1. GMP Inspection Process
World Health Organization
14 November, 2018
Preparation for the Inspection
This module deals with the topic of preparing for an inspection. It is a quarter-day module with the usual arrangement of 30 minutes presentation followed by 45–60 minutes group discussions and 30 minutes feedback.

2. Preparation for an Inspection
World Health Organization
14 November, 2018
Objectives
1. To review the activities in preparation for an inspection
2. To discuss key issues relating to preparing for inspections in this country
The objectives of this module are to review the activities that need to be carried out when you are preparing for an inspection. We will look at the key issues relating to the preparation for an inspection and review the particular issues that relate to inspections in your country.

3. Preparation for an Inspection
World Health Organization
14 November, 2018
Scope of Inspection
Objective
Type
Depth
Timing
Inspectors:
size of team
make-up of team
The first step is to define the objective of the inspection that is to be carried out. Why is the inspection being performed? What is the purpose of the inspection? Is it a first visit to a new company or a continuation of an established inspection programme?
Which type of inspection will be performed? Will it be a routine inspection and review of all aspects of GMP, or a concise inspection of selected aspects of GMP? Can you still remember the other types of inspections and when these are performed? (Follow-up inspections to monitor corrective actions, special inspections to carry out spot checks and quality systems review).
You also need to decide whether the inspection will cover the entire factory or just part of it. You have to determine what the scope and depth of the inspection will be to enable you to prepare properly for the inspection. For a company producing liquids, tablets and sterile products, you will have to prepare by reviewing the guidelines for the dosage forms, and look at the dossiers for some of the products. You may want to spend time in just one area rather than trying to cover all manufacturing sections or departments in the same inspection.
Once the purpose of the inspection has been determined, and the depth, you can then decide on the amount of time that will be required to carry it out.
You can also plan the date when the inspection will take place. Whether this is done in conjunction with the company in question will depend on the objective of the inspection and the accepted practice within your inspectorate.
Some inspections are carried out by individuals while others involve teams of inspectors. In some cases, it may be better to have a team performing the inspection. In such cases, it allows the workload to be split, and the involvement of people with different specializations. It also provides a “sounding board” for developing the conclusions of the inspection.
If the team approach is used, a chief or lead inspector must be appointed to co-ordinate and lead the inspection. The lead inspector is usually the main spokesperson during the closing or exit meeting at the end of an inspection, and has the overall responsibility for the inspection report.

4. Preparation for an Inspection
World Health Organization
14 November, 2018
Notification
The company being inspected
Team members
expert support
other inspectors
Other interested parties
When you have decided when the inspection is due to be performed, it would be proper to notify certain people of the proposed inspection.
If your policy is to announce the inspections in advance to the manufacturers, you would have to contact the manufacturer and inform the company of the proposed inspection.
If the inspection will be performed by a team of inspectors, you would obviously have to inform the other members of the team. Remember to inform the other inspectors who will be part of the team as well as any specialists of the finalized date for the inspection.
There may also be other interested parties that you could inform of the proposed or planned inspection. This could include evaluators of the registration dossiers (as they may request you to investigate any aspect of the dossier or submitted data during your inspection. This will depend on the structure and policy f your regulatory authority.

5. Preparation for an Inspection
World Health Organization
14 November, 2018
Review documentation from regulatory authority
Company file
Site Master File
Manufacturing licence
Registration dossiers
In preparing for the inspection, it is advised that you review some documentation relating to the manufacturer to be inspected.
Most regulatory authorities have a company file in which general correspondence and previous inspection reports are filed. Review the information on file as there may be aspects that you would like to investigate when performing the inspection.
Some regulatory authorities require manufacturers to submit a site master file (SMF) to the DRA. By studying the SMF, you will have a better understanding of the layout and design of the manufacturing facility, and some of the systems the manufacturer has in place to ensure quality in manufacture of products. You can make notes in your aide memoire when reviewing the SMF and verify some aspects stated in the SMF during your inspection, e.g. equipment, procedures and personnel aspects.
Another source of useful information, is the manufacturing licence and registration dossiers. You can use these documents to make notes for verifying compliance with licence conditions, and data verification.
Reports on previous inspections and ADRs may also assist you in guiding you to do some investigations to verify corrective action taken by the manufacturer.
For special inspection, you will have to review records of the company in relation to complaints and recalls, and regulatory test results (surveillance).
The trainer can also make reference to the format of a Site Master File as recommended by the WHO (See WHO GMP Text) and the Pharmaceutical Inspection Co-operation Scheme (PIC/S).

6. Preparation for an Inspection
World Health Organization
14 November, 2018
Review documentation from regulatory authority (continued)
Reports
Adverse Drug Reaction reports (ADRs)
Previous inspections
Records
Complaints and recalls
Regulatory test results (surveillance)
Reports on previous inspections and ADRs may also assist you in guiding you to do some investigations to verify corrective action taken by the manufacturer.
For special inspection, you will have to review records of the company in relation to complaints and recalls, and regulatory test results (surveillance).

7. Preparation for an Inspection
World Health Organization
14 November, 2018
Review documentation from the manufacturer
Annual report
Complaints file
Self inspection/internal audit reports
Send a questionnaire to the manufacturer asking to provide specific information about the company
Layout of site and diagrams
Manuals
Standard Operating Procedures
It can be useful to obtain some information from the manufacturer also before you perform the inspection. Some of this information may not necessarily be available on file in the regulatory authority. Although the annual report normally covers financial aspects of the company, you may find some useful information in the report regarding personnel issues, and products manufactured.
The complaints file is another source of information that could indicate failures in quality systems of the manufacturer.
Self inspection/internal audit reports could be requested from the manufacturer. This is often not advised, as some manufacturers are of the opinion that the inspectors should do an assessment of GMP compliance themselves, and not look at the company’s own findings of inspections. Requesting such reports would be dependent on your own policy in the inspectorate.
You could also draft a questionnaire relating to some activities of the manufacturer, and request them to reply to the questions, and also to submit a layout of site. Diagrams can be helpful in understanding the flow of material, personnel and processes in the facility.
Manuals and procedures could be requested to enable you to prepare specific questions relating to the quality policy, validation policy and procedure for performing certain activities.

8. Preparation for an Inspection
World Health Organization
14 November, 2018
Programme
Checklist
Aide-memoire for inspection
Develop inspection programme
Distribute inspection programme
Company
Team
When reviewing all this documentation, draw up a checklist or aide memoire of points you would like to verify during your inspection.
Having done this, develop the programme for the inspection. From this the inspection team needs to produce an outline of what will be covered each day. It is probably not worth going into too much detail at this point, since all inspections have unforeseen events and plans have to be revised as you go along. However, it is important to know what each member of the team will be doing every day or half-day of the visit. Indicate in your programme which sections or departments will be inspected, and when.
Once it is prepared, the programme will need to be distributed. If it is an announced inspection, you could inform the company of the proposed inspection programme. The managers will find it very useful to see the programme in advance as this will help them in their preparation for the inspection. They can make sure that the appropriate people are available at the right times, rather than keeping everyone on stand-by for the whole time.
The team members should also be given copies of the final version of the programme.
(The trainer should refer the attendees to the hand outs (examples of an aide memoire and a checklist for a sterile manufacturing site).

9. Preparation for an Inspection
World Health Organization
14 November, 2018
Group Session
You will be given a situation that requires an inspection
Prepare a list of documents that you would use in preparation for the inspection
Prepare a checklist or aide-memoire of key issues to be investigated
Draft a programme for the inspection
We are now going to work in groups again.
Each group will be given a situation to discuss.
For your group’s situation, draw up a checklist of issues to be investigated and draft a programme for the inspection
(The trainer should select an option from the following slides)

10. Preparation for an Inspection
World Health Organization
14 November, 2018
Possible Issues – I
The first inspection of a new manufacturer
Plant design and equipment
Processes
Documentation
Personnel
Quality control
You are planning to perform the first inspection of a new manufacturer.
Consider points for inspection in relation to:
Plant design
Equipment
Processes
Documentation
Personnel
Quality control

11. Preparation for an Inspection
World Health Organization
14 November, 2018
Possible Issues – II
Regular inspection of an established manufacturer
Actions arising from the previous inspection
Areas not previously inspected
New areas, processes and products
You are going to perform a routine inspection of an established manufacturer.
Consider points for inspection taking notice of:
Actions arising from the previous inspections
Areas not previously inspected
New areas, processes and products

12. Preparation for an Inspection
World Health Organization
14 November, 2018
Possible Issues – III
Inspection because of complaints about a product
The product in question
Manufacturing process
Premises
Systems for handling complaints and recalls
Quality control records
You have received a complaint from a pharmacy, stating that the label information on a product is incorrect (e.g. wrong strength stated, or wrong strength of tablet in the container).
Consider points to be inspected including checks on the:
Manufacturing process
Premises
Systems for handling complaints and recalls
Quality control records