Good Manufacturing Practice (GMP) Lecture V

Good Manufacturing Practice (GMP) Lecture V

• GMP involves a high level of sanitation and hygiene across all aspects of drug product manufacturing
• Personnel, premises, equipment, production materials, containers & finished products all must be clean and disinfected
• GMP's validation programs are crucial
• Validation studies must follow predefined and approved protocols
• Qualification and validation program must be documented in a master plan
• Premises utilities equipment & processes must comply with GMP standards
• Any modifications to the layout, design, or equipment must be validated and qualified
• All complaints on potentially defective products are carefully reviewed to follow corrective actions
• A documented record of complaints and steps taken should record the reason for complaint and batch records
• Manufacturers should inform the competent authorities if there are quality issues (e.g., faulty manufacture, product deterioration, counterfeiting)
• A system for recalling defective products must be promptly and effectively implemented

Product Recalls

• A designated person with sufficient staff is responsible for execution and coordination.
• Written procedures for product recalls must be regularly reviewed and updated.
• Product recalls should be stored in a secure, segregated area until a decision is taken on handling
• All competent authorities must be notified of the intent to recall products for being defective
• The progress of the recall and disposition of the products should be monitored and recorded in detail
• A final report should reconcile the delivered and recovered quantities.

Contract Production and Analysis

• Contract production and analysis must be clearly defined, agreed upon, and effectively controlled.
• The contract manufacturing must be compliant with the marketing authorization
• Changes in technical or other arrangements are to be documented and approved by the involved parties
• The contract giver is responsible for assessing the contract acceptor's competence to meet GMP standards and procedures.
• All processed products and materials must meet their required specifications to be released by the authorized person

Self-Inspection and Quality Audits

• Self-inspections are to be performed routinely and during special occasions (e.g., product recalls)
• Self-inspection teams should consist of personnel evaluated to implement GMP objectively.
• Written instructions defining GMP requirements, including the procedures for:
  • Personnel, premise, equipment, material & product storage
  • In-process controls, quality control, sanitation, hygiene, validation and calibration.
  • Labeling, recall procedures, complaint management and corrective action.
• Self-inspection reports should include evaluated results, conclusion and recommended corrective actions.
• Quality audits are performed by competent, outside specialists who assess suppliers and contractors to verify compliance with GMP standards.

Personnel

• Manufacturers must have sufficient personnel with necessary qualifications and experience
• Staff must have documented and clearly defined responsibilities
• Overlap in responsibilities should be avoided
• Proper training on GMP principles and hygiene should be provided for all personnel
• Personnel working in areas involving hazardous or sensitive materials should receive specialized training
• Contractors & visitors must receive relevant information about hygiene practices and safety while working in the areas.

Key Personnel

• Heads of production and quality control are independent
• Individuals responsible for GMP compliance, quality, and products.
• Key personnel often need specific qualifications in chemistry, engineering, microbiology, etc. with practical experience
• Their roles should be documented
• Appropriate training needs to be clearly laid out, and provided to each of these individuals

The Head of Production

• Responsible for production processes following proper documentation and controlling in-process controls
• Approves production procedures
• Production records are reviewed and signed by a designated person.
• Maintains equipment and premises
• Documents validation and calibrations
• Ensures personnel receive proper training

The Head of Quality Control

• Approves or rejects starting materials, packaging materials, intermediate & finished products based on specifications
• Evaluates batch records.
• Appropriately manages all necessary testing including sampling, specifications, methods
• Oversees contract analysis
• Validates and calibrates all equipment
• Ensures quality control personnel receive proper training

The Authorized Person

• Complies with technical & regulatory requirements for the finished product quality and approval
• Develops and implements the quality system
• Participates in developing the quality manual
• Oversees quality control dept.
• Oversees external and internal audits and inspections
• Participates in validation programs

Shared Responsibilities

• Authorization of SOPs and related documents
• Monitoring and control of the manufacturing environment
• Plant hygiene
• Validity and calibration of analytical apparatuses
• Training programs, quality assurance, monitoring and approval of materials/suppliers

Approving a Batch for Release

• The product must meet marketing and authorization requirements
• Processes should follow WHO GMP guidelines
• All checks, tests, and relevant records must be accounted for in the production documentation
• Any changes in the production or quality of the product must be notified and approved appropriately prior to releasing the batch
• Additional sampling, testing and verification must be conducted as needed.
• Supervising personnel are trained appropriately to assess these factors

Training

• Manufacturers should have written training programs for all personnel working in manufacturing and control areas
• Training should cover GMP theory and practice
• Newly hired staff should be trained

Personal Hygiene

• All personnel must undergo regular health exams
• Personnel working with materials require specific training
• Personal hygiene practices must be enforced.
• Appropriate preventative measures must be implemented (e.g., appropriate protective clothing)
• Practices like eating, drinking, smoking, or keeping plants/food materials out of the designated production areas are strictly prohibited

Premises

• Locations, designs, construction, adaptation, and maintenance must be appropriate for the specific production activities
• Premise design should prevent contamination, optimize cleaning, and reduce build-up of dust and dirt.
• Operations to maintain premises and their equipment should not jeopardize the quality of product being manufactured.
• Premises must be thoroughly cleaned and disinfected periodically.
• Proper electrical supply, lighting, ventilation, environmental controls (temperature, humidity) are essential

Ancillary Areas

• Rest rooms, changing areas, and restrooms should be separated from manufacturing and control areas
• Separate areas must be allocated to handle rejected, recalled, or returned material to avoid contamination with other material
• All materials must be duly separated and labeled

Weighing Areas

• Separate weighing areas must be provided for accurate measurement of materials without cross-contamination

Production Areas

• Segregated areas for hazardous materials like sensitizing materials (e.g., penicillins), biological preparations, hormones, and cytotoxic substances to minimize cross-contamination
• Manufacturing of technical poisons (e.g., pesticides, herbicides) must be separated from pharmaceutical products.
• Production area design should facilitate proper flow of operations
• Walls, floors, ceilings, pipework, and lighting should allow for easy cleaning.
• Adequate ventilation and air control are crucial.

Quality Control Areas

• Separate QC laboratories from production areas, with adequate storage space
• Cleanliness and proper control of storage of equipment,
• Specific air supply systems for sensitive apparatus

Equipment

• Equipment design should allow for easy cleaning and maintenance and minimize cross-contamination, dust, or dirt accumulation.

Materials

• Materials (starting, packaging, gases, solvents, and labeling) should meet relevant specifications
• Materials for processes like cleaning or sanitation must not be in contact with the produced items when possible
• Materials are to be checked for correct identity and specification against purchase orders.
• Suitable handling and storage procedures (quarantine of incoming materials) must follow proper guidelines.

Packaging Materials

• Packaging materials should be appropriate
• The handling and control of packaging materials are the same as that for starting materials
• Outdated or obsolete packaging materials and other waste must be disposed per defined procedure

Intermediate and Bulk Products

• Materials requiring storage should be dealt with as starting materials handling

Finished Products

• Finished products should be held in quarantine until officially approved for release
• Rejected materials and products should be clearly marked and tracked. Separate quarantine storage to avoid product contamination
• Finished products should be properly labeled, accounted for and kept separate until final release

Recalled Products

• Proper procedures must be followed for the management of recalled products
• Materials or products should be held, returned, or eliminated properly

Reagents and Culture Media

• Records of receipt and preparation of reagents and media are mandatory.
• Correct preparation and labeling of compounds required.

Waste Materials

• Safe storage and disposal of waste materials should be ensured based on national regulations.
• Hazardous or toxic materials must be stored in separate and secure cupboards

Miscellaneous

• Sanitizing materials like rodent repellents must not contaminate other material.