fda investigation readiness: avoiding 483s and...

© 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


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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!


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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


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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


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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


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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.


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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”


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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 …)


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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


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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


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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


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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


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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


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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


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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.


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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)


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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


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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 …”


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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


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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


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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:


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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


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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


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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.


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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


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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


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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


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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


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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


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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


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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


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Other information

• Contact Jack Dhuwalia

– Email: [email protected]

– 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

http://www.jdconsultingsite.com/

http://www.fda.gov/cber

http://www.fda.gov/cder

http://www.fda.gov/