Chapter 4: Jurisdiction and Regulatory Pathway
40
submission. What testing is needed? Is analytical
testing required? What standards and guidance
are applicable to my combination product?
Which are specific to each constituent part? Are
biocompatibility studies needed? How many
clinical trials will be required? When should
human factors testing be started? Will an investi-
gational application be needed?
Conclusion
OCP provides guidance to both industry and
FDA centers on combination products. OCP
provides multiple mechanisms for sponsors and
applicants to assist in determining if a product
is a combination product or noncombination
product. Both the pre-RFD and RFD provide
an opportunity for the sponsor or applicant to
put forth a justification for how their product
should be designated and receive a preliminary
or final decision on the designation. Sponsors or
applicants that are sure of the designation of their
products as combination products have a number
of regulatory pathways depending on the PMOA.
References
1. Federal Register. Vol. 70, No. 164, Thursday, 25 August
2005. Rules and Regulations. Govinfo website. https://
www.govinfo.gov/content/pkg/FR-2005-08-25/pdf/05-
16527.pdf. Accessed 31 March 2021.
2. Definition of Primary Mode of Action of a
Combination Product. A Rule by the Food and Drug
Administration on 25 August 2005. Effective date 23
November 2005. Federal Register website. https://www.
federalregister.gov/documents/2005/08/25/05-16527/
definition-of-primary-mode-of-action-of-a-combina-
tion-product. Accessed 31 March 2021.
3. Code of Federal Regulations Title 21 Part 3(k)(1–3).
Amended 31 December 2013. Govinfo website. https://
www.govinfo.gov/content/pkg/CFR-2012-title21-vol1/
pdf/CFR-2012-title21-vol1-part3.pdf. Accessed 31
March 2021.
4. 21CFR4.2. Revised 1April 2020. FDA website. https://
www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/
CFRSearch.cfm?fr=4.2. Accessed 31 March 2021.
5. Public Health Service Act (PHS Act). Section 351(i).
Amended 5 January 2021. Govinfo website. https://
www.govinfo.gov/content/pkg/COMPS-8773/pdf/
COMPS-8773.pdf. Accessed 31 March 2021.
6. Federal, Food, Drug, and Cosmetic Act (FD&C Act).
Section 201(h)(1)–(3). Amended 5 January 2021.
Govinfo website. https://www.govinfo.gov/content/
pkg/COMPS-973/pdf/COMPS-973.pdf. Accessed 31
March 2021.
7. Ibid, FD&C Act, Section 201(g)(1).
8. Op cit 3, 21CFR3(m).
9. Op cit 3, 21CFR3.4(b).
10. How to Write a Request for Designation (RFD): Guidance
for Industry. Final April 2011. FDA website. https://
www.fda.gov/regulatory-information/search-fda-guid-
ance-documents/how-write-request-designation-rfd.
Accessed 31 March 2021.
11. Classification of Products as Drugs and Devices and
Additional Product Classification Issues: Guidance for
Industry and FDA Staff. September 2017. Final.
FDA website. https://www.fda.gov/regulato-
ry-information/search-fda-guidance-documents/
classification-products-drugs-and-devices-and-addi-
tional-product-classification-issues. Accessed 31 March
2021.
12. Op cit 3, 21CFR3.9.
13. Op cit 6, FD&C Act, Section 563.
14. Op cit 3, 21CFR3.7(c).
15. Op cit 10.
16. Op cit 10.
17. Op cit 10.
18. Op cit 3, 21CFR3.8(b).
19. How to Prepare a Pre-Request for Designation (Pre-
RFD). Guidance for Industry. Final February 2018.
https://www.fda.gov/regulatory-information/
search-fda-guidance-documents/how-prepare-pre-re-
quest-designation-pre-rfd. Accessed 31 March 2021.
20. Ibid.
21. Op cit 19.
22. Op cit 19.
23. Federal Register. Vol. 71, No. 188. Thursday, 28
September 2006. Notices. Review of Agreements,
Guidances, and Practices Specific to Assignment
of Combination Products in Compliance With
the Medical Device User Fee and Modernization
Act of 2002 Request for Comments. Federal
Register website. https://www.federalregis-
ter.gov/documents/2006/09/28/E6-15967/
review-of-agreements-guidances-and-practices-spe-
cific-to-assignment-of-combination-products-in.
Accessed 31 March 2021.
24. RFD Jurisdictional Decisions. Current as of
February 2018. FDA website. https://www.fda.gov/
CombinationProducts/JurisdictionalInformation/
RFDJurisdictionalDecisions/default.htm. Accessed 31
March 2021.
25. Jurisdictional Updates. Current as of February 2018.
FDA website. https://www.fda.gov/combination-prod-
ucts/jurisdictional-information/jurisdictional-updates.
Accessed 31 March 2021.
26. Redacted Decision Letters. Current as of February
2018. FDA website. https://www.fda.gov/
CombinationProducts/JurisdictionalInformation/
RFDJurisdictionalDecisions/ucm2007395.htm.
Accessed 31 March 2021.
40
submission. What testing is needed? Is analytical
testing required? What standards and guidance
are applicable to my combination product?
Which are specific to each constituent part? Are
biocompatibility studies needed? How many
clinical trials will be required? When should
human factors testing be started? Will an investi-
gational application be needed?
Conclusion
OCP provides guidance to both industry and
FDA centers on combination products. OCP
provides multiple mechanisms for sponsors and
applicants to assist in determining if a product
is a combination product or noncombination
product. Both the pre-RFD and RFD provide
an opportunity for the sponsor or applicant to
put forth a justification for how their product
should be designated and receive a preliminary
or final decision on the designation. Sponsors or
applicants that are sure of the designation of their
products as combination products have a number
of regulatory pathways depending on the PMOA.
References
1. Federal Register. Vol. 70, No. 164, Thursday, 25 August
2005. Rules and Regulations. Govinfo website. https://
www.govinfo.gov/content/pkg/FR-2005-08-25/pdf/05-
16527.pdf. Accessed 31 March 2021.
2. Definition of Primary Mode of Action of a
Combination Product. A Rule by the Food and Drug
Administration on 25 August 2005. Effective date 23
November 2005. Federal Register website. https://www.
federalregister.gov/documents/2005/08/25/05-16527/
definition-of-primary-mode-of-action-of-a-combina-
tion-product. Accessed 31 March 2021.
3. Code of Federal Regulations Title 21 Part 3(k)(1–3).
Amended 31 December 2013. Govinfo website. https://
www.govinfo.gov/content/pkg/CFR-2012-title21-vol1/
pdf/CFR-2012-title21-vol1-part3.pdf. Accessed 31
March 2021.
4. 21CFR4.2. Revised 1April 2020. FDA website. https://
www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/
CFRSearch.cfm?fr=4.2. Accessed 31 March 2021.
5. Public Health Service Act (PHS Act). Section 351(i).
Amended 5 January 2021. Govinfo website. https://
www.govinfo.gov/content/pkg/COMPS-8773/pdf/
COMPS-8773.pdf. Accessed 31 March 2021.
6. Federal, Food, Drug, and Cosmetic Act (FD&C Act).
Section 201(h)(1)–(3). Amended 5 January 2021.
Govinfo website. https://www.govinfo.gov/content/
pkg/COMPS-973/pdf/COMPS-973.pdf. Accessed 31
March 2021.
7. Ibid, FD&C Act, Section 201(g)(1).
8. Op cit 3, 21CFR3(m).
9. Op cit 3, 21CFR3.4(b).
10. How to Write a Request for Designation (RFD): Guidance
for Industry. Final April 2011. FDA website. https://
www.fda.gov/regulatory-information/search-fda-guid-
ance-documents/how-write-request-designation-rfd.
Accessed 31 March 2021.
11. Classification of Products as Drugs and Devices and
Additional Product Classification Issues: Guidance for
Industry and FDA Staff. September 2017. Final.
FDA website. https://www.fda.gov/regulato-
ry-information/search-fda-guidance-documents/
classification-products-drugs-and-devices-and-addi-
tional-product-classification-issues. Accessed 31 March
2021.
12. Op cit 3, 21CFR3.9.
13. Op cit 6, FD&C Act, Section 563.
14. Op cit 3, 21CFR3.7(c).
15. Op cit 10.
16. Op cit 10.
17. Op cit 10.
18. Op cit 3, 21CFR3.8(b).
19. How to Prepare a Pre-Request for Designation (Pre-
RFD). Guidance for Industry. Final February 2018.
https://www.fda.gov/regulatory-information/
search-fda-guidance-documents/how-prepare-pre-re-
quest-designation-pre-rfd. Accessed 31 March 2021.
20. Ibid.
21. Op cit 19.
22. Op cit 19.
23. Federal Register. Vol. 71, No. 188. Thursday, 28
September 2006. Notices. Review of Agreements,
Guidances, and Practices Specific to Assignment
of Combination Products in Compliance With
the Medical Device User Fee and Modernization
Act of 2002 Request for Comments. Federal
Register website. https://www.federalregis-
ter.gov/documents/2006/09/28/E6-15967/
review-of-agreements-guidances-and-practices-spe-
cific-to-assignment-of-combination-products-in.
Accessed 31 March 2021.
24. RFD Jurisdictional Decisions. Current as of
February 2018. FDA website. https://www.fda.gov/
CombinationProducts/JurisdictionalInformation/
RFDJurisdictionalDecisions/default.htm. Accessed 31
March 2021.
25. Jurisdictional Updates. Current as of February 2018.
FDA website. https://www.fda.gov/combination-prod-
ucts/jurisdictional-information/jurisdictional-updates.
Accessed 31 March 2021.
26. Redacted Decision Letters. Current as of February
2018. FDA website. https://www.fda.gov/
CombinationProducts/JurisdictionalInformation/
RFDJurisdictionalDecisions/ucm2007395.htm.
Accessed 31 March 2021.