Categories And Varieties Of Drugs With Special Properties

In the 2010 version of GMP, explicit requirements were set forth regarding the layout design of production areas involving drugs with special characteristics. Article 46 specifies six specific requirements concerning the rational design, layout, and use of production areas, with four primarily targeting drugs of special characteristics. Since the original text does not provide specific classifications or types of these drugs, and there is overlap between adjacent articles, many enterprises have encountered misunderstandings in their layout design process related to these concepts. In the following discussion, I aim to clarify these points and welcome criticisms and corrections.

"Drugs with special characteristics" is not a legal concept and is unrelated to the definition of "special drugs" in the Drug Administration Law. In GMP terms, "drugs with special characteristics" refer to medications such as those with high sensitivity, high activity, high toxicity (cytotoxic agents), hormones, and biologics. These drugs require measures during layout design and equipment provisioning to minimize contamination and cross-contamination during production, as well as to protect the health of personnel working in the production areas. The specific range of drugs varies, and according to relevant departments, companies determine appropriate control and protective measures based on factors like pharmacological and toxicological effects, normal dosage, severity of known and unknown side effects, physicochemical properties (e.g., solubility), route of administration, and absorption pathways.

For instance, "highly sensitive drugs" in GMP terms are currently limited to penicillin-class drugs. Other drugs, like cephalosporins, which are more stable and have a lower incidence of allergic reactions compared to penicillin, do not fall under the category of highly sensitive drugs. Penicillin antibiotics encompass a broad range of medications, including natural penicillins and semi-synthetic derivatives.

Regarding "highly active chemical drugs," there is no precise definition either academically or in regulatory terms. It generally refers to drugs with potent biological effects even at very low concentrations, which pose challenges in cleaning and containment. The interpretation and scope of "highly active" vary, and companies are advised to conduct risk assessments to determine whether dedicated facilities are necessary.

The term "highly toxic drugs" in GMP does not align with concepts like "toxic drugs" or "medicinal toxic drugs" in drug regulations. Medicinal toxic drugs are characterized by their potential to cause poisoning or death if improperly used, including substances like arsenic, mercury, and certain digitalis glycosides. The classification of toxic substances in chemical industries differs from that of highly toxic drugs in pharmaceutical contexts.

In pharmaceutical GMP management, "highly toxic drugs" primarily refer to cytotoxic drugs, which have significant biological hazards and can cause harm through skin contact or inhalation, affecting organs like the reproductive, urinary, hepatic, and renal systems, and posing risks of teratogenicity or reproductive harm.

The category of "β-lactam structure drugs" includes penicillin antibiotics, cephalosporins, and atypical β-lactam antibiotics. While penicillin types are discussed under highly sensitive drugs, cephalosporins and atypical β-lactams encompass various subclasses, such as cephalosporin, carbapenem, oxacephem, oxapenem, penem, and monocyclic.

Biologics encompass products made from microorganisms, cells, animal or human tissues and fluids, used in disease prevention, treatment, and diagnosis, including vaccines (including toxoids), antitoxins and antisera, blood products, cytokines, growth factors, enzymes, and other biologically active preparations. The design requirements for biologics production under GMP are similar to those for highly sensitive drugs, though it should be noted that not all biologic products require specialized facilities.

"Contraceptive drugs containing certain hormones" refer to products containing combinations of estrogen and progestin that suppress ovulation, such as short-acting oral contraceptives, long-acting oral contraceptives, injectable contraceptives, and emergency contraceptives.

The term "certain hormones" in GMP encompasses hormones other than those used in contraceptive drugs. WHO's guidelines include a wide range of hormone drugs.