Post on 04-May-2018
transcript
© JD Consulting, 2017
American Society for Quality
Orange Empire Section 0701
FDA investigation readiness:
Avoiding 483s and Warning Letters Presented at ASQ Quality Day, 2017
Jack Dhuwalia, MS, MBA, DTM
President, J D Consulting
October 27, 2017
© JD Consulting, 2017
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FDA investigation readiness, avoiding 483s and warning letter
1. In spite of best efforts, Medical Device companies sometime find themselves behind-the-8-ball
when it comes to facing FDA investigators. I have found that company’s thinking (as
demonstrated by attitudes and preparedness) makes the experience positive or negative.
2. By participating in this interactive presentation, you will receive deeper insights of:
a. What the FDA investigator is looking for and why? (FDA has seen many song-and-dance
routines so “slick” presentation is likely to be counter-productive; they are looking for
evidence.) So what can you do?
b. Preparation, preparation and preparation – 3Ps and preparation of the executive
management
c. How to make it easy on the company staff?
d. How to prepare – it is like a successful play!
e. Execution – flaw-less
3. Q & A through-out!
© JD Consulting, 2017
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Get to know you …
To make our experience meaningful, will help
me to know:
Your industry – simply raise your hand when I
call
Drug
Device
Combination
© JD Consulting, 2017
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Before you leave – question you want answered is …
Will help me to know:
Please raise your hand to get my attention
then shout-out your question – slowly please
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Objective
Prepare you to have a positive experience
during your next FDA investigation… (yes, it
can be done and I’ll show you how we did it?)
Present a case-study
Regulatory, Quality, Manufacturing and
others work together (what a neat concept!)
No more “WAR ROOMS”
Cooperation – working with each other
Interactive – please get my attention
© JD Consulting, 2017
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My background
R&D, Manufacturing, QE in Medical Devices
Learned about Quality and Regulatory
compliance and submissions
Teach Quality & Compliance
Sharing my experience
© JD Consulting, 2017
© JD Consulting, 2017
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FDA
Responsible for public safety
Concerned about safety and effectiveness
Prevent products that may not work, or at
worst, harm people in the US Market
Formulate regulations
Conducts surveillance – 483s and W/L
Food, Medical devices, pharmaceuticals,
biologics, veterinary medicine etc
USDA – Agriculture, meat, poultry etc.
© JD Consulting, 2017
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FDA (contd.) Promulgate and update regulations &
guidance
Funded by US Congress
Reports to Health & Human Services
Centralized area: Policy, regulations,
guidance, submissions & approvals, working
with districts
Decentralized: Regions and Districts –
surveillance including imports and “fire-
fighting”
© JD Consulting, 2017
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Auditing vs. Investigation FDA investigates, all others audit
FDA investigator gather evidence
FDA works for Department of Justice
Evidence is based upon observations,
documentation and interviews
Written reports are on Form 483 - handed to the
company – receiver keeps it
“Fun” begins from 483 receipt to whatever
happens next (response …)
© JD Consulting, 2017
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Top 6 483 categories in 2016
CAPA 36%
Complaints 21%
MDR 12%
Non-conformance 11%
Purchasing 10%
Process Validation 10%
Total 100%
Top 6 contenders – source FDA
© JD Consulting, 2017
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Top 5 W/L citations in 2016
P&PC 36%
CAPA 32%
Design Control 18%
DHR 8%
Management 7%
Total 100%
Top 5 W/L citations – source FDA
© JD Consulting, 2017
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Selected reasons for 483s QMS is not robust
Raising the bar is probably a hollow slogan
Emphasis on quality is probably lacking
Often indicative of the top
Multiple observations
When the biggies are missed such as
Management Review
Internal audits
MDR
DHR
© JD Consulting, 2017
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Selected reasons for 483s (contd.) Company attitudes are quite important
Investigator(s) are on a tight time-table, wasting their
time is never appreciated
For example: giving a1/2 hour video tour of the
company’s quality accomplishments is a no-no
“Just the facts mam!” Joe Friday – Dragnet!
Teaching staff/managers to be concise, answer question
directly with fewer words. If not sure of what the question
was, politely ask!
Preparation of staff/managers is quite important
Rehearsing the set up such as a back-room to support
the investigation is recommended
© JD Consulting, 2017
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Response to 483s Understand the observation and reason(s)
Written by someone knowledgeable to the
situation – defensive attitude is
counterproductive
Acknowledge the deficiency
“Resistance is futile! Other:
Repeat 483 – requires deeper understanding
Address the 483 in other areas
Refrain from offering solutions such as training
Submit a realistic time-line
© JD Consulting, 2017
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Selected reasons for W/L QMS is not robust
Raising the bar is probably a hollow slogan
Not getting it! Getting defensive with FDA
Response missing/or late
“clue-less” response guarantees W/L
When the biggies are missed such as
Management Review – what was decided? Actions?
Internal audits – were they decimated? Conclusions?
CAPA
P&PC
© JD Consulting, 2017
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On with the program - Preparation Preamble to 21 CFR Part 820 – QSR
Serves as foundation to QSR
QSIT
Best tool FDA has for training (summary slides a
bit later)
Documentation
Procedures
Work Instructions
Drawings, Flow-charts etc.
© JD Consulting, 2017
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Preparation (contd.) Preamble to QSR
Serves as foundation to QSR
Preamble summarizes give-and-take between
FDA and the industry
Really get an understanding of why QSRs are
written the way they are and,
Importantly, preamble works like a “implied”
regulation (my opinion)
© JD Consulting, 2017
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Procedures Easiest thing is to copy word-by-word the
applicable QSR clause – prefer paste
function rather than retype to eliminate errors
Highlight (yellow/blue or a color of your
choice) any words that have a will, must,
shall and should
Make sure that the written procedure satisfies
the requirement
Procedure is a higher-level document, often a
policy document
© JD Consulting, 2017
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Procedures (contd.) Highlight (yellow/blue or a color of your
choice) any words that have a “may or
provide an option”
Carefully consider if “it” applies to your
current situation? If yes, then go ahead and
satisfy the requirement
If not, then briefly answer, “why not?” Such
an answer must be documented.
Pleaser remember: “If it is not written, it …”
© JD Consulting, 2017
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Procedures (contd.) “Failure to follow procedures” is commonly
seen on 483s. This is a “low-hanging fruit” for
the FDA inspector. Follow procedure –
always!
“Raising the bar! This is a must!
Please answer: Who is responsible for
quality/compliance? Discussion
© JD Consulting, 2017
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Work Instructions, drawings etc. “Failure to use the latest version of work
instruction, drawing, test procedure”. This is a
“low-hanging fruit” for the FDA inspector
Follow the latest revision – always!
“Raising the bar!” This is a must! Please answer: If someone notices that an
outdated document is being used, how does
it get corrected? Discussion
© JD Consulting, 2017
© JD Consulting, 2017
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CAPA reach per FDA FDA’s CAPT Katherine Jacobitz is an Engineer Officer
with the U.S. Public Health Service assigned to the FDA
ORA Office of Pharmaceutical Quality Operations
Division IV.
In a CAPA workshop last week, she identified CAPA
significant to medical devices but also to
pharmaceuticals as well as to combination products.
She announced that pharma-regulations do not address
CAPA as med-device regulations do, yet the
investigators are likely to ask how a company addresses
CAPA.
Following are selected slides from her presentation:
© JD Consulting, 2017
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QSIT Quality Systems Inspection Technique
Selected slides from FDA are as follows:
The Quality System
Inspection Technique:
“QSIT”
QSIT Workshops
What is QSIT?
Moves FDA closer to Global Harmonization
guideline for regulatory auditing of quality
systems of medical device manufacturers
Incorporates the seven subsystems concept
Provides specific guidance on auditing each
subsystem
Theme #1 = Management
Management is responsible for Implementing Quality System
Start & Finish with Management
All product, process, design & CAPA
problems can be tied to management
Establish - [21CFR 820.3(k)]
Define
Document
Implement
Quality System’s Sub-systems
Design Controls
Material
Controls Records,
Documents, &
Change Controls
Equipment &
Facility Controls
Production &
Process Controls
Corrective &
Preventive
Actions
Management
Order of Systems
Management
Design
CAPA
Production & Process Controls
Conclude with Management
Inspection Conclusion
“Did management ensure that an
adequate and effective Quality System
has been established?” (Mgt. #7)
Implementing QSIT
Training on-going
Compliance Program
Industry Workshops
Monitoring and Improvements
© JD Consulting, 2017
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Case Study The company, located in India, manufactures
Class II devices for export
They have been certified by ISO 13485 – no
major non-conformances
They were expecting their 1st FDA one week
long inspections
They we quite nervous
Background: If a foreign manufacturer has
quality problems, FDA can stop the devices from
entering US – essentially returns the product
© JD Consulting, 2017
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My first experience at the site Hot and humid weather
Written documents in English – English spoken
First look: Pig-Sty (never had pigs but the place
sure looked like one)
Boxes, raw material drums, product everywhere
Documentation department was non-existent
(found out later that their documents were at
another plant – 10 miles away – travel time
about one hour each way). Explained why
documents took one day.
© JD Consulting, 2017
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My first experience at the site (contd.) Management was cooperative and supportive
First move – changed the conference room from
“war room” to “calm room”
Met with the managing director, VP, site
management to really “get” their concerns
Open communication
Permission was granted to dig deep into their
practices and make
suggestions/recommendation
© JD Consulting, 2017
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The Plan Calm the fears and anxiety down, hold plenty of
informal training
Get their spirits high regarding their successful
manufacturing and quality
Noticed people were holding their heads up
Added a computer in the calm room with a
knowledgeable quality person taking notes and
asking for anticipated documents which were
printed and delivered to the QA director
Having the documents ready when FDA
requested made a big difference
© JD Consulting, 2017
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Next few days The manufacturing yield was 99% confirmed
Initial assessment: Engineers, staff knew what
they were doing. They were practically clue-less
on what FDA investigator looks for however
Phase I:
Appearance of the site:
Complete overhaul requested
Site clean-up requested
Drums (latex raw material) lot numbers
identified
Site was broom-swept ready for inspection
© JD Consulting, 2017
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Next few days (contd.) Phase II
Phases were not sequential
Product storage was organized with steel
racks and fork lifts
Entire racks were installed in less than a week
All finished product was stored in a week with
lot number identified
Waste water pond was cleaned and covered
Rest rooms were upgraded and covered
© JD Consulting, 2017
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Next few days (contd.) Phase III
Documentation Room (looked like a phone booth)
Brought the project files from off-site plant
Created project logs
Created project list
Same with CAPA and Process Validation logs
Created a process flow chart 3’ high x 15’ long
The process flow was taped on the “calm room” wall
The process flow showed key inspection points and
daily inspection results were hand-written
The staff was quite proud that anyone unfamiliar with
the complex process could get it in minutes
© JD Consulting, 2017
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Next few days (contd.) Phase IV
Revelation: SMEs were competing for my attention
With management help, decided to keep SMEs
separated from the FDA, arranged to have the Quality
Director (lady) be the sole interface with FDA
The plan was to ask the SME needed for answering
the questions related to the topic, Tamil, the local
language, was used for the SME communication
The VP and I sat in the room yet did not interfere with
the flow of events. We wanted to give plenty of space
to the QA Director
© JD Consulting, 2017
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Lessons learned Obtain cooperation up-front
Understand and address their concerns
Ease their fears and work with them
Anticipate and solve problems
Preparation paid-off
Alignment was the key
Prepared them for future
© JD Consulting, 2017
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Other information
• Contact Jack Dhuwalia
– Email: jdhuwalia@jdconsultingsite.com
– Phone: 949-854-4534
– Mobile: 949-701-0214
– Website www.jdconsultingsite.com
• FDA
– Website www.fda.gov/cber biologics
– Website www.fda.gov/cder drugs
– Website www.fda.gov devices