Leadership For The FDA Inspection The Manager Review

Our Leadershipfor an FDA Inspection:

The Managers’ Review

Adapted by Mitchell W. Manning Sr. from presentations by former FDA Investigators.

Agenda

1. Introduction to the FDA Inspection2. Our Leadership of the FDA Inspection3. Experiences from Inspections4. Critical cGMP elements5. Job performance - scenarios and role

plays6. Review/Wrap-Up/Questions

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1. Introduction to the FDA Inspection

A. Types of InspectionsB. All about cGMP (Current Good Manufacturing Practice)

C. How we get into trouble

D. The need for a successful inspection

E. FDA actions - if we don’t have a successful inspection

F. The FDA’s Inspection Team

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1. Introduction to the FDA InspectionA. Types of Inspections

1. Pre-approval

2. Post-approval

3. Follow up to Warning Letter, etc.

4. “For Cause”, recall, complaint, special program, ADR follow-up, etc.

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1. Introduction to the FDA InspectionB. All about cGMP

1. Requirement of job and our industry

2. Valuable aid to provide properly documented and accurate records

3. Protects the company

4. CGMPs are the law (21 CFR Parts 210 &211)

5. Protects the consumer

6. Protects our professional integrity

7. Protects our profitability

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1. Introduction to the FDA Inspection

C. How we get into trouble

Complacency!

1. Good last inspection

2. Reduce those non-productive quality folk

3. Still runs-why fix or replace

4. Maintenance costs on the bottom line

5. Customer want products first and foremost

6. Protect bonuses at all cost

7. Meet revenue targets

Look at the effects of complacency

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1. Introduction to the FDA InspectionD. The need for a successful

inspection

1. Approvals / Contracts

2. Freedom from legal problems

3. Our reputation(s)

4. Stockholder market issues

5. Stakeholders

6. Insures consumer safety!

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1. Introduction to the FDA InspectionD. The need for a successful

inspection cont’d

7. Company hit with FDA sanctions

8. Jobs are lost

9. Tremendous resources are expended to correct the problems.

10. We may loose our opportunity to work

11. Law suits

12. Company stock falls in value

13. Loss of professional integrity

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1. Introduction to the FDA InspectionE. FDA Actions – if we don’t have a successful inspection

1. Warning Letters

2. Seizures

3. Injunctions

4. Prosecutions

5. Withholding approval

6. Detentions

7. Invoke Application Integrity Policy (AIP)

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1. Introduction to the FDA InspectionF. The FDA’s Inspection Team

1. Investigators2. Microbiologists3. Chemists4. Engineers5. Computer Specialist6. Headquarters Reviewer *7. US Attorney ** Note: off site but involved

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2. Our Leadership for the FDA Inspection

A. Our Team

1. Project Management

2. Production

3. Quality Operations

4. Engineering

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B. Key Roles and Number of People

1. Hosts/4

2. Scribes/4

3. Runners/4

4. Key Divisional Contacts/8

5. Document Room/4

6. Situation Room/6+

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2. Our Leadership for the FDA InspectionC. Instructions to Key Contacts

1. When paged by 9999

1. Immediately call the Situation Room

2. You will receive specific instructions

3. Follow the instructions immediately

2. During the Inspection

1. Notify the Situation Room prior to any absence from site during business hours

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2. Our Leadership for the FDA Inspection D. When the FDA comes calling

1. There is a written receiving procedure

2. Insure security and sign-in are followed

3. Establish, train, and follow alert system

4. Notice of Inspection given to senior executive

5. Keep FDA advised on any delays

6. Inquire about the scope

7. Ask to read the assignment letter

8. Offer short presentation (optional)

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E. Readiness Plan

1. Daily start-up and end of day meetings

2. Who issues the daily summary report?

3. Management evening action sessions?

4. Who plans to receive the FDA 483?

5. Who signs the FDA 483 response?

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F. Readiness Check1. Personnel training

2. Selection of personnel:

To accompany investigators

Key personnel to provide data, etc.

Need to cover the FDA inspection team

3. Inspection management plan

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4. Purpose of Readiness Check

1. Evaluate readiness for FDA inspection

2. Identify system weaknesses

3. Provide opportunity for corrective action

4. Identify key personnel presenters, subject

matter experts and backups

5. Provide an opportunity to critique and/or

change presenters

6. Identify and train coordinators—escorts,

runners and scribes


F. Readiness Check contd

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4. Purpose of Readiness Checks cont’d

7. Provide staff training

8. Refresh staff knowledge of company policies

9. Provide more effective communications

10. Develop an experience base of Do’s and

Don’ts for entire staff

11. Determine availability of documents

A. Can all appropriate documents be found?

B. Practice forwarding in a timely manner.

12. Provide experience in document handling


F.. Readiness Check contd

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1. Provide re-training when necessary

2. Correct identified system weaknesses

3. Verify corrections with spot audits

4. Maintain high awareness level of staff


G. Follow Up to Readiness Checks

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H. Where will the FDA look?

1. Examination of buildings, equipment and materials, cleaningprocedures, HVAC, etc.

2. Facility tour is normally first3. Reviewing rejected batches4. May have complaints to follow-up5. Review of documents

a. Production recordsb. Laboratory recordsc. Logs/chartsd. Written procedures (SOPs)

6. Sampling proceduresa. In-process materialsb. Finished released materialsc. Componentsd. Labelinge. Validation

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I. Current Status and Next Steps

1. Plan in place (FDA inspection procedure)

2. Coordinators identified

3. Key personnel available

4. Designated responsibilities

5. Communications

6. Policies established in writing (Photos; recordings; etc.)

7. Key management positions and changes

8. Major changes in systems or facility since prior inspection

9. Commitment of the company to comply

10. Cover relevant company policy

11. Introduce escorts & key personnel

12. Set a positive tone for the inspection

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I. Current Status and Next Steps cont’d

13. Specify the FDA on-site office

14. Listing of documents requested and copies for firm

15. Summary of Q&As

16. Daily review of findings

17. Office space

18. Escorts identified

19. FDA investigators should be encouraged to discuss observations as they are made with management to minimize surprises/arguments when the FDA-483 is issued.

20. How to say no

21. Know the answer to every question

22. Be responsive to FDA requests

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J. Our Assessment Process

1. Inspection project monitor assigned

2. Document the major findings

3. Insure accurate records on the daily FDA debriefing

4. Keep up with FDA requests vs. corrective actions

5. Follow up on items due FDA

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3. Experiences from other inspections.

Do’s

Don’ts

Possible scenarios

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3. ExperiencesA. Do’s

Answer questions honestly Answer questions directly “ I Don’t Know” is acceptable Provide documents timely Be professional Be prepared Leave room if FDA asks for verbal ok

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3. ExperiencesA. Do’s (continued)

Communicate with the investigator Project a positive,confident attitude Police your area Go over the Readiness plan with your

reports Insure re-reading of SOP and

procedures

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3. ExperiencesB. Don’ts

Volunteer information Guess or estimate Provide any misinformation Provide misleading information Leave Investigator(s) alone Show temper or be argumentative Sign any statement, unless it is policy to

do so

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3. ExperiencesB. Don’ts (continued)

Blame the Investigator or local Office Talk about: FDA approved-

product,process or plant. FDA approves applications, certifies acceptable level of compliance etc.

Talk negative about how the last investigator’s appearance or behavior

Make negative comment about your fellow worker or the company.

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3. ExperiencesC. Possible scenario

Many investigators appear to ramble and be non-specific with questions or comments.

Be careful. Sometimes they are fishing and hoping you will guess what they are asking. This can reveal clues to them that can lead to a fishing expedition.

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3. ExperienceC. Possible Scenarios

Loose notes on desks, information left on chalk board, scrap paper, etc.

Instruct people so there are none of these left in their areas.

A requirement to shred all discarded paper is a good rule.

Situations have occurred where FDA found damaging company information left out in the open.

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3. ExperiencesC. Possible scenarios

These Questions might get you into trouble.

Asking about a related area you are familiar with.

You answer one question, then another. Soon you get to where you are no longer sure.

STOP!

Suggest that the FDA get specific information from the area expert; offer to bring the expert to FDA.

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3. ExperiencesC. Possible scenario

Avoid being robotic in answering FDA questions.

Don’t volunteer any damaging or leading information.

Honestly and completely answer their questions.

Be calm. Maintain a confident,attentive and responsive attitude throughout the inspection.

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3. ExperienceC. Possible scenario

Avoid providing more than is asked for.

If training information is requested for a specific task, for a specific employee, don’t provide the full training file.

Clarify exactly what is wanted and provide it in a timely manner.

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3. ExperienceC. Possible scenario

It is ok to answer general questions about another area.

Do it in a way that your answer leaves the investigator with the understanding that if he or she want’s a final answer he/she will need to talk to the area expert.

Say, “ As I recall” or “Based on my recollection” followed by, “Let’s talk to. . .”

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4. Critical cGMP Elements

I. Write procedures

II. Follow your procedures

III. Document/record work

IV. Validate work

V. Design and build proper facilities

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4. Critical cGMP elements

cont’dI. Maintain the facilities and equipment

II. You must know your job

III. Train to maintain excellence

IV. Be clean

V. Control for quality

VI. Audit for compliance

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5. Job Performance –Scenarios and Role Plays

Evidence of a stability failure is found by the Investigator.

What are you going to say to FDA?

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The FDA Investigator appears confrontational.

What are you going to say and do?


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The investigator makes a leading statement about noncompliance with eye contact, and then there is a long awkward pause.

What are you going to say and do?


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1. FDA: What are they doing?

Potential Answers a. I don’t know. I will check with the

operator

b. Making a batch of cold tablets


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2. FDA: How does Joe know how to do that?

Potential Answers:a. I am sure Joe was trained. Let’s ask him.

b. Our company policy requires that all employees are trained on the process prior to their assignment. Joe also has considerable experience on the job


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3. FDA: Where is the procedure for the job this operator is doing?

Potential Answers:a. I am sure they are around. I will find out

later and get back on that.

b. Official procedures are available in the area of use. Our employees are expected to follow the official procedure.


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4. FDA: Is that the latest procedure?

Potential Answers:a. Yes, only the current procedure is

available for use.

b. This should be the latest issue. Lets go to central data and verify.


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5. FDA: When was Bill trained?

Potential Answers:a. I don’t recall the exact date when when Bill

first came on the job but our policy is to train on a job before the employee conducts cGMP work. Also we conduct periodic re-training.

b. Bill came to work about 10 years ago so I know he was trained then. Let’s go to the training files and check on the date.


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6. FDA: This procedure has been revised, were you trained on the revisions?

Potential Answers:a. Yes, we are required to conduct a formal

training session on the revisions prior to implementing.

b. The area supervisor keeps up with training. I think I will defer your question to that person. I do know a lot of training goes on every Thursday evening.


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Why Challenge ourselves with Role Playing?

Planning vs Implementation

Exercising your brain

Experience leads to wisdom

A picture/experience is worth……….


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From past inspection experience give us a . . . . . . .

“HEAVENLY” situation


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From past inspection experience give us a . . . . . . .

“situation straight from H!!!”


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How do you take the blood off the question mark ?

EXERCISE


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FDA finds a thermometer in the laboratory that has not been calibrated.

What do you say and do?


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Upon reviewing the label room, inserts and labels are found which do not have any status label.

What are you going to do and say?


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There is a temperature excursion showing on the daily chart recordings for the stability chamber.

What are you going to do and say?


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5. Job Performance – Role Plays and Scenarios

A. Discarding original data

B. OOS Investigation

C. First Impressions

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A. Discarding original data

1. Using cheat sheets, sticky sheets, or paper scraps is a common practice for recording some preliminary data.

2. This is a destruction of original data when you discard that scrap paper.

3. Also, your data becomes non-original


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B. OOS Investigations1. Failure to have an adequate written

procedure and follow it can spell trouble. 2. Many errors are assigned a cause based

on a theoretical possibility of a solution.3. This is wrong.4. A full expanded investigation must be

made if the assignable cause is not identified.

5. In some cases, circumstantial evidence can be enough.


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B. OOS Investigations1. Prepare by reviewing and collecting

appropriate documentsa. Batch recordsb. Associated laboratory recordsc. Investigation reportsd. Non-conforming materials reportse. OOS reports


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C. First impressions

1. During a visit to a firm in Cincinnati, Ohio the owner hardly spoke to me.

2. He said go on and inspect, never moving from behind his desk.

3. I proceeded to gather a strong case of violations and when done I presented a shocked owner with a very negative report.


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First Impressions are Lasting Impressions1. Employees facilities and documents make a

lasting impression with the FDA investigator

2. Frequent employee meetings

3. What to expect

4. Know your job

5. Be prepared!


In Conclusion

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6. Review/Wrap-Up/Questions

A. Responses to 483 Observations

B. Managers Can. . .

C. FDA reference sources

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A. Responses to FDA-483 Observations1. At Close Out Discussion

a. Assure clear understanding

b. Correct any errors

c. Provide corrections already in place

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2. At Close Out Discussion

a. Don’t over react or over promise

b. Request clarification on issues

c. Don’t argue


A. Responses to FDA-483 Observations

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3. At the close out discussiona. Keep a positive attitudeb. Don’t blame FDAc. Promise a prompt written

response



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4. In writing alwaysa. Assure clear understandingb. Correct any errorsc. Provide corrections already in placed. Provide additional supporting datae. Provide decisions subsequently

madef. Provide time framesg. Provide periodic updates



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B. Managers Can. . . 1. Manage preparation efforts

2. Insure your work areas are orderly

3. Verify your area equipment and instruments are clean and calibrated

4. Instruct employees that all logs and production documents are filled out completely, accurately and legibly; at time of performance

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C. FDA Reference Sources1. Compliance Programs2. Investigations Operations Manual3. Compliance Policy Guides4. Regulatory Procedures Manual5. Inspection Guides 6. Laboratory Procedures Manual7. Code of Federal Regulations (Part 21)8. Agency Guidance Documents9. Federal Register

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I’m so glad the inspection is over. The FDA is gone.Well, think again.

1. Me responsible? No, you and the Company.2. What is debarment?3. Penalties/prosecution4. Warning letter a warning-or a promise5. Always confident-never complacent6. Now you, the company, and the FDA (we) have a

baseline benchmark for continuous cGMP compliance improvement.

Business

Leadership For The FDA Inspection The Manager Review