Skip to main content
SpringerLink
Log in

Authorised allergen products for intracutaneous testing may no longer be available in Germany

Allergy textbooks have to be re-written

  • Position paper
  • Published:
Allergo Journal International Aims and scope Submit manuscript

Abstract

Background:

Beside the skin prick test, the intracutaneous test represents the most important skin test method for detecting type-1 allergies. With the incorporation of European directives into national law, test allergens used for allergy diagnosis are deemed medicinal products within the meaning of the German Medicinal Products Act (Arzneimittelgesetz) and therefore require marketing authorisation for distribution in Germany. The high costs of acquiring and maintaining these authorisations have lead to no new finished intracutaneous test products being authorized in Germany for more than 20 years. Instead, most manufacturers have voluntarily withdrawn their existing marketing authorisations for intracutaneous test extracts. The last manufacturer to offer approved finished allergen products for intracutaneous tests recently announced that it would now cease production and distribution of these solutions.

Methods:

Research on the current European and German legislation; selective literature search in Medline, including national and international guidelines and Cochrane meta-analyses; licensing information on the Paul-Ehrlich-Institute homepage (www.pei.de) as well as in the Bundesanzeiger (Federal Gazette).

Results:

According to information on www.pei.de, marketing authorisations still existed as of 31.01.2015 for intracutaneous test solutions of six grass/cereal/herbal pollens, seven tree pollens, ten food allergens, twelve moulds and yeasts as well as two fungal mixtures, five house dust and storage mites and five animal epithelia/danders, all held by only one company in Germany. These marketing authorisations were granted between 16th March 1987 and 17th January 1992; more recent marketing authorisations do not exist.

Conclusions:

European legislation and the associated increase in production and licensing costs have already lead to numerous suppliers withdrawing their marketing authorisation for diagnostic test allergens — marketing authorisations for 443 diagnostic allergens were voluntarily withdrawn by manufacturers in 2013 alone. If the announced restrictions on the allergen portfolio go ahead, considerable problems in the management of allergy patients in Germany due to the discontinuation of the intracutaneous test are likely to be encountered. Moreover, the fact that a diagnostic procedure that has been established for decades seems set to disappear quite simply because all the requisite substances vanish from the market in one fell swoop may well be without parallel in modern medicine.

The situation for skin prick test allergens is less dramatic, although, here again, the available range is becoming increasingly limited.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

AIT:

Allergen-specific immunotherapy

AMG:

German Medicinal Products Act (Arzneimittelgesetz)

AR:

Allergic rhinoconjunctivitis

EAACI:

European Academy of Allergology and Clinical Immunology

IgE:

Immunoglobulin E

IHRP:

In-house reference preparation

SIT:

Specific immunotherapy

WHO:

World Health Organization

References

  1. Rueff F, Bergmann KC, Brockow K et al. Hauttests zur Diagnostik von allergischen Soforttypreaktionen. Leitlinie der Deutschen Gesellschaft für Allergologie und klinischen Immunologie (DGAKI). Allergo J 2010;19:402–415

    Article  Google Scholar 

  2. Asher MI, Montefort S, Bjorksten B et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet 2006;368(9537):733–743

    Article  PubMed  Google Scholar 

  3. Blomme K, Tomassen P, Lapeere H et al. Prevalence of allergic sensitization versus allergic rhinitis symptoms in an unselected population. Int Arch Allergy Immunol 2013;160:200–207

    Article  CAS  PubMed  Google Scholar 

  4. Bousquet J, Khaltaev N, Cruz AA et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy 2008;63(Suppl 86):8–160

    Article  PubMed  Google Scholar 

  5. Bousquet J, Schunemann HJ, Samolinski B et al. Allergic Rhinitis and its Impact on Asthma (ARIA): achievements in 10 years and future needs. J Allergy Clin Immunol 2012;130:1049–1062

    Article  CAS  PubMed  Google Scholar 

  6. Schatz M. A survey of the burden of allergic rhinitis in the USA. Allergy 2007;62(Suppl 85):9–16

    Article  PubMed  Google Scholar 

  7. Ring J, Bachert C, Bauer CP, Czech W. Weißbuch Allergien in Deutschland. München: Urban & Vogel; 2010

    Google Scholar 

  8. Bjorksten B, Clayton T, Ellwood P, Stewart A, Strachan D, Group IPIS. Worldwide time trends for symptoms of rhinitis and conjunctivitis: Phase III of the International Study of Asthma and Allergies in Childhood. Pediatr Allergy Immunol 2008;19:110–124

    Article  PubMed  Google Scholar 

  9. Krämer U. Epidemiologie allergischer Erkrankungen: Prävalenzen und Trends in Deutschland In: Ring J, Bachert C, Bauer CP, Czech W, eds. Weißbuch Allergie in Deutschland. München: Urban & Vogel; 2010. p. 33–63

    Google Scholar 

  10. Jacobsen L, Niggemann B, Dreborg S et al. Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study. Allergy 2007;62:943–948

    Article  CAS  PubMed  Google Scholar 

  11. Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S. Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database Syst Rev 2007;(1):CD001936

    Google Scholar 

  12. Calderon MA, Gerth van Wijk R, Eichler I et al. Perspectives on allergen-specific immunotherapy in childhood: an EAACI position statement. Pediatr Allergy Immunol 2012;23:300–306

    Article  CAS  PubMed  Google Scholar 

  13. Brehler R, Klimek L, Kopp MV, Christian Virchow J. Specific immunotherapy-indications and mode of action. Dtsch Arztebl Int 2013;110:148–158

    PubMed  PubMed Central  Google Scholar 

  14. Maurer M, Zuberbier T. Undertreatment of rhinitis symptoms in Europe: findings from a cross-sectional questionnaire survey. Allergy 2007;62:1057–1063

    Article  CAS  PubMed  Google Scholar 

  15. Zuberbier T, Lötvall J. Allergies have a socioeconomic impact: a model calculation. Allergy 2008;63(Suppl 88):612–621

    Google Scholar 

  16. Canonica GW, Bousquet J, Mullol J, Scadding GK, Virchow JC. A survey of the burden of allergic rhinitis in Europe. Allergy 2007;62(Suppl 85):17–25

    Article  PubMed  Google Scholar 

  17. Graf von der Schulenburg JM, Greiner W, Molitor S, Kielhorn A. [Cost of asthma therapy in relation to severity. An empirical study]. Med Klin (Munich) 1996;91:670–676

    Google Scholar 

  18. Biermann J, Merk H, Wehrmann W, Klimek L, Wasem J. Allergische Erkrankungen der Atemwege — Ergebnisse einer umfassenden Patientenkohorte in der deutschen gesetzlichen Krankenversicherung. Allergo J 2013;22:366–373

    Article  Google Scholar 

  19. Zuberbier T, Werfel T. Is European legislation killing allergy diagnostics? Curr Opin Allergy Clin Immunol 2012;12:475–476

    Article  PubMed  Google Scholar 

  20. Heinzerling L, Frew AJ, Bindslev-Jensen C et al. Standard skin prick testing and sensitization to inhalant allergens across Europe — a survey from the GALEN network. Allergy 2005; 60:1287–1300

    Article  CAS  PubMed  Google Scholar 

  21. Heinzerling LM, Burbach GJ, Edenharter G et al. GA(2)LEN skin test study I: GA(2)LEN harmonization of skin prick testing: novel sensitization patterns for inhalant allergens in Europe. Allergy 2009;64:1498–1506

    Article  CAS  PubMed  Google Scholar 

  22. Dreborg S. Histamine reactivity of the skin. Allergy 2001;56:359–364

    Article  CAS  PubMed  Google Scholar 

  23. Nelson HS, Knoetzer J, Bucher B. Effect of distance between sites and region of the body on results of skin prick tests. J Allergy Clin Immunol 1996;97:596–601

    Article  CAS  PubMed  Google Scholar 

  24. Scherer K, Grize L, Schindler C, Surber C, Bircher AJ. Reaction pattern to histamine and codeine in a human intradermal skin test model. Clin Exp Allergy 2007;37(1):39–46

    Article  CAS  PubMed  Google Scholar 

  25. Nelson HS, Rosloniec DM, McCall LI, Ikle D. Comparative performance of five commercial prick skin test devices. J Allergy Clin Immunol 1993;92:750–756

    Article  CAS  PubMed  Google Scholar 

  26. American Academy for Allergy and Immunology. Position Statement: Allergen skin testing. Allergy Clin Immunol 1993;92:636–637

    Article  Google Scholar 

  27. Bernstein IL, Li JT, Bernstein DI et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol 2008;100(3 Suppl 3):S1–148

    Article  Google Scholar 

  28. Koller DY, Pirker C, Jarisch R, Gotz M. Influence of the histamine control on skin reactivity in skin testing. Allergy 1992;47:58–59

    Article  CAS  PubMed  Google Scholar 

  29. Malling HJ. Methods of skin testing. Allergy 1993;48(Suppl 14):55–56

    Article  Google Scholar 

  30. Osterballe O, Weeke B. A new lancet for skin prick testing. Allergy 1979;34:209–212

    Article  CAS  PubMed  Google Scholar 

  31. Adinoff AD, Rosloniec DM, McCall LL, Nelson HS. A comparison of six epicutaneous devices in the performance of immediate hypersensitivity skin testing. J Allergy Clin Immunol 1989;84:168–174

    Article  CAS  PubMed  Google Scholar 

  32. Rasp G. Nadel oder Lanzette? Allergologie 1991;12:480–482

    Google Scholar 

  33. Demoly P, Bousquet J, Manderscheid JC, Dreborg S, Dhivert H, Michel FB. Precision of skin prick and puncture tests with nine methods. J Allergy Clin Immunol 1991;88:758–762

    Article  CAS  PubMed  Google Scholar 

  34. Jeep S, Reiprich G, Kunkel G. Yellow jacket allergy. Comparison of skin prick tests and intradermal tests with three different yellow jacket venom extracts. Allergy 1992;47:35–40

    Article  CAS  PubMed  Google Scholar 

  35. Fisher MM, Bowey CJ. Intradermal compared with prick testing in the diagnosis of anaesthetic allergy. Br J Anaesth 1997;79:59–63

    Article  CAS  PubMed  Google Scholar 

  36. McKay SP, Meslemani D, Stachler RJ, Krouse JH. Intradermal positivity after negative prick testing for inhalants. Otolaryngol Head Neck Surg 2006;135:232–235

    Article  PubMed  Google Scholar 

  37. Wood RA, Phipatanakul W, Hamilton RG, Eggleston PA. A comparison of skin prick tests, intradermal skin tests, and RASTs in the diagnosis of cat allergy. J Allergy Clin Immunol 1999;103(5 Pt 1):773–779

    Article  CAS  PubMed  Google Scholar 

  38. Limpert AS. Quality of allergen products for specific immunotherapy — a guidance for industry for compilation of module 3 for the EU CTD (Quality) considering the German therapy allergen ordinance, the revised European Pharmacopoeia monograph on allergen products (2010:1063) and the new „Guideline on Allergen Products — Production and Quality Issues“ (EMEA/CHMP/BWP/304821/2007). Master Thesis Bonn: 2010

    Google Scholar 

  39. Turkeltaub PC. Biological standardization of allergenic extracts. Allergol Immunopathol (Madr) 1989;17:53–65

    CAS  Google Scholar 

  40. Nordic Council on Medicines, ed. Registration of allergenic preparations. Nordic guidelines. Uppsala: NLN Publications; 1989

    Google Scholar 

  41. Reuter A, Luttkopf D, Vieths S. New frontiers in allergen standardization. Clin Exp Allergy 2009;39:307–309

    Article  CAS  PubMed  Google Scholar 

  42. Van Metre TE Jr, Adkinson NF Jr, Kagey-Sobotka A, Marsh DG, Normal PS, Rosenberg GL. How should we use skin testing to quantify IgE sensitivity? J Allergy Clin Immunol 1990;86:583–586

    Article  PubMed  Google Scholar 

  43. Ownby DR, Anderson JA. An improved prick skin-test procedure for young children. J Allergy Clin Immunol 1982;69:533–535

    Article  CAS  PubMed  Google Scholar 

  44. Dreborg S, Frew AJ, eds. EAACI Subcommittee on Skin tests. Position paper: Allergen standardization and skin tests. Allergy 1993;48(Suppl):48–82

  45. Norman PS. In vivo methods of study of allergy: skin and mucosal technique and interpretation. In: Middleton EJ, Ellis E, Reed CE, eds. Allergy: Principles and Practice. St. Louis: Mosby; 1982

    Google Scholar 

  46. Klimek L. Zulassungen von Testallergenen: Diagnostika in Not. Allergo J 2013;22:522

    Article  Google Scholar 

  47. European Medicines Agency (EMA), Committee for Medicinal Products for Human Use (CHMP), eds. Guideline on clinical evaluation of diagnostic agents. 2009; CPMP/EWP/1119/ 98/Rev. 1. 2009 (coming into effect: 1 February 2010)

    Google Scholar 

  48. European Medicines Agency (EMA), Committee for Medicinal Products for Human Use (CHMP), eds. Guideline on allergen products: production and quality issues. 2008; EMEA/CHMP/BWP/304831/2007 (coming into effect: 20th May 2009)

    Google Scholar 

  49. European Directorate for the Quality of Medicines (EDQM). Monograph: Allergen Products — Producta Allergenica 01/2010:1063. In: Council of Europe, ed. European Pharmacopoeia, 6th ed. Strasbourg; 2010; Suppl 6:679–680, as implemented of 01.01.2010

    Google Scholar 

  50. Gesetz über den Verkehr mit Arzneimitteln (Arzneimittelgesetz — AMG) in der Fassung der Bekanntmachung vom 12. Dezember 2005 (BGBl. I S. 3394), letzte eingearbeitete Änderung: Artikel 1 des Gesetzes vom 10. Oktober 2013 (BGBl. I S. 3813) [berichtigt am 24. März 2014 (BGBl. I S. 272)]

Download references

Author information

Authors and Affiliations

  1. Centre for Rhinology and Allergology, An den Quellen 10, 65183, Wiesbaden, Germany

    Ludger Klimek

  2. Dept of Dermatology, Allergology and Venereology, Division of Immunodermatology and Experimental Allergology, Hannover Medical University, Hannover, Germany

    Thomas Werfel

  3. Department of Pediatrics and Adolescent Medicine, Dresden University Allergy Centre (UAC), Dresden, Germany

    Christian Vogelberg

  4. Group Practice for Dermatology, Immunology and Allergology, Erfurt, Germany

    Kirsten Jung

  5. Medical Association of German Allergologists (Ärzteverband Deutscher Allergologen, AeDA), Dreieich, Germany

    Ludger Klimek & Kirsten Jung

  6. German Society for Allergology and Clinical Immunology (Deutsche Gesellschaft für Allergologie und Klinische Immunologie, DGAKI), Aystetten, Germany

    Thomas Werfel

  7. German Society for Pediatric Allergology (Deutsche Gesellschaft für Pädiatrische Allergologie, GPA), Aachen, Germany

    Christian Vogelberg

Authors
  1. Ludger Klimek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Werfel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christian Vogelberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kirsten Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ludger Klimek.

Additional information

Comment

In consultation with the authors, this article will be published simultaneously in the Allergo Journal International and in the journal Allergologie.

Acknowledgement

The authors thank S. Vieths, S. Kaul und A. Bonertz, Paul-Ehrlich-Institut, Langen for valuable information and committed and straight forward discussions.

Conflict of interest

The authors state that there are no conflicts of interest.

Cite this as

Klimek L, Werfel T, Vogelberg C, Jung K. Authorised allergen products for intracutaneous testing may no longer be available in Germany. Allergy textbooks have to be re-written. Allergo J Int 2015;24:84–93 DOI: 10.1007/s40629-015-0051-7

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Klimek, L., Werfel, T., Vogelberg, C. et al. Authorised allergen products for intracutaneous testing may no longer be available in Germany. Allergo J Int 24, 84–93 (2015). https://doi.org/10.1007/s40629-015-0051-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40629-015-0051-7

Key words

Search

Navigation