The Chemotechnique Story

Preamble

Chemotechnique Diagnostics was founded in 1981 by Bo Niklasson, at that time active in the clinical and scientific work at the Department of Occupational Dermatology in Malmö University Hospital, Sweden, and my wife Marie. This chapter is an attempt to summarize the work since 1981 in developing the company from a small side activity to a world leading company in the field of patch testing products currently providing products to around 100 countries.

Dedication and acknowledgments 
I want to dedicate this chapter to my dear wife Marie with a lot of love. Based on Marie’s idea and inspiration we started the company. Marie has given me faithful support and encouragement since the start of the company. While I was working daytime at the clinic, Marie did the work in handling staff and practical work in the production as well as financial matters and book keeping. She has been a great inspiration for me and a partner in strategic planning on many occasions. Without her support as a working partner for many years in building the company, it would not exist today.
To my bright daughter Helena who serves as our legal counsel, regulatory work, HR, marketing and other areas and David who serves in business development, product development, marketing and design, financial and other areas. In addition, there are many companies and consultants that have been providing valuable contributions to the continuous development.
In the chapter I mention persons that have been important and related to the business in many different ways.

The clinical work and the start of the Company

The birth of Chemotechnique Diagnostics took place in 1981 in Malmö, Sweden.  At that time I had a few years before, in 1978, by Professor Bertil Magnusson and Professor Bert Björkner been offered the opportunity to be part of the new Department of Occupational Dermatology at the University Hospital in Malmö as responsible chemist for the patch testing laboratory. 
I am grateful for all knowledge and guidance that was given to me during my work at the clinic from Professor Sigfrid Fregert, Professor Bertil Magnusson, Professor Halvor Möller and Professor Bert Björkner later followed by Professor Magnus Bruze and Professor Marléne Isaksson and at present Professor Cecilia Svedman. I was involved in many research projects including Bert’s thesis work covering occupational contact allergy to acrylates where I did most of the analytical work and a lot of the Guinea Pig Maximization work originally developed by Magnusson and Kligman. My background within Chemistry and Biomedicine, later followed by Dermatology courses as well as my experience from the clinical work, gave me insight and means to develop a number of different test series related to various occupations and exposures to a wide variety of haptens. These substances were found in products handled at the work place in many different industrial environments. Numerous contacts with companies producing such products providing information on ingredients facilitated the selection of substances to be investigated. An important aspect of patch testing is the knowledge how to prepare the patient’s own products brought in from the work place. I was offered the opportunity to share my experience in this field by professor Jere Guin in his book Practical Contact Dermatitis from 1995 (McGraw Hill) as well as providing hapten information in Handbook of Occupational Dermatology by Kanerva, Wahlberg and Maibach in the year 2000. One important compound that we discovered many contact allergies to was the preservative with the brand name Kathon CG manufactured by Rohm and Haas company in USA. This became a quite sensitive issue and the chief toxicologist from the company visited us to discuss the matter. The outcome from our discussions and findings were that the concentration was lowered in products containing the preservative and the frequency of contact allergy and dermatitis related to the preservative was reduced. Other interesting compounds causing outbreaks of allergic contact dermatitis were various acrylates in the printing industry. 

The actual reason for starting the company was related to a Swedish multicenter clinical trial of a new test series of haptens for diagnosing contact allergy in dental staff and patients undergoing dental treatments. The name of the series for the selected haptens was "Dental Screening series". The clinics had to get the material for testing and as such the possibility and proper time to prepare the material at the clinic was simply not available. The result after discussing the project with the hospital legal department was to provide the material through a company instead of the clinic. So, the objective was clear and the company was founded in 1981, at that time named Kemoteknik, and a partner in the short initial period was my coworker Björn Edman at the Dermatology department. The research work investigating the dental screening series was completed and resulted in a publication in Contact Dermatitis. 

The development of the company

My wife Marie was directly involved in the work and remained so for many years with important contributions to the development of the company. What existed in the early 80’s was the limited Trolab range made by the Danish pharmacists Trolle Lassen in Copenhagen.  In this period of time we started to build an international market organization through distributors.
 

Continued research and development of selected test series took place and the range expanded year by year. Also, the distribution network continued to expand and worth mentioning is the first distributor Bill van der Bend, in the Netherlands followed by Eddy Luyckx (Dermat), in Belgium. I continued working at the Department of Occupational and Environmental Dermatology until 1995 when time just wasn’t enough to allow me to keep on at the same time running and developing the company. As the company grew the production facilities grew as well and several moves to new buildings and locations took place within the Malmö area. The most recent move was made in 2005 and when looking back I find that the adventure started in a 30m2 basement and now the operations take place in a 1800 m2 industrial building in Vellinge just south of Malmö. The latest move involved a lot of work as a completely new state of the art laboratory had to be built.

 All details fulfilling the requirements of a pharmaceutical laboratory working under GMP/GLP conditions needed to be put in place when designing the lab. When the move was completed it was a great pleasure to start working in a modern building with large storage facilities as well. Also, the continuous growth of number of staff in the laboratory, medical device department and order and customer service has been a pleasure to follow and I greatly value the hard work and contributions to the development of the business that my coworkers provide.

The continuous work in research and development of new test substances has resulted in the widest range of commercially available haptens, now covering around 500+ test preparations, and new material will be added continually depending on the needs from the dermatology field.

Distribution network, marketing and cooperation with Contact Dermatitis Research Groups

We have enjoyed a thrilling voyage over the years in building a worldwide network of distributors ranging from small countries in the third world region to large industrialized countries. At present distribution covers around 100 countries. In the early days a major breakthrough was to set up the North American distribution through George Davy of Dormer Laboratories in Toronto, Canada, and long-term valuable cooperation has been established with Crawford Pharmaceuticals in the UK, Laboratoire Destaing in France and many other companies impossible to list in this limited section. Over the decades, participation in numerous congresses such as ACDS/AAD, EADV, World Congress of Dermatology, ISCD, ESCD, EAACI and many domestic congresses throughout the world has been thrilling.

The cooperation with important contact dermatitis groups started with the International Contact Dermatitis Group (ICDRG). The cooperation with the European and Environmental Contact Dermatitis Research Group (EECDRG) providing material for multicenter studies has been most important as well as cooperation with the North American Contact Dermatitis Group (NACDG) providing material for studies of contact allergy frequency starting from 1992. Cooperation with several domestic groups to provide national baseline series for haptens has been a priority and it has been a pleasure to get to know many skillful dermatologists in the field.

 Material for many different multicenter studies including perfume ingredients, corticosteroids, sunscreens, pharmaceuticals and substances causing photocontact allergy has originated from our Swedish laboratory.

Patch test chambers and general considerations

A patch test chamber must be made of an inert material so that no reaction takes place between the material in the chamber and the test preparation applied on the surface of the chamber. Second, it must not elicit any allergic reaction in itself. Third, the carrier tape must be of such quality that it sticks well to the skin so that no reinforcement tape is needed and it should not cause any irritation apart from rare cases of hyper-reactivity to tape material. Ideally, the carrier tape should be of a material such as thin elastic water-resistant film to allow patients to take showers, exercise etc during the test period. Fourth, the test chamber must also provide good occlusion onto the skin.  The chamber should also keep the substance within the chamber compartment to prevent leakage. Ideally it should also be able to be loaded in advance to make patch testing more efficient.

The key development question was what improvements could be made in a new test chamber? First of all the material needed to be inert and recyclable and polyethylene was therefore chosen. The form could perhaps be changed from round to another shape. Some researchers had proposed a square form to better distinguish allergic from irritant reactions so this form was chosen. The carrier tape was an extensively used hypo allergenic surgical tape from 3M. To make a long story short the production machine was completed in 1993 after several difficulties during the process and the production of the IQ Chambers (IQ expressing Inert & Quadrate features) could finally be initiated. 

After almost 10 years in production, improvements needed to be done on the chamber to optimize the performance. The filter papers in the IQ Chamber had to be inserted manually each time a test solution should be applied. The size of the tape unit was too big to allow several test series to be applied at the same time and the chamber material was rather inflexible.

A solution was to use layers of laminated tapes with an integrated filter paper. The patient comfort using such soft material must be far better. Also, now was the time to make sure that the chamber really did prevent leakage, so the rim of the chamber should be equipped with an adhesive to make the chamber become a closed cell. The design of the IQ Ultra® Chamber took place and a patent application was soon filed. The design and production of the machine to be used for serial production of the chambers was made and our team endured a lot of struggle to arrive at the actual production of the chambers in 2003. The process of handling elastic tapes and the actual lamination process proved to be far more complicated than first anticipated. The improvements were in place and now for the first time in the history of patch testing a smooth soft flexible chamber made of inert polyethylene foam with double sided adhesive material, with an integrated filter paper forming a test unit with a suitable small size, utilizing the same principle of preloading as the IQ Chamber and with an ability to secure the test preparation within the chamber was available. The protection cover plate was made in such a way that each chamber with its content (if preloaded) was isolated in the airtight compartment of the cover.

After a few years in production a further development was made to be able to use a carrier film that was water resistant. Through a most valuable cooperation with our skillful developers, we were finally able to arrive at a converted film that fulfilled the criteria. The product was branded IQ Ultimate™ . 

General considerations and prevention

At Chemotechnique, research and development form the foundation on which the business is built. New materials, production processes and compositions are constantly being evaluated in order to improve the various products in our portfolio. The application of our deep understanding of contact allergy extends further than diagnosis.  Solutions for the detection of nickel and cobalt in everyday objects, help patients suffering from contact allergy to these haptens to identify the causative objects.  Venturing into the field of contact allergy protection an active chelating barrier cream that uses DTPA to immobilize nickel and cobalt ions has been developed, preventing them from entering the epidermis. The product is called NIK-L-BLOK and marketed by Chemotechnique Cosmeceuticals Scandinavia.

Legislation, Reimbursement and other Challenges

Patch testing is practiced primarily by Dermatologists.  The regulatory tendency has been to incorrectly combine the regulation of patch testing under the “allergy and allergen” classification as practiced by allergists using allergens. Allergy testing involves the invasion of the skin to determine a patient's allergy.   These two procedures are completely different and do have different levels of patient risk associated with them, patch testing extremely low with allergy testing higher. 

Fundamental to establishing a valid scientific basis for accepting the procedural differences between “dermatological patch testing” and “allergist allergy testing” is a regulatory understanding of not only the medical procedural differences, but most importantly, the scientific difference between a hapten, as used in patch testing, and an allergen, as used by an allergist. Due to this fact it could be argued that haptens could be regulated as medical devices, while allergens should be regulated as pharmaceuticals. 

 Today, haptens are generally distributed as unregistered pharmaceutical products on a “named patient” basis but some countries do not have legislative exceptions allowing for the distribution of unregistered pharmaceuticals. In such cases pharmaceutical registration for individual haptens is enforced. Due to the very high cost associated with pharmaceutical registrations such regulatory demands will result in one of the following scenarios: Comprehensive patch testing will either no longer be offered as the costs associated with pharmaceutical registration will far exceed what is deemed reasonable to transfer onto hapten pricing, or prices will indeed be transferred to clinics rendering patch testing an extremely expensive diagnostic method.

Another possible scenario is that only specified hapten series with defined concentrations, sold as complete sets with a singular expiry, will be available for purchase. Any adjustment in composition or concentration will demand for a new pharmaceutical registration resulting in hapten series that will not be updated based on patient exposure but rather financial viability.

A recent example of the challenges involved came in 2017 when Chemotechnique was obliged to register the previously unregistered whole range of haptens in Canada. The process did not only involve huge costs and a massive strain on our lab department, but major efforts were ultimately spent in confirming that Health Canada, the Canadian health authority, had a correct understanding of the immunological process of contact allergy and allergic contact dermatitis. As a result of this, all of our patch test haptens are now registered pharmaceuticals in Canada.

Moreover, while we see many governments increasing their focus on regulatory compliance, we note that reimbursements for patch testing issued by the very same governments at the same time are being, if not completely removed, reduced from already low levels. We fear that the reduced funding will limit the reach of patch testing, effectively leaving patients underdiagnosed.

Regulators and Health Care Institutions need to recognize the economic value and patient health benefits of patch testing by providing a fair and equitable reimbursement for the services being provided and facilitate legislation in order to increase the availability of patch test haptens.      This would further inspire us in our work as a provider of patch test products.

Reflections

My mission and dedication to the field of contact allergy has been, and will continue to be, to serve all those hard working physicians with the diagnostic tools they need to make a correct diagnosis, all for the benefit of the patients whom we are all ultimately there for.

Bo Niklasson

CEO