Goals:
When you have completed this module, you should be able to:
a. Apply the auditing techniques referenced in this unit to an actual audit.
b. Understand the reasons for using these techniques.
c. Understand and use the auditing components while performing a GMP Audit.
d. Use a range of information tools in support of a GMP Audit.
e. Develop and communicate a complete audit agenda (may also be referred to as audit plan) both to audit team members and the firm/area being audited.
f. Effectively execute an audit agenda.
g. Use generally accepted auditing techniques to conduct the audit.
h. Document and communicate audit findings in a clear, concise report that includes examples of identified deficiencies.
Definitions
Cs”: A list of observations, based on the GMP regulations, generated by the FDA during a plant inspection and given to management at the closing meeting. The observations are known as Cs” because the form that is used to record the observations is Form Number 483.
Auditee: The firm that is being audited.
Close out meeting/exit meeting/closing meeting: The last formal meeting held between the auditee and the auditor(s) before the auditors leave the firm.
Contractor/Contract Operations: Provides a product/service to sponsoring organization (i.e. laboratory testing, producing an intermediate product and producing a finished product) that it cannot provide to other companies (e.g. making/packing products on which a firm owns the intellectual property).
Contributory raw materials: A raw material used in the production of an API that contributes to the final molecular structure of an API.
Due diligence audits: Audits performed to evaluate if an external organization identified for in-licensing, acquisition, or collaboration is fit for purpose.
Freedom of information documents (FOI): Documents that you, as a citizen, can access from the FDA website. Included are warning letters issued by the FDA. This can provide you with information about current audit areas the FDA is interested in.
Open ended question: A question in which respondents are free to reply in their own words rather than being limited to choosing from among a set of alternatives.
Example: How do you check in material coming into the plant site?
An open-ended question is usually followed by a probing question to clarify or amplify information.
Interview: Dialogue or conversation that occurs during the normal course of an audit.
Opening meeting: A meeting held between the auditee and auditors before the audit officially starts.
Pre-PAI audits/Mock-PAI: An audit performed by QA to determine if a site is prepared for a regulatory Pre Approval Inspection (PAI). This audit usually takes place prior to the submission of a regulatory filing.
Probing Question: A question used to clarify answers or discover more in-depth information. It is usually specific, focused and used after a general question has been asked.
Example: You mentioned that you documented the arrival of raw materials, what do you record on that documentation?
Supplier: An umbrella term that covers both Vendors and Contractors supplying API, intermediates, raw materials, packaging components, excipients, formulated products, packaged products and/or providing services, e.g. calibration, validation, laboratory testing etc. to the sponsoring firm.
Vendor: Provider of API, raw material, excipients and packaging components to sponsoring firm. A vendor supplies articles of commerce (i.e. available for purchase by other companies).
Warning Letter: A letter sent by the Food and Drug Administration (FDA) to management of a company indicating that GMP violations were found in a recent inspection and what the violations were. The expectation is that the company will respond within a designated time period with an acceptable corrective action plan.
Explanation of Topic
Introduction
This unit will outline the steps to follow and important factors involved in performing a quality assurance audit. This unit will not only focus on the actual audit process but also the techniques and skills the auditor should have to conduct a GMP audit and key elements of auditing an audit function.
Auditing essentials can be categorized into the following broad topics:
a. The who, what, where, when and why of a compliance audit
b. The Auditor’s Role
c. The Audit Process
The following sections will provide more detailed information on these categories.
The who, what, where, when and why of a GMP Compliance Audit
Who should be audited?
Suppliers (external) and manufacturing sites (internal) should be audited for compliance with GMPs, registered requirements and industry standards. This includes suppliers of the following:
a. Sterile APIs
b. Non Sterile APIs
c. Sterile Product
d. Non Sterile Product
e. Key intermediates
f. Excipients
g. Packaging components (product contact and non-product contact as required)
h. Contributory and Non-Contributory raw materials
i. Biologicals
j. Contractors
k. Critical Services Provider
l. GMP Critical Consumables
Suppliers are audited to monitor compliance/quality assurance with GMP regulations and company requirements, evaluate a potential new source or vendor, evaluate key vendor/contractor changes or investigate a specific problem being experienced by the firm (for cause).
Internal audits of a site is conducted by QA. These audits determine the level of quality and compliance of a particular operation. By conducting these audits, management, both site and quality, can be provided with an unbiased status report of Site’s Operations.
Company internal audits should be performed following a site’s audit program. The quality system should be audited at least on an annual basis.
Who is responsible for auditing?
Both the own firm and supplier audits are performed by members of site QA.
When does QA perform audits?
The site QA management should create specific audit frequency at the planning stage.
Procedures should be in place which define frequencies and timeframes for the performance of routine GMP audits of the site, external vendors and contract operations. (Pre-PAI audit timeframes are defined based on the target filing date). For cause audits are performed upon request in response to compliance issues. Due diligence audits are performed upon request.
In some cases it may be acceptable to perform a Vendor Quality Review (VQR) or Postal Review, in lieu of an on-site audit. A VQR is a documented review of a vendor’s quality performance and should include a recently completed questionnaire as well as a report on the vendor’s quality history (prior audit issues, rejections, deviations, etc.). QA audits must be performed on a regular basis to ensure systems are in control and in compliance.
“QA audits must be performed on a regular basis to ensure systems are in control and in compliance.”
Why perform quality assurance audits?
Performing quality audits of products, processes and systems is important to ensure that a manufacturing site and its suppliers are reviewed for compliance to current FDA Good Manufacturing Practices (GMPs), ICH Guidances, other market regulations, company Quality
Guidelines and Procedures:
A GMP audit is an evaluation tool that can:
a. Verify if company policies and procedures are being followed.
b. Assess sites’ GMP practices.
c. Verify that required systems and controls are in place and in compliance with GMP regulations.
Specific goals of GMP audits are to:
Determine whether QA, production activities and systems comply with GMPs, regulatory agency requirements and site requirements.
a. Facilitate early detection of problems.
b. Help determine the depth of the identified problem in the area as well as across the company.
c. Investigate and determine the root cause of the problem/deficiency.
d. Assure compliance with regulatory agencies’ requirements.
e. Provide management with information regarding the level of compliance at the site and suppliers.
f. Recommend approval and certification of a supplier.
Each audit that is conducted must be based on facts. Auditors are fact finders! All audit observations must be able to reference the GMPs and current industry standards. An audit should be balanced and include good practices as well as deviations. If deviations are found, they must be reported. An audit is a tool to improve site operations or supplier operations to assure that company products are of the acceptable quality, effectiveness and purity.
Long term and tangible benefits of an audit include:
a. Identifying, eliminating and preventing problems early in the design and life of a process or system through pro-action.
b. Decreasing the number of discarded, recalled and reworked lots.
c. Decreasing the number of consumer complaints.
d . Continually improving GMP systems and potentially transferring best practices across the corporation.
e. Providing management with objective feedback based on facts that can help to identify critical liabilities that require capital and personnel resources (risk assessment).
f. Ensuring company customers receive products of acceptable quality, efficacy, and safety.
Remember that the auditee is the primary beneficiary of the audit!
The Auditor’s Role
There are two necessary components for an audit to be successful. The first is an auditor with the right skills, education and experience. The second is the audit process itself.
The auditor is a key component of the audit. To increase the effectiveness of the audit, the auditor must have good auditing practices and techniques that will:
a. Allow the auditor to easily access information about the process, facility or product being audited.
b. Build a respectful relationship with the auditee.
c. Quickly determine the necessary information to conduct an efficient audit.
You, as an auditor, must be aware of the auditee’s emotions and state of mind. One of your goals is to try to reduce the stress level surrounding an audit. Some ways to reduce the stress level are to:
a. Stand in a relaxed position with open hands.
b. Explain what you are doing when you are doing it.
c. Remain calm even when the auditee responds with defensive or derogatory remarks or argumentative behavior.
d. Maintain your normal voice volume. Do not increase it even if the auditee increases theirs.
e. Politely be persistent if the auditee responds with vague answers.
It is important to learn how to successfully deal with stressful situations early in your auditing career. Do not be afraid to investigate provided statements/information to obtain factual answers to your questions. You need to remain objective and professional, but you need to obtain information to determine if a site, operation or practice is compliant. Observing experienced auditors dealing successfully with audit situations is a valuable learning tool.
Before the audit:
You should prepare yourself by “doing your homework”. Successful audits require at technical understanding of the processes involved. This may require prior research, experience or training regarding the areas to be audited. Reviewing flowcharts and consulting with engineers or chemists may increase your technical knowledge.
Using flow charts provided by the auditee is a good way to understand the processes in the auditee’s plant. After previewing the flowcharts you should think about which specific areas of the processes diagrammed on the flowchart have the greatest impact on product quality and/or offer the greatest risk to public health. A risk assessment regarding a process should be made to identify critical points to be covered during the audit.
During the audit:
During the audit, the auditor needs to effectively use the five important skills shown.
Discussions with site personnel are excellent ways to determine potential problems. These may occur during the site’s response to your questions, during the walk through or during documentation reviews. Your interviewing technique is very important. Be polite and do not use a tone that may be perceived as accusatory or confrontational. The following interview techniques can help make your audit more successful.
Interviewing/Questioning:
Introduce yourself to the interviewee.
Ø Be polite, patient, professional, ALWAYS.
Ø Do not exhibit a confrontational attitude.
Ø Don’t become emotional and remain objective.
Ø When asking for information, phrase your question to assure that you are NOT providing the answer.
Ø Don’t ask yes/no questions.
Ø Start with overview questions and open-ended questions.
Ø If you receive answers that fully explain or provide the information you need, stop there.
Ø If you do not receive the information needed, start using probing questions. If probing questions are used, be attentive and encourage further explanation by interjecting response phrases like “I see” from time to time. When appropriate ask to see examples of information provided.
Ø Use your body language to encourage further discussion.
Ø Ask direct questions and if a general answer is given, then request an example or documentation to support the response.
Ø Determine the employee’s function; ask for the pertinent procedures, forms, and data relevant to the task. Confirm your understanding of the task by asking questions.
Ø If you do not believe that you are receiving accurate information, ask confirmatory questions by asking the same question to a different interviewee or ask a different or re-phased question on the same subject to the same interviewee.
Ø Do not criticize an individual’s performance even if you believe that it is not satisfactory. Determine if their performance is a result of their training and/ or procedures they use, or lack of management involvement.
Ø At the completion of the interview always thank the person for their time.
Listening technique
Another key skill that you need is a good listening technique. Unfortunately, most people plan what they are going to say instead of listen to what the other person is saying. You can miss many pieces of information during an audit if you are not prepared to listen and give the auditee their time to talk.
In the following section of the text are some techniques to help increase your listening skills.
Since you will be receiving information verbally, it is important that you confirm the information collected during your interviews with documentation or field verification (observations).
Ø Listen—often people will be happy to provide more information than you originally requested—you just have to give them a chance!
Ø Give the interviewee time to respond. Keep silent. Many times people will attempt to fill awkward silence with more details.
Ø Practice “active listening”. Ask questions at appropriate times or indicate that you are listening by interjecting, at appropriate times, small comments like “ I see”.
Ø Do not let your opinions or expectations influence what you hear!
Ø Listen carefully. Is the interviewee responding to your question or “talking around it”? If they are talking around it, be persistent and phrase it in a different way.
Ø If you are using or interviewing someone who uses English as a second language, make sure you understand each other.
Looking/observing
All audits should include a walk through of the facility and laboratory. During the walk
through you should observe the process and compare it against information that you have
been given to see if there is alignment. This is called field verification.
Some suggestions for increasing your effectiveness are shown in the following text.
Ø Observe everything: the plant, including floors, ceiling, entrances and exits, process, people and equipment.
Ø Try to get as near as possible to a process.
Ø Look for big pictures as well as the smallest details.
Ø During the interview, observe interviewees’ body language. Do they appear to be nervous? Do they avoid looking at you directly? Are they unable to “stand still”? When interviewing operators do they avoid eye contact? Appear to be deferring to their management by providing response to you but making eye contact with their supervisor?
Once you have listened and processed the information, it should be recorded for later reference. If anything was observed that is a cause for concern, raise this with the auditee at the time it is noticed to confirm that a real issue exists and to gather any additional relevant information.
Recording Information
During the audit, you will need to record many different types of information. Some will be responses to questions you ask in interviews, some will be observations that you see, some will be notes about some of the documents you review. Whatever type of information that you are recording, the following text offers some suggestions.
Ø Date your records. This helps you when you review them.
Ø In an interview, record the title of the person and their name. If you are unsure of the spelling ask them to spell it for you or ask the auditee escort to provide the correct name to you.
Ø If you have preparatory audit notes that you are using, leave some room between each of the points to record the information there.
Ø Do not leave your notes unattended. If an auditee sees them, they may make assumptions and conclusions that are not accurate.
Ø If you are reviewing written information, record the title of the document, document identification number and version, the date that it was approved or the date associated with the document.
Ø If the person whom you are speaking to is talking too fast, ask them to repeat their information since you want to accurately record what they say.
Ø Document items reviewed during the audit and include areas toured and SOPs, documents and protocols reviewed.
Ø Record items that you heard or observed so you can investigate them further.
These are some suggestions but you may have others that may also contribute to a successful audit.
Analyzing information and data
Within a short period of time, (e.g. a day or a few days) you will be reviewing many kinds of information, from verbal responses to written documents. You will need to analyze the information and determine what should be communicated verbally in the exit meeting and what should be included in the report that will be given to the auditee and management after the audit is finished.
Ø Use your judgment on what to report. Report deviations from GMPs and local procedures. Identify systematic problems, providing examples.
Ø Identify trends of non-compliance.
Ø Remain objective.
Ø Evaluate the seriousness of each observation.
Ø Determine whether the evidence points to a deficiency that will cause a regulatory action, jeopardize the quality of the product, or whether the observation should be classified as a “recommendation,” not representing a deviation from GMP.
Ø If you have questions about some information and have questions about its classification, contact your QA management.
Ø Remember to use standards. Using standards as reference produces effective, efficient, and objective audits.
Auditors must be knowledgeable about requirements, technical processes, and trained in auditing techniques to be effective.
In summary the auditor should demonstrate the 5 “Ps.”
a. Polite
b. Prepared
c. Professional
d. Patient
e. Persistent
The Audit Process
The audit process may begin many months before the actual audit is conducted. The framework for the audit process is shown below:
Ø Audit preparation
o Determine who will conduct the audit – an individual/team.
o Develop the audit agenda.
o Confirm audit and agree on a date with supplier/area to be audited.
o Gather information, which could include a supplier questionnaire.
o Review documents received from the firm.
o Prepare audit notes.
Ø Potential On-site Audit Activities
o Conduct opening meeting.
o Walk through warehouses, manufacturing facilities and laboratories as
appropriate.
Interview analysts and operators as appropriate.
o Hold daily briefing meetings with both auditor and auditee, if appropriate.
o Hold daily audit team meetings, if audit team approach is used.
o Review auditee’s documentation.
o Conduct closing meeting.
Ø Follow-up Audit Activities
o Document observations in a formal report.
o Evaluate responses received from the firm/site ensuring responses include effective follow up actions.
o Ensure these actions are closed or effective closure plans are in place.
o Close the audit.
Audit Preparation
Determine who will conduct the audit:
An audit can be conducted by a single auditor or an audit team. If you will be conducting the audit by yourself, you will need to
Ø Be prepared.
Ø Dress appropriately.
Ø Respond to auditee escort requirements.
If you are part of an audit team, you will need to:
Ø Attend a preparation meeting to discuss roles, responsibilities, strategies and logistics to be used during the audit.
Ø Meet with your team members at the end of each day to discuss the audit and any issues that may have appeared.
Ø Provide your observations, in written form, to the lead auditor.
The lead auditor will be responsible for ensuring the audit is managed effectively and efficiently. The lead auditor typically organizes the audit team, plans the audit, communicates with the auditee, prepares the agenda, conducts the audit opening and closing meetings, and coordinates and writes the audit reports. The lead auditor also reviews the auditee’s response and formally closes the audit process.
Pre-audit Information Request Form:
A pre-audit information request form is sent to the area managers of the site being audited.
Pre-audit Supplier Questionnaire:
A supplier questionnaire is often sent to suppliers prior to the audit. The questionnaire should be evaluated before the agenda is finalized.
Develop an audit agenda:
To conduct an efficient and effective audit, you should have an agenda. This will help to keep the audit flowing smoothly and will make good use of both your and the auditee’s time.
The audit agenda may include:
1) Identification of the auditee contact person(s)
2) Information on when the auditee was contacted.
3) Identification of audit team members (if appropriate).
4) The purpose and scope of the audit. Internal audits and for cause audits may be limited in scope.
5) The standards that the auditee’s is expected to meet.
6) What technical information should be reviewed to understand the process.
7) documents to be reviewed during the audit.
The purpose of the audit should be clear to both you and the auditee. By defining the purpose, it will help to keep the process focused on a common goal and to increase audit effectiveness. You should always ask yourself “Why is this audit to occur?” By answering the why, it helps to focus all parties involved on the purpose of the audit.
Since you will be performing a GMP audit, you should consider the GMP areas below:
Ø Quality System
Ø Material Handling System
Ø Laboratory Control System
Ø Production System
Ø Facilities and Equipment System
Ø Packaging and Labelling Systems
During the audit, you should plan to pay particular attention to the Quality System. The manner in which a firm handles deviation, complaints and out of specification test results will provide insight to the company’s Quality Culture and adherence to GMPs.
Notify supplier/area to be audited about upcoming audit:
Work with the auditee to determine a time that will fit within your time frame and will be convenient to the auditee. Once a date is agreed upon, notify the auditee in writing with your requirements for the audit and request appropriate documents. Include the purpose summary in the notification to the auditee as well as in the final report.
Review documents:
The following documents and information should be reviewed prior to performing the audit.
Regulatory Documents:
Ø Regulatory Agency Regulations, guidance documents and guidelines
Ø Recent regulatory information which may include: FOI documents, regulatory
issues about the process to be audited, recent 483’s either concerning the auditee
or auditee’s process, and Warning Letter citations
Ø Appropriate regulatory agency compliance programs related to the pharmaceutical
technology/area to be audited
Company Documents
Ø Contracts, including Quality Agreements
Ø Relevant supplier and product changes
Ø Previous QA audit reports, investigations, etc.
Ø Quality standards/specifications for components/products including regulatory
filings
Ø Company guidelines and procedures
a. Relevant QA Auditor training modules
b. Examples of Certificate of Analysis, complaints/atypical reports associated with supplier and a list of lots, including those rejected provided by end user manufacturing site(s) if auditing suppliers
Ø A copy of the draft filing and quality standard, if applicable, before conducting a PAI audit internally
Documents from Auditee:
Ø Organizational Charts
Ø Relevant Standard Operating Procedures
Ø Flowcharts of processes to be audited
Ø Pre Audit Supplier Questionnaires
Preparation of audit notes:
After reviewing the background information and reference documents and standards regarding the auditee, prepare notes to assist you in the performance of the audit.
These notes may include:
GMP Systems and processes to be included during the audit, with the Quality System being mandatory.
a. Known deviations, complaints to be reviewed during the audit.
b. FOI documents such as Warning Letters, FDA 483s and Establishment Inspection Reports.
A list of documents to review during the audit. The list may be kept by the auditor or given to the auditee during the start-up meeting in order to speed the audit process.
If you are working with a team, the lead auditor will coordinate this function and divide audit duties amongst the team.
On-site Audit Activities
All audits should be conducted in an open manner. You should discuss findings and expectations with the auditee while conducting the audit. The audit is an opportunity for the site or supplier to be made aware of current compliance issues and areas of improvement.
As you begin the audit it is essential to remember that the job of the auditor is to gather facts, compare these facts to requirements or standards, perform analysis and report the results to management.
Some general guidelines for conducting an audit are to always:
Ø Meet and communicate with the auditee.
Ø Understand the process and system controls.
Ø Verify that these controls work.
Ø Communicate among audit team members.
Ø Evaluate the audited site’s state of cleanliness, maintenance and suitability for its intended purpose.
Ø Discuss potential observations and concerns with the auditee.
Opening Meeting
Upon arrival at the site, the auditor/audit team should conduct an opening meeting with the site Quality Assurance/Quality Operations, manufacturing management, senior Plant Manager or designee and other auditee representatives as appropriate. The meeting should be efficient and thorough.
The meeting agenda may include:
Ø Introductions of both the auditors (including backgrounds and credentials) and the auditee representatives.
Ø A review of the complete audit agenda and schedule and a review of the supplier questionnaire if applicable.
Ø A review of the audit purpose and scope.
Ø A list of audit activities and auditors assigned to each activity.
Ø Projected times for the beginning and end of daily activities.
Ø Projected times for daily meetings with the auditee, as appropriate.
Ø Auditee information about plant logistics and safety rules as well as other critical administrative issues.
Ø An explanation of how the audit will be conducted.
Ø An explanation of how observations will be communicated during and after the audit.
Ø Projected times for the closing meeting and requested attendees.
Ø Projected times for auditor daily briefing meetings.
During the opening meeting, ensure that the auditee understands their role in the audit. The auditee management should:
Ø Cooperate and assist the audit team.
Ø Provide support to ensure a successful audit.
Ø Review findings.
The opening meeting is an opportunity to gather data and impressions about the supplier or area being audited.
Walk-through
Audits may begin with a “walk through” of the facility and laboratory. This is generally done at the beginning of the audit and should include a review of available records in the processing/laboratory areas. Walk throughs/ tours should be conducted throughout the audit as appropriate.
During the walk through, it is recommended that you “follow a product” beginning with the receipt of raw materials and ending with the release of the finished product. It is expected that the audit program should reflect the process followed by regulatory agency investigators.
Before beginning the walk through, you should obtain a flowchart showing the manufacturing process to be audited. You should observe the:
Ø Appropriateness of the facility design for the ongoing operation.
Ø The level of cleanliness of the facility/laboratory.
Ø The state of repair and maintenance of the facility and equipment (physical appearance).
Ø The demeanor and appearance of personnel.
Ø Personnel and material flow throughout the facility and laboratory.
Ø Documentation practices within a process.
Ø Facility controls, such as calibration, maintenance, validation, temperature/RH control and measurement, as applicable.
During the walk through, verify that procedures are being followed.
You should determine if the documentation is compliant. This would include observing a manufacturing process and completion of concurrent batch record, equipment use and cleaning logs, identification and calibration status of equipment and environmental monitoring, as appropriate. During the walk through, you should verify that SOPs are accessible to operators. You should also ask to see process or operating documents (i.e. in- process batch records/laboratory notebooks) to see what their normal documentation practices are. You should also review records for accuracy and completeness.
The reasons for conducting a walk through are to:
Ø Identify both deficiencies and good compliance practices.
Ø Confirm documentation deficiencies.
Ø Verify corrective actions to previous audit findings or deviations.
Ø Verify information obtained during interviews.
As you perform the audit refer to your preparatory audit notes to assure complete audit coverage. Please refer to specific training modules for items to be reviewed/observed during the field verifications. Auditors should inform the auditee staff of observations at the time that they are observed. Auditee staff may provide information that will explain the observation or assign site resources to correct the observations or non-conformances.
Immediate communication may prevent misunderstandings.
If critical issues or deviations are observed they should be immediately communicated to site’s management and the auditor’s manager or director. This assures that appropriate personnel are notified and appropriate corrective actions are implemented.
Daily briefing meetings with auditee:
At the daily briefing meeting, observations and findings should be reviewed with the auditee as well as areas of concern to ensure that there are no surprises or misunderstandings at the closing meeting. Potential observations should be communicated to maintain openness and give the auditee an opportunity to provide additional information. If there are deficiencies that are discovered, they should also be communicated to the auditee and their staff, including members of QA.
The audit agenda should be updated if changes are required based on observations or resources.
Daily briefing meetings for audit team:
These meetings are held to keep the team focused on the audit objective and the audit on course. This is when discussions should be held to update team members on the status of the audit and clarify any observations. The following should be considered when scheduling these meetings:
Ø They are generally held at the end of the day, as necessary, while everyone still is focused on the observations for that day without the auditee being present.
Ø They should be used to make schedule and/or team assignment changes.
Ø Any observations and findings should be reviewed to gain team consensus.
Ø Complex issues can be discussed and examined by all of the team.
Review Documentation:
Your review may include SOPs, manufacturing and testing documentation, associated raw data, validation and qualification protocols and reports and investigations. It is important to spend time reviewing procedures for deviations, complaints and out-of-specification testing results since this may also help you to determine the company’s commitment to quality.
Closing meeting:
The closing meeting is the forum used to present the audit results verbally to the auditee management. It is essential that all key parties who participated in the audit and the auditee management attend the closing meeting.
The following are some guidelines for the closing meeting.
Ø Be prepared to discuss and clarify all findings/observations with the auditee.
Ø Be objective.
Ø Do not argue.
Ø Verbally explain each observation.
Ø Prioritize the observations in order of significance.
Ø Thank the auditee for their time and coordination function.
Ø Mention positive observations regarding auditee’s operations.
Ø Determine which auditee staff member should receive the audit report and confirm
timelines for issue of the report and response by the auditee.
Recommendations for corrective actions can be discussed at site audits. Please note the audit program should be based on not only identifying problems but also being able to assist with recommendations and provide solutions based on the regulatory compliance experience.
Follow-up Audit Activities:
Document observations in a formal report:
Observations are deviations from recognized standards supported by objective evidence.
When writing observations cite the deviation from GMPs and include specific examples found during the audit. List the examples using objective, clear and concise language. The audit observation reports are issued to the Senior Plant Manager or Quality management.
It is recommended that auditors draft audit reports as soon as possible after the audit.
Audit Observations must be classified into Critical, Major or Minor. Critical observations must be identified to site management and their corrective actions discussed.
Audit reports summarize the results of the audit activities. Information often included in the report is:
Ø Audit team members.
Ø The purpose of the audit.
Ø The areas of the auditee’s operation that were reviewed.
Ø Audit observations and rating, if applicable.
Ø Supplier certification status, if applicable.
Ø A list of systems audited and systems not audited.
Ø Systems that do not comply with GMPs.
Ø Specific areas/systems that were reviewed and were compliant with GMPs.
Ø Good practices observed at the site.
Ø Expected response date for corrective and preventive actions from auditee.
The audit report is sent to the auditee, soliciting a response. Usually the report is issued to the Senior Quality Management.
Evaluation of Responses from auditee:
Once you have issued the summary audit report citing the observations made at the audit, the auditee has a responsibility to respond to the audit within a defined time period, commonly 15 days. After those responses are received, it is necessary to analyze them and determine if the proposed timelines and corrective actions are acceptable. When the responses are deemed acceptable, a close out letter may be sent to the auditee.
Summary
The audit process must be:
Ø Objective and professional
Ø Performed against standards (GMPs, regulatory agency guidelines/company requirements)
Ø Performed by following an approved procedure
Ø Performed by qualified and properly prepared individuals
Audit observations:
Ø Must be detailed and provide an accurate view of an operation. Examples of GMP deficiencies should be provided whenever possible.
Ø May include recommendations for corrective/preventive actions to the observed deficiencies.
Auditing the Audit System
Found on the next page are key parameters for auditing an auditing system.
Key Parameters for Auditing an Auditing Program
Ensure that the Quality System is in place and has established procedures and functions for auditing.
Ø Verify that the site has a procedure that establishes a GMP (Compliance) Committee or equivalent, chaired by a Quality Manager.
Ø Determine if there is a compliance improvement plan.
Ø Verify that there is a training plan for audit staff that provides ongoing and adequate training. The training should include, as applicable:
o Company guidelines and procedures (if an internal site)
o GMP regulations
o FDA Guidelines & Inspection Guides
o EMEA guidelines
o PIC guidelines
o Additional standards, Supplier Auditing,
o current auditing techniques
a. Verify that the auditee has SOPs
b. Ensure that these procedures are being followed. Verify that the site has identified the root causes, if known, of the audit observations and has targeted completion dates for the corrective actions.
Ø Ensure that the status of the corrective actions is monitored.
Ø Identify what type of tracking system is used to follow up on audit findings. If it is electronic, verify that it is validated.
Ø Verify that an annual audit schedule has been established to assure audits of all the GMP systems during the year.
Ø Verify that all Quality Assurance audit reports including Due Diligence reports are labeled as Confidential.
Ø Verify that audit reports are filed in a secure location.
Ø Check annual audit agendas and audit follow-up.