A Review Article ON: cGmp Signaling: A Contemporary Overview and Future Direction

Good Manufacturing Practice (GMP) is a system that ensures products are consistently produced and controlled according to quality standards. Its primary goal is to minimize risks in pharmaceutical production, ensuring products are safe, effective, and of high quality [1,2].

To achieve this, GMP focuses on four key aspects: Raw Material Quality, ensuring materials are of known quality, standardized, and free from contamination; Risk Assessment, identifying and mitigating risks in pharmaceutical production; Inspections, regular inspections of manufacturing facilities to enforce GMP compliance; and Quality Assurance, ensuring products meet quality standards throughout the distribution chain[2,4]. GMP certification can be obtained through organizations like Certvalue and Integrated Assessment Services (IAS), which provide services such as quality management system implementation, product testing, and inspection [3,4,5].  Good Manufacturing Practices (GMP) are guidelines that ensure products are consistently manufactured to high quality standards, preventing harm to end-users. GMP applies to various industries, including [6]:

• Pharmaceuticals
• Cosmetics
• Nutritional supplements
• Food and beverages
• Medical equipment

The main goal of GMP is to ensure products are:

• Free from contamination
• Consistently manufactured
• Thoroughly documented
• Produced by well-trained staff
• Subject to regular quality inspections  

Effective implementation of GMP relies on a quality management system [6].

Purpose :

The World Health Organization's "good manufacturing guidelines" are recognized as GMP regulations under the National Medicines Regulatory Authority Act No. 5 of 2015[6,7]. In order to regulate the production of pharmaceuticals, the National Medicines Regulatory Authority (NMRA) accepts the WHO GMP principles along with any forthcoming modifications. It is expected that manufacturers will adhere to Good Manufacturing Practices in every aspect of their operations. One or more GMP inspections may be necessary before pharmaceutical manufacturers in Sri Lanka can obtain site approval for marketing authorization [7,8,].  The NMRA is obligated to carry out routine inspections as well as unplanned inspections, such as when Products are authorized for commercial use in Sri Lanka. In conjunction with all WHO GMP guidelines, this document will serve as the main basis for the GMP inspection of these production facilities [8]. The purpose of this review is to outline the regulation, production, distribution, and consumption of pharmaceuticals. It aims to depict and provide the current status of Good Manufacturing Practices (GMP) for medicinal products intended for human use, highlighting the significance of ongoing updates, regulatory harmonization, and the necessity of implementation and monitoring/inspection to foster continuous advancement in quality assurance, safety, and efficacy through a broader consensus.  The primary objective of GMP is always to avoid causing harm to the end user [8,9,10]. This entails ensuring the final product is free from contamination, that its manufacturing processes remain consistent, and that thorough documentation is maintained. The personnel involved are adequately trained, and the product has undergone more than just a final quality inspection. Generally, a quality management system is utilized efficiently to guarantee GMP [10].  

GUIDELINES :

1.  The ASUSH products will be manufactured from raw materials corresponding to the specified methods of production and composition given in API/UP/SP/HP [10].

2. The materials procured must meet the standardized specification of API/UP/SP/HP for raw materials [10].

3. The finished AYUSH products shall meet the requirements set forth in API/UP/SP/HP [11].

4. AYUSH products will be manufactured, stored, and packaged in a clean environment according to the GMP, as specified below [10,11]. 

(a) There should be cleanliness [11].

(b) Buildings must be sited, designed, built, modified as required, and kept in a condition that is appropriate for the activities to be performed. Hygienic provisions should be made [11].

(c) Ancillary areas- Rest rooms, refreshment rooms, changing rooms, lavatories should not be in direct communication with the area where production is carried out as well as the area where the stock is kept. Animal houses should be adequately separated from other areas by means of a dedicated entrance and air handling system and should not be intercommunicating [11,12]. 

(d) The area can maintain good storage conditions must be marked for storage. Items must be preserved in an arranged and orderly manner [11].

Requirements:

Materials - All components and final products must be put in quarantine upon receipt, or processing before they are made available for general use or distribution. Water Use Should Be WHO Compliant standards for drinking water quality [9,10].

Starting materials - Starting materials should be You need can have reason to documents all or with only sliprries you. PRODUCER DIRECT from the produced [9].

Labels - Product name, Batch no Content status Analytical no. +def on label of approved material.

Packaging materials - The purchase, handling Improve knowledge and awareness on waste disposal. The Wastes i.e. the waste materials, should be disposed off properly i.e. safely and securely.in a hygienic manner at normal and regular intervals [12].

Packing- The products shall be packed in clean, surgical grade bottles/containers from  made materials dosage forms, as appropriate[10].

Labeling- Name of AYUSH product Quantities of the active ingredients Dosage form Batch no. of the manufacturer Uncoded expiration date How to use directions & warnings and precautions Name & address[13].

Application

1. Pharmaceutical : cGMP guarantee the safety and effectiveness and purity of pharmaceuticals 
2. Food and Drinks: cGMP sets guidelines for hygienic and quality controlled food manufacturing procedures. 
3. Medical Devices: cGMP guarantees that medical devices are produced and controlled consistently to satisfy quality standards.  Dietary Supplements: To ensure the quality of supplements, cGMP controls their manufacture and labeling [13].
4. Cosmetics: To guarantee that cosmetic items fulfill safety standards, cGMP regulates their production and labeling [10]. 
5. Herbal medicine: Application of GMP to AYUSH Medicines (23 June 2000, Voluntary Certification Scheme for AYUSH Products under the Drug & Cosmetic Act 1940) Compared to traditional pharmaceutical products, the methods and approaches utilized in the production and quality assurance of herbal medicine are frequently very different.  Because of this, using GMP in the production of herbal medicines is crucial to ensuring their quality [10].

Principle:

Buildings and Facilities Design and Construction:

1. Facility Design: Buildings and facilities should be designed to facilitate cleaning, maintenance, and operations, and to minimize potential contamination [7,8].
2. Space and Layout: Adequate space should be provided for equipment and materials to prevent mix-ups and contamination [6,7].
3. Equipment Location: Equipment can be located outdoors if it provides adequate protection of the material [8].
4. Material and Personnel Flow: The flow of materials and personnel should be designed to prevent mix-ups or contamination [5,6].

Defined Areas and Control Systems:

1. Receipt and Quarantine: Defined areas for receipt, identification, sampling, and quarantine of incoming materials [11,13].
2. Quarantine and Release: Defined areas for quarantine and release of intermediates and APIs.
3. Sampling: Defined areas for sampling of intermediates and APIs.
4. Rejected Materials: Defined areas for holding rejected materials.
5. Storage: Defined areas for storage of released materials.
6. Production: Defined areas for production operations.
7. Packaging and Labeling: Defined areas for packaging and labeling operations.
8. Laboratory OperationsDefined areas for laboratory operations.

Fig.Defined Areas And Control Systems

Personnel Facilities:

1. Washing Facilities: Adequate, clean washing facilities with hot and cold water, soap or detergent, and air driers or single-service towels [14].
2. Toilet Facilities: Adequate, clean toilet facilities separate from but easily accessible to manufacturing areas.
3. Shower and Changing Facilities: Adequate facilities for showering and/or changing clothes when appropriate [15].

Laboratory Areas:

1. Separation from Production: Laboratory areas should normally be separated from production areas.
2. In-Process Controls: Some laboratory areas, such as those used for in-process controls, can be located near production areas [14].     

Documentation and Records:

1. Documentation System: Establish a documentation system for preparing, reviewing, approving, and distributing documents [7,8].
2. Document Control: Control the issuance, revision, superseding, and withdrawal of documents, with maintenance of revision histories [9].
3. Record Retention: Establish a procedure for retaining documents, including production, control, and distribution records [10].
4. Record Keeping: Make entries in records indelibly, directly after performing activities, and identify the person making the entry.
5. Corrections: Make corrections to entries dated and signed, leaving the original entry still readable.
6. Record Availability: Ensure records are readily available at the establishment where activities occurred [11,12].
7. Specifications: Establish and document specifications for raw materials, intermediates, APIs, and labeling and packaging materials [13].

Fig.Documentation and Records

Equipment Cleaning and Use Record:

1. Equipment Records: Maintain records of major equipment use, cleaning, sanitization, and/or sterilization, and maintenance [12].
2. Equipment Use: Record the date, time, product, and batch number of each batch processed in the equipment [13].
3. Dedicated Equipment: If equipment is dedicated to manufacturing one intermediate or API, individual equipment records are not necessary if batches follow in traceable sequence [14,15].

Fig. Equipment