Unit 4: GLP, GCP and GMP

Good Laboratory Practice (GLP), Good Manufacturing Practice (GMP) and Good Clinical Practice (GCP) are the three quality systems that govern how safety data, medicinal products and human trials are generated so that results are reliable, traceable and reproducible. GLP emerged from the U.S. FDA in the mid-1970s after inspections revealed fabricated and poorly documented toxicology data (notably the Industrial Bio-Test Labs scandal); the FDA issued its GLP regulations under 21 CFR Part 58 in 1978, and the OECD Principles of GLP followed in 1981 to harmonise data acceptance across member countries.

• Definition (GLP): a quality system concerned with the organisational process and conditions under which non-clinical (pre-clinical) health and environmental safety studies are planned, performed, monitored, recorded, archived and reported.
• Scope distinction: GLP covers non-clinical safety testing, GCP covers human trials, GMP covers production of the marketed product.
• Core objective: data integrity — the study record must let an independent reviewer reconstruct exactly what was done.
• Common principles: written procedures, trained personnel, defined responsibilities, full documentation, independent quality checks, and traceability of materials and equipment.

II. Good Laboratory Practices (GLP)

The quality framework for non-clinical safety studies.

A. Principles and application

GLP applies to safety studies submitted to regulators, not to basic academic research.

• Where it applies: toxicology, mutagenicity, ecotoxicology, residue and pharmacokinetic studies on pharmaceuticals, pesticides, food additives, cosmetics and industrial chemicals.
• Where it does not apply: exploratory research, method-development work, and efficacy testing (which falls under other systems).
• Study director principle: each study has a single Study Director who is the point of control and bears overall responsibility for the technical conduct and final report.

B. Training

Competence must be documented before a person contributes to a study.

• Records: each staff member holds a current CV, job description and a signed, dated training record.
• Content: training covers the specific SOPs, instruments and safety procedures relevant to the assigned task, with retraining when procedures change.

C. Resources

Adequate and appropriate resources must be assigned to each study.

• People: sufficient qualified staff so that no individual is overloaded to the point of error.
• Time and facilities: realistic scheduling, and space, equipment and consumables matched to the study protocol.

D. Rules

GLP works through a defined hierarchy of controlling documents.

• Protocol (study plan): the approved, signed document defining objectives, design and methods; amendments are documented and dated.
• SOPs: standing instructions for routine operations (see Section V).
• Regulations: the applicable national code (e.g. 21 CFR Part 58 or OECD Principles) sits above both.

E. Characterization

Every test item, reference item and test system must be defined so results can be attributed correctly.

• Test/reference item: identity, batch number, purity, stability and storage conditions recorded; a retention sample kept.
• Test system: the biological or physical system used (animal, cell line, medium) is identified by source, species/strain, age and condition.

F. Documentation

The record is the study; unrecorded work is treated as not done.

• ALCOA principle: data must be Attributable, Legible, Contemporaneous, Original and Accurate.
• Raw data: original observations recorded directly, in ink, signed and dated; corrections struck through (not erased) with reason, initials and date.
• Final report: signed by the Study Director, with a compliance statement and the QA statement attached.
• Archives: all raw data, specimens, protocols and reports retained for the defined period under controlled access.

G. Quality assurance

An independent QA unit verifies compliance rather than performing the science.

• Independence: QA personnel report to management, not to the Study Director, to avoid conflict of interest.
• Inspections: study-based, facility-based and process-based audits are scheduled and reported.
• QA statement: the final report carries a statement listing inspection dates and dates reported to management and the Study Director.

III. Facilities: Building and Equipment

The physical environment that keeps studies uncontaminated and reproducible.

A. Building

Facility design must separate activities that could interfere with one another.

• Separation: distinct areas for animal housing, test-item storage, archive and administration prevent cross-contamination and mix-ups.
• Environmental control: controlled temperature, humidity, ventilation and lighting, with monitoring records; waste handling and quarantine areas defined.

B. Equipment

Instruments must be fit for purpose and demonstrably reliable.

• Qualification: installation, operation and performance checks before use.
• Calibration and maintenance: scheduled against traceable standards, with logs; defective equipment is labelled and withdrawn.

IV. GLP and FDA

The regulatory anchor of the GLP system.

A. GLP and FDA

The FDA both created the first GLP regulation and enforces it through inspection.

• 21 CFR Part 58: the binding U.S. rule for non-clinical laboratory studies supporting product applications (INDs, NDAs).
• Enforcement: FDA conducts data audits and facility inspections; deficiencies draw a Form 483 and, if unresolved, warning letters or study rejection.
• Global fit: FDA GLP and OECD GLP are closely aligned so data generated under one can support submissions in the other.

V. Stepwise Implementation of GLP and Compliance Monitoring

Turning the principles into an operating system and keeping it compliant.

A. Stepwise implementation of GLP

Implementation proceeds from management commitment to a working, auditable system.

1. Establish structure: management assigns responsibilities, appoints an independent QA unit, and names Study Directors.
2. Build the document system: write SOPs, define protocol templates, and set up the archive.
3. Prepare people and place: train staff, qualify facilities and calibrate equipment.
4. Run and verify: conduct studies under the system, then subject them to QA inspection before release.

B. Compliance monitoring

Ongoing checks confirm the system stays in the compliant state, not just at start-up.

• Internal: routine QA audits, self-inspections and management review of audit trends.
• External: national GLP monitoring authorities inspect and certify facilities; certification is periodically renewed.
• CAPA: deviations trigger corrective and preventive actions, documented and closed out.

VI. Good Manufacturing Practices (GMP)

Quality assurance for the production of medicinal and related products.

A. Definition and principles

GMP ensures products are consistently produced and controlled to the quality standards appropriate to their intended use.

• Governing rule: in the U.S., current GMP (cGMP) under 21 CFR Parts 210 and 211; the "c" stresses use of up-to-date systems.
• The 5 Ps: People, Premises, Processes, Products and Procedures are all controlled.
• Build quality in: quality cannot be tested into a finished batch; it must be designed and manufactured in.

B. Key requirements

GMP controls every input and step that can affect the finished product.

• Validated processes: manufacturing and cleaning processes proven to give reproducible results.
• Batch records: each batch fully documented so it can be traced and, if needed, recalled.
• Controls: qualified premises and equipment, controlled raw materials, in-process and finished-product testing, and released only by an authorised quality unit.
• Contamination control: hygiene, defined air classes and segregation prevent cross-contamination and mix-ups.

VII. Good Clinical Practices (GCP)

Ethical and scientific quality standard for human trials.

A. Definition and principles

GCP is an international standard for designing, conducting, recording and reporting trials that involve human subjects.

• Governing standard: ICH E6(R2) guideline, built on the ethical foundation of the Declaration of Helsinki.
• Subject protection first: the rights, safety and well-being of trial subjects prevail over the interests of science and society.
• Informed consent: freely given, documented consent obtained before any trial procedure.
• Ethics oversight: an Institutional Review Board / Independent Ethics Committee approves and monitors the protocol.

B. Key requirements

GCP assigns clear roles and demands credible, verifiable data.

• Roles: sponsor (initiates and funds), investigator (conducts at the site), and monitor (verifies conduct and data).
• Data credibility: source documents support every case report form entry, allowing reconstruction of the trial.
• Safety reporting: adverse events and serious adverse events recorded and reported within defined timelines.

VIII. Standard Operating Procedure (SOP)

The written instruction that makes routine work uniform and repeatable.

A. Introduction

An SOP is an approved, detailed written instruction for performing a specific routine operation the same way every time.

• Purpose: remove person-to-person variation and preserve institutional knowledge.
• Format: unique identifier, version number, effective date, purpose, scope, responsibilities, step-by-step procedure and references.

B. Preparation

SOPs are drafted by those who do the work and approved by those accountable for it.

• Authorship: written by a subject-expert, reviewed by QA, authorised by management before release.
• Clarity: unambiguous, sequential steps in plain language so a trained user needs no verbal guidance.
• Control: current copies available at the point of use; superseded versions withdrawn to prevent use of obsolete instructions.

C. Validation

An SOP must be shown to work before it becomes binding.

• Verification: the procedure is trialled to confirm it produces the intended, reproducible result.
• Approval: signed and dated by authorised persons; effective date recorded.

D. Revision

SOPs are living documents kept current through controlled change.

• Triggers: periodic review (typically every one to two years), process or equipment change, or an audit finding.
• Change control: revisions raise the version number, record the reason and date, and re-approval follows the original approval route; the previous version is archived, not destroyed.