steven b. hertz, p.e. - ispe.org · pdf fileispe annual meeting 29 october – 1 november...

ISPE Annual Meeting29 October – 1 November 2017

San Diego, CA

1

Combination Product Updates, Initiatives, and Case Studies

Steven B. Hertz, P.E.Consumer Safety Officer, FDA/CDER/OPQ

ISPE Annual Meeting & Expo, October 30th 2017

2

1: CP Overview

2: CDER Updates

3: CP Application Info

4: Case Studies

5: Summary

Agenda



San Diego, CA

2

3

1


2013“Indifference”, “Down”, “No Way”, “Help, Help”, “In Hiding”, “Sad”…

2017“Smile”, “Just Breathe”, “Unthought Known”, “It’s Okay”!!!

Pearl Jam’s CP tour

4

CP Overview1

• 21 CFR Part 4 (Subpart A, CGMP)

regulation https://goo.gl/qjZZfY

preamble https://goo.gl/6GWHiB

guidance https://goo.gl/GtGLsk



San Diego, CA

3

5

CP Overview1

• 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


6

CP Overview1

• 21 CFR Part 4.4(b)(1)

Drug CGMP OS w/ QSR call‐outs

820.20 (mgmt responsibility)

820.30 (design controls)

820.50 (purchasing controls)

820.100 (CAPA)

820.170 & 820.200 (installation & servicing [as applicable])



San Diego, CA

4

7

CP Overview1

• 21 CFR Part 4.4(b)(2) QSR OS w/ drug CGMP call‐outs 211.84 (incoming testing)

211.103 (yield calculation)

211.137 (expiration dating)

211.165 (finished product testing)

211.166 (stability testing)

211.167 (special testing)

211.170 (reserve samples)


8

CDER Updates2

• 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



San Diego, CA

5

9

CDER Updates2


10

CDER Updates2

• Integration of FDA Facility Evaluation and Inspection Program for Human Drugs: A Concept of Operations

https://goo.gl/xDe1jR

• Additional resources

https://goo.gl/jgWWah



San Diego, CA

6

11

• 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

CP Application Info3


12

• Design Control (820.30)

explain how you utilized the design control process to develop the CP

provide a description of your design control procedures




San Diego, CA

7

13

• Design Control (820.30)

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)



14

• 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




San Diego, CA

8

15

• Purchasing Controls (820.50)

explain how the procedure(s) will ensure that changes made by contractors/suppliers will not affect the final CP



16

• 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)




San Diego, CA

9

17

• Corrective and Preventative Action (820.100) 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



18

• Corrective and Preventative Action (820.100)

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




San Diego, CA

10

19

• 21 CFR Part 4 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 820.30 gap analysis)

Case #14


20

• 21 CFR Part 4 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.”

Case #24



San Diego, CA

11

21

• 21 CFR Part 4 controls in place, but inadequate CP management responsibility 820.20 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

820.20 vs ICH Q10 Sec. III vs 211.22

Case #34


22

• 21 CFR Part 4 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.”

Case #44



San Diego, CA

12

23


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.”

Case #44


24


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.”

Case #44



San Diego, CA

13

25



“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.”

Case #44


26



“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.”

Case #44



San Diego, CA

14

27

Summary5

• 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


28

Summary5

[email protected]

(301) 796‐3203



San Diego, CA

15

steven b. hertz, p.e. - ispe.org · pdf fileispe annual meeting 29 october – 1 november...

Documents