BN5208

Biomedical Quality and Regulatory Systems

FDA Auditing process and Quality

System Regulations (QSR)
 Please remember…

FDA has jurisdiction on ‘almost’ all aspects of the

medical device development process, from design to
post market…barring few exceptions…so if the
manufacturer is located in US or the device will be
marketed in US, FDA may ask for documentation/access
to ‘almost’ everything, however small it may be ???
 What we will learn today…

• Practice questions 
• Learning points from the anonymous feedback exercise
• Putting on the hat and shoes of a RA professional being audited
(FDA audition)
• Do’s and Dont’s during the auditing process
• Quality system regulations (QSR)
• Elements of QSR
• ISO 13485 and 21 CFR
• Post lecture presentations
 Warm up…

• Practice MCQ questions

• Takeaway from the anonymous feedback
exercise
 Rationale for midterm feedback exercise

I care for all of you and wanted to make sure we all are working
together and everyone is having a wonderful and enjoyable
learning experience in this module.

The idea is to ensure everyone is enjoying the module, getting

timely feedback and queries answered. Also the post lecture
presentations are providing independent and team-based
learning and thus promoting critical thinking and participation.

Another unique intention is to make this module industry

relevant and hence sharing of my own industrial experience and
external expert talk and sharing session
 Takeaways…good to know
(snippets)

• Weekly practice questions have been very helpful…more such

questions 
• MCQ questions aided in our understanding of lecture
concepts…thanks…
• Feedback session was very helpful… more such sessions
• Interaction with the industry expert was very enriching
• Post lecture presentation provides opportunities for
independent and group learning and promotes critical thinking
• Case studies are fun and interesting…more such case studies 
• Dr Kanti was fun and provided enjoyable learning environment
 Scope for further improvement
(snippets)

• Zoom lessons please….I have to travel a lot to NUS 

• More feedback sessions for the final report/presentation
• Will case studies/ethics appear in final CA quiz?
• Sharing more practical experience from my own career in
JnJ

The process of medical device development and regulation is much more complicated
and is product dependent. The intention of this module is to make it into “bite sized
chunks” (without being overwhelming) so that we all can learn new and salient
features of the whole process, particularly this being a very diverse cohort. Hope it will
be an excellent and holistic learning experience for everyone
Audits and Inspections
 I understand that you don’t plan to be a regulator yourself after
taking this module but rather this is a purely academic endeavor,
but as an educator its my job to give you a holistic picture…

Hence, today I plan to put you on the ‘hot seat’; you are the
‘responsible RA person’ in your company XYZ which makes
medical devices that are exported to US. You are to host
some ‘nice people’ from FDA who are auditing your medical
device development procedures and manufacturing facility

Notice from the whole exercise that product knowledge is as

important as the ‘softer’ skills
Topics

• Preparation for an Audit

• Do’s and Don’ts
• FDA Inspections
 General Definitions
Audits
• The most general definition of an audit is an evaluation of a person,
organization, system, process, project or product. Audits are performed to
ascertain the validity and reliability of information, and also provide an
assessment of a system's internal control.
• Systematic, independent and documented process for obtaining evidence
and evaluating it objectively to determine the extent to which audit criteria
are fulfilled.

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 General Definitions
Similar terms for Audits are:

 Inspection: An inspection is, most generally, an organized examination or

formal evaluation exercise. The results are usually compared to specified
requirements and standards for determining whether the item or activity is in
line with these (mandatory) requirements. Often used by governance and
authority. (in layman terms whether you passed or failed…)

 Assessment: Assessment is the process of documenting, usually in measurable

terms, knowledge, skills, attitudes and beliefs. Often used for voluntary and
self assessment (in layman terms whether you got an A,B, C or a D)

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During…

First and most important of all: Audits are the WORST POSSIBLE
PLACE to explain all the problems in
Don’t be nervous! You are the expert!
your organization!!!

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 During Audit: Process
Opening presentation
 A short overview of company, structure, products and significant changes
since last audit
 Is not a commercial or a sales pitch to impress FDA
 Is a helpful introduction and source of information

Frequently requested documents

 Organization charts
 Facility information – size, configuration (lab, office, manufacturing,
warehouse)
 Product catalogue
 Company annual report
 Quality manual

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 During Audit

Commonly requested lists (generally since last audit):

 Complaints
 MDR (Medical dev reporting, contains mandatory requirements for
manufacturers, importers, and device user facilities to report certain device-
related adverse events and product problems to the FDA)
 Approved Supplier List
 Design Changes
 Engineering / Process Changes
 Recalls, Corrections and Removals
 Internal Audit Schedule
 Management Reviews
 CAPAs (corrective and preventive actions)

Need to be current as of the previous day.

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 Do’s
 Show a friendly, cooperative attitude.

 Be truthful, courteous, and maintain a confident and professional

behavior.

 Make sure you fully understand the question and all of its aspects
before answering it.
 Request a more specific question if not.
 Rephrase questions in your own words if you have
problems in understanding „So you are saying...“.
 Only answer a question if you are the right one to answer it.
 If the auditor asks you a question like "Do you conduct...“ and you
think you don’t do it as the inspector expect
 Explain that e.g. a procedure exists ...

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 Do’s
 Only provide factual information (don’t “estimate” or “speculate”).
 Focus on the positive aspects rather than becoming defensive about
the negative.
 If you lose your line of thoughts - return to your general documents,
procedures, flow diagram etc.
 Always keep with the procedures when explaining processes.
 Sometimes employees are requested to explain how they are
performing their processes and afterwards auditors verifying the
given information with the procedure.

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 Do’s
Answer only what was asked

Yes we do
Do you have
Maytest
I see one? Auditee


instructions?
You
Auditor Bring

 ONE
QM
Partner


If 10 test reports of the latest serial-no. are requested, supply exactly these,
no more, no less!

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Disclosures
Requested information must be provided

 Complaints / incidents, complaint file correspondence and relevant

Quality Systems Regulations procedures.
 Organizational plans specific to the inspected Organization.
 Safety - mandatory equipment or modification requests.
 Service records for a specific site.
 Employee Job Files* consisting of qualifications of technical and
professional personnel performing functions regulated by the FDA.

* See list of non-disclosure documents for those items which are proprietary and
confidential.

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 Don’ts
 Don’t supply the auditor with additional documents or documents that
have not been specifically requested.
 Never supply complete folders (Only the part(s) asked for).
 If you provide complete folders auditors have the right to review them
completely.
 Don’t respond to questions that are outside your area of expertise or
authority
 Don’t attempt to answer hypothetical questions like “What if” or “What’s
your opinion”.
 Don’t volunteer information (unsolicited information to impress)

 Don’t let the auditor unescorted, or take pictures of the facility or use
company computers (dedicated computers only)

 NEVER sign ANYTHING!! Inform the Quality department

 Don’t invite inspector to expensive lunch / dinner. (ethics?)

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Non-Disclosure: Not all requested information must be
provided

 Any financial data as a result of development, manufacturing, service,

installation and sales activities.
 Actual and forecasted sales data including number of units.
 Pricing and marketing data.
 Personnel data (other than qualifications of technical and professional
personnel performing functions regulated by the FDA).
 Internal memoranda.
 Trade secrets.
 Correspondence relating to sales, labor problems, new markets or
marked as attorney client privileged communication.
 Litigation files.

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Non-Disclosure: Not all requested information must be
provided

 Internal Audit files and Supplier Audit files (besides documents which
show that Audits are performed – content, date and who participates).
 Management Reviews (besides documents which show that
Management Reviews are performed – content, date and who
participates).
 Organizational Plans that go beyond the specific office.
 Requests for non-disclosure documents should be forwarded to your
quality department and a lawyer.

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 Company Team

Translation
Inspection & Interface “Interface to
Team (if necessary)
Runners document/file room”

Inspector 

Inspector


Expert
(if needed)

 Team Scribe/
Via NetMeeting/

Leader note taker LiveMeeting

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
Quality System Regulations (QSR)
Salient features of accepted quality standards
ISO 13485 21 CFR 820
Globally accepted standard and Imposed by FDA for US market
facilitates comply with general
regulatory requirements
It was derived from ISO 9001 and It is FDA-regulated good
moreso to make it more specific to manufacturing practices (GMP) for
medical devices medical devices
ISO 13485 is a voluntary standard Mandatory quality system regulation
(guidance document) and not a (QSR) for medical device distribution
compulsory structure/law for QMS in USA, but some flexibility is allowed
Fulfilment is called conformance Fulfilment is called compliance
Onus of Conformance to this standard Compliance is imposed by FDA on
lies with the company medical device manufacturers
FDA provided some input for its No influence by ISO on its
development development
 QSR

• It’s a federal regulation that governs the design, manufacture, packaging,

labelling, storage of medical devices
• ISO 13485 and 21 CFR Part 820 are harmonized, each have additional
requirements but they do not conflict with each other (much is overlapping)
• Foreign manufacturers must comply with QSR and allow FDA compliance
inspections, if they intend to market their medical devices in US
 Quality System Regulation Key Elements

Complaint
Complaint Files
Handling

Design Transfer

Corrective and
Design Review Preventive Actions

Facility & Equipment

Design Controls
Controls

Quality System
Management Training
Record

Production and
Material Controls
Process Controls

Computer System
Records, Documents Validation
Procurement /Handling, Storage, and Change Controls
Distribution & Installation
Process
Validation

Key sub-systems/controls of QSR with Management at the helm/overall responsibility to ensure that all processes are followed
General consideration of QSR: ISO 13485

• Effective QMS (ISO 13485) is a key regulatory consideration for allowing

medical device manufacturers to market their products

• This International Standard specifies requirements for a QMS where an

organization needs to demonstrate its ability to provide medical devices and
related services that consistently meet customer and regulatory requirements

• Audit performed under the ISO 13485 may include an examination of a

product’s design and development

• ISO 13485 certification indicates that the processes for designing and
manufacturing specific medical devices produces consistent product quality
and safety.
 21 Code of Federal Regulation (CFR)
Title Vol. Chapter Part Regulatory entity
21 Food 1 I 1-99 FDA, Dept of Health and
and Drugs 2 100-169 Human Services

3 170-199
4 200-299
5 300-499
6 500-599
7 600-799
8 800-1299
9 II 1300-1399
III 1400-1499
 21 Code of Federal Regulation (CFR)
Part Specifics

800 GENERAL

801 LABELLING

806 CORRCTION AND REMOVAL REPORTS

807 REGISTRATION OF DEVICES AND ESTABLISHMENTS

Regulations 809 IVD

810 RECALL OF MEDICAL DEVICES

21 CFR; Parts 800-1050
- 800-861: Device requirements 812 INVESTIGATIONAL DEVICE EXEMPTION
- 862-1050: Device specific 814 PRE MARKET APPROVAL
requirements
820 QSR

821 MEDICAL DEVICE TRACKING

822 POST MARKET SURVEILLANCE

830 UNIQUE DEVICE IDENTIFICATION

860 MEDICAL DEVICE CLASSIFICATION

861 PERFORMANCE STANDARDS

Medical device advertising,
promotion and labelling

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 Label vs Labelling

‘Label’ is the ‘Physical’ display of written, printed or

graphic matter on the immediate container
whereas
‘Labelling’ is all labels on articles, containers, wrappers
accompanying such article

‘Labelling’ may also include:

Instructions for use, posters, tag, pamphlets, circulars, booklets,
websites and other promotional materials
the term labelling is broad and extends beyond mere physical
association with the product
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Example of Label

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Post Lecture
presentations
 Lets learn together on the following
Medical device controversies

Group 7: Phillips’ CT scanners medical device scandal

Group 8: Tiger Paw medical device scandal
Group 9: DePuy Hip implant controversy

10-12 minutes per group followed by QnA/discussion

Objective: To encourage individual and peer-to-peer learning which is typically followed in an industrial setting where small groups
working together come up a potential suggestion/brainstorm
Suggestions for expected deliverables/
domains that may be covered

In your presentation you can discuss on issues

like;
1. The background of this scandal
2. How and why it happened
3. What effect the scandal/controversy had on medical device regulations? Can
such occurrences be prevented in the future?
4. What role did the regulatory authority play in the controversy? Were there any
shortcomings on their part?
5. How was ethics compromised in your opinion?
6. Any other relevant/interesting findings from your research on the topic…