FDA GLP Requirements for Analytical Instrumentation

1
FDA GLP Requirements for Analytical
Instrumentation

• Rodney T. Allnutt
• Office of Enforcement
• Office of Regulatory Affairs

2
What Well Cover

• GLP Concepts
• Part 58, Subpart D Equipment
• Data Records
• Related Sections
• Validation?

3
GLP Concepts

• The GLP regulation is intended to assure that
  nonclinical study data submitted to FDA are of
  high quality, integrity, and reliability.
• How does the regulation assure quality,
  integrity, and reliability ?

4
GLP Concepts

• The GLP regulation is intended to assure that
  nonclinical laboratory study data are of high
  quality, integrity and reliability.
• The regulation requires maintenance of records
  documentation demonstrating that controlled
  conditions are maintained and procedures are
  followed to insure the quality, integrity and
  reliability of data.

5
GLP Concepts

• Controlled conditions?
• Infrastructure
• Management
• Facilities
• Support
• Personnel
• Supervision
• Quality Assurance

6
GLP Concepts

• Controlled conditions?
• Methodology
• Protocols SOPS describing all methods? Written?
  Approved?
• Expectations for accuracy reliability are
  predetermined and documented?
• Literature references support methodology
• Records

7
GLP Concepts

• Controlled conditions?
• Equipment
• Designed specifically for what?
• Adequate capacity?
• Properly maintained, cleaned, inspected?
• Tested, calibrated, and/or standardized?
• Records

8
GLP Concepts

• Controlled conditions?
• Records Data reliability and integrity
• A attributable
• L legible
• C contemporaneous
• O original
• A accurate
• Data trails must be clear and traceable

9
Subpart D Equipment

• 58.61 Equipment Design.
• 58.63 Maintenance and calibration of equipment.

10
Subpart D Equipment

• 58.61 Equipment Design.
• Equipment used in the generation measurement, or
  assessment of data 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.
  

11
Subpart D Equipment

• Under GLP, computerized systems used in the
  generation, measurement, or assessment of data
  equipment
• How are the appropriate design and adequate
  capacity to function according to protocol
  assured verified for computerized analytical
  instruments?

12
Subpart D Equipment

• 58.63 Maintenance and calibration of
  equipment.
• (a) Equipment shall be inspected cleaned and
  maintained. Equipment used for generation
  measurement or assessment of data shall be
  adequately tested, calibrated, and/or
  standardized.

13
Subpart D Equipment

• Computerized systems used in the generation,
  measurement, or assessment of data equipment
• How are computerized analytical instruments
  adequately tested?

14
Subpart D Equipment

• 58.63 Maintenance and calibration of
  equipment.
• (b) The written SOPs required under 58.81(b)(11)
  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. The written
  SOPs shall designate the person responsible for
  each action.

15
Subpart D Equipment

• 58.63 Maintenance and calibration of
  equipment.
• (c) Written records shall be maintained of all
  inspections, maintenance, testing, calibrating
  and/or standardizing operations. These records,
  containing the date of the operation, shall
  describe whether the maintenance operations were
  routine and followed written SOPs. Written
  records shall be kept of non-routine repairs
  performed on equipment as a result of failure and
  malfunction. Such records shall document the
  nature of the defect, how and when the defect was
  discovered, and any remedial action taken in
  response to the defect.

16
GLP Records Data
17
GLP Records Data
18
Raw Data

• 58.3(k) ..are the result of original
  observations and activities.
• Originally recorded by hand to paper ? computer
  medium ? hand written data on paper raw data
• Originally recorded to computer ? data on
  computer memory raw data

19
Raw Data

• Raw data may include photographs, microfilm,
  computer print outs, magnetic media, and
  recorded data from automated instruments.
• The term raw data includes forms that are
  generated by automated instruments including
  computer printouts, and electronic, magnetic, or
  optical memories.

20
Raw Data

• In the event that exact transcripts of raw data
  have been preparedthe exact copy or exact
  transcript may be substituted for the original
  source as raw data.
• Transfer of data from medium to medium without
  loss of the raw data
• Must have suitable safeguards to ensure each
  transfer occurs completely accurately

21
Data Control

• 58.130 Conduct of a nonclinical laboratory study
  58.130(e) -
• All data generated during the conduct of a
  nonclinical laboratory study, except those
  generated by automated data collection systems,
  shall be recorded directly, promptly, and legibly
  in ink.
• All data entries shall be dated on the date of
  entry and signed or initialed by the person
  entering the data.

22
Data Control

• 58.130 Conduct of a nonclinical laboratory study
  58.130(e) cont.
• Any change in entries shall be made so as not to
  obscure the original entry, shall indicate the
  reason for such change, and shall be dated and
  signed or identified at the time of the change.

23
Data Control

• 58.130 Conduct of a nonclinical laboratory study
  58.130(e) cont.
• In automated data collection systems, the
  individual responsible for direct data input
  shall be identified at the time of data input.
• Any change in automated entries shall be made so
  as not to obscure the original entry, shall
  indicate the reason for the change, shall be
  dated, and the responsible individual identified.
  

24
Data Control some considerations for automated
systems

• Data Definition
• What data will be collected?
• Data Collection
• How will data be collected?

• Error Correction
• How are data errors corrected?
• Data Verification
• How are data verified?

25
Data Control some considerations for automated
systems

• Data Security
• How will data loss or tampering be prevented?
• Data Storage
• How will data be maintained retrieval of data
  be assured?

• Data Analysis
• How will the ability to process data be assured?
• Data Validation
• How will accuracy consistency be audited?

26
SOPS - Controls

• 58.81 Standard Operating Procedures
• Procedures are fixed in writing.
• Management reviews for adequacy to insure quality
  and integrity of data.
• Managements written authorization required
  before SOP implementation.
• Any deviation from approved SOP must be
  authorized by study director, and documented in
  raw data.

27
SOPS - Controls

• 58.81 Standard Operating Procedures are required
  for, but not limited to
• 58.81 (5) Laboratory tests.
• 58.81 (8) Collection and identification of
  specimens.
• 58.81 (10) Data handling, storage, and retrieval.
  
• 58.81 (11) Maintenance and calibration of
  equipment.

28
Protocol - Control

• 58.120
• Written and approved by sponsor and study
  director.
• Indicates all methods.
• Methods for control of bias.
• Tests, analyses, measurements.
• Records to be maintained.
• Statistical methods.
• Any change or revision documented

29
Reagent Control

• 58.83 Reagents and solutions
• Labeled with identity, titer or concentration,
  storage requirements, expiration date.
• No mix-ups or, use of deteriorated or outdated
  reagents and solutions.
• Term includes materials used as standards and in
  calibration.

30
Validation?

• Analytical instrumentation is equipment that must
  be of appropriate design adequate capacity to
  function according to the protocol
• User requirements, design specifications,
  functional specifications?
• Assessment that automated instrumentation meets
  its specifications?

31
Related GLP Controls forAnalytical Instruments

• 58.3 (k) Definition of Raw Data
• 58.29 Personnel
• 58.31 Test Facility Management
• 58.33 Study Director
• 58.35 QAU
• 58.41 Facilities
• 58.49 Laboratory Operation Areas
• 58.61 Equipment Design
• 58.63 Equipment Maintenance Calibration
• 58.81 SOPs
• 58.83 Reagents Solutions
• 58.120 Protocol
• 58.130 Study Conduct
• 58.185 Final Reports
• 58.190 Storage Retrieval of Records and Data
• 58.195 Retention of Records

32
GLP Model

• Management Responsibilities
• Supervision Requirements
• Personnel Qualifications
• Quality Assurance Procedures Requirements
• Facility Specifications Maintenance
• Environmental Controls
• Equipment Design Requirements
• Performance Specifications
• Equipment Maintenance Requirements
  Justification
• Analytical Methodology
• Equipment Calibration Standardization
  Requirements Justification
• Study Protocol
• SOPs
• In-process QA Audits with Managerial Review
  Correction
• Data Specifications
• Data Accuracy Completeness Audits (QC QA)
• Records Specifications
• Records Accuracy Completeness Audits
• Records and Data Retention Specifications

33
Validation?

• Validation A continuing process that involves
  confirmation through the examination of objective
  evidence that an intended function is reliably
  performed in conformance with specifications
  established for the function.

34
Questions?