Effective Auditing for Manufacturing Quality

Introduction

The speaker introduces herself and the topic of the webinar, and explains how participants can ask questions during the presentation.

• Participants can ask questions at any time during the presentation by typing them in the provided area.

• The speakers for today's webinar are introduced, including their experience in quality assurance and regulatory compliance.

• The topics that will be covered during the webinar are briefly outlined.

Auditing for Manufacturing Quality

The speakers discuss various areas to pay attention to when auditing for manufacturing quality, including data integrity, quality culture, aging facilities, investigations and deviations, and risk management.

Data Integrity

• Data integrity is defined as a critical aspect of manufacturing quality.

• Alcoa principles and alcoa plus should be considered when auditing data systems.

• Significant events related to data integrity are discussed as examples of what can go wrong without proper attention to accountability and legibility.

Quality Culture

• A strong quality culture is essential for maintaining manufacturing quality.

• Leadership plays a crucial role in establishing a positive quality culture within an organization.

Aging Facilities

• Aging facilities can present challenges to maintaining manufacturing quality.

• Regular maintenance and upgrades are necessary to ensure continued compliance with regulations.

Investigations and Deviations

• Proper investigation procedures must be followed when deviations from established processes occur.

• Root cause analysis is an important tool for identifying underlying issues that contribute to deviations.

Risk Management

• Risk management strategies should be implemented throughout all stages of manufacturing processes.

• Effective risk management requires ongoing evaluation and adjustment based on changing circumstances.

Introduction to Quality Culture and Manufacturing

This section introduces the importance of quality culture in manufacturing and how it relates to data integrity.

Importance of Data Security

• Integrity guidance emphasizes the importance of keeping computer systems secure.

• Warning letters from FDA cite shared passwords and lack of secure login requirements as potential issues that can lead to data manipulation accusations.

Quality Culture

• Quality culture refers to how a company treats its data, information, and employees.

• It is important for companies to encourage a "speak up" culture among employees during audits.

• Signs of a bad quality culture include unprofessional behavior during audits.

Measuring Quality Culture

• Quality attributes such as deviations reporting, change control, and kappa systems are tangible measures of quality culture.

• A quality culture is a scale with varying levels of maturity.

Facility Maintenance

• Drug shortages have been tied to quality metrics, which require facilities to be properly maintained.

Key Elements in Manufacturing Quality Control

This section discusses key elements in manufacturing quality control.

Process Validation

• Process validation ensures that products consistently meet specifications.

• The three stages of process validation are: process design, process qualification, and continued process verification.

Risk Management

• Risk management involves identifying potential risks in the manufacturing process and taking steps to mitigate them.

• Failure mode effects analysis (FMEA), hazard analysis critical control points (HACCP), and fault tree analysis (FTA) are common risk management tools.

Change Control

• Change control is the process of managing changes to a product or process.

• It involves assessing the impact of changes, documenting them, and obtaining approval before implementing them.

Training

• Proper training is essential for ensuring that employees understand their roles and responsibilities in the manufacturing process.

• Training should be ongoing and include regular assessments to ensure comprehension.

Conclusion

This section summarizes the importance of quality culture and key elements in manufacturing quality control.

• Quality culture is important for maintaining data integrity and ensuring a successful audit.

• Key elements in manufacturing quality control include process validation, risk management, change control, and training.

Aging Facilities and Drug Shortages

This section discusses the impact of aging facilities on drug shortages and data integrity issues.

Causes of Drug Shortages

• Many facilities are aging and need to be updated.

• Manufacturing daily, 24/7 makes it hard to update facilities.

• Aging facilities contribute to drug shortages and data integrity issues.

Modernizing Facilities

• Recognizing signs of an aging facility: increased waste, deviations, lower yield.

• Filing with the FDA is required when modernizing a facility.

• Contract manufacturers face challenges in shutting down busy lines for modernization.

• Regulatory expectations around updating facilities can help slow the aging process.

Investigations and Deviations

This section emphasizes the importance of investigations and deviations in maintaining manufacturing quality.

Investigating Deviations

• Investigations, deviations, complaints all feed into the health of an organization and manufacturing quality.

• Regulations require thorough investigation of deviations to find root causes.

• Resources such as ICH Q10 and ISO provide information on performing investigations.

Kappa Process

• The Kappa process is important for tracking and tracing issues that arise from audits or other sources.

• Everything funnels into investigations in Kappa management.

Risk Management

This section stresses the importance of risk management plans in preventing drug shortages and ensuring high-quality products.

Risk Management Plans

• A risk management plan should be in place for supplier manufacturing troubles or going out of business.

• ICH Q9 discusses risk management in pharmaceutical quality systems.

• Critical thinking promoted by risk management is essential for auditing, deviation, or investigation jobs.

Introduction to Manufacturing Quality

The speaker discusses the importance of manufacturing quality and highlights key areas to focus on during audits.

Key Areas for Auditing Manufacturing Quality

• Quality risk management plans, investigations, facility maintenance, data integrity issues, and risk management programs are important areas to focus on during audits.

• It is important to look at these areas holistically in order to get a comprehensive picture of an organization's manufacturing quality.

• The speaker emphasizes that auditing is inevitable in the pharmaceutical industry and encourages listeners to prepare by focusing on key areas.

Importance of Investigating Deviations

The speaker shares a story about investigating deviations and highlights the importance of looking beyond human error when identifying root causes.

Investigating Deviations

• The speaker discovered a repeat deviation caused by an operator who kept forgetting to sign a batch record in the correct spot.

• After interviewing the operator, it was revealed that the batch record was poorly designed and inconvenient for signing at that point.

• The speaker emphasizes the importance of investigating deviations thoroughly and not just attributing them to human error.

Discussion on Human Error and Metrics Tracking

The speakers discuss human error and metrics tracking in relation to manufacturing quality.

Human Error

• The speakers discuss how often deviations are attributed solely to human error without further investigation into root causes.

• They emphasize the importance of looking beyond human error when identifying problems with manufacturing quality.

Metrics Tracking

• One speaker suggests looking at metrics during audits to see what is being tracked and why.

• They encourage listeners to ask questions about the metrics being tracked in order to gain a better understanding of an organization's manufacturing quality.

Investigating Deviations

The speakers discuss the standard 30-day time frame for investigations and tracking deviations. They also mention the need to find the real root cause of an issue, rather than relying on human error or training as a fix.

Extensions for Investigations

• Investigations have a standard 30-day time frame.

• Deviations can be extended beyond 30 days.

• Procedures should outline how extensions are approved.

Finding the Root Cause

• Repeat issues indicate that the root cause was not found in previous investigations.

• Risk assessment is important in identifying process failures and mitigations needed.

• Use tools like five whys or fishbone diagrams to find root causes.

Assessing Product Risk

The speakers discuss assessing product risk during investigations and ensuring that all operators follow procedures correctly.

Following Procedures Correctly

• It's important to assess whether other operators followed procedures correctly during an investigation.

• All deviations must be investigated thoroughly, even if it's a big task.

• Data integrity is crucial in determining whether product was at risk.

Touching on Key Areas of Focus

The speakers reflect on how this one deviation touched on key areas of focus such as data integrity, quality culture, aging facilities, investigations, and risk management.

Key Areas of Focus

• This deviation touched on key areas of focus such as data integrity, quality culture, aging facilities, investigations, and risk management.

• The poorly designed batch record casts shadows on aging facilities.

• Data integrity is important in determining whether operators followed procedures correctly.

Mitigating Human Error

The speakers discuss how human error is often attributed to issues, but it's important to find the real root cause and mitigate it.

Mitigating Human Error

• Human error is often attributed to issues, but it's important to find the real root cause.

• Use error assessment instead of user error in medical device investigations.

Root Cause Analysis and Human Error

In this section, the speakers discuss the importance of root cause analysis in preventing problems and avoiding human error. They also talk about how regulatory inspectors view human error.

The Importance of Root Cause Analysis

• Identifying trends can lead to a kappa and prevent future problems.

• Having proper procedures in place is crucial for preventing human error.

• Root cause analysis is key to identifying the underlying issues causing problems.

Regulatory Perspective on Human Error

• Regulators view human error as an easy excuse that does not get to the root cause of the problem.

• Inspectors will dig deeper into situations where there are multiple instances of human error to ensure that it is not just being used as an excuse.

• It is important to look beyond just labeling something as "human error" and identify the true reason behind it.

Virtual Audits and Paper Reviews

In this section, the speakers discuss virtual audits and paper reviews, which have become more common due to social distancing measures during the pandemic.

Conducting Virtual Audits

• Virtual audits have become more common due to social distancing measures during the pandemic.

• Most virtual audits involve a paper review rather than an in-person inspection.

• It is important for companies to have their documentation organized and easily accessible for virtual audits.

Recommendations for Paper Reviews

• Companies should ensure that their documentation is complete, accurate, and up-to-date.

• It is important to have a system in place for managing and tracking documentation.

• Companies should be prepared to answer questions and provide additional information during virtual audits.

Virtual Audit Preparation

In this section, the speakers discuss how to prepare for a virtual audit and what information to request from the company being audited.

Requested Information

• Request SOPS, charts, quality manual ahead of the audit.

• Ensure privacy of information is kept intact due to exposure on the internet.

• Account for time differences and ensure equipment works properly.

• Have more than one person involved with the audit.

Upfront Work

• Takes more upfront work than an on-site audit.

• Think through what you're going to ask for and does the company even have it.

• Request quality metrics for past year or two to gather trends.

Key Issues

• Use deviations kappas and other metrics to focus in on key issues.

Quality for the Company

In this section, the speakers discuss quality for the company and how it relates to operations. They also explore ways to conduct a virtual tour of a manufacturing line.

Conducting a Virtual Tour

• The group discusses whether it is possible to conduct a virtual tour of a manufacturing line.

• Steve suggests using 360 cameras or plain old iPhones to conduct virtual tours.

• He also recommends testing signal strength around the facility and using signal boosters or repeaters if necessary.

• Another suggestion is to take videos ahead of time and supplement them with live tours during inspections.

• Syed adds that presentations and process flows can complement virtual tours, but technology issues must be worked out beforehand.

Implementing Quality Across an Organization

In this section, the speakers discuss how to implement quality across an organization. They talk about starting with a strategy and turning it into actual plans, setting objectives for the year, and using metrics to ensure that the plan is being implemented.

Quality Planning

• Objectives are set for the overall organization and trickled down to supervisors who ensure they are met.

• Quality planning involves implementing and assuring quality across the organization using metrics to track progress.

• A quality manual is part of quality planning but not the same as a quality plan.

Quality Plan vs Risk Management Plan

• A quality plan ensures that the health of your quality system is kept intact by addressing issues proactively.

• A risk management plan lists methods for estimating risk, decisions criteria, deliverables, and documents risk analysis. It also evaluates residual risk and selects appropriate controls.

Relationship Between Quality Plan and Risk Management Plan

In this section, the speakers discuss how a quality plan relates to a risk management plan. They talk about how both plans involve assessing risks but have different approaches.

Risk Management Plan

• The risk management file has a risk management plan that lists methods for estimating risks and decision criteria.

• The preliminary hazards analysis looks at intended use, claims, failure scenarios, impact assessment, etc.

• Criteria are established for when you require risk controls. Residual risks are evaluated based on acceptability criteria.

Relationship between Plans

• Both plans assess risks but have different approaches. Quality planning is about ensuring the health of your quality system, while risk management planning is about assessing risks and selecting appropriate controls.

Risk Management and Quality Culture

In this section, the speakers discuss risk management plans and quality culture in manufacturing. They provide insights on how to manage risks, assess them, and mitigate them. They also talk about how to determine the health of quality culture in an organization during virtual audits.

Risk Management Plan

• The risk-benefit analysis should be used to determine if the technology available is worth using.

• A risk management plan should be created to address any potential risks.

• To manage risks, it's important to assess them and then mitigate them through a deliberative process.

• A cross-functional team may be needed to look at various risks around a process.

Quality Culture

• It can be harder to assess quality culture virtually than on-site during an audit.

• When looking at investigations, it's important to assess how thoroughly they were tackled by going deep and wide instead of just focusing on what's in front of you.

• Thorough and substantive corrective action is necessary for thorough investigations that don't just focus on one issue but consider all possible issues.

Determining the Health of a Quality Culture

In this section, the speakers discuss how to determine the health of a quality culture virtually. They emphasize that top management commitment and employee engagement are crucial factors in assessing quality culture.

Factors to Consider

• Top management commitment is essential for a healthy quality culture.

• Employee engagement is also critical for a healthy quality culture.

• Processes must be ingrained into the concept of quality culture.

• Critical thinking should be used to solve problems during investigations or risk-based approaches.

Assessing Quality Culture Virtually

The speakers discuss practical ways to assess an organization's quality culture virtually. They suggest interviewing people, looking at their procedures, and judging if they are using critical thinking to solve problems.

Practical Ways to Assess Quality Culture Virtually

• Interview people and talk to them about their procedures.

• Judge if employees are parroting rehearsed answers or providing genuine responses.

• Determine if employees are afraid to bring up issues or problems.

Training for Effective Virtual Audits

The speakers discuss additional training that may be necessary for effective virtual audits. They suggest training on tools such as Zoom and Microsoft Teams, collaboration within platforms, presentation skills, and reading body language.

Additional Training for Effective Virtual Audits

• Training on using tools such as Zoom or Microsoft Teams.

• Collaboration within platforms should also be taught.

• Presentation skills are crucial for effective virtual audits.

• Reading body language is difficult during virtual audits.

Conducting Virtual Audits

In this section, the speakers discuss how to conduct virtual audits and provide tips for getting the same experience as in-person audits.

Preparation is Key

• Lack of ability to judge body language makes preparation key.

• Request information ahead of time and get ready for it.

• Think about what kind of questions you want to ask.

• Ask for documentation from the site that you are going to audit.

Asking the Right Questions

• Ask open-ended questions about how people use processes.

• Ask specific questions about critical elements of a process, such as calibration procedures for measurement equipment.

Using Vocal Inflection and Video

• Use vocal inflection to gauge potential nervousness or discomfort.

• Use video to watch eyes and facial expressions when possible.

Documentation Needed for Virtual Audits

• Request SOP list, site master file, and a list of complaints.

Overview of Auditing and Risk-Based Approach

In this section, the speakers discuss the importance of having an overall picture of a company and its processes when auditing. They also emphasize the need for a risk-based approach to determine where to focus audit efforts.

Importance of Overall Picture

• Having an overall picture of a company and its processes is important when auditing.

• P&ID provides information on process layout, equipment, validation master plan, etc.

• Calibration issues with measurement equipment should be given more attention during audits.

Risk-Based Approach

• A risk-based approach helps determine where to spend audit time.

• Cybersecurity is an important consideration in virtual auditing.

• IT department involvement is necessary to ensure technology used for virtual audits is secure and privacy-compliant.

• Validation of computer systems and audit trails are crucial for data integrity in laboratory systems.

Cybersecurity Considerations in Virtual Auditing

In this section, the speakers discuss cybersecurity considerations when conducting virtual audits. They highlight the importance of assessing technology used for virtual audits ahead of time to ensure it is secure and compliant with privacy regulations.

Assessing Technology Used for Virtual Audits

• Assessing technology used for virtual audits ahead of time is crucial to ensure security and compliance with privacy regulations.

• Not all pieces of technology used for virtual audits are designed to be secure.

• Secure data rooms may be necessary if sharing information online poses too much cybersecurity or privacy risks.

Validating Computer Systems and Audit Trails

• Validation of computer systems and audit trails are crucial for data integrity in laboratory systems.

• Data governance, retention, and risk assessment are important considerations throughout the lifecycle of data.

Conclusion

The speakers emphasize the importance of having an overall picture of a company's processes when auditing and using a risk-based approach to determine where to focus audit efforts. They also highlight the need to assess technology used for virtual audits ahead of time to ensure security and compliance with privacy regulations. Validating computer systems and audit trails is crucial for maintaining data integrity in laboratory systems.

Delayed Denying and Inspection Guidance

In this section, the speakers discuss how to prepare for inspections and audits. They suggest that companies should ensure they are secure and not hackable before giving live demonstrations of their systems. They also recommend having a document ready to show auditors how the system works.

Live Demonstrations

• Companies can give live demonstrations within the live system using technologies like Microsoft Teams.

• During these demos, companies can show auditors an audit trail and walk them through the system or let them point out specific features.

• It is important to let investigators take the lead during inspections.

Refusing to Share Documents with Regulatory Agencies

In this section, the speakers discuss whether companies ever deny showing regulatory agencies quality plans or risk management plans if it could be damaging to share. They also talk about what happens if a company refuses to share documents.

Sharing Quality Plans

• Companies should give up quality plans related to GMPs or any GX piece for that matter from trials through supply chain stuff.

• If a company does not give up its quality plan, it raises a big flag because it is part of their overall quality system.

• Refusing to share documents could turn the mood of an inspection or audit around pretty quickly.

Internal Audits

• The FDA has a compliance policy that says they do not routinely request internal audits because they want them to be part of an improvement tool within a quality system.

• However, FDA can request internal audits in certain situations. If they do so, companies should start asking questions and have discussions behind the scenes.

Auditing for Manufacturing Quality

The speakers discuss the importance of auditing for manufacturing quality and provide insights on how to prepare for internal and external audits.

Regulatory Perspective

• The FDA does not routinely request internal audits unless there is a big issue.

• Other health authorities around the world may ask for internal audits.

Requests for Internal Audits

• Agencies have been requesting internal audits, and it's becoming a growing trend.

• Findings can be redacted, but companies should be aware of these requests.

Closing Thoughts

Syed Hussain, Senior Director of Quality Assurance at Pacira BioSciences

• Preparation is key to ensure a successful audit, especially in virtual audits.

• Good practices are necessary to achieve successful outcomes from both the auditor and auditee perspective.

Steve Niedelman, Lead Quality Systems and Compliance Consultant at King & Spalding LLP

• A company's overall culture is crucial to maintaining quality manufacturing.

• Management creates the system that people work in.

Conclusion

The speakers conclude by thanking participants and encouraging them to fill out a survey. Feedback is important to improve future webinars.