How To Survive FDA Inspection (003)

  • FDA versus EU, what we should know
  • Preparation:  What could help us
  • Some advices

US FDA versus EU

  • EU and the US want safe, efficacious medicinal products of highest quality for the benefit of the patients.
  • The principles to achieve high quality are the same all over the world.
  • Therefore worldwide the cGMPs have a lot in common. 
  • Nevertheless, the inspection reality shows a lot of differences due to the different cultural and historical background.
  • It is our interest to prepare best for these differences.

FDA what we need to know

  • There are significant differences between the US and the EU inspection system.
  • Both systems reflect the different historical and cultural backgrounds of both systems.
    • US FDA was founded due to criminal activities related to drugs resulting in harm and death of many people
    • US FDA’s history has been influenced by many critical incidents which formed today’s self understanding of US FDA.
  • Despite many recent changes, FDA’s inspection culture persists.
  • The typical US FDA inspector had the job title “Investigator” until 1980 – and that is still his understanding.
  • Todays they are “Consumer Safety Officer”
  • It is the goal of every investigator to identify illegal or non-compliant activities.
  • Therefore, the company is a potential criminal subject in his understanding – and he treats us like that.
  • FDA    : challenges the compliance
    Europe: challenges the science

Goal of an Inspection

  • Check that the system has worked and was compliant with the regulations in the past,
  • Be convinced that it will work in the future and stay compliant .
  • Win trust in employees and company

Rational:

If a complete set of SOPs exist and if they are followed and if people are trustworthy it is predictable how the company will react in case of problems (if the inspectors are not on site)

Consequences:

Inspection is not only focused on science and product.
The way things were done and the documentation of decisions is more important.

Today’s overall goal of a FDA inspection is:

To evaluate wheter management with executive responsibility ensures that an adequate and effective quality system has been established and maintained.

Todays FDA expectations:

  • corporate commitment to quality ( senior management engagement and support of quality)
  • measurement of quality culture and encouragement of this practice (metrics, regular
    review, KPIs and PQR, CAPA effectiveness)
  • learning organization
  • systems monitoring
  • driving continuous improvement ( based onpreventing the initial occurence,( PA), or
    recurrence (CA)
  • developing compliance with an innovativequality management system ( quality metrics to
    assess the overall state of quality of product and processes)

Q System established in line with FDA guidance

Quality System for FDA Guidance

9 key QA management systems

  • Documentation
  • Training
  • Validation/Qualification
  • Contamination control
  • Review
  • Incident / CAPAs
  • Risk
  • Change
  • Continuous improvement

 

Q Formulate policies, define standards, implement systems Operations is running the systems

Preparation:

Production Area:

Short visual Self Inspection

Each visible item may raise questions

  • Label everything: Equipment/materials, identity/status
  • Remove unused or out-of-service items
  • Repair damaged areas (cracks)
  • Clean

Never underestimate an inspection or an inspector

Inspections are milestones

No chance to give a second „first impression“

  • Logistic support in advance
  • Welcome the inspectors
  • Start meeting

During the Inspection

  • Do not panic: Be professional and courteous, friendly and cooperative; be calm and confident
  • Do not be confrontational: No emotions; remain neutral and stick to the facts, even if a question feels threatening or accusatory

Remember: The investigator controls the question, but you control the answer.

Listen carefully:

Respond directly to the question and only to the question. Ensure you understand the question; ask investigator for clarification or repeat/rephrase the question if needed:

(“Do I understand correctly: You would like to know…”).

Respond truthfully, factually, and accurately:

But: Only to what you are competent and what you were asked for. Don’t provide opinionsand don’t guess

Only answer questions within your scope of knowledge; defer if needed, but provide a followed-up response ASAP (“I don’t know, I’ll have to find out” may be the best answer – need to balance this with demonstrating staff’s competence)

Respond specifically to question asked: Provide complete responses but don’t volunteer information not requested or needed for a complete response (no need to show that you know everything!!!)

Respond with current practices (not past or future)

Stop talking after answering question: silence is fine

Avoid terms such as “typically,” “usually,” “generally,” I assume,” “I think,” “I believe,” etc.

Do not play games: Do not try to confuse the inspector by responding to something that has not been asked or by providing irrelevant information.

Do not guess: If you do not know or if you are not sure ask for more time to review details or other people to answer.

Document Review

  • Provide documentation, ( only stamped) and only requested documentation! Remove Post-Its, hand notes and extra pages.)
  • Allow investigator to review document; assist or point out information only if prompted by auditor/investigator
  • Don’t point out errors or correct during the audit/inspection
  • Don’t criticize data,
  • do not contradict colleagues in front of the inspector.
  • Remain friendly, cooperative, and professional; be calm and confident
  • Be careful how you use humor
  • Don’t be hostile, argumentative, or defensive
  • Don’t verbally commit to anything
  • Don’t seek the Investigator’s recommendation or advice
  • Collaborate!

Words never to be used

  • Usually
  • Generally
  • Sometimes
  • Occasionally
  • Normally
  • Mostly
  • Mainly
  • Maybe
  • To be honest…
  • To be perfectly honest..
  • If I can speak frankly
  • I think
  • I suppose
  • I guess
  • Be as positive as possible in all situations
  • Assume that the inspector does not know:
    – your company
    – your product
    – You
  • Realize the inspector may not always be correct
  • Ask the inspector exactly which regulations are the source of his observations
  • Inspectors are trained to read your body language

Inspectors are used to be „important“ persons.

  • They don’t like to wait.
  • People and documents quickly available.
  • In time at start, – wrap up, -final meeting
  • Be ready after the facility tour, after lunch…
  • telephone on “silence” or “vibrator” in your pocket (the inspector is more important than any other call!!! Or go out of the inspection room to call; we have to show that we are concentrated on the inspection Do not “play” with your phone in presence of the inspectors.
  • Introduce yourself (name, function, responsibility in our organization, business card) before starting a presentation.
  • Silence in the inspection room, don’t speak with your colleagues or go out of the room.
  • Close the door of the inspection room silently.
  • Don’t speak during the tour with colleagues in the back of the inspectors in an other language that the inspection language. If needed tell to the inspectors what you are asking to your colleagues.
    (FDA inspectors may understand German incl. Swiss German!!!)
  • During the facility tour show that your outfit is always in accordance to the hygiene principles ( feet or body against the wall!!!, touch any surface or equipment if not needed…)
  • No need to show that you are tired when sitting in the inspection room!
  • During lunch, break, before or after inspection time don’t speak about the company, our processes, people…
    choose topics like the Alps, Museum, Switzerland etc. 

 

5 Essentials to passing an FDA Inspection

  • Trained staff
    – projecting an aura of competence
  • Validated methods
    – Process, analytical,computer,cleaning,utilities
  • CAPA system in place
    – effective data collection
    – effectcive root cause analysis
    – effective Corrective and Preventive actions
  • Documentation systems work
    – SOPs for all actions
    – effective change control
  • Management knows what is going on

Philippe Paroz, November 2020