In pharmaceutical manufacturing maintenance of high product quality is a top priority. When products do not meet the required standards for quality, regulatory enforcement actions and product recalls may result in harm to patients as well as negative and long-term impacts on company's reputation.
With time, patterns emerge regarding why products were deemed to be of low quality. By understanding the common causes of low-quality products, quality teams will be able to better prepare for risks, build adequate control measures and ensure compliance with GMP regulations.
In this post, we will understand some of the major and frequent contributing factors to low quality of pharmaceutical products and possible solutions to these issues.
Some of the root causes contributing to manufacturers falling to have an effective QMS include:
A. Outdated SOPs: When an SOP is outdated, it creates variability in how operations are performed.
B. Weak Change Control Process: Manufacturers do not identify and assess risk when implementing changes to equipment or processes, which may lead to unintended consequences related to product quality.
C. Lack of Quality Culture: Teams that don’t feel responsible for compliance create an environment where compliance is a transactional relationship rather than one that is embedded within the organization.
Some of the most common documentation problems include:
A. Lack of Raw Data: Inspectors want to see your source data, not just a summary.
B. Handwriting Errors and Corrections without Justification: Any corrections or changes to handwritten document entries can create doubts on correctness of the entry.
C. Electronic Records which Lack Secure Audit Trails: If electronic documents cannot be tracked or audited, there is no way for anyone to verify that the data has not been altered.
Some common issues that affect the process:
A. Uncontrolled Process Parameters: Temperature, pH, mixing time and filtration conditions will cause a reduction in product potency or purity when outside validated ranges.
B. No Validation has been Performed for Worst-case Scenarios: If these processes are not validated for worst-case situations, they could cause failures during routine production.
C. Human Error: Lack of formal training or supervision can cause human error during critical steps of the manufacturing processes.
The following are some of the most common problems associated with raw materials:
A. Poor Supplier Qualification: When companies do not conduct proper supplier qualifications, the unknown risks are associated with the materials when received.
B. Testing of Raw Materials: Companies mostly rely on supplier certificates of analysis as evidence of the quality of raw materials. Relying solely on certificates creates possibilities for errors.
C. Storage of Raw Materials: If the materials are not stored properly according as per manufacturer’s recommendations, they may degrade or contaminated before use.
Major environmental concerns:
A. Poor Cleanroom Practices: Improper gowning, traffic control (men movement) and area sanitation increases risk of product contamination.
B. Weak Environmental Monitoring: If a company does not have effective and consistent sampling and trend analysis, then possible contamination will remain undetected.
C. Equipment Hygiene Gaps: Equipment that is not clean or maintained properly will increased risk of cross-contamination.
Some examples of the major issues happened due to inadequate quality control testing are:
A. Validation of Testing Methods: Testing Methods that are not validated for the specific product can produce unreliable results.
B. Sampling Plans: Sample sizes that are not appropriate or are poorly representative based on the population may create artifacts and distort the conclusion regarding product quality.
C. Time Delays: Quality issues may go unnoticed and later manifest when there are backlogs or slow analysis, therefore the quality concern has already occurred and it is too late to fix.
Key issues related to training:
A. Inadequate Structured Training: Staff have insufficient depth of understanding of procedures to complete a task as required.
B. No Evaluation of Competency: No evaluation of personnel who are trained (without an evaluation or measuring point, the process understanding of the individual cannot be evaluated).
C. Overlooking Written Procedures: People are overdependent on their memory rather than written procedures (variability of product occurs as a result of people's individual methods of performing the same task).
Examples of the negative effects of poor risk management include:
A. Lack of Root Cause Identification: When root causes are only superficially investigated, it creates many duplicate problems.
B. No Prioritization of Risk: Without prioritizing the highest-risk product, a lot of resources are wasted on lower-risk products.
C. No Post-implementation Evaluation of Effectiveness: When actions are taken to reduce risk without assessment of their contribution to reducing risk, risk is never controlled.
In this post, we will understand some of the major and frequent contributing factors to low quality of pharmaceutical products and possible solutions to these issues.
1. Inadequate Quality Management System
A well-developed quality management system (QMS) is the foundation of any pharmaceutical company. Quality is established, managed and improved through the use of QMS. There are still many manufacturers without complete standard operating procedures (SOPs) or a disorganized quality assurance process.Some of the root causes contributing to manufacturers falling to have an effective QMS include:
A. Outdated SOPs: When an SOP is outdated, it creates variability in how operations are performed.
B. Weak Change Control Process: Manufacturers do not identify and assess risk when implementing changes to equipment or processes, which may lead to unintended consequences related to product quality.
C. Lack of Quality Culture: Teams that don’t feel responsible for compliance create an environment where compliance is a transactional relationship rather than one that is embedded within the organization.
Corrective Action
Manufacturers should review and update SOP on a regular basis to ensure current operations are reflected. The responsibility for quality should be defined for all members of the manufacturing team. Quality metrics should be made visible and developed in conjunction with the production team to improve quality.2. Documentation and Data Integrity Problems
Documentation errors are among the most common topics of concern noted during regulatory inspections. If your documentation has missing, inconsistent or altered records, it will cast doubt on the quality of your decision-making.Some of the most common documentation problems include:
A. Lack of Raw Data: Inspectors want to see your source data, not just a summary.
B. Handwriting Errors and Corrections without Justification: Any corrections or changes to handwritten document entries can create doubts on correctness of the entry.
C. Electronic Records which Lack Secure Audit Trails: If electronic documents cannot be tracked or audited, there is no way for anyone to verify that the data has not been altered.
Corrective Action
Train your staff properly on good documentation procedures. Use technology to create and maintain document integrity through secure audit trails and access control. Regularly review your documentation with audits and appropriate corrective actions.3. Deviations in Manufacturing Process
Process deviation (non-conformance) of manufacturing process is to be controlled closely. When approved procedure is not followed during the manufacturing process, this often leads to a decline in product quality.Some common issues that affect the process:
A. Uncontrolled Process Parameters: Temperature, pH, mixing time and filtration conditions will cause a reduction in product potency or purity when outside validated ranges.
B. No Validation has been Performed for Worst-case Scenarios: If these processes are not validated for worst-case situations, they could cause failures during routine production.
C. Human Error: Lack of formal training or supervision can cause human error during critical steps of the manufacturing processes.
Corrective Action
Validate processes thoroughly before they are used routinely. Monitor Processes in real-time whenever possible. Make sure you have structured training and going back for competency evaluations of Operators.4. Problems with Raw Material Quality
The quality of the finished product is determined by the quality of raw materials. Low-quality, contaminated or improperly identified raw materials will negatively impact the quality of the finished product.The following are some of the most common problems associated with raw materials:
A. Poor Supplier Qualification: When companies do not conduct proper supplier qualifications, the unknown risks are associated with the materials when received.
B. Testing of Raw Materials: Companies mostly rely on supplier certificates of analysis as evidence of the quality of raw materials. Relying solely on certificates creates possibilities for errors.
C. Storage of Raw Materials: If the materials are not stored properly according as per manufacturer’s recommendations, they may degrade or contaminated before use.
Corrective Action
The prevention of these types of issues is to develop an effective supplier qualification process, perform testing of raw materials immediately after receipt and to store raw materials in a controlled environment with proper rotation policies.5. Insufficient Environmental and Contamination Control
Producing pharmaceutical products involves exposing those products to microbial and particulate contaminants through the manufacturing process, particularly sterile products. Companies that do not have proper controls of their environment will be more likely to manufacture less than desired quality product.Major environmental concerns:
A. Poor Cleanroom Practices: Improper gowning, traffic control (men movement) and area sanitation increases risk of product contamination.
B. Weak Environmental Monitoring: If a company does not have effective and consistent sampling and trend analysis, then possible contamination will remain undetected.
C. Equipment Hygiene Gaps: Equipment that is not clean or maintained properly will increased risk of cross-contamination.
Corrective Action
Establish a risk based environmental monitoring program with trend analysis and defined action limits. Train all employees on proper hygiene and cleanroom behavior. Establish a strong cleaning and qualification program for all manufacturing equipment.6. Lack of Quality Control Testing
Quality Control Testing must be thorough and scientifically valid, otherwise, products may inadvertently be passed during release simple because they have not been correctly tested against their specifications.Some examples of the major issues happened due to inadequate quality control testing are:
A. Validation of Testing Methods: Testing Methods that are not validated for the specific product can produce unreliable results.
B. Sampling Plans: Sample sizes that are not appropriate or are poorly representative based on the population may create artifacts and distort the conclusion regarding product quality.
C. Time Delays: Quality issues may go unnoticed and later manifest when there are backlogs or slow analysis, therefore the quality concern has already occurred and it is too late to fix.
Corrective Action
All test methodologies must be validated and documented. Sampling plans should be developed based on Risk and Complexity of the product. Timely testing and review can be accomplished by developing Workflow Controls and Setting Performance Targets.7. Training Gaps and Human Errors
All procedures are subject to the influence of humans. Inadequate or insufficient training programs lead to increased operator error, resulting in decreased quality products.Key issues related to training:
A. Inadequate Structured Training: Staff have insufficient depth of understanding of procedures to complete a task as required.
B. No Evaluation of Competency: No evaluation of personnel who are trained (without an evaluation or measuring point, the process understanding of the individual cannot be evaluated).
C. Overlooking Written Procedures: People are overdependent on their memory rather than written procedures (variability of product occurs as a result of people's individual methods of performing the same task).
Corrective Action
Solutions to the above include competency-based training; competency-based training connected to specific roles and tasks; competency-based training evaluated by assessments of the individual; competency-based training supported by on-the-job coaching and/or feedback on performance.8. Ineffective Risk Management Strategies
Commonly classified as a reactive organisation the majority of issues faced in terms of product quality occur because the organisation does not have sufficient risk management practices in place to forecast possible future problems and develop a pattern of similar occurrences.Examples of the negative effects of poor risk management include:
A. Lack of Root Cause Identification: When root causes are only superficially investigated, it creates many duplicate problems.
B. No Prioritization of Risk: Without prioritizing the highest-risk product, a lot of resources are wasted on lower-risk products.
C. No Post-implementation Evaluation of Effectiveness: When actions are taken to reduce risk without assessment of their contribution to reducing risk, risk is never controlled.
Corrective Action
The use of structured assessment tools, for example, FMEA or HACCP, will allow for the prioritization of risks based on severity and likelihood. The effectiveness of corrective actions will need to be reviewed on an ongoing basis.
The following are some of the challenges faced:
A. Not Enough Supplier Audits: If audits are conducted only remotely and there is no on-site verification, it is possible to discover issues that are not visible without physically visiting the vendor.
B. Poorly Defined Contracts: If there is not enough detail about how quality must be defined between vendor and contractor, it will result in large variations in product quality between suppliers.
C. Lack of Communication: Not enough communication between contractors and their suppliers can delay detection of quality problems.
Weak culture indicators are:
A. Production Deadlines over Product Quality: The urgency to produce product is greater than the need for good quality.
B. Employee’s Reaction to Mistakes: Employees will withhold their mistakes rather than report them. The attitude of blaming others for mistakes will cause more mistakes to be made.
C. No Corporate Culture of Continuous Improvement: There is no company culture of developing and implementing initiatives to reduce defects and improve processes.
The inadequate quality of a pharmaceutical product is not commonly due to one isolated incident. It is the result of multiple issues and an after-effect of having insufficient systems, processes, staff and cultures in place. By identifying many of the commonalities in the root causes such as inadequate quality systems & documentation, insufficient staff training and ineffective risk management processes, organizations have the opportunity to develop a more effective quality framework.
The objective of a quality organization is not to achieve compliance with governmental regulations but the goal of a quality organization is to have an organized methodology to identify errors before their occurrence at the patient level. The establishment of a routine for assessing the effectiveness of the organization's quality systems, providing robust training programs for staff, integration of risk-based decision-making into the daily operations of the organization and maintaining a quality-first organizational culture are vital to achieving this goal.
Quality in pharmaceuticals is a continuous journey and not a destination. By clearly and consistently addressing the root causes, organizations can ultimately improve both their products' and organization's credibility.
9. Supply Chain and Outsourcing Challenges
External suppliers of raw materials and packaging materials are used by several manufacturers to purchase materials for their products. Inadequate oversight means that the quality problems happening from these vendors end up in every step of the manufacturing process.The following are some of the challenges faced:
A. Not Enough Supplier Audits: If audits are conducted only remotely and there is no on-site verification, it is possible to discover issues that are not visible without physically visiting the vendor.
B. Poorly Defined Contracts: If there is not enough detail about how quality must be defined between vendor and contractor, it will result in large variations in product quality between suppliers.
C. Lack of Communication: Not enough communication between contractors and their suppliers can delay detection of quality problems.
Corrective Action
Companies should conduct regular audits of their suppliers and the suppliers' contract facilities. They should have a clear quality contract in place with specific metrics and reporting requirements, including a shared quality dashboard and routines for communication.10. Leadership and Culture Issues
Ultimately, quality is determined and measured by the way a company treats quality as an essential core value that encompasses the entire organization. When a company treats quality as a cost to be managed it results in problems such as skipping necessary controls to save money or create products that are not as good as possible due to inadequate or ineffective quality systems.Weak culture indicators are:
A. Production Deadlines over Product Quality: The urgency to produce product is greater than the need for good quality.
B. Employee’s Reaction to Mistakes: Employees will withhold their mistakes rather than report them. The attitude of blaming others for mistakes will cause more mistakes to be made.
C. No Corporate Culture of Continuous Improvement: There is no company culture of developing and implementing initiatives to reduce defects and improve processes.
Corrective Action
Leaders must visibly support quality; establish the company’s standard of expectation regarding Quality as well as creating a way for employees to showcase their proactive quality behavior. Establish culture of continuous open communication with employees and implementing continuous improvement programs.The inadequate quality of a pharmaceutical product is not commonly due to one isolated incident. It is the result of multiple issues and an after-effect of having insufficient systems, processes, staff and cultures in place. By identifying many of the commonalities in the root causes such as inadequate quality systems & documentation, insufficient staff training and ineffective risk management processes, organizations have the opportunity to develop a more effective quality framework.
The objective of a quality organization is not to achieve compliance with governmental regulations but the goal of a quality organization is to have an organized methodology to identify errors before their occurrence at the patient level. The establishment of a routine for assessing the effectiveness of the organization's quality systems, providing robust training programs for staff, integration of risk-based decision-making into the daily operations of the organization and maintaining a quality-first organizational culture are vital to achieving this goal.
Quality in pharmaceuticals is a continuous journey and not a destination. By clearly and consistently addressing the root causes, organizations can ultimately improve both their products' and organization's credibility.
Frequently Asked Questions (FAQs) on Low Quality Products in Pharmaceuticals
Q1. Why do pharmaceutical products fail quality standards?
Answer: Weak quality systems, improper documentation and poorly controlled manufacturing processes are commonly responsible for many of the reasons due to which pharmaceutical products do not meet quality standards.Q2. How does documentation impact product quality?
Answer: Proper documentation enables traceability; however, if the documentation is incomplete or has errors in it, that creates a barrier to identifying a deviation that creates an effect on final product quality.Q3. How do raw materials affect final product quality?
Answer: Substandard or contaminated raw materials used in manufacturing reduce the safety and effectiveness of the finished product.Q4. What role does training play in quality?
Answer: Proper training of employees eliminates the occurrence of human error again and again and ensures consistent compliance with the established procedures.Q5. How can environmental controls prevent quality issues?
Answer: Environmental controls can help prevent quality problems by using effective contamination control and monitoring systems to reduce the risk of microbes and particulates.Q6. What is process validation?
Answer: Process validation helps to verify that a manufacturing process is capable of consistently producing compliant and standard quality products over a period of time.Q7. Why is supplier oversight important?
Answer: Mismanagement of suppliers allows to enter defective or noncompliant materials to the production process that can harm the product quality.Q8. How does company culture influence quality?
Answer: Company culture has a direct influence on product quality, as companies that focus their culture on quality will generate an environment that promotes the reporting and prevention of quality issues, as well as the ongoing improvement of products.
Dr. Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of pharmaguideline.com, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
.moc.enilediugamrahp@ofni :liamENeed Help: Ask Question
No comments:
Post a Comment
Please don't spam. Comments having links would not be published.