The Impacts of FDA Combination Product Rulings on Medical Devices

Transcription

1 The Impacts of FDA Combination Product Rulings on Medical Devices Khaudeja Bano Arlington, VA - June 14 th th Product Complaint Congress for Life Sciences

2 Disclaimer Speaker s personal opinion and interpretation and does not reflect any company or organizational position Scenarios discussed are hypothetical and do not reflect any specific product or class

3 Our Objective Safety, Efficacy and Effectiveness Ease of use All populations protected populations Drug delivery systems / platforms, on-body systems, Drug Eluting Stents, Infusion Pumps, Photosensitizers, Orthopedic Combination Products, Wound Care Combination Products, Inhalers, Transdermal Patches, Intraocular Implants and Drug Eluting Beads

4 Regulations - FDA The cgmp Final Rule for combination product addresses how to comply with CGMP requirements for co-packaged and single-entity combination products. It recognizes the multiple quality systems and addresses how to maintain them for combination products [21 CFR 4.4(b)(1) and (b)(2)]. Rule was effective 22 July 2013

5 (Drug) cgmp (Device) QS Combination product compliance (Drug) cgmp + Sec Management responsibility. Sec Design controls. Sec Purchasing controls. Sec Corrective and preventive action. Sec Installation. Sec Servicing (Device) QS + Sec Testing and approval or rejection components, drug product containers, closures Sec Calculation of yield. Sec Tamper-evident packaging requirements for (OTC) drug products Sec Expiration dating. Sec Testing and release for distribution. Sec Stability testing. Sec Special testing requirements. Sec Reserve samples.

6 Combination Product types A combination product as defined in 21 CFR 3.2(e), as a product comprised of any combination of a drug and a device; a biological product and a device; a drug and a biological product; or a drug, device, and a biological product. (1) Single entity combination product (2) Co-packaged / Kits (3) Cross-Labeled Products

7 Key Focus Areas Risk Management Drug / Biologic considerations for validation testing Dependencies between the constituent parts Timing of Validation and verification studies Clinical trial readiness Change management / controls Pre / post market change controls Human Factors

8 Expectation Product as a Whole or as a system Risk based review, prioritization and reporting One report with all the relevant information One integrated set of reporting timelines Reported to one system

9 Post Market Safety reporting (PMSR) Final Rule Applies to all combination product applicants (CPA) and constituent part applicants (cpa) of combination products A. Application type drives primary reporting B. Constituent parts determine additional reporting requirements Data sharing requirements Data retention

10 Key Timelines Leverage existing industry experience, Consistency and single-report with the whole story Comply with requirements associated with application type (Jan 2017) Additional requirements to be met by July 2018

11 Report Types 1. 5-Day Reports 2. Malfunction Reports 3. Correction or Removal Reports 4. Field Alert Reports (combination product with drug constituent part) Day Reports that can be filed in 30 days(combination product with drug or biological constituent part) and 6. Biological Product Deviation Report (BPDR) (combination product with biological constituent part) Periodic safety reporting of combination products with a device constituent part for new drug application (NDA), biologic license application (BLA) or abbreviated new drug application (ANDA), Summary and analysis of the 5-day [device] reports and 30-day device malfunction reports that were submitted during the reporting interval. Drugs: 21 CFR 310 & 314 / Medical Devices: 21 CFR 803 / Biologics: 21 CFR 600 & 606

12 Who is responsible for what? CPA and cpa All PMSR requirements associated with application type ONLY CPA (+) Additional requirements related to constituent part ONLY cpa information sharing requirements Combination product applicants (CPA) and constituent part applicants (cpa)

13 Information Sharing Requirements (cpa) Death or serious injuries - 21 CFR and Adverse experiences - 21 CFR (a) or (a) Within five calendar days Forward information One time forwarding of information per event Set up processes / procedures / quality agreements

14 Recommended Best Practices Inventory of combination products (pipeline?) Application type Reassess compliance / gap assessment for 2018 Platform approach Establish risk-based approach to reporting Risk management constituent part assignable cause of adverse event / malfunction Organizational / resource changes Guidance IT / infrastructure changes

15 Device Scenarios 1 Device constituent as suspected cause of SAE Application type Device Event is assessed for submission as an MDR. In this scenario, the MDR would primarily contain device information elements. Example: While using a drug-eluting stent to treat a coronary artery stenosis the stent failed to deploy resulting in the need to remove and deploy another stent causing procedural complications due to prolongation of procedure. Seriousness: Yes Labeledness: No (not in IFU or drug label). Causality/Contribution/Association/Relatedness: Device Malfunction: Yes MDR filing: 30-day malfunction report (only if this is a non-labeled event) Field Alert Report Requirement: No, Device remedial action report: No Periodic Safety Report Inclusion: N/A

16 Device Scenarios 2 Drug constituent as suspected cause of SAE Application type Device Event is assessed for submission as an MDR. In this scenario, the MDR would primarily contain device information elements. Example: While using a drug-eluting stent to treat a coronary artery stenosis there was an infection. Seriousness: Yes Labeledness: Yes (in drug label). Causality/Contribution/Association/Relatedness: Drug Malfunction: No MDR filing: 30-day malfunction report Does labeledness matter? Field Alert Report Requirement: No, Device remedial action report: No Periodic Safety Report Inclusion: N/A

17 Drug Scenarios 1 Device constituent as suspected cause of SAE Application type - drug/biologic. Report where the device is the suspected cause of the event is assessed for submission as an ICSR Example: An autoinjector used to treat an autoimmune disease resulted in a needle misfire / broken embeded needle causing a serious injury. Seriousness: Yes, Labeledness/Expectedness: No Causality/Contribution/Association/Relatedness: Device Malfunction: Yes ICSR: Yes 15 Day report with all device details Field Alert Report Requirement: No (if drug constituent part is involved) / Biologic Product Deviation Report: No (if biologic constituent part is involved) / Periodic Safety Report Inclusion: Yes

18 Drug Scenarios 2 Drug / Biologic constituent as suspected cause of SAE Application type - drug/biologic. Report where the drug/biologic is the suspected cause of the event is assessed for submission as an ICSR Example: A pre-filled syringe (PFS) used to treat an autoimmune disease resulted in an allergic reaction requiring hospitalization. Additionally, the solution is reported to have looked cloudy. Upon investigation it was determined that the product did not meet stability criteria at time point T1. Please note that in this scenario, device related causes are ruled out (e.g. no impact from leaching of silicone from the PFS walls and associated denaturing of the product). Seriousness: Yes, Labeledness/Expectedness: No Causality/Contribution/Association/Relatedness: Drug Malfunction: No, ICSR: Yes 15 Day report Field Alert Report Requirement: Yes (if drug constituent part is involved) / Biologic Product Deviation Report: Yes (if biologic constituent part is involved) / Periodic Safety Report Inclusion: Yes

19 References Final rule and guidance CGMP guidance for medical products: oryinformation/default.htm ancedocuments/default.htm efault.htm

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