| Comment Record |
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Commentor |
Mr. James McCarthy |
Date/Time |
2001-12-21 12:24:37 |
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Organization |
Bristol-Myers Squibb Co. |
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Category |
Company |
| Comments for FDA General |
| Questions |
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1. General Comments
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Bristol-Myers Squibb
Pharmaceutical Research Institute
Richard L. Gelb Center for Pharmaceutical Research and Development
5 Research Parkway P.O. Box 5100 Wallingford, CT 06492-7660
December 21, 2001
Dockets Management Branch
Food and Drug Administration, HFA-305
5630 Fishers Lane, Room 1060
Rockville, MD 20852
Re: Docket No. OOD-1538: Draft Guidance for Industry; 21 CFR Part 11; Electronic
Records; Electronic Signatures, Validation [66 Federal Register 48886, (September 24,2001)]
Dear Sir or Madam:
Bristol-Myers Squibb is a diversified worldwide health and personal care company with
principal businesses in pharmaceuticals, consumer medicines, nutritionals and medical devices.
We are a leader in the research and development of innovative therapies for cardiovascular,
metabolic and infectious diseases, neurological disorders, and oncology. In 2000 alone, Bristol-Myers
Squibb dedicated more than $1.8 billion for pharmaceutical research and development
activities. The company's more than 4,300 scientists are committed to discover and develop
best in class therapeutic and preventive agents that extend and enhance human life. Our current
pipeline comprises more than 50 compounds under active development.
For these reasons, we are very interested in and well qualified to comment on this FDA draft
guidance on Electronic Records; Electronic Signatures, Validation.
We commend the U.S. FDA for taking a leadership role in developing standards for the
acceptance of electronic records and signatures. The use of electronic records and signatures can
be beneficial to both industry and the FDA. We further commend the agency on developing this
validation guidance. Validation of systems, as one of the key controls for ensuring that electronic
records and signatures are accurate, reliable and trustworthy, must be clearly understood. This
guidance along with the references listed in Appendix A, provide an understanding of the key
validation principles. We believe the guidance is appropriately written at a high level, focusing
on general requirements rather than the details of validation procedures. We especially find
beneficial the emphasis that has been placed on thorough documentation of validation activity,
change control, and independence of review. Additionally, the guidance adequately addresses
the different approach toward Commercial Off- The-Shelf Software. Of particular benefit in
determining the extent of system validation needed is the use of an assessment of risk that the
system poses to product safety, efficacy, and quality. In general, we find this guidance to be
beneficial in providing useful information and recommendations to all involved with electronic
records and electronic signatures within the scope of21 CFR Part 11. We do, however, have a
few recommendations that may improve the document and these are listed below.
General Comment
The validation guidance provides general basic information on system validation. The
CDRH draft guidance on the General Principles of Software Validation additionally
provides validation information. It is recommended that the two guidances be merged into
one document providing one consistent approach to validation.
Recommendation: Combine the Electronic Records; Electronic Signatures Validation
Guidance with the CDRH Guidance on the Principles of Software Validation and issue one
guidance on validation.
2. Scope
This section of the guidance indicates that this draft guidance provides information on
acceptable ways of ensuring that electronic records and signatures are . ..compatible with
FDA' s public health responsibilities. This wording does not appear to be consistent with
that of the Part 11 regulation.
Recommendation: Replace the phrase compatible with FDA' s public health responsibilities
with generally equivalent to paper records and handwritten signatures executed on paper.
2.1 Applicability
According to this section the validation guidance applies to electronic records and electronic
signatures. For consistency with the Part 11 regulation we recommend enhancing this
wording.
Recommendation: FDA should consider adding the following phrase to the end of the first
sentence of Section 2.1 :
. ..including electronic records or signatures submitted to the agency even if such records
are not specifically identified in agency regulations.
5. Key Principles
For completeness a general explanation of validation should be added to this section of the
guidance. The explanation should indicate that validation is a continuous process that
follows the life cycle of a system from requirements specifications through system
retirement.
Recommendation: FDA should consider adding a general explanation of validation and the
need to follow an established methodology to Section 5.
5.1 System Requirements Specifications
-Traceability from Requirements Specifications through system design specifications is
important for computer systems validation. However, for purchased systems, traceability
may not be possible to design requirements and design specifications, since the vendor may
not make these available.
Recommendation: FDA should consider adding the following phrase to the beginning of the
fourth sentence to limit design specifications to in-house developed systems: For systems
developed or configured in-house, it is important. ..,
-The second paragraph addresses system performance. With the exception of realtime data
collection systems, in which performance issues should be specified in the requirements
specifications, we do not feel that performance is relevant to record authenticity, integrity,
and trustworthiness.
Recommendation: FDA should consider removing specific references to system performance
from this section of the validation guidance document.
-Examples of factors that should be considered when establishing appropriate requirements
specifications are provided. These examples may imply that all conceivable conditions must
be addressed. To avoid this misunderstanding, we feel that the list of examples should be
reduced or eliminated.
Recommendation: FDA should consider reducing or eliminating the examples of factors that
should be considered when establishing requirements specifications.
5.2.2 Validation Procedures
It is unclear whether this section refers to a detailed Test Plan/Protocol, Test Cases/Scripts,
or documented evidence of conducting the actual tests.
Recommendation: FDA should consider clarifying this section of the guidance document
with examples and/or use of accepted terminology such as Test Protocol or Test Cases.
5.3 Equipment Installation
Installation Qualification (IQ}, Operational Qualification (OQ}, and Production Qualification
(PQ} are terms commonly used throughout the industry when referring to equipment
installation and testing. It may be useful to discuss these terms in this guidance.
Recommendation: FDA should consider adding information on IQ, OQ, and PQ to the
guidance.
5.4.1 Key Testing Considerations
-The draft guidance indicates that test conditions should extend to ...branches, data flow,
and combinations of inputs. This terminology is unclear .
Recommendation: FDA should consider either providing examples to clarify these tenus or
eliminating the tenus.
-A key testing consideration listed in the draft guidance is simulation tests which, according
to the draft guidance, should be conducted off-line, The use of the term off-line may be confusing.
Recommendation: FDA should consider changing the term off-line to conducted in an
environment that is separate from the actual users computing environment.
-A key testing consideration listed in the draft guidance is Live, user-site tests which,
according to the draft guidance are . ..performed in the end user's computing environment
under actual operating conditions. This sentence is unclear and in order to avoid confusion
we recommend that the FDA consider clarifying this statement. Additionally, the draft
guidance indicates that this Testing should cover continuous operations for a sufficient time
to allow the system to encounter a wide spectrum of conditions and events in an effort to
detect any latent faults that are not apparent during normal activities. We believe that this
statement may be confusing in that the wide spectrum of conditions and events may be
considered normal activity.
Recommendation: FDA should consider clarifying the statement regarding live, user-site
tests indicating that the user environment should be closely monitored to assure conformance
to requirements. We further recommend that FDA consider clarifying the last sentence of
section 5.4.1 by eliminating the last phrase, ...that are not apparent during normal
activities.
5.7 Independence of Review
The draft guidance indicates that . ..computer system validation should be performed by
persons other than those responsible for building the system. We agree with the agency on
the importance of independence of review but recommend clarification of the term
computer system validation. Computer system validation is a process made up of various
components including designing and building the system.
Recommendation: FDA should consider changing the term computer system validation in
this case to computer system testing.
5.8 Change Control
We agree with the agency on the importance of change control and maintaining a system in a
validated state. However, we feel that the term revalidation may be misleading since the
process of change control, if properly implemented, should allow for an evaluation of
changes and a determination of any additional testing required to maintain the system in a
validated state.
Recommendation: FDA should consider replacing the term revalidation with retesting in
this section of the draft guidance.
BMS appreciates the opportunity to provide comment and respectfully requests that FDA
give consideration to our recommendations. We would be pleased to provide additional
pertinent information as may be requested.
Sincerely,
Daniel Klingler, PhD
Sf. Vice President
Information & Knowledge Management
Susan Voigt
Vice President
Environmental Health & Safety and Corporate Product Quality
Laurie Smaldone, M.D.
Sr. Vice President
Global Regulatory Science
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