Review of ISPE's Baseline Guide for Oral Solid Dosage Forms

The author outlines the key concepts of ISPE's recently revised Baseline Pharmaceutical Guide for New and Renovated Facilities. This article is part of a special supplement on Excipients and Solid Dosage.
May 01, 2010


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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.

Key concepts

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:

  • Airlocks
  • Multiple pressurization levels
  • One-way personnel flow
  • Special gowning procedures
  • Special cleaning procedures (1).

Risk-based approach. 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).

Non-GMP technologies. 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.