Regulation of the pharmaceutical industry is conducted by national and international agencies such as FDA, EMA, and Japan's
Ministry of Health, Labor, and Welfare (MHLW). The key legislative and regulatory provisions in the US are set forth in the
US Food, Drugs, and Cosmetics Act (FD&C Act), and GMP requirements are specified in the US Code of Federal Regulations Title 21 (i.e., 21 CFR 210 and 21 CFR 211) (7, 8). In Europe, the EU Directive 2003/94/EC requires medicinal products to be manufactured in accordance with current
good manufacturing practices (CGMP), which is set out in EudraLex Volume 4: EU Guidelines to Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use (9, 10). In Japan, GMP is required for manufacturing and marketing approval under Article 14.2, Paragraph 4 of Japan's Pharmaceutical Affairs Law (11). GMP requirements for OSD facility design are in the MHLW ordinance, Regulations for Buildings and Facilities for Pharmacies (12).
These regulatory provisions are a framework for the basic requirements within OSD facilities to ensure product quality and
operator safety during the manufacturing process. OSD facilities may be designed and constructed to operate under different
production scenarios. The products manufactured in OSD facilities may vary in dosage form and degree of product hazard. The
equipment used to produce OSD forms can range from open-type manual processing to enclosed and highly automated processing.
The different types of processing can lead to numerous possible facility layouts, all of which are governed by the same basic
GMP requirements for the design, construction, and validation of OSD facilities and equipment. To meet these requirements,
the facility should:
Be of suitable size, construction, and layout to allow all required manufacturing operations, movement of personnel, product,
and equipment, and permit effective cleaning and maintenance
Be designed with adequate space and orderly flow to prevent product mix-ups and product cross-contamination
Provide protection of the product from chemical, physical, microbiological, and environmental contamination
Be designed and operated with facilities for breaks, toilets, handwashing, and garment changing, as appropriate for product
Include specific precautions to ensure that hazardous materials do not present an unacceptable level of product cross-contamination
risk or a risk to personnel or the environment
Qualify elements of the facility and equipment that are critical to product quality (1).
OSD facilities have common issues across the different unit operations and product types. Dust containment often presents
a design challenge for OSD forms, particularly with highly hazardous active ingredients. The ISPE OSD guide is intended to
help establish consistent and minimum parameters for facility design, which address these concerns and meet GMP requirements.
The guide provides guidance on risk-based approaches, product-protection requirements, design concepts for product protection,
process-control concepts, and commissioning, qualification, and validation (1, 3, 5, 6, 13–19).
Each manufacturer should define the level of control, protection, and validation appropriate to each manufacturing operation
based upon a sound understanding of the critical product and process parameters and determine the risk of product contamination
to the product mix within each manufacturing area. When existing facility renovations or modifications are made or manufacturing
procedures are changed, these changes should be evaluated in advance to determine how they may affect patient safety and product
quality. Appropriate change-control procedures should be followed in making any change to qualified equipment, systems or
validated processes. Depending upon the extent of the change and its potential to affect patient safety and product quality,
the governing regulatory agency may require notification or prior approval of a change before it is implemented. Understanding
the potential impact of a proposed change and the corresponding regulatory requirements is critical to maintaining facilities,
equipment, and processes in a qualified and validated state (1).
The ISPE Baseline Guide Risk-MaPP (i.e., Risk-Based Manufacture of Pharmaceutical Products, Rev. C is under technical review
by FDA) describes a scientific risk-based approach for the prevention of cross-contamination. The guide will, on a case-by-case
basis, determine the need for dedicated or segregated facilities in the manufacture of pharmaceutical products (4, 13).