Advertisement

Combination Products/Drugs in Devices

  • Jon V. Beaman
  • Roisin Wallace

Abstract

The purpose of this chapter is to cover additional considerations, guidelines and requirements to help the reader design stability strategies for drug-device combination products. Tests and challenges to be included in stability studies are considered from a regulatory and scientific point of view and these are also related to the stage of development of the product. A number of drug-device combination types including inhaled/nasal products, pen injectors, drug-eluting stents and transdermal products are discussed specifically.

Keywords

Combination Product European Medicine Evaluation Agency Product Quality Research Institute Medical Device Directive Deliver Dose Uniformity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    European Council (1993) Directive 93/42/EEC of 14 June 1993 concerning medical devices.Google Scholar
  2. 2.
    European Council (1990) Directive 90/385/EEC of 20 June 1990 on active implantable medical devices.Google Scholar
  3. 3.
    European Council (1998) Directive 98/79/EC of 27 October 1998 on in vitro diagnostic medical devices.Google Scholar
  4. 4.
    FDA CDRH Overview of device regulations. http://www.fda.gov/cdrh/devadvice/overview.html
  5. 5.
    Global Harmonization Task Force. http://www.ghtf.org/index.html
  6. 6.
    Center for Drug Evaluation and Research (CDER) guidelines, http://www.fda.gov/cder/regu-latory/default.htm
  7. 7.
    Center for Biologics Evaluation and Research (CBER) guidelines, http://www.fda.gov/cber/guidelines.htm
  8. 8.
    European Agency for the Evaluation of Medicines (EMEA) Committee for Medicinal Products for Human Use (CHMP) guidelines. http://www.emea.europa.eu/index/indexh1.htm
  9. 9.
    International Conference on Harmonisation technical requirements for registration of pharmaceuticals for human use (ICH) guidelines. http://www.ich.org/cache/compo/276–254–1.html
  10. 10.
    FDA Office of Combination Products. http://www.fda.gov/oc/combination/
  11. 11.
    FDA (2006) Guidance for industry and FDA staff: early development considerations for innovative combination products, Sep. 2006.Google Scholar
  12. 12.
    European Council (1965) Directive 65/65/EEC of 26 January 1965 on the approximation of provisions laid down by law, regulation or administrative action relating to proprietary medicinal products.Google Scholar
  13. 13.
    European Council (2004) Directive 2004/27/EC of 31 March 2004 amending Directive 2001/83/EC on the community code relating to medicinal products for human use.Google Scholar
  14. 14.
    EMEA (2001) Vol. 1, Pharmaceutical Legislation, 2001/83/EC and amendments.Google Scholar
  15. 15.
    EMEA (2001) Guidelines relating to the application of the council directive 90/385/EEC on active implantable medical devices the council directive 93/42/EEC on medical devices, MEDDEV 2.1/3 rev 2 (July 2001).Google Scholar
  16. 16.
    Pharmaceutical and Medical Devices Agency (PMDA) Japan website. http://www.pmda.go.jp/english/index.html
  17. 17.
    Japan Pharmaceutical Manufacturers Association website. http://www.jpma.or.jp/english/index.html
  18. 18.
    International Organization for Standardization (ISO) standards. http://www.iso.org/iso/iso_catalogue.htm
  19. 19.
    ISO 11608 Pen injectors for medical use.Google Scholar
  20. 20.
    EMEA CHMP (Oct 2006) Guideline on the pharmaceutical quality of inhalation and nasal products, EMEA/CHMP/QWP/49313/2005 Final.Google Scholar
  21. 21.
    EMEA CHMP Overview of comments received on draft guideline on the pharmaceutical quality of inhalation and nasal products, EMEA/CHMP/CVMP/QWP/103155/2006.Google Scholar
  22. 22.
    FDA CDER (1998) Guidance for industry: metered dose inhaler (MDI) and dry powder inhaler (DPI) drug products, Oct. 1998, DRAFT.Google Scholar
  23. 23.
    FDA CDER (2002) Guidance for industry nasal spray and inhalation solution, suspension, and spray drug products.Google Scholar
  24. 24.
    Relie H (2007) Implications of the new CHMP Guideline on the Pharmaceutical Quality of Inhalation and Nasal Products, Scientific Thesis for Master of Drug Regulatory Affairs, University of Bonn http://www.dgra.de/studiengang/pdf/master_reile_h.pdf
  25. 25.
    IPAC-RS (2001) A parametric tolerance interval test for improved control of delivered dose uniformity in orally inhaled and nasal drug products.Google Scholar
  26. 26.
    United States Pharmacopoeia (2008) USP 30-NF 25 Aerosols, nasal sprays, metered-dose inhalers, and dry powder inhalers <601>.Google Scholar
  27. 27.
    European Pharmacopoeia (2007) 5th Edition, Preparations for Inhalation, pp 2843–2847.Google Scholar
  28. 28.
    Berry J et al. (2003) Influence of the storage orientation on the aerodynamic particle size of a suspension metered dose inhaler containing propellant HFA-227. Drug Dev Ind Pharm 29 (6):631–639CrossRefPubMedGoogle Scholar
  29. 29.
    Murata S, Ito H, Izumi T, Chikushi A (2006) Effect of moisture content in aerosol on the spray performance of Stmerin® D HFA Preparations. Chem Pharm Bull 54 (9):1276–1280CrossRefPubMedGoogle Scholar
  30. 30.
    Borgstrom L et al. (2005) An in vivo and in vitro comparison of two powder inhalers following storage at hot/humid conditions. J Aerosol Med 18 (3):304–310.CrossRefPubMedGoogle Scholar
  31. 31.
    Chi Lip Kwok P, Chan HK (2008) Effect of relative humidity on the electrostatic charge properties of dry powder inhaler aerosols. Pharm Res 25 (2):277–288CrossRefGoogle Scholar
  32. 32.
    IPAC-RS Foreign Particles Working Group (Dec 2004) Foreign particles testing in orally inhaled and nasal drug products. Pharm Res 21 (12):2137–2147Google Scholar
  33. 33.
    IPAC-RS Foreign Particles Working Group (March 2007) Best practices for managing quality and safety of foreign particles in orally inhaled and nasal drug products, and an evaluation of clinical relevance. Pharm Res 24 (3):471–479Google Scholar
  34. 34.
    WHO Stability testing of active pharmaceutical ingredients and pharmaceutical products QAS/06.179/Rev.2 DRAFTGoogle Scholar
  35. 35.
    EMEA CPMP (2001) Note for guidance on in-use stability testing of human medicinal products CPMP/QWP/2934/99.Google Scholar
  36. 36.
    ASEAN Guideline on stability study of drug product (2005)Google Scholar
  37. 37.
    FDA Device advice, premarket notification 510(k).Google Scholar
  38. 38.
    FDA Jurisdictional Update: Drug-Eluting Cardiovascular Stents.Google Scholar
  39. 39.
    Boam AB (2003) Drug-eluting stents: an FDA case study on regulating combination products. Regul Aff Focus Mag, 18–23Google Scholar
  40. 40.
    EMEA CHMP (2007) Guideline on the development of medicinal substances contained in drug-eluting (medicinal substance-eluting) coronary stents, draft January 2007, EMEA/CHMP/EWP/110540/2007.Google Scholar
  41. 41.
    FDA (2008) Guidance for industry: Coronary drug-eluting stents–nonclinical and clinical studies [DRAFT] March 2008.Google Scholar
  42. 42.
    FDA (2003) Cypher™ Sirolimus-eluting coronary stent, summary of safety and effectiveness data.Google Scholar
  43. 43.
    FDA (2004) Taxus™ Express 2™ coronary stent, summary of safety and effectiveness data.Google Scholar
  44. 44.
    Hunter WL (2006) Drug-eluting stents: Beyond the hyperbole. Adv Drug Delivery Rev 58:347–349CrossRefGoogle Scholar
  45. 45.
    Kamath KR, Barry JJ, Miller KM (2006) The Taxus™ drug-eluting stent: A new paradigm in controlled drug delivery. Adv Drug Delivery Rev 58:412–436CrossRefGoogle Scholar
  46. 46.
    FDA (2005) Guidance for industry and FDA staff: non-clinical tests and recommended labeling for intravascular stents and associated delivery systems.Google Scholar
  47. 47.
    ANSI Biological evaluation of medical devices – Part 13: Identification and quantification of degradation products from polymeric devices, ANSI/AAMI/ISO 10993-13:1999Google Scholar
  48. Dilcher C et al. (2004) Effect of ionizing radiation on the stability and performance of the TAXUS Express2 paclitaxel-eluting stent. Cardiovas Radiat Med 5:136–141CrossRefGoogle Scholar
  49. 49.
    Sternberg K et al. (2007) In vitro study of drug-eluting stent coatings based on poly(l-lactide) incorporating cyclosporine A – drug release, polymer degradation and mechanical integrity. J Mater Sci: Mater Med 18 (7):1423–1432CrossRefGoogle Scholar
  50. 50.
    Sharkawi T et al. (2007) Intravascular bioresorbable polymeric stents: A potential alternative to current drug eluting metal stents. J Pharm Sci 96 (11):2829–2837CrossRefPubMedGoogle Scholar
  51. 51.
    Lewis AL et al. (2002) Long-term stability of a coronary stent coating post-implantation. J Biomed Mater Res 63 (6):699–705CrossRefPubMedGoogle Scholar
  52. 52.
    Boam AB (2003) Innovative systems for delivery of drugs and biologics; drug-eluting stents current approach to review. FDA workshop Innovative systems for delivery of drugs and biologics: scientific, clinical and regulatory challenges.Google Scholar
  53. 53.
    Portnoy S, Koepke S (2005) Obtaining FDA approval of drug/device combination products. Part I: Regulatory strategy considerations for preclinical testing; Part II: Drug testing requirements. http://www.pharmanet-cro.com/pdf/whitepapers/Combo_Products.pdf
  54. 54.
    Van Antwerp B, Gulati P (2003) Protein delivery from mechanical devices; Challenges and opportunities, FDA workshop Innovative Systems for Delivery of Drugs and Biologics: Scientific, Clinical and Regulatory Challenges.Google Scholar
  55. 55.
    Brennan JR, Gebhart SS, Blackard WG (1985) Pump induced insulin aggregation. A problem with the Biostator. Diabetes 34:353–359CrossRefPubMedGoogle Scholar
  56. 56.
    Jones SA, Brown MB (2005) Evolution of transdermal drug delivery. Pharmaceutical Formulation and Quality, September 2005Google Scholar
  57. 57.
    Wokovich AM et al. (2006) Transdermal drug delivery system (TDDS) adhesion as a critical safety, efficacy and quality attribute, Eur J Pharm Biopharm 64:1–8CrossRefPubMedGoogle Scholar
  58. 58.
    Minghetti P, Cliurzo F, Casiraghi A (2004) Measuring adhesive performance in transdermal delivery systems, Am J Drug Deliv 2 (3):193–206CrossRefGoogle Scholar
  59. 59.
    Mukherjee B et al. (2006) Nefopam containing transdermal-matrix patches based on pressure-sensitive adhesive polymers. Pharm Tech 30(3):146–163Google Scholar
  60. 60.
    Gupta R, Mukherjee B (2003) Development and in vitro evaluation of diltiazem hydrochloride transdermal patches based on povidone–ethylcellulose matrices. Drug Dev Ind Pharm 29 (1):1–7CrossRefPubMedGoogle Scholar
  61. 61.
    EMEA (2005) Guidance guideline on plastic immediate packaging materials, CPMP/QWP/4359/03.Google Scholar
  62. 62.
    FDA (1999) Guidance for Industry: Container Closure Systems for Packaging Human Drugs and Biologics, May 1999.Google Scholar
  63. 63.
    ITFG/IPAC-RS (2001) Leachables and extractables testing: Points to consider, March 2001.Google Scholar
  64. 64.
    PQRI (2006) Safety thresholds and best practices for extractables and leachables in orally inhaled and nasal drug products. PQRI (September 2006) http://www.pqri.org/pdfs/LE_Recommendations_to_FDA_09-29-06.pdf
  65. 65.
    Norwood DL et al. (2008) Best practices for extractables and leachables in orally inhaled and nasal drug products: An overview of the PQRI recommendations. Pharm Res 25 (4):727–739CrossRefPubMedGoogle Scholar
  66. 66.
    Ball D et al. (2007) Development of safety qualification thresholds and their use in orally inhaled and nasal drug product evaluation. Toxicol Sci 97 (2):226–236CrossRefPubMedGoogle Scholar
  67. 67.
    International Conference on Harmonisation Guideline Q1D: Bracketing and matrixing designs for stability testing of drug substances and drug products.Google Scholar
  68. 68.
    Munden R (2005) The role of bracketing and matrixing in efficient design of stability protocols. Pharm Tech Europe 17 (12):48–52Google Scholar
  69. 69.
    International Conference on Harmonisation Guideline Q5C: Quality of biotechnological products: stability testing of biotechnological/biological products.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Pfizer Global Research and DevelopmentSandwichUK
  2. 2.Analytical Science (Chemistry) at Dublin City UniversityDublinIreland

Personalised recommendations