1.

Introduction

Quality Control (QC) is a critical component of Pharmaceutical Quality Assurance (QA) that ensures
drug products meet predefined standards of safety, efficacy, purity, and consistency before reaching
consumers. QC involves testing raw materials, in-process samples, and finished products using
validated methods to detect deviations from specifications.

This detailed note covers:

 Definition and importance of QC in pharmaceuticals

 Differences between Quality Control (QC) and Quality Assurance (QA)

 Regulatory requirements (FDA, EU GMP, ICH, WHO)

 QC laboratory setup and instruments

 Key QC tests for solid, liquid, and sterile dosage forms

 Stability testing and shelf-life determination

 Out-of-Specification (OOS) and Out-of-Trend (OOT) investigations

 Good Documentation Practices (GDP)

 Challenges and best practices in QC

2. Definition and Importance of QC in Pharmaceuticals

2.1 Definition

Quality Control (QC) refers to the system of checks and tests performed on raw materials,
intermediates, and finished products to ensure they meet established specifications before release.

2.2 Importance of QC

 Ensures patient safety by detecting impurities, contaminants, or subpotent drugs.

 Complies with regulatory standards (FDA, EMA, WHO).

 Prevents batch recalls by identifying defects early.

 Maintains brand reputation by delivering consistent quality.

 Supports legal compliance (GMP, ICH Q7, 21 CFR Part 211).

3. Difference Between QC and QA

Parameter Quality Control (QC) Quality Assurance (QA)

Focus Testing products (detects defects) Ensures processes (prevents defects)

Lab testing, sampling, OOS SOPs, audits, validation, compliance

Responsibility Conducts analytical tests Oversees entire quality system

Regulatory
USP, EP, BP, JP FDA, EU GMP, ICH Q10
Basis

4. Regulatory Requirements for QC

4.1 Key Regulations

 FDA 21 CFR Part 211 (cGMP) – Mandates QC testing for raw materials and finished products.

 EU GMP Annex 8 (Sampling) – Defines sampling procedures.

 ICH Q2(R1) – Guidelines for analytical method validation.

 USP/EP/BP/JP – Pharmacopeial standards for testing.

4.2 Key Requirements

 Qualified personnel (analysts, microbiologists).

 Validated test methods (HPLC, dissolution, sterility).

 Calibrated instruments (balances, pH meters, HPLC).

 Stability studies (ICH Q1A-Q1E).

5. QC Laboratory Setup and Instruments

5.1 Laboratory Design

 Controlled environment (temperature, humidity).

 Separate areas for:

o Chemical testing (HPLC, UV-Vis).

o Microbiological testing (sterility, endotoxin).

o Sample storage (stability chambers).

5.2 Essential QC Instruments

HPLC/UPLC Purity, assay, dissolution testing

GC (Gas Chromatography) Residual solvents, volatile impurities

Dissolution Apparatus Drug release testing

UV-Vis Spectrophotometer Content uniformity, assay

FTIR (Fourier Transform IR) Raw material identification

Karl Fischer Titrator Moisture content

Microbiological Incubators Sterility, microbial limits

6. Key QC Tests for Different Dosage Forms

6.1 Tablets & Capsules (Solid Dosage Forms)

 Assay (Potency) – HPLC/UV to measure active ingredient.

 Dissolution Testing – Ensures drug release within specified time.

 Content Uniformity – Checks dose consistency.

 Friability & Hardness – Tests mechanical strength.

 Disintegration Time – Measures breakdown in simulated gastric fluid.

6.2 Liquid Dosage Forms (Syrups, Injectables)

 pH Testing – Ensures stability and compatibility.

 Viscosity – Checks flow properties.

 Particulate Matter Testing – For injectables (USP <788>).

 Sterility Testing – Membrane filtration/direct inoculation.

 Endotoxin Testing (LAL Test) – Detects bacterial toxins.

6.3 Sterile Products (Injectables, Ophthalmic)

 Sterility Assurance (USP <71>) – No microbial growth.

 Leak Testing (Container-Closure Integrity) – Prevents contamination.

7. Stability Testing & Shelf-Life Determination

7.1 Purpose of Stability Studies

 Determines expiry date (shelf-life).

 Evaluates effect of temperature, humidity, light (ICH Q1A).

 Ensures product quality over time.

7.2 Types of Stability Studies

Study Type Conditions Duration

Long-Term 25°C ± 2°C / 60% RH ± 5% 12-36 months

Accelerated 40°C ± 2°C / 75% RH ± 5% 6 months

Intermediat
30°C ± 2°C / 65% RH ± 5% 6-12 months
e

7.3 ICH Guidelines

 ICH Q1A (Stability Testing) – Defines protocols.

 ICH Q1B (Photostability) – Evaluates light sensitivity.

 ICH Q1E (Bracketing & Matrixing) – Reduces testing burden.

8. Out-of-Specification (OOS) & Out-of-Trend (OOT) Investigations

8.1 OOS Investigation (FDA Guidance)

 Phase 1 (Lab Investigation) – Check for analyst error.

 Phase 2 (Manufacturing Review) – Identify process deviations.

 Phase 3 (Full-Scale Investigation) – Root cause analysis (RCA).

8.2 OOT Investigation

 Detects gradual deviations (e.g., dissolution drift).

 Requires statistical trend analysis.

8.3 CAPA (Corrective & Preventive Actions)

 Retest affected batches.

 Modify procedures if needed.

 ALCOA+ Principles:

o Attributable, Legible, Contemporaneous, Original, Accurate.

 Electronic Records (21 CFR Part 11 Compliance) – Ensures data integrity.

 Batch Records – Must be reviewed by QA before release.

10. Challenges in QC