This webinar will define what is the US FDA's expectations for proper laboratory practices, systems, equipment usage, and documentation / record-keeping. It will evaluate the requirements for how basic Quality Management System (QMS) expectations/requirements are addressed in the lab environment. The webinar with evaluate pharma GMPs and 21 CFR 58 and associated regulations to see how the GLPs can be implemented in the real world to achieve FDA requirements and ensure the accuracy and repeatability/reproducibility of lab results. This webinar is intended to provide guidance regarding Good Laboratory Practices (GMP) and lab equipment and analytical methods validation for use in pharmaceutical manufacturing and clinical trials and for use by contract laboratories that support the regulated medical products industries. Register, https://conferencepanel.com/conference/good-laboratory-practices-glp-and-usp-1058-validation

1. Webinar on
“US FDA Good Laboratory
Practices (GLP) and USP 1058
Validation”
Speaker: John E. Lincoln
J. E. Lincoln and Associates LLC
© 2023 by J. E. Lincoln & Associates LLC. All rights reserved.
1

2. AGENDA
• Introduction to the GLPs
• 21 CFR 58
• Pharmaceutical CGMPs, 21 CFR 210 and – 211
• Drug “QSIT” for Key CGMP Sections
• USP 1058, Analytical Equipment Qualification
• Q&A
2

3. The GLPs
3
Scope:
• 21 CFR 58 prescribes Good Laboratory Practices for conducting nonclinical laboratory
studies that support or are intended to support applications for research or marketing
permits for products regulated by the Food and Drug Administration, including food
and color additives, animal food additives, human and animal drugs, medical devices
for human use, biological products, and electronic products.
• Compliance with Part 58 is intended to assure the quality and integrity of the safety
data filed pursuant to the Federal Food, Drug, and Cosmetic Act and applicable sections
of the Public Health Service Act.

4. Facilities
4
• Each testing facility shall be of suitable size and construction to facilitate the proper
conduct of nonclinical laboratory studies.
• It shall be designed so that there is a degree of separation that will prevent any
function or activity from having an adverse effect on the study.
• As necessary to prevent contamination or mix-ups, there shall be separate areas for:
(1) Receipt and storage of the test and control articles;
(2) Mixing of the test and control articles with a carrier;
(3) Storage of the test and control article mixtures.
• Storage areas for the test and/or control article and test and control mixtures shall be
separate from areas housing the test systems and shall be adequate to preserve the
identity, strength, purity, and stability of the articles and mixtures.
• Separate laboratory space shall be provided, as needed, for the performance of the
routine and specialized procedures required studies.
• Space shall be provided for archives, limited to access by authorized personnel only, for
the storage and retrieval of all raw data and specimens from completed studies.

5. Equipment
5
• Equipment used in the generation, measurement, or assessment of data and
equipment used for facility environmental control shall be of appropriate design and
adequate capacity to function according to the protocol and shall be suitably located
for operation, inspection, cleaning, and maintenance.
• Equipment shall be adequately inspected, cleaned, and maintained. Equipment used
for the generation, measurement, or assessment of data shall be adequately tested,
calibrated and/or standardized; per SOP(s).
• SOPs shall set forth in sufficient detail the methods, materials, and schedules to be
used in the routine inspection, cleaning, maintenance, testing, calibration, and/or
standardization of equipment, and shall specify, when appropriate, remedial action to
be taken in the event of failure or malfunction of equipment, and shall designate
responsibilities.
• Records shall be maintained of all inspection, maintenance, nonroutine repairs, testing,
calibrating and/or standardizing operations.
• Records of nonroutine repairs shall document the nature of the defect, how and when
the defect was discovered, and any remedial action taken in response to the defect.

6. Facilities / Operations / Changes
6
• A testing facility shall have SOPs setting forth nonclinical laboratory study methods that
management is satisfied are adequate to insure the quality and integrity of the data
generated in the course of a study.
• All deviations in a study from standard operating procedures shall be authorized by the
study director and shall be documented in the raw data.
• Significant changes in established standard operating procedures shall be properly
authorized in writing by management.
• Each area shall have immediately available laboratory manuals and SOPs relative to the
laboratory procedures being performed. Published literature may be used as a
supplement to standard operating procedures.
• A historical file of standard operating procedures, and all revisions thereof, including
the dates of such revisions, shall be maintained.

7. Storage / Retrieval of Records / Data
7
• All raw data, documentation, protocols, final reports, and specimens (except those
specimens obtained from mutagenicity tests and wet specimens of blood, urine, feces,
and biological fluids) generated as a result of a nonclinical laboratory study shall be
retained.
• There shall be archives for orderly storage and expedient retrieval of all raw data,
documentation, protocols, specimens, and interim and final reports.
• Conditions of storage shall minimize deterioration of the documents or specimens in
accordance with the requirements for the time period of their retention and the nature
of the documents or specimens.
• A testing facility may contract with commercial archives to provide a repository for all
material to be retained.
• Raw data and specimens may be retained elsewhere provided that the archives have
specific reference to those other locations.
• An individual shall be identified as responsible for the archives.
• Only authorized personnel shall enter the archives.
• Material retained or referred to in the archives shall be indexed to permit expedient
retrieval.

8. Disqualification of Testing Facility
8
• The FDA may disqualify a testing facility upon finding all of the following:
• The testing facility failed to comply with one or more of the regulations set forth in
this part (or any other regulations regarding such facilities);
• The noncompliance adversely affected the validity of the studies; and
• Other lesser regulatory actions (e.g., warnings or rejection of individual studies)
have not been or will probably not be adequate to achieve compliance with the
good laboratory practice regulations.
• Once a testing facility has been disqualified, each application for a research or marketing
permit, approved or not, containing or relying upon any study conducted by the
disqualified testing facility may be examined to determine whether such study was or
would be essential to a decision. If so, the FDA shall also determine whether the study is
acceptable, notwithstanding the disqualification of the facility.
• The FDA may refer the matter to another Federal, State, or local government law
enforcement or regulatory agency for any action.
• The FDA may refuse to consider any study, if it finds it was not conducted in accordance
with the GLPs, without disqualifying the testing facility.
• A disqualified facility can be reinstated upon proof of compliance to the GLPs.

9. Drug CGMPs, 21 CFR 210 / 211
9
210.1 Status of CGMP Regulations –
“(a) The regulations set forth in this part… contain the minimum current
good manufacturing practice for methods to be used …”
“(b) The failure to comply with any regulation set forth in this part and in
parts 211 through 226 of this chapter in the manufacture, processing,
packing, or holding of a drug shall render such drug to be adulterated …
such drug, as well as the person who is responsible for the failure to
comply, shall be subject to regulatory action.”

10. Drug CGMP Elements, 21 CFR 211
10
• Subpart A- General
• B- Organization and Personnel
• C- Buildings and Facilities
• D- Equipment
• E- Control of Components …
• F- Production and Process Control
• G- Packaging and Labeling Control
• H- Holding and Distribution
• I- Laboratory Controls
• J- Records and Reports
• K- Returned and Salvaged Drug Products
= 11 elements

11. Key Drug CGMP Elements
11
US FDA’s QSIT - a “model”:
• For Medical Devices, but similar emphasis with the other industries
• Quality System Inspection Technique (devices; but note principles for
all GMP systems)
• Guidance for inspecting medical device manufacturers against the
Quality System Regulation (21 CFR Part 820) and related regulations.
• Distills the 15 subparts of 21 CFR 820 into 7, then 4 key areas (with
linkages / ties to others)
• ‘Top-down’ (vs. old ‘bottoms up’)
• ‘Subsystem’ approach
• Pre-announced inspections.

12. 2. Design Controls
12
Key Issues (adapt to Drugs / Formulation Controls):
• SOP defined / followed
• Development of new / changed product under design control,
documented
• Preparation of Risk Management Files per ISO 14971 (or ICH Q9)
• Preparation of Human Factors / Use Engineering Files per IEC 62366-
1
• All product changes documented (DHF, DMR, change control …)
• Changes verified / validated, monitored
• Compilation / maintenance of the Design History File or comparable
documentation
• Comparable pharma / dietary supplements lab controls / production
monitoring / controls …

13. 3. CAPA
13
Key Issues:
• SOP defined / followed
• Timely
• Documented
• “Closed – loop”
• Failure Investigations
• Root Cause Analysis
• Verified / validated
• Monitored, revisited
• Trended

14. 4. P & PC
14
Key Issues:
• SOP defined / followed
• HACCP principles employed
• Calibrated instrumentation
• PM program
• SOP defined
• Verified / validated
• All software / firmware validated
• E-CGMP systems validated, including to 21 CFR Part 11
• Statistical controls / trending; GR&R; Cpk …
• See QSIT Guidance Document for more inspection questions / flow
charts.

15. 15
Basic Purpose of V&V
• Not just “compliance” …
• Don’t miss the “forest” (purpose of V&V) for the “trees” (definitions,
mechanics … of V&V) …
• To prove that the system being V&V’d does what it is expected to do:
• When installed properly (IQ);
• With settings / parameters optimized (OQ);
• With “worst case” inputs (PQs);
• Repeatedly (PQs);
• Without any surprises (i.e., doesn’t do what it shouldn’t do;
PQs).

16. 16
“Qs”, “V & V”
Throughout this presentation the following “working definitions” will be
used (to be fully explained later):
• Verifications: Tests, Checks, Inspections, most Qualifications;
Verifications are performed against Requirements
• Validations: A collection of verifications / qualifications, to prove all
Requirements have been met.
• Requirements: Marketing, Manufacturing / Engineering, Standards,
Regulatory, Guidance Documents, Specifications, etc.

17. 17
Verification or Validation?
“Working Definitions”:
• Verification: Inspection, testing or checking; most “qualifications”;
Decommissioning; Product Verification: Design Output = Design Input.
• Validation: A series of verifications; may involving destructive
testing … :
– Product Validation: Customer Requirements = Resultant Product
– Process / Equipment / Facility: DQ, IQ, OQ, PQ
– Software: In-product, As-product, Process / Equipment; 11
elements (U.S. FDA guidance “model”)
– Software: QMS; 21 CFR Part 11 ER / ES
– Site “-Qualification”;
– Commissioning;
– FAT; SAT …
– Master Validation Plan or Validation Master Plan
• Protocols – the whole document, or just the test portion.

18. 18
V&V “Hierarchy”
Verification and Validation Planning [activity]
and
Development of the
Validation Master Plan [controlled document]
And Related
SOPs [controlled documents]
Proceed Somewhat Concurrently;
Then Develop
A Specific Validation Plan for each Item to be V&V’d
[part of the Test Report, a formal document];
Then Run The
Validation;
And Compile the
Validation Test Report.

19. 19
The Validation Master Plan
• Or Master Validation Plan
• Corporate, Site, Process / Product Family – Products, Process /
Equipment, Test, Software Systems
• Life cycles: concept through decommissioning
• Risk-based (ISO 14971/device; Q9/drugs/biologics)
• Product V&V : Actual Product / Output = Market Requirements / Input
• Equipment / Process V&V: DQ, IQ, OQ, PQs
• Software: As product;
In product;
Equipment / Process;
QMS (21 CFR Part 11)
• Revalidation (on “demand”, not scheduled / periodic)

20. 20
Training
Training to the GLPs should cover the information just discussed:
• Develop the Lesson Plan
• Publish the Agenda, including Description, Location, Duration,
Instructor
• Have an SOP and Training and a Record of Attendance (Attachment?)
• Conduct training (quiz with grading recommended)
• Attendees sign Record of Attendance
• Follow-up recommended
• Copies of Attendance and Agenda in personnel files.
• Enhance with CAPA findings and CGMP/GLP audit findings.
• CGMP / GLP training should be periodic / annual.

21. Course Disclaimer
21
The information provided in this workshop is taken from sources and material
which we believe to be reliable, and/or express the opinions of the writers
and/or presenter. In such condensed and generalized form, the material certainly
should not be considered a complete study or report on the subject mater,
especially as to how it might relate to a specific company / user’s application.
Conclusions are based solely on available data, and the judgments and analysis of
technical factors offered are not intended to replace the utilization of additional
research and/or appropriate professional counsel in adapting material to a
specific application.
© 2023 by J. E. Lincoln & Associates LLC. All rights reserved. Reproduction in whole or in
part without written permission is prohibited.

22. 22
➢ This is the chance to address issues that may not have been covered
to your satisfaction; or
➢ To expand a point; or
➢ To clarify a point.
➢ If there are any further questions which we were not able to get to
today please feel free to contact me directly.
Q & A