Professional Documents
Culture Documents
PHARMACEUTICAL ENGINEERING
The Official Magazine of ISPE A New ASTM Standard
November/December 2007, Vol. 27 No. 6
This article
clarifies the Commissioning and Qualification:
principles and
practices in the A New ASTM Standard GMP
new ASTM
Standard and Regulations
presents how
the new
standard will by Robert E. Chew and David Petko
impact the ISPE
C&Q Baseline
Guide Revision.
I
n May, 2007, the ASTM Committee E55 regulations, one can easily find the basis for
voted to approve a new standard, A Stan- what we call qualification, but no specific re-
dard Guide for Specification, Design, and quirements that relate to how qualification is
Verification of Pharmaceutical and practiced today - Sidebar 1. Furthermore, if one
Biopharmaceutical Manufacturing Systems reviews the 1987 Guideline to Process Valida-
and Equipment. This recently published stan- tion, which is where installation qualification
dard has the ASTM designation of E2500. It was first mentioned, one finds qualification
has been three years since the risk-based con- concepts discussed, but not specific how to
cept for this standard was first discussed at a implementation nor the controls and practices
meeting at ISPE headquarters in Tampa. Sev- typically applied today.
eral draft versions have been issued in the It can be argued that many of the non-
intervening time, and people at a number of valued-added aspects of qualification as prac-
conferences and speaking engagements have ticed today stem from a lack of understanding
addressed the concepts in the standard to audi- as to the intent of the GMPs related to equip-
ences around the world. It is ISPEs intent to ment suitability. Instead of acquiring and de-
update the Commissioning and Qualification ploying this understanding, companies have
Baseline Guide to reflect the principles and chosen to avoid ill perceived risk, seeking to
practices outlined in this standard; other create procedures that are at least as onerous if
Baseline Guides will be updated in due time. not more so than those of their fellow manufac-
Due to the general guidance nature of this turers (safety in numbers). Thus, they have
standard, there is significant room for inter- implemented a plethora of structural, over-
pretation. This article is intended as a precur- sight controls, and other rigid practices, which
sor to the update of the C&Q Baseline Guide when taken to the extremes many companies
in order to clarify certain aspects of the stan- take them, obscure the underlying value that
dard and to help ensure that industry doesnt can and has been added by the intent of current
misinterpret and then misapply the new Good Manufacturing Practices (cGMPs). This
standard. concept is simple: were the equipment and
For most companies, qualification is a costly systems properly installed, do they operate
and time consuming process that in some cases properly, do they perform to meet process
can delay the launch of critical medicines to requirements, do they control risks to prod-
patients. There are aspects of qualification uct quality, and will they support process
that can add value in terms of ensuring the validation?1 It is the spirit and practical ap-
equipment and systems are ready to reliably plication of this concept that is addressed by
manufacture a quality product. There are other the ASTM Standard.
aspects and documentation practices that The ASTM standard adheres to the current
clearly do not add this value. And it can be Good Manufacturing Practice (cGMP) regula-
argued that the rigid rules that surround quali- tions and describes a high level process to ensure
fication (as practiced today) can detract from manufacturing systems and equipment (includ-
its overall effectiveness. If one examines GMP ing automation) are fit for intended use such
that risks to product quality and public fication or to qualify. Several projects the World Trade Organization. Objec-
health are effectively managed. To ac- have taken the step of deleting IQ/OQ tions to any portion of the standard
complish this, the standard (1) specifies per se, and have passed an FDA pre- must be justified based on science; good
a minimum set of activities that meet approval inspection. However, we can- science was the same criteria by which
GMP regulations to form a framework not use this standard as an excuse for comments to the draft standard were
for specifying, designing, and verifying not meeting GMPs. But we can use this assessed. Use of the standard is volun-
manufacturing equipment, systems, and standard to separate GMP require- tary. However, if one chooses to use the
associated automation; (2) describes an ments from folklore qualification standard, it must be implemented in
approach to specifying, designing, and practices and expectations we ourselves its entirety; a piecemeal or partial ap-
verifying that incorporates the science have invented over the past 20 years, proach is the same as not implement-
and risk-based concepts of ICH Q8 and not to meet the intent of GMPs, but in ing the standard at all.
Q9. The standard is based on a set of 10 an ill-designed attempt to avoid regu-
principles that were first presented to latory risk. Frequently, systems that ASTM E2500 and
the Societys International Leadership were qualified via formal qualification the GMPs
Forum in April 2005 - Sidebar 2. The protocols simply did not work correctly, The first thing to note about ASTM
standard was purposefully written at a even though they had been signed off E2500 is absence of the term qualifi-
relatively high level to allow firms the as qualified. We can use this stan- cation. The term appears, but once, in
flexibility to adapt to their particular dard to help us devise and implement the definitions section: Verification...
organizational breakdown of responsi- better, more effective ways of ensuring is an umbrella term that encompasses
bilities, and to allow firms to develop our facilities, equipment, systems, and all types of approaches to assuring sys-
innovative approaches to implement- associated automation are delivered in tems are fit for use such as Qualifica-
ing these principles. Figure 1 illustrates an efficient manner using good engi- tion, Commissioning... It is interest-
how the standard fits within a regula- neering practices. Regardless of which ing to note that the US GMPs do not
tory framework and incorporates prin- methodology we choose, at the end of mention the term qualification,
ciples of Quality Risk Management the day our manufacturing systems nor do the US GMPs require docu-
(QRM). must be fit for purpose able to sup- ments labeled IQ, OQ, or PQ
The preceding paragraphs give us port the reliable manufacture of qual- and hence, neither does the stan-
cause to celebrate, but also pause to ity products and able to control risks to dard. Instead, the standard describes
exercise caution. By studying both the the patient to an acceptable level. a process, backed by key concepts, that
letter and understanding the intent of The standard was developed using allows a project team to meet the in-
the GMPs, and by understanding this a consensus approach, with content tent of what the GMPs do require -
ASTM standard, we can expunge many based on science and sound quality Sidebar 1.
of the non-value added qualification assurance principles. The ASTM orga-
practices of today. We can even rede- nization and the consensus process 1. The GMPs (211.22c) require the
fine what we mean by the term quali- mean this standard can be traceable to quality unit to approve procedures