A quality agreement is a crucial document that defines the responsibilities and expectations of the parties involved in the manufacturing of pharmaceutical products.
The quality agreement helps in ensuring that the product is produced in compliance with the regulatory requirements and also meets the quality standards. One of the essential aspects of the quality agreement is its organization.
In this article, we will discuss how to organize a quality agreement in the same sequence as the Part 211 subparts, along with the details of each section.
Section 1 – General :
The General section of the quality agreement provides an overview of the agreement and defines the scope and purpose of the document. It should include the following information in clear, concise and easy to understand manner :
- Date of the agreement
- Parties involved in the agreement
- Products covered by the agreement
- Purpose of the agreement
- Definitions of key terms used in the agreement
- Regulatory requirements to be followed
Section 2. Organization and Personnel
This section of the quality agreement should describe the organizational structure of both parties involved in the manufacturing process and their respective roles and responsibilities.
It should include:
- Names and titles of the key personnel involved in the manufacturing process
- Description of the quality unit and its responsibilities
- Description of the manufacturing unit and its responsibilities
- Communication channels between the parties
- Procedures for handling deviations, change controls, and investigations
- Training requirements for personnel involved in the manufacturing process
- This section should also outline the qualifications and experience required for personnel involved in the manufacturing process.
3. Buildings and Facilities :
This section of the quality agreement should describe the facilities used for the manufacturing process and their maintenance requirements. It should include:
- Description of the manufacturing facility, including location and size
- Description of the equipment used for the manufacturing process
- Maintenance requirements for equipment and facilities
- Cleaning and sanitation procedures for the facility and equipment
- Environmental monitoring requirements
- Procedures for handling environmental excursions
- The procedures for validating and qualifying the facilities and equipment used in the manufacturing process.
4. Control of Components :
This section of the quality agreement should describe the procedures for controlling the quality of the components used in the manufacturing process.
It should include:
- Requirements for the quality of the raw materials, packaging materials, and other components used in the manufacturing process
- Procedures for handling and storing the components
- Testing requirements for the components
- Procedures for handling out-of-specification results for the components
- Procedures for handling deviations and change controls related to the components
- The requirements for the qualification of suppliers and the procedures for approving and monitoring them.
5. Production and Process Controls :
This section of the quality agreement should describe the procedures for controlling the manufacturing process. It should include:
- Procedures for the manufacturing process, including the steps involved and the sequence of the steps
- Control of critical process parameters and critical quality attributes
- In-process controls and testing requirements
- Procedures for handling deviations and change controls related to the manufacturing process
- Procedures for handling environmental excursions
- The procedures for process validation and the procedures for handling process changes.
6. Packaging and Labeling :
This section of the quality agreement should describe the procedures for packaging and labeling the finished product. It should include:
- Requirements for the packaging and labeling materials used
- Procedures for handling and storing the packaging and labeling materials
- Procedures for packaging and labeling the finished product
- Testing requirements for the packaging and labeling materials
- Need for batch records, in-process controls
- Procedures for label approval and change control
- The procedures for labeling, including the use of approved labels and the format and content of labeling information
- Procedures for handling deviations and change controls related to packaging and labeling
- The procedures for validating the packaging and labeling process.
7. Holding and Distribution
The Holding and Distribution subpart of Part 211 sets forth the regulatory requirements for the storage, transportation, and distribution of drug products. Hence, an effective Quality Agreement should address the following:
- Procedures for the storage, transportation, and distribution of drug products, including the requirements for maintaining appropriate storage conditions
- Need for temperature control
- Procedures for handling nonconforming products, complaints, and recall, including the need for a complaint management system
8. The Laboratory Controls:
Subpart of Part 211 sets forth the regulatory requirements for the establishment and maintenance of a quality control laboratory.
An effective Quality Agreement should address the following:
- Procedures for the establishment and maintenance of a quality control laboratory
- Qualifications of personnel, equipment, and facilities
- Procedures for testing raw materials, intermediates, and finished products
- Procedures for handling deviations and investigations
9. Records and Reports :
The Records and Reports subpart of Part 211 sets forth the regulatory requirements for the maintenance of records. An effective Quality Agreement should address the following:
- Procedures for the maintenance of records
- Requirements for batch records, laboratory notebooks, and quality control records
- Procedures for data integrity, retention, and archiving
10. Handling Returned Products:
This section should contain details about below activities how to :
- Determine of procedures for handling returned products, including the need for quarantine, investigation, and disposition.
- Determine the need for returning the product to the contract facility for investigation, and establish procedures for returning and receiving the product.
- Define the criteria for determining the disposition of the returned product, such as rework, disposal, or release for sale.
- Establish procedures for documentation of returned products, including the need for investigation reports and batch records.
- Ensure that returned products are handled in accordance with cGMP regulations, including the need for segregation and appropriate storage conditions.
11. Handling Customer Complaints:
- Establish a complaint management system for handling customer complaints, including the need for procedures for receiving, documenting, and investigating complaints.
- Define the criteria for categorizing and prioritizing complaints based on the severity of the issue and the potential impact on patient safety.
- Establish procedures for tracking and trending customer complaints to identify trends and implement corrective actions.
- Ensure that customer complaints are handled in accordance with cGMP regulations, including the need for appropriate investigation, evaluation, and reporting.
12. Handling Investigations and Corrective Actions:
- Establish procedures for conducting investigations of returned products and customer complaints, including the need for root cause analysis and risk assessments.
- Define the criteria for determining the scope and depth of the investigation based on the severity of the issue and the potential impact on patient safety.
- Establish procedures for implementing corrective and preventive actions (CAPAs) to address the root cause of the issue and prevent its recurrence.
- Define the criteria for determining the effectiveness of CAPAs and establish procedures for monitoring their implementation and effectiveness.
13. Change Control Section :
The Change Control Procedures section outlines the process for making changes to the products, processes, or services covered by the quality agreement. It helps enforce the changes are made in controlled and documented manner and all parties involved are aware and agree to the changes before the change happens
- Change Control Procedures section should contain:
- Definition of Change: Define what constitutes a change that requires formal change control. This may include changes to specifications, processes, equipment, or personnel.
- Change Control Process: Define the process for submitting, reviewing, approving, and implementing changes in a flow chart or diagram that outlines the steps in the process and each party responsibility.
- Change Request Form: Provides a template for submission of the change request form, which should include information about the reason for the change, the proposed solution, and the potential impact of the change.
- Change control Impact Assessment: Describe the process for conducting an impact assessment of the proposed change. It contains review of the potential impact on product quality, regulatory compliance.
- Change Review Board section: Define the composition and responsibilities of the Change Review Board, which is responsible for reviewing and approving change requests and contains the representatives from all parties involved in quality agreement.
- Documentation section specifies the documentation required for change control, which includes the creation of a change control record, description of the change, the date and reason of the change.
- Training: Describe the training requirements for personnel involved in the change control process, including training on the change control procedure, the change request form, and the impact assessment process.
- Change control Approval: This section outlines the requirements for approving proposed changes and contains information about the need for a formal approval process, the identification of the individuals responsible for approving changes, and the timeframe for approval.
- Change control Implementation: This section should describe the process for implementing approved changes, including the need for testing, validation, and documentation.
14. The Auditing and Inspection Procedures section :
It outlines the process for conducting audits and inspections of the products, processes, or services covered by the agreement.
This section is important for ensuring that both parties are aware of the expectations and requirements for audits and inspections, and that they have a common understanding of how these activities will be conducted. Key components are
- Scope and Frequency of Audits and Inspections:
- list of the products, processes, or services that will be audited or inspected,
- frequency of these activities.
- Audit and Inspection Requirements: that specifies not only the requirements for conducting audits and inspections but also the standards that will be used, the qualifications of auditors and inspectors, and the documentation that will be required.
- Notification of Audits and Inspections: Define the process for providing advance notice of audits and inspections, the timeframe for notification and the information that should be available as part of notification.
- Access and Accommodation: Specify the requirements for access and accommodation during audits and inspections.
- Audit and Inspection Reports: Define the requirements for audit and inspection reports, including the format, content, and timeframe for submission.
- CAPA Plans :This should also include requirements for corrective action plans and follow-up activities.
- Communication and Collaboration: Define the requirements for communication and collaboration between the parties during audits and inspections. This should include procedures for sharing information, coordinating activities, and resolving issues.
- Regulatory Compliance: Specify the requirements for ensuring regulatory compliance during audits and inspections, including adherence to applicable regulations, guidelines, and standards.
15. Dispute Resolution Procedures:
Dispute resolution procedures are necessary for resolving any disagreements or conflicts that arise between the drug product owner and the contract facility.
Key components of dispute resolution procedures :
- Arbitration: This section outlines the procedures for resolving disputes, including the need for mediation or arbitration, and the criteria for selecting a mediator or arbitrator.
- Notification: This section describes the requirements for notifying the other party of a dispute, the timeframe for notification, and the information that should be included in the notification.
16. Governing Law and Jurisdiction:
This section should describe the governing law and jurisdiction for the quality agreement, including the country or state whose laws will govern the agreement, and the forum for resolving any disputes that arise under the agreement.
The following are some of the key components of governing law and jurisdiction that should be included in the quality agreement:
- Choice of Law: This section should specify the governing law for the quality agreement, including the jurisdiction whose laws will govern the agreement.
- Forum Selection: This section should outline the forum for resolving disputes, including the need for jurisdiction, venue, and the criteria for selecting a court or arbitrator.
Conclusion:
Organizing a quality agreement is a critical step in ensuring that a contract facility is compliant with cGMP regulations and producing high-quality drug products.
By including the above sections in a quality agreement, drug product owners can establish clear expectations and procedures for managing key aspects of the contract facility’s operations