Typical GMP Audit Topics and Schedule
PCS has 32 years of experience in auditing pharmaceutical organizations. We assess the Quality Management System (QMS/PQS), the process(es) and the organization as a whole.
The presentation below shows the topics PCS would normally cover on a one-day GMP audit. We have based the audit on a production organization. Process-specific topics have been excluded for the purpose of this presentation e.g. cell banks, autoclaving, etc.
1. Arrival & Introductory Meeting
Start of the Audit
Upon arrival to the site the auditee will welcome the auditors and give a presentation on the company. Details will be discussed including the auditee's team, their products and organization. Next, the auditors will present their agenda, the purpose and focus points of the audit.
Points of Attention
Is all essential staff present? Gowning supplies for auditors present? Previous observations have been closed? Documentation inspection-ready?
2. Plant Tour
Introduction
The auditors will usually tour the facility after the introductory meeting. The focus will very much depend on the available time and process but will usually include; incoming goods, solution preparation (steriles), filling, terminal sterilisation and finishing (steriles), primary and secondary packaging operations, dispensing, mixing and granulation area (sdf) and compression (sdf). Additionally, the audit team may split up (in case there is more than one auditor) to review the documentation (QMS/PQS) while the other auditor(s) visit the plant.
3. Plant Tour
Incoming Goods
The incoming goods area is usually the first to be toured by the auditors. The behavior of staff, cleanliness of this area and overall handling of goods usually provide a pretty good indication of how the rest of the site functions. If the incoming goods are not handled properly it can lead to big problems further down the line.
Points of Attention
Pest and water free? Procedure and checklist for goods receipt? Handling of incoming goods including labelling and checking, quarantine area labelling and location, how fast are goods moved to temperature controlled area's? facility cleanliness and staff cleanliness
4. Plant Tour
Sampling (QC)
Incoming goods/raw materials will be sampled by the Quality Control (QC) laboratory. Sampling must occur according to a defined and tested procedure to ensure uniformity of methods, sample location(s) and to ensure samples are randomly selected. When sampling is not performed properly, production may be working with starting materials which are not according to specification. This could lead to deviations and possibly rejection of the finished product.
Points of Attention
Are sampling tools properly cleaned? Logs and registers readily available and complete? calibration, qualification and validation in order? Is traceability of sample history guaranteed and auditable? Does QC have modern, fit-for-purpose equipment? Cleaning procedures for sampling area's and QC lab, microbial testing and reference strains.
5. Plant Tour (Sterile)
Solution Preparation (Sterile Production)
Solutions can be prepared before the filling of products. Strict requirements exist for the equipment, facility and environment when you are preparing solutions. The right room grade (A-D) must be used, which also differ between terminally sterilized products and aseptic preparations.
Points of Attention
Using the right grade for the environment for the right type of product? Is the monitoring of these area's based on solid Risk Assessment? Measuring is done "at rest" and "in operation"? Is there a sampling plan available? Do you have a sampling procedure for these specific area's? Are all you mixing vessels state-of-the-art and validated?
6. Plant Tour (Sterile)
Aseptic Filling (Sterile Production)
When filling aseptically there are a great number of factors to consider, when you receive an audit of your aseptic filling line make sure your staff behaves in accordance to the regulations and that the amount of people in the cleanroom is kept to a minimum. These are points an auditor will always look for when observing your aseptic filling line.
Points of Attention
Definition of critical parameters, holding times of the finished product, equipment selection and design, monitoring and sampling, autoclave validation, measures to avoid contamination of starting materials and products by other material and products, routing of personnel and materials, access control to production premises.
7. Plant Tour (Sterile)
Terminal Sterilization (Sterile Production)
Products which are sterilized after packing are terminally sterilized products. The manufacturer should ensure the hold times have been defined and validated to reduce possible microbial contamination before the sterilization process. Additionally, product stability studies should be made available to the auditors so they can ensure that terminal sterilization does not result in unacceptable degradation of the product.
Points of Attention
Definition of critical parameters, validation of the holding times of the unsterilized product, equipment selection and design, monitoring and sampling, measures to avoid contamination of products by other material and products, routing of personnel and materials, access control to production premises.
8. Plant Tour (Sterile)
Finishing of Sterile Products (Sterile Production)
When auditing the finishing of sterile products, auditors will usually first check the validation of your container closure process, whereby the 100% integrity checks must absolutely be guaranteed for glass or plastic ampoules. The integrity checking should be proceduralized and reviewed regularly.
Points of Attention
Vial rejection due to missing/misplaced stoppers prior to capping performs as it should? Is vial crimping equipment placed at a separate station? If operators are used for visual inspection, have these been regularly checked for eyesight and do they receive regular breaks?
9. Plant Tour (Solid Dosage Forms)
Weighing and Dispensing (Solid Dosage Forms)
It should be remembered that the risk of cross-contamination here is possibly the highest because drug substances are handled in the undiluted state. Thus, great stress must be placed on a disciplined way of working and the use of carefully written and understood weighing and dispensing procedures.
Points of Attention
Avoidance of cross-contamination, appropriate clothing for this area, data integrity of scales and other equipment, calibration of equipment, validation of supporting software, are there any materials which are not necessary for the current operation stored within the area? Are weighing results independently checked (2nd operator / software)?
10. Plant Tour (Solid Dosage Forms)
Tablet Compression (Solid Dosage Forms)
An audit of your tablet compression operation will usually revolve around the design of the machinery, its validation and whether or not it is producing the expected results. Important parameters such as compression speed, depth of fill and punch penetration depth will usually be reviewed by auditors.
Points of Attention
Definition of critical parameters, cleaning holding times, equipment selection, design and validation, monitoring and sampling, measures to avoid contamination of products by other material and products (incl cleaning validation), routing of personnel and materials, access control to production premises, in process controls, hopper design and height, depth of fill, punch penetration depth, force main compression, compression speed
11. QMS & Data Integrity
Quality Management System Review
During this phase of the audit the auditors will want to review your Pharmaceutical Quality System (PQS) / Quality Management System (QMS). It is important to have procedures but are these procedures actually being adhered to? More importantly, are the data integrity principles known throughout and applied?
Points of Attention
Are Data Integrity principles applied throughout? Is documentation written according to Good Documentation Practices (GDocP)? Are procedures adhered to? Are all procedures up-to-date? Are procedures according to GMP/GDP? How well are deviations investigated? How well are risk assessments performed? Is the distribution of documents centrally organized?
12. Wrap-Up Meeting
End of the Audit
When the factory tour has been completed and all documentation has been reviewed (for as far as possible), the audit team will usually check if they have conveyed all their observations to the auditee and summarize their audit observations. Often, these observations will be categorized according to a Minor/Major/Critical/Other ranking system. Obviously, the auditee is free to respond to these observations but the auditee is advised to make sure his response is based on scientific or regulatory information.
Points of Attention
Is senior management present? Are all observations based on scientific/regulatory knowledge and do they represent the actual situation? Have deadlines been agreed upon regarding report submission and responses by the auditee? Have all disagreements been resolved? Are there any open issues which haven't been discussed prior to the auditor's departure?