Factors That Facilitate Regulatory Approval for Drug-Device Combination Products in the European Union and United States of America: A Mixed Method Study of Industry Views

Abstract

Background:

The regulatory environment is one of the key factors in successfully bringing an innovative medical product, like a drug-device combination product, to market. This paper offers insight into the experiences of those involved in obtaining regulatory approval of drug-device combination products in the European Union and the United States.

Methods:

The research consisted of two phases, qualitative data collection (through semi-structured interviews) and analysis, followed by quantitative data collection (through an online survey) and analysis.

Results:

A conceptual model was developed that depicted the facilitating factors for obtaining regulatory approval of a drug-device combination product, relevant to the European Union and United States systems, respectively.

Conclusions:

This model provides, for the first time, a comprehensive understanding of these factors, providing a foundation that could be adapted to reflect specific drug-device combination products. This research demonstrated originality of approach in interviewing thought leaders in the life sciences sector as well as conducting a survey that spans two of the largest jurisdictions for drug-device combination products in the world.

Keywords

interviews survey regulatory strategy medical device medicinal product

Get full access to this article

View all access options for this article.

References

Zenios

. Biodesign: The Process of Innovating Medical Technologies. Cambridge: Cambridge University Press; 2009.

Chowdhury

. Case study on borderline medical products in Europe. In: European Regulation of Medical Devices and Pharmaceuticals. Cham, Switzerland: Springer; 2014:141–159.

Masterson

Cormican

. Elemental essentials: regulation of combination products in the USA and the EU. J Med Device Regul. 2013;10:74–79.

FDA. Federal Food, Drug, and Cosmetic Act: 21 CFR 3.2(e). In: Code of Federal Regulations. Washington, DC: US Department of Health and Human Services; 2006.

Lauritsen

Nguyen

. Combination products regulation at the FDA. Clin Pharmacol Ther. 2009;85:468–470.

Sweet

Schwemm

Parsons

. Review of the processes for FDA oversight of drugs, medical devices, and combination products. J Manag Care Pharm. 2011;17:40–50.

Foote

Berlin

. Can regulation be as innovative as science and technology—the FDA’s regulation of combination products. Minn J Law Sci Technol. 2005;6:619–644.

O’Grady

Bordon

. Global regulatory registration requirements for collagen-based combination products: points to consider. Adv Drug Deliv Rev. 2003;55:1699–1721.

Kramer

Kesselheim

. Regulation of medical devices in the United States and European Union. N Engl J Med. 2012;366:848–855.

10.

Grainger

. Drug/device combinations for local drug therapies and infection prophylaxis. Biomaterials. 2006;27:2450–2467.

11.

Masterson

Cormican

. Overview of the regulation of medical devices and drugs in the European Union and the United States. Therapeutic Innovation & Regulatory Science. 2013;47:715–722.

12.

European Commission. Council Directive 93/42/EEC of 14 June 1993 concerning medical devices. Off J Eur Commun. 1993;L169:1–43.

13.

European Commission. Council Directive 90/385/EEC of 20 June 1990 on the approximation of the laws of the Member States relating to active implantable medical devices. Off J Eur Commun. 1990;L189:17–36.

14.

European Commission. Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on in vitro diagnostic medical devices. Off J Eur Commun. 1998;L331:1- 37.

15.

European Commission. Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use. Off J Eur Union. 2001;L311:67–128.

16.

Jefferys

. The regulation of medical devices and the role of the Medical Devices Agency. Br J Clin Pharmacol. 2001;52:229–235.

17.

Kaplan

Baim

Smith

. Medical device development: from prototype to regulatory approval. Circulation. 2004;109:3068–3072.

18.

Kingham

Bogaert

Eddy

. The New European Medicines Agency. Food Drug Law J. 1994;49:301.

19.

Pignatti

Boone

Moulon

. Overview of the European regulatory approval system. J Ambul Care Manage. 2004;27:89–97.

20.

Lisman

Lekkerkerker

JFF

. Four decades of European medicines regulation: what have they brought us? Int J Risk Saf Med. 2005;17:73–79.

21.

European Commission. Regulation (EC) No 1394/2007 of the European Parliament and of the council on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004. Off J Eur Commun. 2007;L324:121–137.

22.

Committee for Medicinal Products for Human Use. Guideline on fixed combination medicinal products. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003689.pdf. Published 2008. Accessed March 16, 2017.

23.

Brewer

Hunter

. Foundations of Multimethod Research: Synthesizing Styles. Thousand Oaks, CA: Sage Publications; 2006.

24.

Tashakkori

Teddlie

. Sage Handbook of Mixed Methods in Social & Behavioral Research. London: Sage Publications; 2010.

25.

Bryman

. Integrating quantitative and qualitative research: how is it done? Qual Res. 2006;6.

26.

Castro

Kellison

Boyd

Kopak

. A methodology for conducting integrative mixed methods research and data analyses. J Mix Methods Res. 2010;4:342–360.

27.

Erzberger

Kelle

. Making inferences in mixed methods: the rules of integration. In: Tashakkori

Teddlie

, eds. Handbook of Mixed Methods in Social and Behavioral Research. Thousand Oaks, CA: Sage; 2003:457–488.

28.

Bernard

Ryan

. Analyzing Qualitative Data: Systematic Approaches. London: Sage Publications; 2009.

29.

Braun

Clarke

. Using thematic analysis in psychology. Qual Res Psychol. 2006;3:77–101.

30.

Cooper

Schindler

Sun

. Business Research Methods. Homewood, UK: McGraw-Hill/Irwin; 2006.

31.

Wood

Foote

. Targeted Regulatory Writing Techniques: Clinical Documents for Drugs and Biologics. Berlin: Springer Science & Business Media; 2009.

32.

Schindler

. What defines good quality in a clinical study report? Therapeutic Innovation & Regulatory Science. 2015;49:544–546.

33.

Morley

. Regulatory writing basics. Med Writing. 2014;23:81–82.

34.

Modali

. Post-approval regulatory writing. How different is it from writing pre-approval documents? Med Writing. 2014;23:262–266.

35.

Feigal

Tsokas

Zhang

. Perspective: communications with the Food and Drug Administration on the development pathway for a cell-based therapy: why, what, when, and how? Stem Cells Translational Medicine. 2012;1(11):825–832.

36.

Couto

Perez-Breva

Saraiva

. Lessons from innovation in drug-device combination products. Adv Drug Deliv Rev 2012;64(1):69–77.

37.

Lewis

Thornhill

Saunders

. Research Methods for Business Students. Harlow, Essex, UK: Pearson Education; 2007.