Good Manufacturing Practices Overview

Good Manufacturing Practices (GMP)

• GMP is a system to consistently produce and control products (drugs) according to quality standards.
• It minimizes risks that can't be eliminated during testing, such as contamination.
• Risks include incorrect labels, wrong medicine, insufficient/too much active ingredients, and contamination.
• GMP applies to all production steps, beginning with materials, premises and equipment to staff training.
• Detailed, written procedures for each GMP-related process are critical.
• Documentation of consistent procedures at every stage of production is crucial.
• WHO established GMP guidelines.
• Many countries have formulated their own GMP requirements.

Early Beginnings of GMP

• Early 1900s saw house calls, home remedies, ointments, and "miracle elixirs."
• No regulations existed until 1902.
• Exposure of unsanitary meatpacking plants (1905) by Upton Sinclair increased public awareness.
• The 1906 Pure Food and Drug Act, created the earliest regulations requiring truthful labelling.

1941 Initiation of GMP

• Sulfathiazole tablets contaminated with phenobarbital led to 300 deaths/injuries (1941).
• FDA enforced revisions of manufacturing and quality control.
• Thalidomide tragedy (thousands of birth defects) strengthened regulations regarding human experimentation and drug approval.

GMP Guidelines

• Components like personnel, premises, equipment, sanitation & hygiene, documentation, quality control, and complaints are crucial.

Areas to be Covered

• Personnel (Experienced, Adequate Number, Job Descriptions, Trained)
• Health (Diseases, Open Lesions)
• Premises (Location, Design, Construction, Hygiene)
• Equipment (Location, Material, Calibration, Cleaning)
• Sanitation & Hygiene (Written Procedures, Practices, Clothing)
• Warehousing Area
• Reference Samples
• Validation and process validation
• Labels And Other Printed Materials
• Quality Control

Personnel

• Qualified and experienced personnel.
• Sufficient staff numbers.
• Well-defined job descriptions and training.
• Health checks (disease, open lesions) are essential.
• Personnel should be trained on GMP principles that affect them.
• Personnel must be qualified with appropriate education and responsibilities in writing.
• Should practice good sanitation and health habits
• Personnel should wear suitable clothing for manufacturing activities
• Avoiding direct contact with intermediates or active ingredients
• Restrictions on smoking, eating, drinking, chewing and storage of food.
• Those suffering from infections/diseases should not engage in activities.

Premises

• Location: Minimizes cross-contamination risks. Addresses geography, climate and economic factors. Minimizes risk from neighbours.
• Design: Maximum protection against insects, birds, and animals. Designated areas (production, quality control, weighing, storage, ancillary).
• Construction: Prevent cross-contamination, dust control, easily cleanable surfaces, proper air supply, use of HEPA filters (High-Efficiency Particulate Air filters), smooth impervious surfaces (floors, walls, and ceilings).
• Hygiene considerations: Prohibit eating, drinking, and smoking in production areas.

Equipment

• Equipment must be appropriate for its intended use (appropriate range, precision, and accuracy)
• Non-reactive materials for equipment surfaces that come into contact with drugs.
• Minimizes risks of contamination from lubricants, dust, and other foreign materials.
• Layout should facilitate easy cleaning and prevent cross-contamination.
• Maintenance records are kept.

Sanitation

• Written procedures, hygiene, health and clothing practices.
• Waste disposal procedures.
• Practices not permitted (eating, smoking, unhygienic practices).
• Clothing requirements (grade D and grade C).
• Sanitation regulation demands written sanitation programs developed and overseen by qualified personnel.
• Cleaning procedures, cleaning intervals, and disinfection (product application, dilution, and equipment).
• Procedures for waste material and debris, pest control, rodenticides, insecticides, and fumigation.

Verification, Qualification, and Validation

• Operational methods and procedures in manufacturing and testing are validated to ensure intended functionality.
• Validation activities conducted according to approved protocols and appropriate guidance.
• Process validation builds product quality, safety, and effectiveness into the final product.

Process Validation

• Commercial processes are based on knowledge gained during development and scale-up.
• Process qualification confirms the process's ability to produce reproducible products.
• Process verification ensures continuous process control throughout routine production.

Method Validation

• Each method used to analyze the drug substance (product identity, strength, purity, and potency) must have associated validation.

Key GMP Concepts

• Applicability of GMPs for production of innovator and generic drugs.
• GMP requirements for marketed products and clinical trial supplies including placebos.
• Maintaining product quality cannot be tested into, it must be built in through facility, equipment design, and production.
• GMPs (Good Manufacturing Practices) are continually updated or changing.

Storage Areas

• Storage capacity for various drug materials (starting, packaging, intermediates, bulk, quarantined, released, rejected, recalled).
• Clean, dry, well-lit, and temperature-controlled storage.
• Receiving and dispatch areas to protect materials from weather.
• Special storage for temperature-sensitive or high-risk materials (narcotics, radioactives, highly active materials).
• Separate areas for rejected, recalled, or returned materials.
• Separate sampling areas.

Quality Control Areas

• Separate quality control labs from production areas with appropriate space.
• Adequate storage for samples, standards, solvents, and records.
• Separate areas for instruments to reduce external contamination.

Ancillary Areas

• Separate rest, refreshment, and facilities for cleaning/changing.
• Dedicated maintenance workshop or storage areas for tools and parts away from main production.
• Animal housing well-separated.

Working areas are well-lit

Heating, ventilating, and air conditioning systems.