Good Laboratory Practice - GLP

Scope of this post
- GLP from a Regulatory perspective
- GLP from a Quality System perspective

What is Good Laboratory Practice ?
- GLP is NOT just some good practices in a Laboratory
- GLP is a Quality System concerned with the organizational process and the conditions under which laboratory studies are
  - Planned, Performed and Monitored
  - Recorded, Reported and Archived
- Thus GLP covers the whole gamut of Laboratory Processes

Why Good Laboratory Practice ?
- The purpose of GLP is to
  - Ensure quality test data
  - Ensure sound laboratory management
  - Ensure robust conductance of laboratory testing
  - Ensure accurate reporting of test findings
  - Ensure safe archival of laboratory data

Laboratory Data Integrity
Data integrity is very critical ‐ Analytical results should
- Accurately describe the properties of the samples assessed
- Permit correct conclusions to be drawn about the quality of the samples
- Form the basis for any subsequent administrative and legal actions
- Form the basis for any customer responses

Laboratory Data Global Acceptance
Laboratory data integrity has an important international dimension
- Global acceptance of C of A
- Duplicative testing can be avoided
- Costs saved to nation and industry
- Faster disposal of registration submissions

GLP Compliance Perspective

The Drugs and Cosmetics Act, 1940
Schedule L‐1 on GLP effective Nov 2010
Schedule M ‐ Section 14 on Quality Assurance and Section 16 on Quality Control mentions about GLP
Schedule U Part III – Particulars to be recorded in Analytical Records pertains to GLP
21 CFR Part 211, US FDA cGMP
- Subpart I, Laboratory Control – stipulates detailed laboratory controls to be followed
EU GMP EudraLex Volume 4 Part 1,updated version effective Oct 2014
- Chapter 6 – Quality control
- Mentions Good QC Laboratory Practice stipulates detailed control measures
Recent Guideline from MHRA on Data Integrity essentially deals with GLP
WHO GMP Guidelines
- TRS 957 Annex 1 – WHO Good Practices for Pharmaceutical QC Laboratories
- TRS 961 Annex 2 – WHO Good Practices for Pharmaceutical Microbiology Laboratories
Other statutes and Guidelines like ICH Q7
Compliance is essential
- For patient safety primarily
- Meeting regulatory expectations
- For high level of customer confidence
- In dealing with any future litigations

Organization
- Management responsibility
  - Defining Laboratory manager’s role and responsibilities
  - Independence of laboratory function (QC&QA)
  - GLP compliance must be referred to in the Quality Manual
  - Making resources available
  - Controls on external testing labs if any
  - Use of metrics related to laboratory operations

Laboratory Facilities
- A factor that is overlooked in many organizations
- Effective and accurate laboratory activities possible only if adequate space is provided
- Adequate space includes – sample receiving and storage areas, testing areas, chemical storage areas, glassware washing areas, office areas, retention sample storage areas, document storage areas, training room etc.
- Logical workflow to avoid crisscross movements
- Crisscross movements kills productive man‐ hours in the laboratory
- Consider space requirements 10 years ahead and make provisions
- Apply principles of Lean Lab

Personnel and training
- People make or break the GLP systems
- Responsibilities should be defined, communicated and documented to avoid overlapping
- Mere training is not enough
- Talent identification and development plans
- Personnel – How crucial they are ?
  - Good facility + Good systems + Right people = Good product
  - Average facility + Good systems + Right people = Good product
  - Average facility + Average systems + Right people = Good product (still possible)
  - Good facility + Good systems + Not the right people = Poor product

Laboratory Equipment
- Automation is the answer for many of the laboratory illness
- Ideally all needed equipment should be available
- Outsourcing any tests only if justified
- Equipment qualification, maintenance
- Controls on computerized systems in line with 21CFR Part 11 and EU GMP Annex 11
- Avoid data integrity breaches involving computerized systems in the laboratory by having robust controls

Chemicals and reagents
- Chemicals, reagents and reference substances pay a vital role in the correctness of laboratory results
- Microbiological cultures and media
- Traceability in all records
- Uncontrolled cost cutting in this area could lead to increased number of laboratory deviations and OOS results

Sampling and Testing
- Sampling is a critical activity
- Sampling should be done by trained personnel
- Sample identification, samples controls and sample disposition should be as per written procedures
- Sampling of stability samples as per written procedures for stability testing
- Pharmacopoeial test procedures should be verified
- Other test procedures should be validated
- Concurrent recording of test results
- Trending of test results
- Stability testing as per written procedures

Laboratory Documentation
- Documentation is key to the laboratory process
- Laboratory documentation – Manual system, electronic system or a hybrid system
- Robust controls for original raw data and traceability
- Secured storage of documents
- Equipment qualification documents
- Method validation documents
- Method transfer documents from R&D
- Method transfer documents from other labs
- Test reports and Certificates of Analysis

Out of Specification Investigations
- Management of OOS results need special mention
- OOS and atypical results arise due to
  - Laboratory error
  - Operator error
  - Process related error (usually in mfg.)
  - Material related errors
  - Environment related factors
- Robust investigations process
- Identification of root cause
- Trending of OOS results
- CAPA process

Self Inspection
- One of the strongest tools for continual improvement if done diligently
  - Cover all laboratory areas and systems
  - Issue report as soon as possible
  - Get CAPA commitments and put CAPA tracking system in place
  - Findings discussed in management review meetings

Good housekeeping & Laboratory Safety
- Good Housekeeping and safety go hand in hand
- Employee safety, personnel protective equipment
- Laboratory garment regime and contamination control
- Equipment and facility safety; fire hazards

Risk Assessment in Laboratory
- Identifying risks in laboratory operations is business critical
- Still this is an area seldom addressed by the industry
- Lack of knowledge and / or lack of commitment
- Many a problem could have been avoided if a robust Risk Assessment process was in place.