Putting Together the Marketing Application for a Combination

Transcription

1 CMC Strategy Forum - Summer 2012 Drug Product for Biological Medicines: Novel Delivery Systems, Challenging Formulations and Combination Products Session Four: Combination Products for Biological Products: Regulatory Pathways, Marketing Applications and Post-licensure. July 17, 2012 Putting Together the Marketing Application for a Combination Product Suzanne Kiani, MedImmune, Gaithersburg, MD USA Douglass Mead, Janssen Research & Development, LLC, Malvern, PA USA Disclosures: The following presentation includes the personal views of the presenters and do not necessarily represent the official views of MedImmune or Janssen R&D, LLC. Any data presented should not be associated with any specific medical product. Regulatory requirements presented may differ from actual regulatory requirements imposed by Health Authorities for specific combination products. 1

2 Scope In line with the scope of the CMC Strategy Forum, this presentation ti will focus on the vast majority of drug delivery devices in development today for biologics i prefilled or nonprefilled subcutaneous injection devices. These combination products are among the most commonly reviewed by Health Authorities. Outside of scope are other novel delivery devices, which may present unique device, CMC or clinical development challenges. 2

3 CTD 3

4 Traditional 510(k) Table of Contents Medical Device User Fee Device Description Cover Sheet (Form FDA 3601) Substantial Equivalence Cover Letter Discussion Indications for Use Statement Proposed Labeling 510(k) Summary or 510(k) Sterilization and Shelf Life Statement Biocompatibility Truthful and Accuracy Software Statement Electromagnetic Compatibility and Financial Certification or Electrical Safety Disclosure Statement Performance Testing Bench Declarations of Conformity and Performance Testing Animal Summary Reports Performance Testing Clinical Executive Summary Other 4 Guidance for Industry and FDA Staff: Format for Traditional and Abbreviated 510(k)s, August 12, 2005

5 Medical Device User Fee Cover Sheet (Form FDA 3601) Cover Letter Indications for Use Statement 510(k) Summary or 510(k) Statement Truthful and Accuracy Statement Financial Certification or Disclosure Statement Declarations of Conformity and Summary Reports Executive Summary ISSUE Device Description Substantial Equivalence Discussion Proposed Labeling Sterilization and Shelf Life Biocompatibility Software Electromagnetic Compatibility and Electrical Safety Performance Testing Bench Performance Testing Animal Performance Testing Clinical Human Factors/Usability 5

6 It is essential to have multiple submission i content t options 1. Appropriate p cross-reference to a master file or another marketing application (eg, 510(k)). 2. Incorporation by including device-specific information i in one section of the CTD structure (3.2.R or 3.2.P.7). 3. Incorporation by including device-relevant information that is common to established CTD sections (3.2.P.1, 3.2.P.2.2, 3.2.P.2.4, etc.). 4. A mixture of one or more of the above options. 6

7 When might these options make sense? 1. Appropriate cross-reference Utilizing someone else's finished device or a platform device to be used for multiple drugs non-prefilled devices 2. Incorporation by including device-specific information in one section of the CTD structure (3.2.R or 3.2.P.7). Simple devices prefilled syringes 3. Incorporation by including device-relevant information that is common to established CTD sections (3.2.P.1, 3.2.P.2.2, 3.2.,P.2.4, etc.). Single entity drug delivery device with specific development, manufacturing or stability information transdermal device 4. A mixture of one or more of the above options. Prefilled device that is kitted with an accessory 7

8 What device data is typically required in most tdossiers and where does it go? INDs/IMPDs: Should include device descriptions, operating principles, p intended use, and suitability information in 32P24, and drawings, materials, and specs in 32P7. 32R-Medical Devices for all device information is an alternative. BLA/NDA/MAA/NDSs: Depends on device complexity. 32P24 & 32P7 (or 32R) may be sufficient. For complex devices, Module 3-32P221; P23; P24: P25; P33; P34; P35; P51; P52; P53; P54; P56; P7; P81; P82; P83; A; R (Technical File), may be required (per FDA/OCP) Expectations are to submit device test data as guided by product-specific guidances (e.g., FDA MDI/DPI, Injector, Patches, Nasal sprayers, etc.) and ICH guidances (e.g., stability and process validation data) Device Master Files (MAF) submitted for review to CDRH may be part of a platform delivery device strategy. 8

9 When should device content be treated differently? Device test method validation typically does not require the rigor of drug analytical method validation Method descriptions and calibrated instruments have been acceptable to CDRH. (3.2.P.5.2 sections alone may be adequate) Formal release and stability specifications can be limited to key critical quality attributes of performance and safety Most design specifications can be verified and validated under Design Controls and reported as characterization or suitability information. Some release specifications and acceptance criteria can be justified (3.2.P.5.6) using Design Inputs (user requirements) rather than originate i from clinical i l batch records E.g., PFS glide forces, autoinjector force to actuate & delivery time The special case for cross-labeled separately regulated The special case for cross labeled, separately regulated delivery devices 9

10 When should device content be treated differently? Manufacturing information for drug delivery devices should start when components/subassemblies enter the fill/finish facility. 510(k) s for Class 2 Medical Devices typically do not include manufacturing information Device In Process Controls (3.2.P.3.4) can be process monitoring based rather that intermediate sample based Instructions for Use (Module 1) While the content is similar to that of a Medication Guide, it is developed in accordance with Design Validation. When we get last minute tweaks at the end of the review process from FDA, we may have to re-validate the IFU 10

11 The Device Design Controls Paradigm for a PFS Health Authorities have treated piston break loose and travel forces like biochemical release specifications. Force specifications for commercial release may be restricted to test results on clinical trial lots Should a device Design Controls approach be considered in setting specifications? Users can accommodate resistance forces with slower injections. PFS plunger thumb rest and finger flange designs are as important to usability as PFS injection forces Separate human factors studies* can establish user requirements and justify force specifications Dermal/tissue fillers approved by FDA (CDRH) have much higher injection forces than typical mab solutions. (e.g., Artecoll, Coaptite, Radiesse ) * Example: Cilurzo F et al. Injectability Evaluation: An Open Issue, AAPS PharmSciTech, Vol. 12, No. 2, June 2011 Note: Artecoll /Artefill, Coaptite, Radiesse are trademarks of Suneva Medical, Inc., Boston Scientific Corp, and Merz Aesthetics, Inc., respectively. 11

12 Functionality specifications for combination products Functional device specifications can be derived from Design Inputs (user requirements and technical design requirements) which are then verified and validated. This is in contrast to biological drug product specifications that are determined by the production process, studied in clinical trials, and then registered. Autoinjector examples: Delivery time: 15 seconds based on market research; a 510(k) cleared predicate autoinjector has a 20 second maximum delivery time Injection depth: determined by user requirements and dermal thickness data Actuation forces: determined by human factors studies in intended population. The ectd Justification of Specifications module (32P56) should include a discussion of specification development in the context of user requirements (Design Inputs). 12

13 Post Approval Changes FDA/OCP is finalizing a guidance on submission requirements for post-approval changes (in-progress over several years). There is currently no clear guidance other than to follow the respective center (drug) requirements. FDA recommends pre-market discussions, post-market comparability assessments (e.g., bench tests, HFS, clinical studies), and inventory planning sufficient to allow for FDA approval prior to implementation. 13

14 Post Approval Changes Types of Changes NDA/BLA PMA 510(k) Major Changes PAS PMA/S 180-day 135-day NEW 510(k) Moderate Changes CBE PMA/S 30-day notice 510(k) decision tree Minor Changes AR Document to File (summarized in AR) Document to File 14

15 Practical Options Without regulatory guidance you have two options: Take the most stringent path ok for NDA/PMA, BLA/PMA or NDA/BLA combination products Predefine your intent recommended for NDA/510(k) and BLA/510(k) 510(k) Device Modifications: Deciding When to Submit a 510(k) for a Change to an Existing Device DRAFT GUIDANCE (Issued July 27, 2011) This guidance applies to devices that are subject to premarket notification requirements. This guidance does not address issues unique to combination products, although the principles discussed in this guidance may be applied to submissions for combination products on a case-by-case basis. (emphasis added) 15

16 Questions? 16