BIOTECHNOLOGY - V. H. Herasymenko - 2006

Part I. General Biotechnology

Chapter 2. INTERNATIONAL GLP AND GMP SYSTEMS FOR THE QUALITY OF BIOTECHNOLOGICAL PRODUCTS

2.2 THE GMP SYSTEM

To ensure high product quality, the World Health Organization (WHO) approved the "Drafting Requirements for Good Manufacturing Practice in the Manufacture and Quality Control of Drugs and Pharmaceutical Personnel" in 1968. A year later, these requirements—incorporating minor amendments and clarifications—became part of the Good Manufacturing Practice (GMP) rules and were recommended by the WHO Assembly for international trade. In 1971, they were published as addenda to the second edition of the International Pharmacopoeia.

GMP is a unified system of quality control requirements for medicinal products spanning every stage from raw material Processing to finished drug production, including general specifications for facilities, equipment, and personnel. Since 1975, The Scope of GMP guidelines has expanded to cover various chemical and biological substances, veterinary drugs, starting Materials for use in dosage forms (provided they fall under the legislation of exporting and importing countries), and, finally, safety and efficacy data for all listed substances, materials, and preparations.

Following the release of the ISO 9000–9004 series of quality management standards by the International Organization for Standardization (ISO) in 1987, the existing GMP requirements had to be revised. In 1991, a special conference in Moscow reviewed a draft of the updated GMP guidelines, which comprises three parts:

1. "Quality Management in the Industrial Production of Medicinal Products: Philosophy and Core Components."

2. "Good Manufacturing Practice and Quality Control."

3. "Supplementary and Auxiliary Areas."

The first part contains 12 sections covering the organization of production quality control, sanitation and hygiene, contract manufacturing, standard operating Procedures, required documentation management, and related topics.

The second part consists of two sections: production and quality control. Regarding drug manufacturing, it stipulates that production must rely on strict adherence to technological processes in accordance with regulatory and technical documentation to yield a product of the required quality, consistent with its manufacturing and marketing authorization. Any deviation from procedures or instructions should be avoided whenever possible. If such deviations occur, they require approval, authorization, and the signature of a designated responsible person, with the involvement of the quality control department when necessary.

Operations involving different products must not be carried out in the same room unless the risk of mix-ups or cross-contamination has been eliminated.

Access to production areas must be restricted strictly to manufacturing personnel. The production of non-medical products in areas and on equipment dedicated to pharmaceutical manufacturing must be avoided. When handling dry materials and products, safety regulations must be followed to prevent the generation, accumulation, and spread of dust, which could lead to cross-contamination or microbial contamination of the manufactured products. Microbes can be introduced into the air and onto dust particles from other materials and products during their manufacture, as well as from contaminated equipment, work clothing, or personnel Skin. This can be prevented by manufacturing each target product in separate areas (such as Penicillins, live Vaccines, and other BIOLOGICALLY ACTIVE SUBSTANCES) or, at the very least, by scheduling campaigns separately; providing appropriate airlocks; utilizing protective work clothing; implementing effective equipment and wall decontamination procedures; and employing "closed system" manufacturing, among other measures.

The correct and secure connection of pipelines and other equipment used to transfer products (materials) from one area to another must be verified. Distilled or deionized Water supplied via piping must comply with sanitary and microbiological standards. Maintenance or repair operations must not compromise product quality.

Product quality control encompasses sampling, testing, documentation, and other procedures. All testing must be conducted in accordance with approved instructions for each material or product.

Sampling must be performed in a manner that prevents contamination or undesirable alterations affecting product quality, while also ensuring that the sampled material does not pose toxic or health hazards to the operator.

For each batch of product, laboratory documentation confirming that the final product meets specifications must be available prior to release.

Retention samples from each batch of the target product must be kept for a period exceeding the product's shelf life by one year. These samples must be stored in a quantity sufficient to allow at least two full re-examinations if necessary.

The third part of the GMP requirements includes sections on sterile pharmaceutical products and good manufacturing practices for bulk active pharmaceutical ingredients.

It is important to note that individuals with hypersensitivity to a specific substance (active ingredient or excipient) must not be included among the manufacturing crew. They may be assigned to work in packaging departments or workshops where contact with the allergen is absent.

In 1991, GMP regulations governing the production and quality control of medicinal products were approved. These rules align with the International GMP System and include the following sections: Introduction, terminology, personnel, buildings and premises, equipment, manufacturing process, technical control department, validation and production control, and specific requirements and manufacturing features for sterile medicinal products.

Compliance with GMP rules ensures the release of high-quality products and guarantees consumer safety. In 1995, at the proposal of the International Pharmaceutical Federation (FIP), the WHO approved GPP (Good Pharmacy Practice).

The State Department of Veterinary Medicine of Ukraine is taking measures to harmonize the existing legislative and regulatory framework with European pharmaceutical legislation by introducing standards that regulate veterinary drug manufacturing processes, distribution activities, and the inspection of pharmaceutical production. One of the stages in developing these standards is their Translation into Ukrainian and Russian by leading Ukrainian scientists and specialists.