Current Good Manufacturing Practice regulations establish the minimum requirements that must be met in the process of manufacturing, testing, packaging, storage and distribution of human medicinal products. This article focuses on GMP audits, their purpose and processes as they are implemented for manufacturers of human drug products and intermediates.
NOTE: This will focus exclusively on internal GMP audits and supplier GMP audits and will NOT address health authority inspections of manufacturing sites.
What Is A GMP Audit?
A GMP audit refers to regular visits to evaluate facilities, production and ensure that all activities are in line with current good manufacturing practices (cGMP).
GMP audits are performed by either company staff or qualified contracted auditors (e.g., Qualifyze), generally from consulting companies. Periodically verifying compliance with Good Manufacturing Practice GMP regulations and guidelines is a requirement for manufacturers of human drugs. However it’s important to note that inspections are performed by health authorities or their delegate. Audits are performed by customers or the company itself and are required under GMPs. They are different.
An audit provides an independent assessment of a firm’s compliance with Good Manufacturing Practice and relevant guidelines.
The evaluation of GMP compliance determines whether the auditee meets the applicable GMP regulations in which they manufacture and distribute product.
What Does A GMP Audit Include?
When people ask what is a GMP audit, what most want to know is what is involved with a GMP audit, and what does it include? Self-audits are generally conducted by the company itself to assess compliance with applicable GMPs. The audits are performed by qualified company staff or qualified consultants in assessments of internal company sites or vendors who provide services or materials to the company. These audits are part of the supplier and vendor qualification process, and include routine oversight on a predefined frequency.
In general terms, a GMP audit contains the following:
- Planning, programming and organization:
The planning of the audit identifies the scope and its objectives, the duration and how many auditors will be present. When it is an announced inspection, the date and time of the audit will be agreed on with the establishment.
- Execution: It consists of two stages: tour and document evaluation. The evaluation is performed based on the applicable GMPs, E.g., FDA 21CFR , PIC/S GMPs, WHO GMPS, etc.
- Closing: is scheduled between the Auditors and the representative Auditees at the end of a GMP audit. This is when a draft report of audit findings and observations are discussed and presented.
A GMP Audit checklist usually covers aspects related to:
- QUALITY SYSTEM
- PERSONNEL
- PREMISES AND EQUIPMENT, CRITICAL SYSTEMS
- DOCUMENTATION
- COMPUTERIZED SYSTEMS AND DATA INTEGRITY
- QUALIFICATION AND VALIDATION
- SANITARY OPERATIONS
- QUALITY CONTROLS
- OUTSOURCED ACTIVITIES
- COMPLAINTS, QUALITY DEFECTS AND PRODUCT RECALLS
- WAREHOUSING AND DISTRIBUTION
Each category contains requirements listed in the GMP regulation, for example, a premises and equipment audit might assess the following: Physical facility space, maintenance and repair function, utilities qualification, temperature/humidity controls, equipment qualification, cleaning validation, and other related systems.
| AUDIT CHECKLIST EXAMPLE | |||||
| No. | DESCRIPTION | YES | NO | N/A | OBSERVATIONS |
| 3.1 | Are all utensils and equipment constructed of adequately cleanable materials and suitable for their intended use? | ||||
| 3.2 | Is the equipment installed and maintained so as to facilitate the cleaning of equipment and adjacent areas? |
Hybrid GMP Audits: What Are They And Do You Need One?
GMP Audits can be:
- On-site: auditors arrive at the facility in person to conduct the tour and document evaluation. This is the most used GMP audit method.
- Remote: this type of audit is conducted using desktop auditing methods and focusing more on the documentary evaluation with tours either recorded in advance or conducted using other visual methodology.
- Hybrid: this type of audit is conducted partially onsite and partially using desktop auditing methods.
Hybrid audits are growing in popularity due to the Covid pandemic, even to the point in which regulatory agencies such as FDA and EMA, have switched to hybrid audits to help reduce on site time. However, it’s important to note that The FDA has specifically said their remote documentation reviews NOT inspections or audits.
Hybrid audits can help optimize resources particularly when travel is limited. Each site on the audit schedule should be assessed as to the type of audit that will provide adequate information to determine compliance with GMPs. It is ideal to perform on site audits for qualification of suppliers and vendors although performance may dictate that remote audits may be used occasionally for routine oversight audits of qualified suppliers.
The Importance Of cGMP Audits To Your Products
cGMP audits, or current Good Manufacturing Practises, are important to your products as health authorities expect that firms conduct self inspections in line with the requirements in EU GMP Chapter 9, which are the most up-to-date published guidelines for cGMP audits. Suppliers must keep their products and processes not just compliant, but up to date with current regulations.
Preparing For A GMP Audit
It doesn’t matter whether it is your first GMP audit or if it is your 100th, it has always been useful and important to know your weak points in advance to work on them before it is too late.
This is where a GAP analysis comes into play, a GAP analysis helps you identify your system weaknesses.
To do a GAP analysis you can use a GMP checklist, to verify your current compliance status, and then use the results of the gap analysis to recommend actions that your company should take to meet its compliance goals.
To avoid being surprised when a GMP audit arrives:
- PREPARE A GMP AUDIT SOP AND TRAIN YOUR PERSONNEL: having an established audit procedure will help you in knowing how to act and what to do when an audit arrives, it can also help you avoid mistakes or situations that could be misinterpreted as non-conformities or as lack of cooperation.
- PERFORM AUDIT MOCK-UPS: this will desensitize your personnel to the audit process, and this will help reduce any mistake that may arise due to nerves. You could also teach your personnel how to respond when an auditor asks them a question, doing this can be really helpful to avoid personnel giving incomplete information that may be interpreted as a non-conformity. All personnel must be prepared to respond naturally, with confidence.
Audit mock-ups will also help you evaluate your current compliance status.
What To Expect/Look Out For During A GMP Audit?
On announced audits, the best option to know what to expect is knowing the audit plan. Knowing the audit plan before the start of the audit will provide you some advantage as you can prepare your evidence before the time of the audit.
This may not be possible during an unannounced audit, for unannounced audits take into special consideration the following, as these may be the focus of the audit:
- Any past warning letters
- Any past non-conformity or audit observation, and ensure that documented evidence of their correction is available.
- Your current deviations, CAPAs, complaints and product recalls
- Any change in your facilities, equipment, processes and products
- Any new product, process, equipment or facility
- Lot history for those made since the last audit
During an audit you can expect the auditors or inspectors to request your written procedures and records, to verify compliance of the records to the SOP described process and to the regulations, you can also expect to have situations where you don’t agree with an observation or non-conformity, once the auditor is ready to notify what the non-conformities are, you can tell the auditor/inspector why you do not agree with any point and present data to support your position. Remember to be polite, as good communication is key to clear up any doubts or misinterpretations. Learn more about how we qualify our auditors at Qualifyze here.
Good Manufacturing Practises (GMP) Auditing Solutions
Having a GMP audit on the front door can be nerve-racking, but fear not, here you can find 5 tips to pass your audit with flying colors:
- KNOW YOUR WEAKNESSES:
Doing regular self-assessments and knowing your weaknesses, will help you identify compliance gaps more easily, this will allow you to close those gaps before they become a regulatory issue.
- KNOW THE INTENTION OF THE AUDIT:
When it comes to audits, failing to prepare will cause you several troubles. Take time to know and understand what will be required of you to demonstrate compliance, to do this you can use inspection guides or review past audits, make sure that any documents you may need during the audit are correct and easily accessible.
As a general rule of thumb, during an audit, it’s best to meet the inspector at arrival and discuss the agenda for the day.
- PREPARE YOUR EVIDENCE:
It’s critical that you have records of all the things that may demonstrate compliance to the GMP regulation, remember that your records must be in compliance with the ALCOA+ principles and be traceable.
- TAKE NOTES:
Taking notes of the auditor’s comments is a sign of interest towards his/her input , possible observations or non-conformities that may exist. Taking notes can also be helpful when it comes to raising further questions and disagreements.
- BE TRANSPARENT AND HONEST WITH THE AUDITORS:
In most cases, auditors already know the difficulties that arise in the day-to-day operations of GMP facilities; therefore, they have an advantage when it comes to detecting any type of excuse or explanation aimed at not presenting evidence.
Stalling or hiding evidence will act against your favor, therefore, it is best to say you don’t have a record or process and receive an observation than trying to cover up the situation, as telling the truth will show your willingness to cooperate and do reparations. In fact, communication of false information to the FDA is a crime.
Finally, the real key to passing an audit is to simply be prepared as if your company could be inspected at any moment. A mock inspection carried out in advance by experienced auditors will help you be prepared for any announced or unannounced audit, while helping you identify compliance gaps you may have missed during your self-evaluations.
How Does Reliable Third-Party Auditing Improve The Quality Of Your GMP?
Ensure that you employ a third-party auditing provider with expertise and experience in relevant GMP regulations and type of manufacture and testing being performed.
A comprehensive GMP audit is seen as more than just an on-site inspection. Normally we tend to become so accustomed to our environment and way of doing things, that we overlook when something is not going right, having an experienced third-party GMP auditor team performing your GMP evaluation will provide you with an opportunity to collect valuable data, identify overlooked issues, establish workable solutions to daily challenges, and develop better training programs where needed.
FAQs
A Good Manufacturing Practices (GMP) checklist is a tool that aids in the evaluation of the compliance of GMP regulation requirements. It helps ensure that nothing is missed when reviewing the processes in order to confirm the requirements are being met. A checklist serves only to jog an auditors memory and make sure topics are not missed.
A GMP audit duration may vary depending on the size of the company, the processes to be audited, the scope of the audit and the specific agreements within the QUality Agreement if auditing a supplier outside of company owned and operated sites. . Normally these may take from 2 to 5 days, for audits of CDMO sites, and 1-2 days for audits of contract laboratories or suppliers of components and raw materials.
A comprehensible audit checklist should be a list of every aspect and sub-aspect that is required by the client or customer commissioning the audit. The audit checklist depends heavily on the product being audited and the type of facility.
The best way to prepare for a GMP audit is to perform mock up audits at your own facilities, as these will help you identify any potential issues when the time for the audit arrives.
A GMP inspection is a regulatory process that seeks to prove that a GMP facility complies with the GMP regulations requirements, in order to assure its products are safe. It’s important to note that GMP inspections are only conducted by health authorities, whereas GMP audits are conducted by customers and clients of suppliers. A GMP inspection and a GMP audit are not the same.
A GMP compliance audit is a comprehensive review of an organization’s adherence to Good Manufacturing Practice regulatory guidelines. A compliance audit is simply another way to refer to an audit.
Identify the lead GMP auditor with the specific expertise required for your audit. Then plan and schedule your audit – Identify specific risks and evaluation criteria. Perform the audit including confirming that corrective actions promised at the prior audit were completed, or observations identified. Conduct daily closeout meetings to communicate potential observations. Then write and communicate the audit report including observations and recommendations, and as a final step, evaluate the auditee response to the audit report to determine if it is acceptable to correct the observations and prevent their recurrence.
A GMP audit refers to regular visits to evaluate facilities, production and ensure that all activities are in line with current good manufacturing practices (cGMP).