ISPE Annual Meeting 29 October 1 November 2017 San Diego, CA. Combination Product Updates, Initiatives, and Case Studies. Steven B. Hertz, P.E.

Transcription

1 Combination Product Updates, Initiatives, and Case Studies Steven B. Hertz, P.E. Consumer Safety Officer, FDA/CDER/OPQ Agenda 1: CP Overview 2: CDER Updates : CP Application Info : Case Studies 5: Summary 2 1

2 Pearl 1 Jam s CP tour 201 Indifference, Down, No Way, Help, Help, In Hiding, Sad 2017 Smile, Just Breathe, Unthought Known, It s Okay!!! 1 CP Overview 21 CFR Part (Subpart A, CGMP) regulation preamble guidance 2

3 1 CP Overview This presentation will focus on drug/device CPs (21 CFR 211/820) drug PMOA (BLAs, NDAs, ANDAs) single entity CPs finished CP manufacturing pre and post approval CP CGMP issues 5 CP Overview 1 21 CFR Part.(b)(1) Drug CGMP OS w/ QSR call outs (mgmt responsibility) (design controls) (purchasing controls) (CAPA) & (installation & servicing [as applicable]) 6

4 1 CP Overview 21 CFR Part.(b)(2) QSR OS w/ drug CGMP call outs (incoming testing) (yield calculation) (expiration dating) (finished product testing) (stability testing) (special testing) (reserve samples) 7 CDER Updates 2 PDUFA VI, GDUFA II, BsUFA II streamlined CP review to enhance coordination and transparency between FDA and industry ORA Program Alignment improved resource allocation for inspections and facility evaluation 8

5 2 CDER Updates 9 CDER Updates 2 Integration of FDA Facility Evaluation and Inspection Program for Human Drugs: A Concept of Operations Additional resources

6 CP Application Info Management Responsibility (820.20) summary of how a firm s management has established responsibility provide a description of the functions and responsibility of each facility 11 CP Application Info Design Control (820.0) explain how you utilized the design control process to develop the CP provide a description of your design control procedures 12 6

7 CP Application Info Design Control (820.0) provide a summary of the plan used to design the CP, and explain how the design control process was used to develop the CP may integrate into existing systems (see case #1) 1 CP Application Info Purchasing Controls (820.50) provide a summary of the procedure(s) for purchasing controls describe your supplier evaluation process define how you maintain records of acceptable suppliers and how you address the purchasing data approval process explain how you will balance purchasing assessment and receiving acceptance 1 7

8 CP Application Info Purchasing Controls (820.50) explain how the procedure(s) will ensure that changes made by contractors/suppliers will not affect the final CP 15 CP Application Info Purchasing Controls (820.50) provide a description of how you apply the purchasing controls to the suppliers/contractors used in the manufacturing of the CP (e.g., through supplier agreement) 16 8

9 CP Application Info Corrective and Preventative Action ( ) summarize the procedure(s) for your CAPA system identification of sources of quality data and analysis of these data to identify existing and potential causes of nonconforming practices and products investigation of nonconformities and their causes 17 CP Application Info Corrective and Preventative Action ( ) summarize the procedure(s) for your CAPA system identification and implementation of actions needed to correct and prevent recurrence of nonconformities verification or validation of the actions taken 18 9

10 Case #1 21 CFR Part controls not implemented CP manufacturing development firm had claimed it implemented a QbD approach with defined QTPPs firm failed to integrate design controls in this approach (no gap analysis) 19 Case #2 21 CFR Part controls in place, but not compliant CP manufacturing design changes your firm failed to implement its established procedure for design validation. your firm failed to conduct design validation of the device constituent part of this CP, as required by SOP

11 Case # 21 CFR Part controls in place, but inadequate CP management responsibility applies to device constituent parts as well as the CP mgmt rep must have appropriate authority to ensure CGMP/QSR requirements are established and maintained performance of QS is reported to executive mgmt vs ICH Q10 Sec. III vs Case # 21 CFR Part controls in place, but inadequate CP manufacturing design your firm has not completed any validation testing of the design of [the CP] in order to ensure that the products conform to the defined intended uses

12 Case # 21 CFR Part controls in place, but inadequate CP manufacturing design you have not reviewed or updated the risk analysis... [therefore] you have not provided adequate risk analysis in your design validation to ensure that the products conform to their defined intended uses. 2 Case # 21 CFR Part controls in place, but inadequate CP manufacturing CAPAs your firm does not adequately analyze processes to identify existing and potential causes of nonconformities related to product or other quality problems. 2 12

13 Case # 21 CFR Part controls in place, but inadequate CP manufacturing CAPAs Your firm does not use appropriate statistical methodology for process capability in order to analyze the quality of production machinery output at critical process steps and to detect recurring quality problems. 25 Case # 21 CFR Part controls in place, but inadequate CP manufacturing CAPAs Your firm does not employ appropriate statistical methodology for analyzing complaint trends to identify recurring quality problems and/or existing and potential causes of nonconforming product. 26 1

14 Summary 5 If you have CP questions about X, contact Y Application info Center RPM Inspection observations ORA (CDER will assist if needed) CP guidance and policy OCP 27 5 Summary steven.hertz@fda.hhs.gov (01)

15 15