Bioprocessing Piping and Equipment Design

A Companion Guide for the ASME BPE Standard

William M. (Bill) Huitt

• Publisher: Wiley-ASME Press Series
• Year: 2016
• Print ISBN: 9781119284239
• eBook ISBN: 9781119284253
• Edition: 1
• Topic: Technology & Engineering
• Subtopic: Technology & Engineering Research & Skills
• Index: Technology & Engineering

The only comprehensive and authoritative reference guide to the ASME Bioprocessing Piping and Equipment (BPE) standard

This is a companion guide to the ASME Bioprocessing Piping and Equipment (BPE) Standard and explains what lies behind many of the requirements and recommendations within that industry standard. Following an introductory narrative to the Standard's early history, industry related codes and standards are explained; the design and engineering aspects cover construction materials, both metallic and nonmetallic; then components, fabrication, assembly and installation of piping systems are explored. Examination, Inspection and Testing then precede the ASME BPE certification process, concluding with a discussion on system design.

The author draws on many years' experience and insights from first-hand involvement in the field of industrial piping design, engineering, construction, and management, which includes the bioprocessing industry. The reader will learn why dimensions and tolerances, process instrumentation, and material selection play such an integral part in the manufacture of components and instrumentation.

This easy to understand and navigate guide will assist engineers (design, piping, chemical, etc.) who need to understand the basis for much of the Standard's content, as do the contractors and inspectors who have to meet and validate compliance with the BPE Standard.

1
Introduction, Scope, and General Requirements of the BPE

1.1 Introduction

While the scope of the BPE Standard defines the physical and technical boundaries of what it covers, its introduction provides an overview of its intent. It also touches on the philosophical aspect of the Standard when content relevant to the needs of a user is not specifically addressed in the Standard. Meaning that, based on the relevant requirements and recommendations contained in the Standard, it is advisable to interpolate from those guidelines and requirements what would be appropriate for a particular situation not specifically covered in the Standard.

The BPE Standard, as explained in its introduction, applies to components in a processing system that come in contact with product, product intermediates, and raw material fluids. What is not mentioned, but is included by inference, is process fluids. And to be clear, what is also covered by the BPE Standard are utility services such as those that handle compendial waters and steam. Compendial waters as well as steam are those utilities that meet the requirements of the pharmacopoeias for utility fluid services. Fluid services include Water for Injection (WFI), purified water, and clean steam.

In the case of pharmaceutical manufacturing, a compendial is essentially a specification that complies with the US Pharmacopoeia (USP). There are three main pharmacopoeia organizations around the world: USP, European Pharmacopoeia (Ph. Eur.), and the Japanese Pharmacopoeia (JP). These organizations harmonize in creating drug formulary (specifications) as well as specifications for water used in the manufacture of drugs and drug products.

The BPE Standard is not a stand‐alone standard, but instead works in association with the Boiler and Pressure Vessel Code (BPVC) Section VIII and the B31.3 Process Piping Code. From a pressure vessel standpoint, the primary requirements for any pressure vessel will default to Section VIII requirements. The high‐purity (HP) BPE aspects and requirements of a pressure vessel will overlay those Section VIII requirements. That is to say, Section VIII provides the safety and integrity requirements of a pressure vessel, while BPE provides the HP cleanability requirements in addition to that.

The same holds true for BPE’s association with the B31.3 Process Piping Code. B31.3 provides the safety and integrity requirements of a piping system while BPE provides the HP cleanability requirements in addition to that. The reader of the BPE Standard will find many references to Section VIII and B31.3 throughout the Standard. There are liaison members of the BPE Standard that are also members of the BPVC and B31.3. This indeed is essential in harmonizing these codes and standards as they change and evolve over the years. Liaison efforts between the various codes and standards help provide coordination and harmonization between such codes and standards. Section 7.4.3 goes into greater detail with regard to the ways in which BPE and B31.3 work together.

1.2 Scope of the ASME BPE Standard

The ASME BPE Standard (hereinafter referred to as “Standard,” “BPE,” or “BPE Standard” depending on context) is the pseudo accepted international standard for system design, component standardization, and equipment design for the bioprocessing and pharmaceutical industries as well as other industries that require clean‐in‐place (CIP) or steam (sanitize)‐in‐place protocols. Essentially this is any process or segment of a process in which living organisms are used to facilitate the manufacturer of a product. Whether the end product is related to pharmaceutical, food, biofuel, or any other end product whose manufacturing process at some point contains living organisms, it does not matter. The need to preserve the appropriate cleanliness of a process system and its ability to prevent cross‐contamination, external contamination, and leachable contamination from wetted parts is essential.

While the Standard is specifically designated to apply only to new systems, it is acceptable to apply it to in‐service or existing systems. During the period of time this book was being written, modification to the wording of the Standard was voted on and approved to make this fact abundantly clear in the Standard. This is discussed further in Chapter 4 of this book. Before applying the Standard to existing systems, it is recommended that the existing system’s Fitness for Service (FFS) be assessed. Where applicable, this means wall thickness examinations, fatigue assessment, corrosion under insulation examination, and much more depending on the expanse of the system, its years in service, and its operating conditions while in service. All of this being of chief concern with regard to a system’s integrity with respect to its intended continued service. Such analysis should be performed by personnel experienced in FFS analysis.

With regard to existing systems that have been abandoned in place, from a purity standpoint, it is suggested that while such systems may prove to be structurally sound, they may pose a contamination risk that is simply too problematic to undertake in attempting to remediate for hygienic use. If, on the other hand, after being thoroughly examined with consideration given to verifiable cleanability, an acceptable remediation plan established, and a proper protocol written, an existing system may be deemed acceptable for possible use in HP processing. Otherwise such systems should be dismantled, left as is, or simply not considered for the purpose of a HP process or utility service.

In referring to Figure 1.2.1, the BPE Standard consists of three main segments: Preamble, Body, and Appendices, which is typical of most ASME codes and standards. And, I might add, some of the terminology used here is not necessarily what ASME would use in describing the makeup and compilation of their codes and standards. It is instead my way of compartmentalizing and describing how these code and standard books are assembled. To continue, The Preamble portion of the book describes the document’s context, points out ASME policy, acknowledges the membership, provides general information, gives a brief timeline history, and provides instruction. The Body of the Standard contains essential elements of the document divided into categories of interest referred to as Parts. This is where the requirements, recommendation, and guidance of the Standard reside. The Appendices is where ancillary dialog is added to expand on and further explain essential content contained in the body.

Figure 1.2.1 Main segments of the BPE standard

With regard to the Body of the Standard, the 2014 edition is currently divided into 10 sections referred to as Parts, as follows:

• Part GR—General Requirements: This section sets the tone and defines the scope and intent of the Standard. It defines terms that are specific to the bioprocessing industry and other terms that may have originated elsewhere and have been adopted by the BPE standard and given a definition that better relates to its intended use. It also provides a listing of documentation that is essential in meeting Food and Drug Association (FDA) compliance requirements. These are documents that would serve other industries well in proving verifiable and traceable evidence of material and workmanship.
• Part SD—Systems Design: Part SD creates a forum for lessons learned in the bioprocessing industry and also establishes standardized methodologies for achieving cleanable process systems. It provides discussion on how to design cleanability and sterility into a system and covers specific design issues with regard to instrumentation, hose assemblies, filtration, and other equipment. In addition to hydrostatic testing, this section also touches on testing fundamentals for spray balls, drainability, cleanability, and sterility. This section is one place in which the BPE Standard steps beyond the main focus of the B31.3 format. For instance, B31.3 is written and developed around the cornerstone of safety and system integrity, and the BPE, while also integrating safety and integrity, is focused mainly on providing acceptable criteria for system design. Since its inception, the SD subcommittee (SC) has taken on the task of researching accepted industry design practices that are currently being used in the bioprocessing industry. This, in an effort to validate, and, where necessary, rectify those largely unsubstantiated design practices and criteria while developing new and beneficial design criteria for adoption into the BPE Standard.
• Part DT—Dimensions and Tolerances for Process Components: Part DT has created standard dimensions for HP fittings. Prior to the availability of the BPE Standard and Part DT, there were no industry standard dimensions on fittings and valves and no common set of manufacturing tolerances. This meant that components from one manufacturer to the next were not necessarily interchangeable. This was a situation that had long presented a nightmare for many designers, forcing a situation in which all fittings had to be purchased from the same manufacturer to ensure compatibility. By working with the fitting manufacturers, they were able to create a standardized set of fittings. In addition they added a much needed option for the sulfur content of ASTM A270 stainless steel to support the use of autogenous orbital welding. This will be discussed in depth in Chapter 4 of this book.
• Part MJ—Materials Joining: For both metallic and nonmetallic material Part MJ touches on all aspects of the welding and bonding of pressure vessels, tanks, tubing, and fittings. It provides guidance on acceptable requirements related to material selection, inspection, examination, and testing. It also discusses joining processes and procedures, weld joint design and preparation, weld acceptance criteria, procedure and performance qualification, and documentation requirements. Several tables list weld acceptance criteria, and detailed graphics illustrate ac...

Table of contents

• Cover
• Title Page
• Table of Contents
• ASME BPE 2014
• List of Figures
• List of Tables
• List of Forms
• Series Preface
• Preface
• Acknowledgments
• About the Author
• 1 Introduction, Scope, and General Requirements of the BPE
• 2 Materials
• 3 Process Components
• 4 Fabrication, Assembly, and Installation
• 5 Examination, Inspection, and Testing
• 6 Equipment and Component Quality
• 7 Design
• 8 BPE Appendices
• Appendix A: Cleaning and Leak Testing Procedure
• Appendix B: Biotechnology Inspection Guide Reference Materials and Training Aids
• Appendix C: Guide to Inspections of High Purity Water Systems
• Appendix D: Guide to Inspections of Lyophilization of Parenterals
• Appendix E: Guide to Inspections and Validation of Cleaning Processes
• Appendix F: Guide to Inspections of Dosage Form Drug Manufacturer’s—CGMPR’s
• Appendix G: Guide to Inspections Oral Solutions and Suspensions
• Appendix H: Guide to Inspections of Sterile Drug Substance Manufacturers
• Appendix J: Guide to Inspections of Topical Drug Products
• Appendix K: BPE History—Letters and Notes
• Appendix L: Component Dimensions
• Further Reading
• Index
• End User License Agreement