BOTOX® and VISTABEL® are leading the way in toxin innovation,” said Douglas Ingram, President of Allergan in Europe, Africa and the Middle East. “The decisions by the MHRA, AFSSAPS and the IMB will allow us to replace the current animal testing requirements with the new cell-based assay for the release and stability testing of BOTOX® and VISTABEL®. Along with the relevant European regulatory agencies, we are committed to securing national approvals and releasing the product using the new assay as rapidly as possible.”
Currently all pharmaceutical manufacturers are required by the European Medicines Agency (EMA), US Food and Drug Administration (FDA) and by other worldwide health regulatory agencies to protect patients and consumers by assuring product safety and efficacy through animal testing and other methods. BOTOX® is a unique and complex biological product with many different approved medical uses, and is derived from natural sources – in this case from the bacterium C. botulinum. When manufacturing biological products, testing is particularly critical to ensuring the consistent safety and efficacy of each batch of product. BOTOX® and VISTABEL® are the same product, manufactured in exactly the same way, and therefore the potency and stability of each batch must be determined before release, regardless of whether the batch is intended for medical or aesthetic use. BOTOX® and VISTABEL® are Allergan’s only products that have required use of an animal-based assay for commercial release, as mandated by global regulatory authorities to ensure safe product use in humans.
“I applaud Allergan’s long-term dedication to putting research and patient safety before profit in developing a ground-breaking new method for testing BOTOX® and VISTABEL®” said Mr Rajiv Grover, Consultant Plastic Surgeon, King Edward VII Hospital in London and President Elect of the British Association of Aesthetic Plastic Surgeons. “I know that my patients will welcome this initiative, and that they will continue to feel confident about the ethos and efficacy of these products. The time has definitely come for people interested in medical aesthetics to select very carefully what is used to treat them.”
About the BOTOX® and VISTABEL® Cell-Based Potency Assay (CBPA)
Over the years, a number of attempts have been made to find ways to replace the animal-based LD50 assay for testing of botulinum neurotoxins but have fallen short for a variety of reasons. Botulinum neurotoxin is one of the most potent naturally occurring substances and has a complex multi-stage mechanism of action. Purified botulinum neurotoxin type A is the active ingredient in BOTOX®/VISTABEL® and blocks the release of neurotransmitters from nerves, resulting in a localized and temporary reduction in the overacting muscle or gland. The amount of neurotoxin in BOTOX®/VISTABEL® is extremely small; in fact, less than one gram per year is required to supply the entire world.
A suitable replacement potency assay to the LD50 assay must therefore be sensitive enough to measure the complex mode of action of extremely small amount of the neurotoxin used in BOTOX®/VISTABEL® at the cellular level. Established performance criteria against which the new cell-based potency assay needed to be validated included the ability to assess all primary modes of action of the neurotoxin. In addition, the new assay format had to be suitable for use in an intensely quality-controlled environment and at the high capacity needed to support commercial production. The new assay does not impact the manufacturing process for BOTOX® or VISTABEL® as the product remains exactly the same. The units will not change either.
“This significant achievement was made possible by Allergan long-standing commitment to scientific leadership and deep expertise in neurotoxin research and development, and by our corporate commitment to the “3R” principles of refinement, reduction and eventual replacement of laboratory animals in the testing of BOTOX®,” said Mr Ingram.
It’s important to recognise that the unit doses for botulinum toxins are not interchangeable. The new cell-based potency assay for BOTOX® and VISTABEL® is specific to Allergan’s formulations of botulinum neurotoxin type A. Allergan is discussing how to license the technology to other parties that share its commitment to implementing non-animal alternatives to animal-based assays in the manufacture of their medical products.
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Countries involved in the Mutual Recognition Procedure (MRP)
For BOTOX®, Ireland serves as the Reference Member State in the Mutual Recognition Procedure. The other countries involved are Austria, Belgium, Denmark, Finland, Germany, Greece, Iceland, Italy, Luxemburg, Norway, Portugal, Spain, and Sweden. National licence variations have been filed in the other European Union countries.
For VISTABEL® (called VISTABEX® in Italy), France serves as the Reference Member State covering 29 countries in the EU, namely Austria, Belgium, Bulgaria, Czech Republic, Cyprus, Denmark, Estonia, Finland, Germany, Greece, Hungary, Ireland, Iceland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden and the United Kingdom.
About BOTOX®
BOTOX® (botulinum toxin type A) from Allergan is a prescription-only medicine that contains tiny amounts of highly purified botulinum toxin protein refined from the bacterium, Clostridium botulinum.
In the UK, BOTOX® is licensed in adults for the treatment of1:
- glabellar lines (frown lines)
- blepharospasm (uncontrolled blinking of the eyelids)
- hemifacial spasm (a neuromuscular disorder characterised by unpredictable and involuntary twitching of facial muscles on one side of the face)
- cervical dystonia (a muscle condition affecting the neck making it difficult to hold the head up straight)
- severe axillary hyperhidrosis (excessive sweating) of the armpits
- cerebral palsy (dynamic equinus foot deformity in paediatric patients aged two years and older)
- upper limb spasticity (wrist and hand disability associated with stroke in adults)
- prophylaxis of headaches in adults who have chronic migraine (headaches on at least 15 days per month of which at least 8 days are with migraine)
In addition, BOTOX® is also indicated to treat dynamic equinus foot deformity in children aged two years and older who have cerebral palsy.
With approximately 2,500 articles in scientific and medical journals,2 BOTOX® neurotoxin is one of the most widely researched medicines in the world. Approximately 30 million vials of BOTOX® and VISTABEL®3 have been distributed worldwide (1989-2010) during 21 years of clinical experience.4
About Allergan, Inc.
Allergan is a multi-specialty health care company established more than 60 years ago with a commitment to uncover the best of science and develop and deliver innovative and meaningful treatments to help people reach their life’s potential. Today, we have approximately 10,000 highly dedicated and talented employees, global marketing and sales capabilities with a presence in more than 100 countries, a rich and ever-evolving portfolio of pharmaceuticals, biologics, medical devices and over-the-counter consumer products, and state-of-the-art resources in R&D, manufacturing and safety surveillance that help millions of patients see more clearly, move more freely and express themselves more fully. From our beginnings as an eye care company to our focus today on several medical specialties, including eye care, neurosciences, medical aesthetics, medical dermatology, breast aesthetics, obesity intervention and urologics, Allergan is proud to celebrate more than 60 years of medical advances and proud to support the patients and physicians who rely on our products and the employees and communities in which we live and work.
Forward-Looking Statement
This press release contains "forward-looking statements", including but not limited to the statements by Douglas Ingram and Michelle Thew from ECEAE, statements regarding the anticipated reduction in use of animal-based assay testing and other statements regarding the Cell-Based Potency Assay and the safety, efficacy, and product availability BOTOX®. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from Allergan's expectations and projections. Risks and uncertainties include, among other things, general industry and pharmaceutical market conditions; technological advances and patents attained by competitors; challenges inherent in the research and development and regulatory processes; challenges related to new product marketing, such as the unpredictability of market acceptance for new pharmaceutical products and/or the acceptance of new indications for such products; inconsistency of treatment results among patients; potential difficulties in manufacturing a new product; general economic conditions; and governmental laws and regulations affecting domestic and foreign operations. Additional information concerning these and other risk factors can be found in press releases issued by Allergan, as well as Allergan's public periodic filings with the U.S. Securities and Exchange Commission, including the discussion under the heading "Risk Factors" in Allergan's 2010 Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q.
© Allergan Ltd. BOTOX® and VISTABEL® are registered trademarks owned by Allergan, Inc.
References
1. BOTOX® Summary of Product Characteristics; www.medicines.org.uk
2. Allergan data on file; VIS/006/JUL2011
3. VISTABEL® Summary of Product Characteristics; www.medicines.org.uk
4. Allergan data on file; BOT/001/DEC2011