GAMP Life Cycle Documents

This article Reprinted from The Official Journal of ISPE

discusses two PHARMACEUTICAL ENGINEERING® May/June 2003, Vol. 23 No. 3

life cycle

GAMP Life Cycle Documents as

documents: the
User
Requirements
Specification
(URS) and the
Effective Communications Tools
Functional
Specification by Matt Bothe, PE
(FS).

I
Introduction ning with the URS and FS, represents only one
magine a resource from which engineers, stage of overall product development, and does
designers, and end users can draw practi- not stop at the successful completion of Perfor-
cal information that compiles the good mance Qualification (PQ) testing. However,
practices, procedures, and technical compe- since much of the work is required to essen-
tence of top operators and researchers, and has tially “break the ground” of a new production
validation significance. This compilation of best line (or product line enhancement), many enti-
practice may be found in the GAMP Guidance, ties with a broad range of differentiated tasks
a comprehensive reference of good practice, are often involved, thereby requiring some
tailored specifically to automated systems. An mechanism to organize the thought processes
article covering all aspects of GAMP could not and communication among players; and as a
be justified if limited to a few pages or less; tool to coordinate the construction effort. Fol-
therefore, this article covers two key life cycle lowing PQ and throughout the useful life of the
documents: product line, the end user is generally respon-
sible for the continuation, refinement, and
• the User Requirements Specification (URS) maintenance of these life cycle documents al-
• the Functional Specification (FS) though some external consultation or support
may be retained. Therefore, the life cycle con-
The User Requirements Specification (URS) is cept as defined by the GAMP guidance is “an
intended to define end user expectations with approach to computer system development that
regard to features, functions, and overall ap- begins with identification of the User Require-
pearance of proposed process equipment and ments, continues through design, integration,
associated operations. The Functional Specifi- qualification, user validation, control and main-
cation (FS) is intended to provide a working tenance, and ends only when the commercial
interpretation of the URS and an implementa- use of the system is discontinued.” The signifi-
tion strategy by external consultants or con- cance of the FS is emphasized as a key compo-
tractors. Unlike the Code of Federal Regula- nent to life cycle documentation due to its
tions, neither the URS nor FS are directly inseparable link to the URS.
enforced by FDA mandates. Nevertheless, the According to the GAMP Guidance, the URS
development and adherence to both makes “describes what the equipment or system is
practical sense with regard to speedy develop- supposed to do, and as such is normally written
ment, competitive engineering, and the FDA- by the user. The URS may be sent to suppliers
enforced validation practices. as part of the vendor selection process. This
version should include all essential require-
URS and FS Defined ments (musts), and if possible, a prioritized set
Before the URS and FS can be defined in of desirable requirements (wants).” Therefore,
accordance to GAMP guidance, it is important the URS is essentially a document that is
to understand the association they have with generated (directly or indirectly) by the end
the stages of development or “life cycle” of a user, often with assistance from an external
particular product line. The series of life cycle consultant working on behalf of and sensitive
documents prepared up to and throughout vali- to the performance issues expressed by the end
dation, start-up, and commissioning, begin- user. It defines the key aspects of system per-

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GAMP Life Cycle Documents
formance following start-up/commissioning as verified by resource allocation issues), one may perhaps agree that it can
PQ, often initiated during Site Acceptance. Following end be quite a challenge to secure the assistance of those within
user sign-off and distribution, the end user is generally bound an end user hierarchy most closely associated with the
by the “agreed-upon” terms and conditions, as detailed in the operation and maintenance of associated equipment. As a
URS throughout the detailed design and validation periods. consequence, the dissemination of reliable and complete
The FS, on the other hand, “describes the detailed func- information on end user-anticipated performance regarding
tions of the equipment or system, i.e., what the system will do. new or revised operational equipment more often than not
An initial version of the FS may be produced as part of the falls short of an accurate and comprehensive reflection of the
supplier response. Further revisions of the FS are prepared actual needs of the ultimate users.
in conjunction with the user. The FS links to OQ which tests For the sake of accuracy and coverage of information to be
all the functions specified,” communicated by those typically included in a user requirements document, management
responsible for interpreting the URS in an effort to satisfy the support is essential to ensure all ultimate users (i.e., opera-
objectives of the end user. Therefore, the FS represents the tions and maintenance personnel) are involved. This end
effort generally put forth by those contracted by the end user user-sponsored mandatory involvement should persist
(or contractor representing the end user) to engineer, design, throughout the evolution of the URS - a level of involvement
and build equipment and/or systems to meet end user expec- mandated by the end user management team whose enforce-
tations as outlined in the URS. The assessment performed by ment policy should not interrupt normal activities of the
the end user of such effort generally occurs during Factory employees, but should be strongly encouraged such that
Acceptance Testing (i.e., at the site of development) through appropriate measures and precautions are applied (in what-
the execution of Operational Qualification (OQ) test protocols ever form that is best for the end user). If human resource
assembled by validation consultants, auditors, or groups allocation shortfalls exist and persist, the end user manage-
within the end user hierarchy. ment team should strongly consider external support that
Both the URS and FS are vital documents essential to a can be readily relied upon to fill these voids. The key objective
successful validation program -- the details of which are here is to ensure that the URS is an accurate and complete
typically outlined in the Validation Master Plan (VMP). The reflection of the precise end user expectations after project
relative positions of these key life cycle documents (under- completion. Some time also should be allocated by the end
lined) are illustrated in Figure 1. user hierarchy to review the content of the FS to ensure
Since the author of the FS is typically a contractor hired by external contractors are not only properly interpreting all
the end user to satisfy the objectives of the URS, a traceability provisions of the URS, but possess the capacity and compe-
matrix is usually advised to objectively identify and link all tencies to do so.
characteristics and propositions of the FS to the require-
ments detailed in the URS. Although not generally required, URS/FS Evolution
the preparation of a matrix is strongly encouraged to help Among the multitude of steps required for project planning
ensure the FS is an accurate and complete interpretation of and execution, all associated disciplines should find resolve
the URS. An effective matrix example (Table A) is one that is through the evolution of a vehicle tied to regulatory mandates
structured in tabular form, listing all requirements of the and enforcement. From an automation point of view, the URS
URS, followed by a brief description of the methods, proce- is typically the first document to be issued following the Basis
dures, and tangibles (i.e., hardware and software) proposed Of Design (BOD) and VMP documents that govern the design
by the FS to address each item. A ‘checked by’ column should and validation efforts respectively. During the early phases
be included for verification. of project execution, the URS may function more like a “scope
of activities” document than a document with validation
URS and FS Enforcement significance. The evolution of the URS (throughout the project
Although the URS and consequently the FS are not enforce- life cycle) progressively adds credibility to the document as a
able through FDA validation policy (i.e., 21CFR Parts 11, 210 “validation mandate” - to be verified by way of PQ testing
and 211), they are widely accepted and frequently referenced during the Site Acceptance Testing (SAT) - accepted by not
by FDA compliance auditors in determining the “validatable” only the end user, but third-party regulatory auditors as well.
state of a process unit, control system, or entire operation. By The FS, generated after the URS has been drafted, may follow
using the GAMP life cycle documents as communication tools a similar evolutionary trail with emphasis placed on equip-
to collect and refine important information pertinent to end ment operations (verified via OQ protocol execution) as op-
user performance expectations and operational requirements, posed to performance. In many cases, the end user justifiably
elements of the FDA enforcement can be derived through places more emphasis on the FS (particularly if the engineer-
validation-specific detail as referenced in the URS and FS. ing and design of a particular process is placed in the hands
These “enforcement factors” add “bite” over standard “Scope of outside contractors) to ensure compliance to the require-
Documents” and “Operational Guidelines” most often ap- ments of the end user - even if a URS has not formally been
plied as communication tools. prepared. Note, however, given the circumstance just men-
Since the End User may often lack the time and focus on tioned, an FS without a formal URS places more risk than
any particular project (often due to other priorities and/or necessary on the contractor. Therefore, the evolution of a

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URS Part Description of URS Part FS Part Description of FS Part Checked By
2.1 Control System shall utilize brand X PLC… 2.2 Model “A” PLC from X, Inc. shall be applied QRS
to perform sequential logic…
3.4 Analog I/O shall be 4-20mADC with 24 VDC 3.4 The PLC analog I/O cards shall be provided TUV
primary power for… with 250 Ohm precision…
5.2 All discrete tie-ins from field devices shall 6.3 The discrete field devices shall be linked WXY
be fieldbus… together using Devicenet…
7.1 Control System Historian shall be 21 CFR 8.2 The Historian shall consist of OS/drivers, QRS
Part 11 compliant… applications S/W, H/W…

Table A. Sample matrix.

formal URS, with “FDA bite,” is strongly encouraged to 3. FS as Key Contractor Document
improve two-way communications and assist in the solidified The FS is the key life cycle document by which external
notion of shared accountability. contractors base their designs. Therefore, an accurate, com-
plete, and end user-approved version of the FS is essential.
Benefits Many external integrators and programmers, for example,
The advantages derived through the use of GAMP-supported impose substantial “cost adders” to their proposed project
documents as vehicles to establish initial contact and main- budgets without formal end user acceptance of the FS and all
tain continuous dialog between the engineering/design and its constituents. These “cost adders” are justified and often
build contractors, and between the contractors and end users necessary to cover the increased risk of frequent and unsup-
alike are numerous; ten of these are listed: ported “after-the-fact” design changes. Therefore, the alloca-
tion of some review time toward FS acceptance often saves
1. URS as Viable Communications Tool the end user considerable costs due to “risk reduction,” as well
The importance of assembling input from the end user cannot as a reduction in unsolicited change requests. As a side note,
be underestimated. After all, the focus of most any design the end user should be cautious of any contractor who claims
project, pharmaceutical or otherwise, is to provide the end the FS is an unnecessary project component for the sake of
user the equipment and services they require to sustain a “budget reduction” and competitive bidding.
competitive margin in their respective market. Communicat-
ing the needs of the end user to those entities with the 4. Required by Validation Auditors
resources to fulfill the expectations of the end user is often a Although not an FDA mandate per se, most (if not all) entities
complex task. This is a particularly viable statement if the involved with the validation of automated systems reference
end user may not be familiar with the variety of options the URS and related documents to enhance the efficiency and
available or lack the resources to best achieve their ultimate effectiveness of the validation effort, while reducing the total
goals. Therefore, the preparation and subsequent utilization amount of preparation work, risk, and associated costs.
of GAMP life cycle documents (at least in principle) are well Therefore, the use of GAMP guidance encourages the end
positioned to “unravel” the complexities of associated infor- user to directly involve those responsible for the operation
mation exchanges - primarily through the URS and FS as and upkeep of the equipment and systems engineered and
effective communications media. specified.

2. URS as Primary Reference Document 5. URS/FS and the Divisions of Responsibilities

Considering that the BOD reflects the conceptual expecta- The associations between the URS and FS as described in this
tions of the end user with regard to capacity and approach, article provide clear distinction as to the roles and responsi-
the URS (as a working and evolutionary document) should be bilities of the external contractors/suppliers and end user.
prepared to provide direction and distinction far beyond the The importance of various project controls aimed at regulat-
intent of its earlier ancestors (including the VMP). The URS ing the effects end user “wish lists” and contractor “extras”
must contain sufficient detail to accurately and effectively have on project budgets and schedules is paramount.
direct the authors of the FS to assemble a design consistent
with the needs of not only those marketing the products of the 6. Evolution of URS/FS
end user, but also should include the needs of the operators, The evolution of the URS/FS helps to ensure continuity from
maintenance technicians, parties involved with safety/envi- one execution phase to the next, and may, depending on the
ronmental regulatory enforcement, procurement specialists, nature of the documents prepared, assist in interdisciplinary
and onsite engineers. The URS and subsequent FS are coordination - often a complex “web to untangle.”
essential components in the assurance that detailed design
efforts, as described in the Detail Design Specifications and 7. Management Of Change (MOC)
other related life cycle documents, follow the appropriate The URS/FS can be viable tools during their evolution to help
path toward compliance (to both the end user and regulatory manage change requests by both the end user and contractors
agencies). associated with a particular project. The value of the Trace-

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GAMP Life Cycle Documents
ability Matrix can be felt by ensuring the FS is updated, Significance of 21 CFR Part 11
reviewed, and approved accordingly. The URS/FS should not With the increasing availability of highly sophisticated com-
replace existing MOC procedures on either the end user or puter systems capable of processing and centrally registering
contractor side, but be structured to work with these (often enormous quantities of information, the advantages of full-
existing) sets of vital policies and procedures. Note that it is scale automation had become evident. However, with the
not uncommon for an entity’s MOC processes to have strict increased power and capacity of computer systems, coupled
CFR implications due to their potential impacts on the with the desire to electronically register, process, and file
environment and safety (i.e., 29 CFR, Part 1910.119). production data in the form of batch records, security likewise
had become an area of considerable concern. For this reason,
8. Work Scope Boundaries the FDA (in association with other regulatory agencies,
Some end users desire turnkey installations with little inter- standards organizations, manufacturing facilities, and con-
nal employee involvement, others desire absolute control. In tractors) have compiled a set of rules that the end user, and
either case, the URS, through an element of enforcement, and those in association with the end user, must comply with in
the FS, as a formal interpretation of user requirements, may order to maintain, manage, and preserve the integrity of
better define the lines between designer creativity and user historical electronic records. This set of rules are collectively
expectations, helping to minimize the occurrence of stray presented and organized in the 21 Code of Federal Regula-
tasks. tions (CFR) Part 11 (or Part 11).
The Part 11 structure consists of two key components: 1)
9. Establishing Positive Relationships Electronic Records and 2) Electronic Signatures. Per code,
Using the URS as a “scope of design” and the FS as an the concept of Electronic Records (or Erecs) “applies to those
“acknowledgement of design,” their transformations to com- in electronic form that are created, modified, maintained,
prehensive and formal validation documents for use by exter- archived, retrieved, or transmitted, under any records re-
nal validation consultants is greatly facilitated (and may quirements set forth in Agency regulations.” Therefore, for
even be greatly appreciated by both auditors and end user example, it is not in the best interests of the end user to
alike, thereby leading to additional opportunities for rela- assume all data in electronic form are subject to Part 11.
tionship building). Therefore, the URS should be the key component precisely
differentiating what information collected (by the end user) is
10. Standardization through GAMP vital for maintaining and ensuring the safety and efficacy of
The URS, FS, along with other key life-cycle documents, are their human-consumable product offerings from data to be
established validation deliverables described in the GAMP used for academic and internal purposes.
guidance to provide an element of standardization through- To ensure continued compliance to Part 11, the Electronic
out the industry. This standardization effort provides a Signatures (or Esigs) component links the electronic record
common language, terminology, and procedural task flow (and any data contained within the record) to an individual or
essential to accurate, comprehensive, and competitive project group that can verify the information is derived from reliable
implementation and maintenance - it simply makes sense. validated sources.

Figure 1. A basic framework for specification and qualification.

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 GAMP Life Cycle Documents
In addition to the identification of data subject to Part 11 3. CRB Reference Library on GAMP-related Policies and
policy, the URS (and subsequently the FS) should contain Procedures. CRB Consulting Engineers, Plymouth Meet-
references and/or statements regarding specific procedures ing, PA. Various applications and releases.
detailing the handling, security, and authentication of such
information (via username/password prompts, audit trails, About the Author
and other metrics). The overall objective of the URS/FS Matt Bothe is a licensed Professional Engi-
combination is to ensure end user compliance to Part 11 and neer in four states (NY, CT, PA, and TX) and
the total elimination of “483” violation letters issued by FDA serves as Senior Automation Engineer for
auditors. CRB Consulting Engineers, Inc. at their Ply-
This article is not intended to cover all the details of Part mouth Meeting, PA office. He is responsible
11 policy or its implementation. However, the importance of for the specification and selection of instru-
the URS/FS as vital communications tools among those mentation and process control methodolo-
parties involved in Part 11 interpretation, implementation, gies (for both continuous and batch opera-
and compliance is stressed. Note that Part 11 is a subcompo- tions), and provides comprehensive services in the areas of
nent of validation and is not intended to replace any compo- FAT/SAT/IQ/OQ/PQ, 21 CFR Part 11, and general validation
nents of the validation process. support. He possesses BS degrees in both chemical and
electrical engineering from NC State University, Raleigh,
Conclusion NC, a Certificate of Graduate Completion in hybrid circuit
Until the next revolutionary communications processes design from National Technological University, Fort Collins,
emerge, and more viable tools are identified, GAMP philoso- CO, and an MBA from Texas A&M-Corpus Christi. He is
phy can be readily applied in validated projects such as those currently an active member of ISPE and ISA, and former Key
with an automation scope. Starting with the URS/FS combi- Person Chairman for the IMC. His experiences are primarily
nation of life cycle documents, the GAMP methodology may centered on Instrumentation and Process Controls (includ-
be employed to help manage dialog between the contractors ing Advanced Control) in a variety of industries that include
and associated parties (including the end user), establish automotive, power, commodity and bulk chemicals, and
enforcement protocols, and cover bases of inconsistencies and biopharmaceuticals. Some of his major accomplishments
deviations. As the URS and subsequently the FS evolve include the design and installation of a comprehensive 17-
throughout the detailed design phases, for example, the node Power Quality Monitoring System, design and installa-
compromise between flexibility and rigidity can lead to stron- tion of redundant model-based PLC-resident Rectifier Con-
ger and more profitable end user-contractor relationships trol systems for a Chorine-Caustic production facility, ad-
well into the future…and of course, a positive reputation vanced custom controller based on Iterative Convergence
breeds a persistent flow of opportunities (not only for the end Control Technology for a major chemicals manufacturer, and
user through increased profitability, but for the contractor’s participated in and supervised numerous large and small
continued contributions to the bottom line of the customer). DCS/PCS installations in large scale chemical facilities. In
support of his areas of responsibilities, he has created numer-
References ous database and software applications using VBA, SQL, and
1. GAMP Guide for Validation of Automated Systems, GAMP Visual C++. He can be contacted at: matt.bothe@crbusa.com.
4 (ISPE (GAMP Forum), 2001). CRB Consulting Engineers, Inc., 220 W. Germantown
Pike, Suite 170, Plymouth Meeting, PA 19462.
2. Code of Federal Regulations 21, Parts 11 (August, 1997),
210, and 211.

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