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Seiberling
The literature began to address CIP in the pharmaceutical environment as
Seiberling (6) described a1978 vintage large-scale parenteral solutions system that
was fully designed and engineered for CIP but cleaned by rinsing with
distilled water (rinse-in-place) and sterilized by steaming (SIP). In 1987, abook
written for the pharmaceutical industry (7) reported asummary of the development
of CIP in the dairy, brewery, wine, and food processing industries prior to
1976 as background leading to the application of this technology by pharmaceutical
users. The 1987 book provided more detail about the large IV Solution
process of 1978 vintage designed to CIP standards, but only rinsed and SIP.
Attention was also given to asterile albumin process and ablood fractionation
process, both of early 1980s vintage, installed to 3-A (dairy) standards and cleaned
with full CIP programs. These projects involved the first efforts to apply an
integrated approach to piping design for the pharmaceutical process. Acomparison
of dairy and pharmaceutical piping processes and the unique problems
involved with installation of CIP/SP systems in clean rooms were also discussed
in this book.
Adams and Agarwal (8) contributed concepts in “CIP System Design and
Installation” based on current experiences in 1990, and added information about
integrated piping design was further described in “Alternatives to Conventional
Process/CIP Design—for Improved Cleanability” by Seiberling (9) in 1992. A
comprehensive review of current technology was offered by Seiberling and Ratz
(10) in the chapter “Engineering Considerations for CIP/SIP,” in Sterile Pharmaceutical
Products—Process Engineering Applications edited by Avis in 1995, and this
was perhaps the first major effort to use pharmaceutical and biotech design
examples and installation photographs. This book gave attention to the large
U-Bend TPs and mixproof valves than being placed into current projects, and
also addressed the dry drug segment of the industry.In1996, Stewart and Seiberling
(11) reported aproject which applied CIP very successfully to an agricultural
herbicide process and provided all of the challenges of the current API processes.
This project applied fully automated CIP via aCIP Skid to clean asolvent-based
process with alkali and acid in essentially the conventional manner.
Engineering design approaches and validation were jointly described by
Seiberling and Hyde (12) in (1997) in an article titled “Pharmaceutical Process
Design Criteria for Validatable CIP Cleaning,” an early effort to address the design
of avalidatable CIPable process in an exclusive publication by the Institute of
Cleaning Validation Technology. Marks (13) further explored and explained
“An Integrated Approach to CIP/SIP Design for Bioprocess Equipment” in 1999,
and in 2002 Cerulli and Franks (14) compared the cleaning regimen currently
employed in much of the API segment of the industry to the alternative CIP
procedures now being applied, but generally under manual control. Greene (15),
writing about “Practical CIP System Design” in 2003, has addressed in ascholarly
manner the subjects of flow rate and pressure, and the kinetics of CIP. Heobserved
that even with 15 years of industry experience, “Proper implementation of CIP
appears to be a mixture of art and science,” a valid observation from the
editor/author’s viewpoint also. Forder and Hyde (16) elaborate on everything
taught in the early pages of this chapter under process system design for CIP,
noting that “For the most effective use of CIP, circuits must be designed into the
facility from the beginning” and not developed as an afterthought. This article
mentions the use of potable water in some newer biopharmaceutical facilities for all