Quality Control in Pharmaceutical Manufacturing

Administrative Order No. 43 S. 1999

• Administrative Order No. 43 S. 1999, dated September 29, 1999, outlines guidelines for Current Good Manufacturing Practice (GMP) for drugs.
• The Bureau of Food and Drugs adopts these GMP guidelines.

Part 1: General Provisions

• Section 1: Authority

  • The order is issued under the authority of Section 26(a) of RA 3720.

• Section 2: Statement of Policies

  • Drugs must be manufactured using methods, facilities and control procedures adequate to maintain their identity, quality, strength, and purity.
  • Drug manufacturing licenses are issued upon compliance with GMP guidelines.
  • Overall control is essential for the quality, efficacy, and safety of manufactured drugs.
  • Drug product quality depends on materials, production processes, facilities, equipment, and personnel involved in the production.

• Section 3: Statement of Objectives

  • The 1999 GMP guidelines are designed to prescribe standards for drug manufacturing and ensure drug products are manufactured under proper conditions.

Part 2: Basic GMP Guidelines - Personnel

• Section 1: Personnel
  • There must be adequate personnel with the knowledge, skills, and qualifications to execute their duties; good mental and physical health is required.
  • The organizational structure will have separate yet coordinated quality assurance and production management teams to facilitate effective operation and prevent conflict of interest.
  • All employees involved in manufacturing activities must be trained on GMP principles.
  • Training records should be kept and assessed regularly to ensure effectiveness.

Part 2: Basic GMP Guidelines - Premises

• Section 2: Premises
  • Facilities must be appropriately located and protected against contamination from the environment(i.e.weather, pests, floods.)
  • They must be carefully designed and laid out to prevent cross-contamination between products or operations(e.g. Penicillins should be produced in separate buildings, using separate equipment). Manufacturing areas must be clearly demarcated to prevent mix-ups, and to ensure orderly and efficient material flow with minimal traffic. Environmental conditions (e.g. temperature, humidity, pressure, airborne contaminants) must be maintained and monitored.

Part 2: Basic GMP Guidelines - Equipment

• Section 3: Equipment
  • Equipment suitable for the process should be used for both manufacturing and testing with appropriate design, construction, size, location, cleaning, sanitizing.
  • Equipment must not alter the properties of manufactured drugs or reactants beyond acceptable ranges; cleaning of equipment should be easy and conveniently done and the products.
  • Filters must not release fibers or substances into products.
  • Maintenance, calibration, and validation for equipment must be properly documented and performed routinely.

Section 4: Sanitation and Hygiene

• 4.1 Personnel
  • Employees must undergo health examinations to ensure they are free from illnesses or other conditions which could affect product quality.
  • Proper personal hygiene practices should be observed.
• 4.2 Premises
  • Areas used for manufacturing should be adequately designed and maintained to facilitate cleanliness and sanitation.
  • Storage, preparation, and consumption of food/beverages should only be permitted in designated areas such as cafeterias/lounges.
• 4.3 Equipment
  • Equipment shall be designed, installed, and maintained for ease of cleaning, sanitation, and sterilization.
  • Regular procedures for cleaning and sterilization must follow a written protocol

Section 5: Storage of Materials, Intermediates, Bulk Products, and Finished Products

• 5.1 Proper storage procedures with measures taken to ensure that the product contents/packaging won't mix or be subject to contamination. Materials/products must be stored in a designated storage space in accordance with relevant standards and procedures.
• 5.2 Materials should be stored in an orderly manner that is easy to monitor and maintain. Materials' storing conditions shall be properly identified, monitored and followed.
• 5.3 Outdoor storages are permitted for materials suitably sealed and handled.
• 5.4 Storage procedures must be segregated from other operations
• 5.5 All deliveries of materials, products, bulk, etc., must be documented properly.

Section 6: Production

• 6.1 Basic Manufacturing Requirements
  • GMP-compliant and validated equipment and processes
  • Proper sanitation, and hygiene
• 6.2 Process Validation
  • Validation of equipment, systems, processes, materials, or any procedures should be performed/verified.
  • The validation criteria may vary depending on the nature/complexity of the product being produced.

Section 7: Packaging

• 7.1 Packaging operations must adhere to an approved standard operating procedure (SOP).
  • Pre-checks of materials, equipment, workspaces
  • Verification of coded materials before packaging.
  • Strict adherence to documentation and tracking of packaging process
• 7.2 All product-packaging operations must be reviewed thoroughly by quality control staff before releasing products for distribution/delivery.
  • A thorough check should be done that verifies packaged items are according to the master procedure/packaging order
• 7.3 Verification of finished products and packaging labels against production procedures, batch records, etc.
• 7.4 Coding of Packaging Materials/Components
• Proper procedures should be followed to avoid mix ups and confusion

Section 8: Finished Product Quarantine & Delivery

• 8.1Finished products should be properly and thoroughly checked against SOPs and Quality Control standards; records should be made of the quality assessments and reprocessing procedures.
  • Finished products will be under quarantine until released by quality control staff.
  • Only authorized personnel are allowed to access the quarantine area.

Section 9: Quality Control

• 9.1 General Provisions
  • Quality control systems should consistently ensure that manufactured products meet established quality and safety standards.
  • The Quality Control Unit (QCU) has responsibility for reviewing, recording, and managing tests, standards, and monitoring processes.
  • QCU has a clear role in product inspection, testing, evaluating and determining release/rejection status of any manufacturing output.
• 9.2 Control Laboratory
  • QCU premises/facilities should conform to relevant standards and procedures in terms of suitability, size, equipment, and safe storage of any sensitive samples. -Personnel involved in Quality Control must be properly trained and educated for their roles(laboratory technicians, analysts, etc.). -Equipment calibration, maintenance, monitoring of samples should be done properly and documented thoroughly and promptly.
• 9.3 Validation
  • Quality control procedure validations/method testing, procedures should be based on established parameters.
  • Records of the testing and evaluation processes must be maintained and stored for reference.
  • Validation should be performed based on the nature and complexity of the product being manufactured. -9.4 Control of Starting, Intermediate, Bulk and Finished Products
  • Validation and control procedures/materials must be regularly performed and maintained.
• 9.5 Environmental Control
  • Procedures for gowning, cleaning, and disinfection, or pest control should be adhered to and appropriately documented.
• Environmental monitoring should monitor and control contaminants and maintain clean areas that are free from pollutants.

Section 10: Documentation

• 10.1 General Provisions
  • Documentation should be easily understood.
  • Records of production, quality control, maintenance, warehouse, distribution, and all other Good Manufacturing Practices must exist.
• 10.2 Specifications
  • Materials are thoroughly documented to track their unique characteristics;
  • Product specifications including details on identity, purity, quality, expiration date, storage conditions, etc.
• 10.3 Production Documents
  • Master Batch Processing Record: This detailed record tracks every stage of the manufacturing process for each batch, from the starting materials to the final product.
  • Master Packaging Procedure: This record specifies how the products are processed/handled.
  • Batch Processing Record: Includes data on quantity, dates, equipment used, location, results of in-process controls, and other relevant details.
• 10.4 Quality Control Documents
  • Procedures for sampling, analysis, and testing.
  • Records of analysis and test report with testing methods, calculations, tolerances, and approval/rejection data for each batch or lot.
• 10.5 Warehouse and Distribution Documents
  • Inventory cards: A record of quantities and stock status of each product at any point in time, including location, status (quarantined, released, rejected).
  • Distribution record: Maintains a history of product distributions(shipment details, recipients' names).

Section 11: Self Inspection

• 11.1 Items for Self Inspection
  • A checklist for the requirements of Good Manufacturing Practices.
• 11.2 Team of Self Inspection
  • A team of experts, drawn from inside or outside the company, is responsible for conducting periodic self-inspections.
• 11.3 Coverage and Frequency of Self Inspection
  • Detailed guidelines describing the frequency and scope of self-inspections should be available.

Section 12: Handling of Product Complaints & Returns

• 12.1 Product Complaints
  • Procedures for evaluating and addressing product complaints(adverse reactions, quality-related issues), including specific documentation requirements(details of product characteristics, locations/dates of incident, investigation results, etc.).
• 12.2 Product Recall
  • Process for product recall in response to complaints, defects, health risks, quality issues, etc, including procedure/timing for executing the recall and communication/documentation of recall steps.

Section 13: Finishing of Sterile Products

• Sterile product finishing procedures; protocols for maintaining sterility.

Section 15: Testing for Sterility

• Guidance/procedures on sample size and required testing/sampling techniques.

This quiz covers essential concepts related to quality control systems in pharmaceutical manufacturing. It explores the function of air handling facilities, the segregation of production areas, and key activities within quality control processes. Test your understanding of safety protocols and quality assurance standards in drug product production.