1. HANDLING FDA INSPECTIONS Nombre del moderador Fecha de la presentación

2. Topics to be discussed Pre-Inspection Arrangements FDA Mechanics FDA General Conduct Post Inspection

3. Pre-inspection Arrangements Designate an escort/facilitator, a note taker (scribe), runner(s), copier(s) to cover entire inspection For an investigation team, double the above arrangement Arrange back-ups for facilitator and note taker Appoint a department point person

4. Pre-inspection Arrangements Have a designated room for “FDA room” to contain copier and documents. Review documents before presenting to FDA. Present FDA question to Company personnel in the “FDA room” and prepare response before meeting with FDA Have a department control center to trace/recover documents and to ensure return to originating department.

5. Pre-Inspection Arrangements Prepare lists of: – Organization chart(s) to operator/analyst level – Site SOP Master Index – Manufactured lots and date of manufacture at least 2 years including lot disposition (approval, rejection) – Manufactured lots vials and date of manufacture at least for 2 years, including lot disposition (approval, rejection) – OOS logbook/OOS investigation reports – Deviation logbook/deviation reports

6. Pre-Inspection Arrangements Training plans At least 2 years Change Control Log At least 2 years Complaint log Master Equipment List (Manufacturing and QC) and qualification status

7. Pre-Inspection Arrangements Master Computerized Systems List (Manufacturing and QC) and qualification status Master Critical Utilities List and qualification status Assembly of equipment qualification reports (manufacturing and QC) Assembly of process validation reports Availability of current SOPs Availability of retired SOPs

8. Pre-Inspection Arrangements Formal job descriptions Test methods Method validation reports Water data – WFI, PW, CS. Stability data of selected products Facility layout As built drawings Have ready access to archived materials

9. Pre-Inspection Arrangements Part 11 strategy, compliance status update, remediation efforts Have supplies ready (paper clips, stapler, post-it notes, etc.) Unauthorized pages or copies of procedures in desks or walls should be avoided.

10. FDA Mechanics Guard house to call Company's coordinator upon FDA arrival Have FDA sign-in Escort FDA to conference room Senior Person on site to receive FD- 482 and verify accuracy of FD-482 contents, will also receive FD- 483’s

11. FDA Mechanics Explain site rules – log in/log out, escort, safety access Request daily wrap-up, openness (FDA concerns during inspection) Ask if FD-483, if issued will be annotated Ask permission to present brief update on Company´s plant (history, organization chart, plant layout, etc.)

12. FDA Mechanics At start of day, ask the agenda for that day Periodically ask investigator if he/she has any concerns Periodically ask investigator if he/she has received the information requested from the Company.

13. General Conduct Ask clarification if question or request is vague. Make sure you understand the question before you answer. Answer questions succinctly ( Do not elaborate) Do not answer unless certain of the response. Agree to obtain the information. Keep cool all the time (even when under fire). Avoid being defensive.

14. General Conduct Avoid emotions and/or negative body language. Avoid unrelated discussions/chatter in the room with FDA. This may distract the FDA personnel. Keep technical discussions outside the room. Be careful of what is said in the room in the presence of FDA. Do not create documents for FDA. (Evaluate on a case by case basis.)

15. General Conduct Decide who makes and who keeps copies of FDA requested documents. Use CONFIDENTIAL stamp on FDA copies. Show originals. (Guard carefully.) Do not give FDA copies unless requested. Screen records before giving them to FDA BUT DO NOT DELAY DELIVERY TO FDA. If unavoidable, EXPLAIN REASON FOR DELAY. Do not be argumentative or defensive.

16. General Conduct Anticipate FDA requests so appropriate documents can be made available. If FDA concern is valid, acknowledge. Commit to correct in a timely manner. Provide evidence of corrections made during the inspection. When the firm asks what the investigator wants to see (documents, data, etc.) expect an “All” response.

17. General Conduct Escort FDA at all times. Do not leave them alone. Make sure Company´s personnel are available when FDA arrives daily. Only give information requested. Do not volunteer information. Do not admit shortcomings unless pressed.

18. General Conduct If FD-483 is issued, obtain clarification of findings. Ask what appropriate corrective actions should be taken. After FD-483 issuance it is not necessary to answer additional questions. It is proper to provide information on corrective action(s) to FD-483, if appropriate.

19. FD-483 Upon conclusion of the inspection, the findings are presented in an FD-483. Section 704 (b) of the Food, Drug and Cosmetic Act (The Act) provides for the issuance of the FD-483. The firm should prepare a written response which addresses each observation in the FD- 483. The response should be sent to the District Office within about 15 days.

20. FD-483 The written response to the FD-483 is a legal document containing representation to the government which must be factual. The written response is subject to verification.

21. FD-483 NAI – No Action Indicated VAI – Voluntary Action Indicated OAI – Official Action Indicated

22. FD-483 The response to the FD-483 should include: -Correct any inaccurate statements in the FD-483 -Demonstrate, if possible, how and why the existing systems in question are in conformance with GMP and, therefore, not deficient. -Establish a realistic time frame for corrective actions as needed.

23. Establishment Inspection Report (EIR) The EIR is the investigator’s official report of the inspection. The EIR includes a description of the results of the exit interview and the firm’s GMP compliance profile.

24. Questions?