Oral solid dosage (OSD) forms are the most common dosage forms for patients worldwide, and the use of OSD forms (i.e., tablets,
capsules, or powders) is likely to increase as access to medical care expands on a worldwide basis. As a result, OSD production
in established markets such as the United States and Western Europe is likely to increase as is production in emerging markets
such as India, China, Brazil, Mexico, and South Korea. Pharmaceutical companies may make product internally or use contract
manufacturers, which use multipurpose production facilities. At the same time, highly active and highly hazardous substances
are becoming more and more part of drug development and, therefore, of manufacturing processes. The term highly hazardous substances refers to cytotoxic, cytostatic, teratogenic, mutagenic, or retrotoxic products. These factors have changed the picture of
pharmaceutical production in recent years and will continue to play a role in global pharmaceutical production in the future.
To address these issues, the International Society for Pharmaceutical Engineering (ISPE) released a revised Baseline Pharmaceutical Engineering Guide for New and Renovated Facilities–Volume 2 Oral Solid Dosage Forms in November 2009 (1). More than 30 industry professionals worked on the OSD guide for more than five years through a partnership
with the US Food and Drug Administration and European Medicines Agency (EMA) to develop a common understanding and interpretation
of good manufacturing practice (GMP) requirements for production facilities. The purpose of the ISPE OSD guide is to support
the design and construction of renovated and new facilities.
The recently revised ISPE OSD guide has several key elements:
Proper application of facility design and procedures to assist with GMP compliance
A risk-based approach
Non-GMP technology and its effect on facility design and costs
Contamination risk as assessed by the manufacturer
Design conditions versus operating range
Good engineering practice (GEP)
Enhanced documentation (1).
Proper balance of facility design and procedures.
To achieve the proper balance of facility design and procedures, the guide addresses each GMP issue by facility design as
well as through procedural control, facility layout, containment, and barrier technologies. This approach allows the flexibility
to design for appropriate levels of protection or containment while avoiding costly designs that may result in no significant
improvement in quality and efficacy of the drug product, or protection of personnel. For example, based upon an assessment
of contamination risk within a tableting room, one or more of the following may be applied to prevent contamination:
Multiple pressurization levels
One-way personnel flow
Special gowning procedures
Special cleaning procedures (1).
The risk-based approach involves using innovative manufacturing science and technology to assess, mitigate, and control the
potential hazard in a manufacturing process that affects the quality of the drug product. As an example, using statistical
data analysis in conjunction with process analytical technology (PAT) for continuous process monitoring and control can lead
to higher quality product. Sharing such risk-mitigation strategies with FDA may be beneficial (2).
Some facility-design requirements arise from decisions made to address non-GMP issues or preferences of the manufacturer
such as operator safety or strategic-operating decisions. These non-GMP-driven technologies often affect facility-design features
aimed at achieving GMP compliance (3). With proper planning, both GMP and non-GMP risk assessments may be completed in parallel,
enabling key drivers for capital investment to be included in the project scope.