Current Good Manufacturing Practices (cGMP) are regulations enforced by the US Food and Drug Administration (FDA) that provide systems to ensure proper design, monitoring, and control of manufacturing processes and facilities. Adherence to cGMP regulations assures the identity, strength, quality, and purity of drug products by requiring that manufacturers adequately control manufacturing operations.

The concept of Good Manufacturing Practices originated in the early 20th century, but modern cGMP regulations were significantly strengthened after several pharmaceutical disasters. The 1938 Federal Food, Drug, and Cosmetic Act was the first major legislation, but the most significant development came after the thalidomide tragedy in the 1960s, leading to the Kefauver-Harris Amendments of 1962.

• Each person engaged in manufacturing must have education, training, and experience to perform assigned functions
• Training must include cGMP regulations and specific job functions
• Personnel must practice good sanitation and health habits
• Protective apparel (like uniforms, gloves, masks) must be worn as necessary
• Only authorized personnel should enter limited access areas
• Consultants advising on manufacturing must have sufficient education and experience

• Equipment must be appropriately designed, sized, and located for its intended use
• Surfaces contacting components or products must not be reactive, additive, or absorptive
• Equipment must be constructed to facilitate cleaning and maintenance
• Automatic, mechanical, or electronic equipment must be routinely calibrated, inspected, or checked
• Filters for liquid filtration must not release fibers into products

The Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S) is an influential international instrument that harmonizes GMP standards and promotes mutual recognition of inspections. PIC/S membership includes most major regulatory authorities worldwide, making its guidelines highly influential in global pharmaceutical manufacturing.

FDA conducts several types of inspections to ensure cGMP compliance:

• Pre-approval Inspections: Before approving new drug applications
• Routine Surveillance Inspections: Periodic inspections of manufacturing facilities
• For-cause Inspections: In response to specific problems or complaints
• Follow-up Inspections: To verify corrections of previously cited deficiencies

Based on FDA inspection data, the most common cGMP deficiencies include:

1. Failure to thoroughly investigate batch failures or discrepancies
2. Failure to establish adequate written procedures
3. Lack of adequate laboratory controls
4. Inadequate cleaning and maintenance of equipment
5. Poor documentation practices
6. Inadequate validation of processes and methods
7. Failure to review production records for errors
8. Inadequate stability testing programs

Modern cGMP implementation has evolved from a prescriptive, rule-based approach to a more flexible, risk-based system. The FDA's "Pharmaceutical cGMPs for the 21st Century" initiative emphasizes:

• Risk-based inspection approaches
• Science-based policies and standards
• Integrated quality systems
• International cooperation and harmonization
• Stronger post-market surveillance

QbD is a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management. Key elements include:

• Define Quality Target Product Profile (QTPP)
• Identify Critical Quality Attributes (CQAs)
• Link raw material attributes and process parameters to CQAs
• Implement control strategy
• Continuously monitor and update process

With increasing digitization, data integrity has become a critical cGMP concern. ALCOA+ principles define requirements for data: