All products manufactured in pharmaceutical facilities must meet three criteria; safety, effectiveness and consistency in their quality. To achieve this goal each manufacturer must comply with cGMP regulations which are enforced by regulatory agencies around the world.
Current Good Manufacturing Practices (cGMP) standards establish that each component of the manufacturing from raw material to final product must be controlled, verified and documented. The standards are designed to protect patients and maintain product quality.
Current Good Manufacturing Practices our regulations and guidelines which define how pharmaceutical manufacturers should manufacture, process and pack their drug products.
The c in cGMP stands for current and requires that manufacturers use up to date regulations. For these regulations, the practice needs not only to be "good" but also "current". Controls, equipment and methodology being used by the manufacturer must be current. Current can imply what is generally acceptable in the industry. Therefore, if new standards are introduced which are better than the current, the manufacturer is under obligation to comply with the new procedures.
cGMP regulations are enforced on a global basis by a number of regulatory organizations including:
USFDA (United States Food and Drug Administration): 21 CFR Parts 210 and 211
WHO (World Health Organization): WHO-GMP guidelines
EU (European Union): EU GMP (EudraLex Volume 4)
India: Schedule M of the Drugs and Cosmetics Act
PIC/S: Pharmaceutical Inspection Co-operation Scheme - a global harmonized framework for Inspectorates
1. To ensure that products are manufactured consistently meet the necessary quality standards.
2. To prevent contamination, cross contamination and mix-ups by establishing control of critical processes and the facility.
3. To document each operation being performed during the manufacturing process.
4. Investigate and correct any deviation from standard procedure.
5. To ensure that all products remain safe and effective throughout their shelf life.
In short, cGMP ensures the quality of product at each step of manufacturing process, not at the end.
1. Patient Safety: Products must be free from contamination, correctly labeled and manufactured with correct strength and dose.
2. Product Consistency: Every match must be similar in quality to the approved specification.
3. Regulatory Compliance: cGMP compliance is a legal requirement for market authorization.
4. Risk Reduction: Adherence to the cGMP guidelines reduces the risk of recalls and warning letters.
5. Public Trust: cGMP complaint manufacturing facility has public trust in the safety and efficacy of medicines.
- QMS outlines and defines the responsibilities of the Quality Assurance and Quality Control functions.
- The QMS should also define and implement systems for document control, deviation control, change control and corrective and preventive action (CAPA).
- The QMS should include processes for conducting regular internal audits and for conducting management reviews for cGMP to ensure continued compliance.
- Only those personnel that have been trained and qualified to perform GMP operations should perform these activities.
- It is mandatory that all GMP personnel receive regular training on GMP principles, hygiene and safety, as well as training on the specific products that they manufacture.
- Training record and effectiveness of training should be maintained and reviewed at regular intervals.
- Visitors or untrained personnel should not be allowed in production or QC area without being supervised.
- Clean rooms and HVAC systems used to maintain a controlled environment must be adequate for the type of product being manufactured.
- Cleaning and maintaining equipment to ensure that it is in compliance with GMP is important.
- Maintenance and calibration programs for manufacturing equipment must be there.
- All processes and procedures carried out within a GMP facility must be fully documented from receiving raw material to finished product release.
- All standard operating procedures (SOPs) must be in written format, duly signed and then followed.
- All documentation and records must be legible, traceable and maintained for the required retention period.
- Electronic records must comply with the standards of data integrity such as ALCOA+ (Attributable, Legible, Contemporaneous, Original, Accurate, Complete).
- Before using any material, the quality control department must take samples, test and release each material.
- All materials must be segregated into approved, rejected, and quarantine areas.
- Each material must be maintained in accordance with the appropriate storage condition outlined in specifications.
- Before starting any new batch manufacturing operation, the line clearance must be performed.
- A variety of in-process control tests must be completed to ensure quality control through consistency such as weight variation, pH and temperature.
- Process parameters that the company considers to be critical must be regularly monitored and then documented.
- All batch manufacturing records must be examined and approved through Quality Assurance before the release of final products.
a) Equipment Qualification: Installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ).
b) Process Validation: Validating that processes are consistent and reproducible.
c) Cleaning Validation: Verifying that no cross contamination occurs between different production batches.
d) Analytical method Validation: Confirming the accuracy and precision of test methods.
- In addition to these validations, companies must periodically validate all aspects of their validation program to verify continued compliance with regulatory requirements.
- Sampling plants must be developed using statistically sound sampling methodologies.
- Analytical instruments require periodic maintenance and recalibration of the instruments used for testing.
- Instability studies must be conducted to establish the shelf life of products.
- Retained samples and reference standards must have proper labelling and storage procedures.
- Root cause analysis must be conducted to identify the underlying problem.
- Corrective and preventive action (CAPA) plans must be developed, implemented and completed.
- Complaint handling must ensure that received complaints are investigated promptly and product is recalled if necessary.
- Trained auditors should conduct audits at predetermined intervals.
- Audit findings must be categorized based on the severity of the identified issues as either critical, major or minor and corrective and preventive actions must be taken in response to the identified issues.
- Management must have periodic review meetings to review the outcome of the audit and utilize it as an opportunity for continuous improvement.
2. Data Integrity: ALCOA+, a set of principles endorsed by the FDA and WHO is designed to provide reliable, traceable and transparent electronic records.
3. Continuous Manufacturing: Technology advances (PAT, Automation and AI) are shifting manufacturers from batch manufacturing towards continuous manufacturing and ultimately improving the quality of the products manufactured by providing more consistent quality through real time monitoring of manufacturing process.
4. Lifecycle Validation Approach: Validation is now recognized as a continuous process that occurs at various points within the product life cycle rather than as a standalone activity in the manufacturing process.
5. Global Regulatory Harmonization: Global regulatory harmonization through international partnerships between regulatory authorities such as PIC/S and ICH is increasing the uniformity of scientific and regulatory requirements thereby decreasing the amount of duplication in regulatory inspections.
Download cGMP Compliance Checklist
- Inadequate or incomplete process validation
- Inadequate laboratory controls
- Incomplete or falsified records
- Poor area cleaning and maintenance
- Absence of stability study data
- Improper investigation of deviations and OOS results
1. Prepare SOPs: Create standard operating procedures in detail and clear language for every operation done in the company. Display SOPs in local language in all departments.
2. Implement Quality by Design (QbD): Integrate quality into the system from product development to final product dispatch.
3. Invest in Automation and Technology: Use Laboratory Information Management System (LIMS), electronic batch records and other technologies to reduce human errors during manufacturing and analysis.
4. Conduct Regular Training: Train staff as well as labor not only on SOPs but also on cGMP regulations regularly.
5. Build a Culture of Quality: As we always focus on culture of quality, everyone from operator to higher management must own the quality of the product.
6. Always Be Audit-Ready: Unannounced inspections are becoming more common these days, so stay ready for inspection always.
In order to create that quality culture:
- Leadership commitment is required to prioritize quality over the cost and speed of manufacturing.
- Create an environment where deviation reporting can be done without fear.
- Appreciation of good manufacturing behaviour.
- Invest time and money in training, providing digital tools and creating opportunities for continued learning.
- When quality is viewed as everyone’s responsibility, then compliance is easy to achieve. Also see: Common Ways to Avoid Making the Most Frequent GMP Errors
Current Good Manufacturing Practices (cGMP) standards establish that each component of the manufacturing from raw material to final product must be controlled, verified and documented. The standards are designed to protect patients and maintain product quality.
What are Current Good Manufacturing Practices (cGMP)?
Current Good Manufacturing Practices our regulations and guidelines which define how pharmaceutical manufacturers should manufacture, process and pack their drug products. The c in cGMP stands for current and requires that manufacturers use up to date regulations. For these regulations, the practice needs not only to be "good" but also "current". Controls, equipment and methodology being used by the manufacturer must be current. Current can imply what is generally acceptable in the industry. Therefore, if new standards are introduced which are better than the current, the manufacturer is under obligation to comply with the new procedures.
cGMP regulations are enforced on a global basis by a number of regulatory organizations including:
USFDA (United States Food and Drug Administration): 21 CFR Parts 210 and 211
WHO (World Health Organization): WHO-GMP guidelines
EU (European Union): EU GMP (EudraLex Volume 4)
India: Schedule M of the Drugs and Cosmetics Act
PIC/S: Pharmaceutical Inspection Co-operation Scheme - a global harmonized framework for Inspectorates
Key Objectives of cGMP
The intent of cGMP is to protect and improve public health by improving product quality and minimizing contamination of drug products.1. To ensure that products are manufactured consistently meet the necessary quality standards.
2. To prevent contamination, cross contamination and mix-ups by establishing control of critical processes and the facility.
3. To document each operation being performed during the manufacturing process.
4. Investigate and correct any deviation from standard procedure.
5. To ensure that all products remain safe and effective throughout their shelf life.
In short, cGMP ensures the quality of product at each step of manufacturing process, not at the end.
Why cGMP Matters in Pharmaceutical Manufacturing
Pharmaceutical industry is different from other manufacturing industries like textiles, metals and automobiles. Current manufacturing practices are non-negotiable because of following the regions.1. Patient Safety: Products must be free from contamination, correctly labeled and manufactured with correct strength and dose.
2. Product Consistency: Every match must be similar in quality to the approved specification.
3. Regulatory Compliance: cGMP compliance is a legal requirement for market authorization.
4. Risk Reduction: Adherence to the cGMP guidelines reduces the risk of recalls and warning letters.
5. Public Trust: cGMP complaint manufacturing facility has public trust in the safety and efficacy of medicines.
cGMP Principles for Pharmaceuticals
There are a number of cGMP fundamental principles that form the foundation of good manufacturing practices for pharmaceutical products. Together these principles ensure that pharmaceutical manufacturers produce consistent quality products that comply with regulatory requirements.1. Quality Management System (QMS)
- A strong quality management system (QMS) is the foundation of cGMP. A QMS includes an organization’s quality policies, processes and procedures. These must be integrated within and across all functions and departments to support compliance with cGMP and continual improvement.- QMS outlines and defines the responsibilities of the Quality Assurance and Quality Control functions.
- The QMS should also define and implement systems for document control, deviation control, change control and corrective and preventive action (CAPA).
- The QMS should include processes for conducting regular internal audits and for conducting management reviews for cGMP to ensure continued compliance.
2. Personnel and Training
- Personnel are important to maintaining the quality of the products manufactured under cGMP regulations.- Only those personnel that have been trained and qualified to perform GMP operations should perform these activities.
- It is mandatory that all GMP personnel receive regular training on GMP principles, hygiene and safety, as well as training on the specific products that they manufacture.
- Training record and effectiveness of training should be maintained and reviewed at regular intervals.
- Visitors or untrained personnel should not be allowed in production or QC area without being supervised.
3. Facility and Equipment
- The facility design and equipment can have a direct impact on the quality of the product manufactured. The facility must be laid out and designed to minimize the potential for product contamination and mix up.- Clean rooms and HVAC systems used to maintain a controlled environment must be adequate for the type of product being manufactured.
- Cleaning and maintaining equipment to ensure that it is in compliance with GMP is important.
- Maintenance and calibration programs for manufacturing equipment must be there.
4. Documentation and Record Keeping
- According to Good Manufacturing Practice (GMP), there is a very straightforward guideline which states: “If it is not documented, it did not happen.”- All processes and procedures carried out within a GMP facility must be fully documented from receiving raw material to finished product release.
- All standard operating procedures (SOPs) must be in written format, duly signed and then followed.
- All documentation and records must be legible, traceable and maintained for the required retention period.
- Electronic records must comply with the standards of data integrity such as ALCOA+ (Attributable, Legible, Contemporaneous, Original, Accurate, Complete).
5. Materials Management
- Raw materials, intermediate materials and packaging materials must come from approved suppliers.- Before using any material, the quality control department must take samples, test and release each material.
- All materials must be segregated into approved, rejected, and quarantine areas.
- Each material must be maintained in accordance with the appropriate storage condition outlined in specifications.
6. Production and In-Process Controls
- Production activities must be performed according to approved master manufacturing and master packaging instructions.- Before starting any new batch manufacturing operation, the line clearance must be performed.
- A variety of in-process control tests must be completed to ensure quality control through consistency such as weight variation, pH and temperature.
- Process parameters that the company considers to be critical must be regularly monitored and then documented.
- All batch manufacturing records must be examined and approved through Quality Assurance before the release of final products.
7. Qualification and Validation
- The validation ensures that system, process and methods perform as they were intended. The types of validation include but are not limited to:a) Equipment Qualification: Installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ).
b) Process Validation: Validating that processes are consistent and reproducible.
c) Cleaning Validation: Verifying that no cross contamination occurs between different production batches.
d) Analytical method Validation: Confirming the accuracy and precision of test methods.
- In addition to these validations, companies must periodically validate all aspects of their validation program to verify continued compliance with regulatory requirements.
8. Quality Control and Testing
- Quality control ensures that materials and products are manufactured according to the requirements of the acceptable quality standards.- Sampling plants must be developed using statistically sound sampling methodologies.
- Analytical instruments require periodic maintenance and recalibration of the instruments used for testing.
- Instability studies must be conducted to establish the shelf life of products.
- Retained samples and reference standards must have proper labelling and storage procedures.
9. Handling of Deviations, Complaints, and CAPA
- Any deviation from approved procedure must be documented and investigated.- Root cause analysis must be conducted to identify the underlying problem.
- Corrective and preventive action (CAPA) plans must be developed, implemented and completed.
- Complaint handling must ensure that received complaints are investigated promptly and product is recalled if necessary.
10. Self-Inspection and Audits
- A company should perform regular internal audits to determine whether it is complying with cGMP regulations.- Trained auditors should conduct audits at predetermined intervals.
- Audit findings must be categorized based on the severity of the identified issues as either critical, major or minor and corrective and preventive actions must be taken in response to the identified issues.
- Management must have periodic review meetings to review the outcome of the audit and utilize it as an opportunity for continuous improvement.
Recent Updates and Trends in cGMP
1. Quality Risk Management: Risk based approach in quality risk management for cGMP is supported through ICH Q9 for the identification, evaluation and control of risks to the quality of pharmaceutical products.2. Data Integrity: ALCOA+, a set of principles endorsed by the FDA and WHO is designed to provide reliable, traceable and transparent electronic records.
3. Continuous Manufacturing: Technology advances (PAT, Automation and AI) are shifting manufacturers from batch manufacturing towards continuous manufacturing and ultimately improving the quality of the products manufactured by providing more consistent quality through real time monitoring of manufacturing process.
4. Lifecycle Validation Approach: Validation is now recognized as a continuous process that occurs at various points within the product life cycle rather than as a standalone activity in the manufacturing process.
5. Global Regulatory Harmonization: Global regulatory harmonization through international partnerships between regulatory authorities such as PIC/S and ICH is increasing the uniformity of scientific and regulatory requirements thereby decreasing the amount of duplication in regulatory inspections.
Download cGMP Compliance Checklist
Common cGMP Violations Observed by FDA
The FDA inspects pharmaceutical companies worldwide for cGMP compliance. Common noncompliance includes:- Inadequate or incomplete process validation
- Inadequate laboratory controls
- Incomplete or falsified records
- Poor area cleaning and maintenance
- Absence of stability study data
- Improper investigation of deviations and OOS results
How to Maintain cGMP Compliance
Companies can maintain a strong compliance system by taking following steps.1. Prepare SOPs: Create standard operating procedures in detail and clear language for every operation done in the company. Display SOPs in local language in all departments.
2. Implement Quality by Design (QbD): Integrate quality into the system from product development to final product dispatch.
3. Invest in Automation and Technology: Use Laboratory Information Management System (LIMS), electronic batch records and other technologies to reduce human errors during manufacturing and analysis.
4. Conduct Regular Training: Train staff as well as labor not only on SOPs but also on cGMP regulations regularly.
5. Build a Culture of Quality: As we always focus on culture of quality, everyone from operator to higher management must own the quality of the product.
6. Always Be Audit-Ready: Unannounced inspections are becoming more common these days, so stay ready for inspection always.
Role of Quality Culture in cGMP
Compliance is not about the system, it’s also about the mindset. Having a solid well established quality culture means every employee is aware of how their work affects product quality and patient safety.In order to create that quality culture:
- Leadership commitment is required to prioritize quality over the cost and speed of manufacturing.
- Create an environment where deviation reporting can be done without fear.
- Appreciation of good manufacturing behaviour.
- Invest time and money in training, providing digital tools and creating opportunities for continued learning.
- When quality is viewed as everyone’s responsibility, then compliance is easy to achieve. Also see: Common Ways to Avoid Making the Most Frequent GMP Errors
Frequently Asked Questions on cGMP
Q1. What is cGMP in pharmaceuticals?
Answer: cGMP is known as Current Good Manufacturing Practices, that is a set of regulatory guidelines enforced by regulatory authorities like US-FDA, EMA and WHO. It ensures the quality, safety and efficacy of pharmaceutical products produced by pharmaceutical manufacturing facilities.Q2. Why is the term “current” used in cGMP?
Answer: As we discussed above, the “current” world shows that companies are following up to date technologies and systems. As regulatory expectations evolve, the manufacturers must continuously improve their quality system to stay complaint.Q3. Who enforces cGMP regulations?
Answer: Various regulatory agencies enforce cGMP regulations such as:- FDA (USA) – 21 CFR Parts 210 and 211
- EMA (Europe) – EudraLex Volume 4
- WHO – WHO GMP guidelines
- CDSCO (India) – Schedule M of Drugs & Cosmetics Rules
Q4. What are the main components of cGMP?
Answer: Key components of cGMP regulations include:- Quality Management System (QMS)
- Personnel training and hygiene
- Clean facilities and equipment
- Process validation
- Raw material control
- Good documentation practices (ALCOA+)
- Product testing
- Change control and CAPA
Q5. How is cGMP compliance monitored?
Answer: cGMP compliance in pharmaceuticals is monitored through regulatory inspections, internal audits, CAPA system performance and product quality reviews.Q6. What happens if a company violates cGMP regulations?
Answer: If a company violates cGMP regulations, it can lead to FDA warning that involve alerts and product recall, suspension of manufacturing license, legal actions or fines and loss of market trust and reputation.Q7. How is documentation handled under cGMP?
Answer: In a cGMP environment, documentation must follow ALCOA+ principles.- Attributable
- Legible
- Contemporaneous
- Original
- Accurate
- Plus: Complete, Consistent, Enduring, Available
Q8. What is the role of training in cGMP?
Answer: All personnel must be trained in their job responsibilities, SOPs and cGMP principles. Continuous training ensures updated staff with regulation changes and it helps to maintain compliance.Q9. How often are GMP inspections conducted?
Answer: Regulatory GMP inspection frequency depends on risk level of product and compliance history of company. Generally, inspections occur in every two to three years for complaint facilities or sometimes more frequently if any issues are identified.Q10. What is a batch record, and why is it important?
Answer: Batch manufacturing record (BMR) is a document that has information of entire manufacturing process of a batch. It is helpful in product traceability, ensuring product consistency and compliance and audit.
Get documents for Audit preparation in MS-Word FormatView List
No comments:
Post a Comment
Please don't spam. Comments having links would not be published.