1. World Health Organization
25 February, 2019
Basic Principles of GMP
Self-Inspection and quality audits
This session deals with the topic of self-inspections.
The session is a quarter-day module, with approximately 30 minutes of presentation, followed by 45 minutes of group discussion and 30 minutes of feedback. Test is 10 minutes and 20 minutes for discussion

2. World Health Organization
Self-Inspection
World Health Organization
25 February, 2019
Objectives
To identify the role of self-inspection in the quality management system
To review the way in which a self-inspection programme should be carried out
To discuss what to inspect and verify in a company’s self- inspection system
There are three objectives for this session.
Firstly, we will look at the self-inspection process and discuss the role that it plays in the maintenance of the quality system within a company.
Secondly, we will look at the way in which a self-inspection programme is organized, who is involved and with what frequency it takes place.
Finally, we will talk about self-inspection in the context of the factories that you are visiting and the practical issues that may arise when you want to check that the company is complying with GMP.

3. World Health Organization
Self-Inspection
25 February, 2019
Principle (1)
Purpose of self-inspection is to evaluate whether a company’s operations remain compliant with GMP
Assists in ensuring quality improvement
The programme should
cover all aspects of production and quality control
be designed to detect shortcomings in the implementation of GMP
recommend corrective actions
set a timetable for corrective action to be completed
8.1 Principle. The purpose of self-inspection is to evaluate the manufacturer’s compliance with GMP in all aspects of production and QC. The self-inspection programme should be designed to detect any shortcomings in the implementation of GMP and to recommend the necessary corrective actions. Self-inspections should be performed routinely, and may be, in addition, performed on special occasions, e.g. in the case of product recalls or repeated rejections, or when an inspection by the health authorities is announced. The team responsible for self-inspection should consist of personnel who can evaluate the implementation of GMP objectively. All recommendations for corrective action should be implemented. The procedure for self-inspection should be documented, and there should be an effective follow-up programme.
8.1

4. World Health Organization
Self-Inspection
25 February, 2019
Principle (2)
Performed routinely
Also on special occasions such as
Recalls
Repeated rejections
When a GMP inspection is announced by the national drug regulatory authority
Self-inspections should be performed routinely, and may, in addition, be performed on special occasions, e.g. in the case of product recalls or repeated
rejections, or when an inspection of the health authorities is announced.
8.1

5. World Health Organization
Self-Inspection
25 February, 2019
Principle (3)
Self-inspection team should consist of personnel who:
Are objective and have no revenge in mind
Have no conflict of interest (That is, normally not from the same department as the one being inspected)
should have experience as observers of a self-inspection team before becoming a team member
The team should be led by an experienced person
Procedure should be documented
Effective follow-up programme (CAPA implemented)
The team responsible for self-inspection should consist of personnel who can evaluate the implementation of GMP objectively; all recommendations for corrective action should be implemented. The procedure for self-inspection should be documented, and there should be an effective follow-up programme.
It can also be a good training exercise to involve operators in the process. It is also possible to bring in people from other parts of the company, or even outside the company, if it will add value to the process.
8.1

6. World Health Organization
Self-Inspection
World Health Organization
25 February, 2019
1. Self-inspection - informal
(daily) Immediate correction
2. Self-inspection - formal
(quarterly) Improve systems
3. QC - Internal Confirm compliance
(half-yearly)
This is not a WHO requirement, but an example of what some companies do.
The informal self-inspection that takes place on a daily basis is carried out by operators and managers. If something is seen to be wrong, it is immediately put right.
Next is the formal self-inspection process that takes place on a regular basis. The purpose of this is to take a step back from the day-to-day activities to review for compliance to GMP and to look for ways in which the system can be improved. There may also be a need to conduct self-inspections as a result of a specific problem such as frequent rejections. This is the process we are looking at in this module.
The next stage may or may not take place, depending on the size of the organization. It involves the use of QC staff as “internal auditors” to review the system for compliance. (In a smaller company, this step and the previous one may blend into one).

7. World Health Organization
Self-Inspection
25 February, 2019
Items for Self-Inspection (1)
Written instructions provide minimum and uniform standard
Covering all aspects of GMP:
personnel
premises including personnel facilities
maintenance of buildings and equipment
storage of starting materials and finished products
equipment
production and in-process controls
quality control
There should be written instructions for self-inspection detailing what is to be inspected and at what frequency.
It should be used to ensure that a consistent approach is achieved. The areas to be inspected will include (but will not be limited to):
personnel
premises including personnel facilities
maintenance of buildings and equipment
storage of starting materials and finished products
equipment
production and in-process controls
quality control
8.2

8. World Health Organization
Self-Inspection
25 February, 2019
Items for Self-Inspection (2)
documentation
sanitation and hygiene
validation and revalidation programmes
calibration of instruments or measurement systems
recall procedures
complaints management
labels control
results of previous self-inspections and any corrective steps taken
documentation
sanitation and hygiene
validation and revalidation programmes
calibration of instruments or measurement systems
recall procedures
complaints management
labels control
results of previous self-inspections and any corrective steps
taken
In other words, a complete review of all aspects of GMP.
8.2

9. World Health Organization
Self-Inspection
25 February, 2019
The Self-Inspection Team
Team appointed by management, with:
authority
sufficient experience
may be from inside or outside the company
experts in their own field
familiar with GMP
Frequency should be at least once a year
Depends on company size, requirements, actrivities
Often, departments are inspected according to a calender – one department per month over a one year cycle
8.3, 8.4
The self-inspection team is appointed by the management of the company and is made up of a mixture of people, including experts in GMP and persons familiar with the area to be inspected. It is useful to have people from production, QC and engineering on the team, as they will bring different perspectives to the inspection.
The team leader needs to be someone who has access to the resources to produce a report at the end of the process, and with the authority and experience to organize and manage a team activity. Hence it is usually, but not always, a manager or supervisor.
The leader should be from a different department so that he/she can take a more impartial viewpoint.
It is important that the team members are encouraged to be objective in their evaluation.
The frequency with which self-inspections are carried out will depend on the company. For a small company that can cover all its operations in one inspection, a three or six-monthly review might be sufficient. However, for a larger company that needs to split the inspection into a number of sections, a programme of monthly inspections covering the whole factory in three to six months might be more appropriate.

10. World Health Organization
Self-Inspection
25 February, 2019
Self-Inspection
Report prepared at completion of inspection, including:
results
evaluation
conclusions
recommended corrective measures
Follow-up action
Effective follow-up programme
Company management to evaluate both the report and corrective actions
All inspections need reports as an outcome; otherwise there is no formal record of the findings and recommendations.
This report should be issued as quickly as possible while things are fresh in people’s minds. It does not need to be an elaborate, wordy document that no one will read. A simple list of findings with recommendations for corrective action is sufficient. However, it is important that responsibility for action and a time frame are agreed, either during the inspection or soon after the report is issued.
A self-inspection without follow-up is unlikely to be particularly effective and it is important that the company management ensures that the corrective measures are carried out to the agreed timetable.
8.5, 8.6

11. World Health Organization
Self-Inspection
World Health Organization
25 February, 2019
Quality Audit
This is an examination of all or part of quality system
The aim is to improve it
Usually conducted by outside experts or team appointed by management
Useful to supplement self-inspection programme with quality audits
May be extended to suppliers and contractors
A quality audit is an examination of all or part of quality system with specific aim of improving it
It is usually conducted by outside experts or team appointed by management and it is useful to supplement self-inspection programme with quality audits
It may be extended to suppliers and contractors
It may be useful to supplement self-inspections with a quality audit. A quality audit consists of an examination and assessment of all or part of a quality system with the specific purpose of improving it. A quality audit is usually conducted by outside or independent specialists or a team designated by the management for this purpose. Such audits may also be extended to suppliers and contractors.
8.7

12. World Health Organization
Self-Inspection
25 February, 2019
Suppliers’ audits and approvals
Quality Unit (e.g. QA or QC) responsible together with other relevant departments for approving suppliers
Ensure that suppliers can reliably supply materials that meet established specifications
Suppliers should be evaluated and approved before they are included in approved supplier's lists
Should take into account the supplier’s history and nature of materials to be supplied
Evaluation may also lead to an audit to assess compliance, e.g. with GMP
The quality control department should have responsibility, together with other relevant departments for approving suppliers who can reliably supply starting and packaging materials that meet established specifications.
Before suppliers are approved and included in the specifications, they should be evaluated. The evaluation should take into account a supplier’s history and the nature of the materials to be supplied. If an audit is required, it should determine the supplier’s ability to confirm with GMP standards for active pharmaceutical ingredients.
Cross reference can be made to the Module for Active Pharmaceutical Ingredients.
8.8, 8.9

13. World Health Organization
Self-Inspection
World Health Organization
25 February, 2019
Inspecting the Self-Inspection Programme (1)
GMP inspectors should preferably check self-inspection programme at end of an inspection
Evaluate:
SOP, team composition
Annual program / schedule
Checklists used by the company (are these up to date?)
Check that inspections are done as schedules
Reports are available
CAPAs are taken, implementation is verified, management involvement
In your inspection, you can assess the self inspection and quality audit programme of the manufacturer.
Check the self-inspection SOP and programme of the company at the end of your own assessment/inspection. It is recommended that you review the SOP and checklist, and verify that the company is ding self inspections in accordance with their own programme, that there is a report and follow up action. (You should not review their findings – you should be able to do your own inspection and have your own findings!).
GMP inspectors should assess:
the SOP
programmes
checklists or “aide memoirs”
It is advisable to check the self-inspection programme at the end of a formal government GMP inspection, not at the beginning.
If your own inspection is properly formalised and systematic you won’t need to look at their own non-conformities because you will have noted them all already

14. World Health Organization
Self-Inspection
World Health Organization
25 February, 2019
Auditing the Self-Inspection Programme (2)
The SOP should describe teams, process, items covered, and the frequency of self-inspection
Company policy may not permit GMP inspector to see actual deficiency reports and corrective actions
GMP Inspectors should be looking for compliance with the self-inspection SOP - not necessarily at actual deficiencies recorded
Seek objective evidence of reports and action
The SOP should describe the teams, process, and the frequency of self inspection. Check that there is a formal program. Typically it should cover at least the next year’s activities.
Company policy may not permit the GMP inspector to see the actual deficiency reports and corrective actions. Don’t fight this unless you have very good reasons to do so eg if investigating an injury or death as a result of a GMP breakdown.
GMP Inspectors should be looking for compliance with the self-inspection SOP and not necessarily at the actual deficiencies recorded.
Seek objective evidence of reports and action, even if these are “purged”, and audit team composition, frequency and areas covered.

15. World Health Organization
Self-Inspection
World Health Organization
25 February, 2019
Auditing the Self-Inspection Programme (3)
Ensure company is not just doing housekeeping or safety audits
Check there are “Vertical” as well as normal “Horizontal” audits; both play valuable role in self-inspection
Check if there is “Vertical” as well as normal “Horizontal” audits; both play a valuable role in self-inspection
A “horizontal” audit is the room to room to room approach, a “vertical” audit will start with eg a batch number of a released product and then determine traceability, to training records of the people who made and tested it, to raw materials, to retention samples, to stability testing, to product registration details, etc.

16. World Health Organization
Self-Inspection
World Health Organization
25 February, 2019
Group Session
You are a GMP inspector in a large company with a diverse range of products
You are given the SOP, deficiency report form, and the self- inspection schedule
Prepare a report of your observations as to whether the company’s approach to self-inspection meets GMP guidelines
We are now going to move into the group discussion.
The slide describes a hypothetical factory that produces a range of product types. What does the group expect the company to have as an appropriate self-inspection programme? Be prepared to state any assumptions you have made.
You have the SOP, self-inspection schedule and a blank form that the company uses to report deficiencies.
Who in the company should lead the self-inspection team and what inspection schedule would be appropriate?

17. World Health Organization
Self-Inspection
World Health Organization
25 February, 2019
Possible Issues
Size of the factory; phased inspection
Source of team leader
Source of team members
Reports and feedback
In the example given, the factory is a large one with a number of different areas. It is unlikely that the same team would be able to carry out a full inspection in one go. It may be better to have a phased approach.
The team leader should be impartial. For example, head of tabletting leads sterile products team, and so on.
The teams could be a mixture of managers and operators, plus QC staff, engineers, etc. In some case, such as sterile products, particular expertise may be needed.
There needs to be a system for preparation of the reports and for ensuring that follow-up action is carried out.