Glossary Terms

1. Active Pharmaceutical Ingredient (API)

A substance or blend used in making a drug that provides the intended effect, like
treating or diagnosing a disease.
2. Airlock
A space with multiple doors, between areas of different cleanliness levels, to control
airflow and prevent contamination when moving between rooms.
3. Authorized Person
A person approved by regulatory authorities to ensure each drug batch is manufactured,
tested, and released following regulations.
4. Batch (or Lot)
A set quantity of material processed together to ensure uniformity. In continuous
production, it's defined by a certain time or process.
5. Batch Number (or Lot Number)
A unique identifier, often a mix of numbers/letters, for each batch, used on labels,
records, and analysis certificates.
6. Batch Records
Documents detailing the history and quality aspects of each drug batch, covering all
manufacturing steps.
7. Bulk Product
A product that has completed processing but hasn’t been packaged.
8. Calibration
Process of adjusting and verifying measuring instruments against a reference standard
under specific conditions.
9. Clean Area
A space with controlled environmental conditions to reduce contamination, used in the
production of drugs.
10. Consignment (or Delivery)
The quantity of drugs supplied at one time by one manufacturer in response to an order,
potentially comprising multiple batches.
11. Contamination
Unwanted introduction of impurities (chemical, microbial, or foreign matter) during
production or storage.
12. Critical Operation
A manufacturing step that can significantly affect drug quality.
13. Cross-Contamination
Contamination of a material or product with another product during manufacturing.
14. Finished Product
The final drug form, completely manufactured, packaged, and labeled.
15. In-Process Control
Checks done during production to ensure products meet specifications, including
environment and equipment controls.
16. Intermediate Product
A partly processed item that needs further ma nufacturing before becoming a bulk
product.
17. Large-Volume Parenterals
Sterile solutions of 100 mL or more, intended for injection into the body.
18. Manufacture
All activities in making a pharmaceutical, from purchasing materials to production,
quality control, and distribution.
19. Manufacturer
A company involved in making, packaging, labeling, and handling pharmaceuticals.
20. Marketing Authorization (Product License, Registration Certificate)
A regulatory document granting approval for a product’s composition, packaging,
labeling, and shelf life.
21. Master Formula
Document outlining materials, quantities, processes, and precautions for making a
specific product quantity.
22. Master Record
A reference document that serves as the base for batch records.
23. Packaging
The process that a bulk product undergoes, including filling and labeling, to become a
finished product.
24. Packaging Material
Materials used in packaging a drug, classified as primary (direct contact) or secondary
(outer layer for shipping).
25. Pharmaceutical Product
Any substance or finished dosage intended for human or animal use, regulated by
pharmaceutical laws.
 26. Production
All steps in preparing a drug, from receiving materials to processing, packaging, labeling,
and finalizing the product.
27. Qualification
Confirming that equipment, systems, and locations function correctly and produce
expected results, often part of validation.

Glossary Terms (Continued)

28. Quality Unit(s)

A team or department separate from production, responsible for quality assurance (QA)
and quality control (QC). This could be separate QA and QC units or a single team,
depending on the organization’s size.
29. Quarantine
Temporary isolation of materials or products while awaiting approval, rejection, or
further processing.
30. Reconciliation
A comparison between expected (theoretical) and actual quantities.
31. Recovery
Reintroducing parts of previous batches or purified used materials into a new batch, after
ensuring quality.
32. Reprocessing
Repeating a manufacturing step on a batch that didn’t meet specifications. Common for
biological medicines, with procedures pre-approved by regulatory authorities.
33. Reworking
Applying an alternative manufacturing process to fix a batch that didn’t meet
specifications. Unlike reprocessing, reworking is not pre-approved and is done only as
needed.
34. Self-Contained Area
A fully separated area for specific operations, with barriers, separate air systems, and
controlled movement of people and equipment.
35. Specification
A detailed list of requirements that materials and products must meet for quality
assurance.
36. Standard Operating Procedure (SOP)
A written guide for performing specific tasks (like equipment use, cleaning, validation)
that apply broadly and may supplement specific production documents.
37. Starting Material
Any quality-assured substance used in making a drug, excluding packaging.
38. Validation
Proof that any process, material, or system produces the intended, consistent results,
following Good Manufacturing Practices (GMP). (Also see Qualification.)
Quality Management in Pharmaceuticals
Definition
In the pharmaceutical industry, quality management involves managing and implementing the
organization’s "quality policy," which is the formal direction regarding quality set by top
management.
Essential Elements of Quality Management
1. Quality System (Infrastructure):
An organization’s structure, procedures, processes, and resources.
2. Quality Assurance (QA) Activities:
Actions that ensure products or services meet quality requirements and give confidence
to customers and regulatory bodies.
These combined actions form Quality Assurance (QA), a tool for management that provides
reliability and customer confidence, especially in contracts. QA, Good Manufacturing Practices
(GMP), Quality Control (QC), and Quality Risk Management (QRM) are all interrelated parts of
quality management and involve everyone in the organization.

1. Quality Assurance (QA)

1. Principle
QA is comprehensive and includes all aspects that affect product quality, ensuring
pharmaceutical products meet the required standards for their intended use. It covers
GMP and other elements such as product design and development.
2. Key Points QA Ensures:
o Design & Development comply with GMP, Good Laboratory Practice (GLP), and
Good Clinical Practice (GCP).
o Clear Procedures: Written specifications for production and control, following
GMP.
o Defined Responsibilities: Clear managerial roles.
o Correct Materials: Ensuring appropriate starting and packaging materials.
o In-Process Controls: Regular control checks, calibrations, and validations for
consistent quality.
o Batch Certification: Ensuring finished products meet regulatory standards before
sale or supply.
 o Storage & Handling: Procedures to maintain quality during storage, distribution,
and shelf-life.
o Self-Inspection: Regular quality audits to review the QA system.
o Deviation Reporting: Recording and investigating any production issues.
o Change Approval: Evaluating and authorizing changes that may impact product
quality.
o Continuous Improvement: Regular evaluations to verify consistency and enhance
quality.
o Quality Risk Management (QRM): A structured approach to manage quality-
related risks based on science and process experience.
3. Responsibility
The manufacturer is responsible for ensuring product quality, safety, and effectiveness.
This goal requires senior management’s leadership, teamwork across departments, and
collaboration with suppliers and distributors.

2. Product Quality Review (PQR)

1. Objective
Regularly (typically yearly) assess the consistency of processes, material specifications,
and identify areas for product or process improvement.
2. Key Review Areas Include:
o Materials Used: Review of raw and packaging materials, especially from new
suppliers.
o In-Process and Finished Product Controls
o Batch Review: Analysis of failed batches and their investigation.
o Deviation & Investigation Records: Effectiveness of corrective and preventive
actions.
o Process/Method Changes
o Stability Monitoring Results: Trend identification.
o Quality Complaints and Returns
o Equipment and Utilities Qualification: Such as HVAC and water systems.
 3. Corrective Actions:
Any actions identified during reviews should be documented and completed effectively
and timely. Management procedures ensure these are regularly checked for
effectiveness.

3. Good Manufacturing Practices (GMP)

GMP is a part of QA focused on consistent product quality and safety. It is designed to reduce
risks like cross-contamination and product mix-ups.
1. Principles of GMP:
o Defined Processes: Production methods are reviewed and validated for
consistency.
o Resources: Ensure adequate staff, facilities, equipment, and materials.
o Clear Procedures: Written instructions that are specific and clear.
o Training: Ensuring operators understand and perform procedures correctly.
o Documentation: Keeping detailed records to track manufacturing and
distribution.
o Storage & Distribution: Proper handling to maintain product quality.
o Recall System: Procedures to recall any problematic batches.
o Complaint Handling: Investigating complaints and implementing corrective
measures.
Each of these points helps ensure that products meet the required standards for their intended
use and minimize risks associated with production.
Introduction
The pharmaceutical industry plays a key role in health care worldwide. It focuses on discovering,
developing, manufacturing, and selling medicines that support human health. Quality control
(QC) in the pharmaceutical industry is essential to ensure that medicines meet the required
standards and specifications, preventing problems in production and ensuring quality, identity,
and purity.
1. Goal of Quality Control: The main goal of QC in pharmaceuticals is to produce high-
quality products. This involves checking manufacturing quality to detect issues and
prevent them from recurring, ensuring the product complies with official standards.
 2. Importance of Good Manufacturing Practice (GMP): Oral liquid preparations must be
made under GMP, which ensures ingredient quality, reduces microbial contamination,
and prevents cross-contamination.
3. QC in Packaging and Storage: During packaging, storage, and distribution, measures are
taken to maintain product quality.
Types of Quality Control (QC)
1. In-Process Quality Control (IPQC): IPQC tests are done at different stages during
production to ensure the product is on track to meet quality standards. This includes:
o Monitoring and adjusting the manufacturing process to comply with standards.
o Testing for identity, strength, quality, and purity of in-process materials.
o Rejecting any materials that don’t meet standards.
2. Finished Product Quality Control (FPQC): After the manufacturing process, FPQC tests
check that the final product meets all quality requirements, which are set to ensure
stability throughout its shelf-life.
Role of Pharmacopoeias
Pharmacopoeias are official books of drug standards, providing detailed descriptions,
formulations, and quality standards. Different countries follow various pharmacopoeias, such
as:
 British Pharmacopoeia (BP)
 United States Pharmacopoeia-National Formulary (USP-NF)
 European Pharmacopoeia (PhEur)
 Indian Pharmacopoeia (IP)
These standards are used by manufacturers and regulatory authorities to maintain quality
across active pharmaceutical ingredients (APIs), excipients, and finished products.
Regulatory Agencies
International agencies like:
 FDA (USA)
 EMA (Europe)
 MHRA (UK)
 TGA (Australia)
These agencies regulate and enforce compliance with current Good Manufacturing Practices
(cGMP) to ensure the safe production of pharmaceutical products. Products that do not meet
GMP standards are not allowed on the market.
Types of Oral Liquid Preparations
1. Syrups: Thick liquids containing one or more active ingredients dissolved in a sugar-
based vehicle (often sucrose) and may have preservatives or sweeteners.
2. Elixirs: Clear, flavored solutions with high sugar or alcohol content that dissolve active
ingredients.
3. Linctuses: Thick liquids, mainly used to relieve cough; intended to be sipped slowly.
4. Mixtures: Contain active ingredients dissolved, suspended, or dispersed in a liquid; may
need shaking before use.
5. Oral Solutions: Active ingredients fully dissolved in a liquid, typically water or a mix of
water and organic solvents.
6. Oral Suspensions: Active ingredients suspended in a liquid; should be shaken to evenly
distribute particles before use.
7. Oral Emulsions: Oil-in-water mixtures where active ingredients are dissolved; need
shaking to prevent phase separation.
8. Oral Drops: Concentrated liquids administered in small doses using a dropper.
Universal Tests for Quality Control in Oral Liquid Preparations
1. Description: A visual and sensory check to assess appearance, color, odor, and taste. For
example, a syrup might be described as "red, with a mild, sweet taste and slight odor."
2. Identification: Confirms the presence of the intended active ingredient to verify the
product’s identity.
3. Assay: Measures the strength or concentration of the active ingredient to ensure proper
dosage.
4. Impurities: Checks for any unwanted substances, such as process-related impurities or
degradation products, ensuring these are within safe limits.
1. Visual Inspection
 Goal: To check if the liquid looks right and shows no signs of spoilage or contamination.
 For Oral Solutions & Oral Drops: Should be clear without any particles, cloudiness, or
color changes.
 o Why?: If it’s cloudy or discolored, this might mean the product has degraded
(chemical changes) or has been contaminated by microbes.
 For Oral Suspensions & Oral Drops (if they are suspensions):
o Issue Signs: Instability shows as "flocculants" (small clumps or particles) or
sediments (settled material) that won’t mix back in with gentle shaking.
 For Oral Emulsions & Oral Drops (if they are emulsions):
o Issue Signs: Phase separation (the layers of liquid separate) that won’t mix with
gentle shaking.
 For Powders & Granules for Liquid Preparations:
o Issue Signs: Changes in appearance or texture, like clumping, may suggest
instability.
 Key Points: Look for cloudiness, clumps, separation, or clumping as signs of problems in
these preparations.
2. pH Measurement
 Goal: Check the acidity or alkalinity (pH level) to ensure it’s stable and safe.
 Why Important?: Correct pH keeps the medicine stable and ensures it works well in the
body.
 Method: Measure the pH using a special meter and electrodes at 25°C (±2°C) to stay
consistent.
 In Practice: Pharmacopoeias (official drug quality books) list pH standards for each drug
that must be met.
3. Assay of API (Active Pharmaceutical Ingredient)
 Goal: Confirm the exact amount of API, which is the active ingredient providing the
therapeutic effect.
 Method: Use lab testing (like chromatography) to check API strength.
 Importance: Ensures the medicine works as intended since too much or too little API can
affect efficacy or safety.
4. Uniformity of Content
 Goal: Make sure each single-dose unit (like a vial or ampoule) has a consistent amount
of the active ingredient.
  Applies to: Single-dose liquids with less than 2 mg of API or less than 2% of the total
mass.
 Method: Randomly select 10 units and measure each for API content.
 Criteria: No unit should vary more than ±15% from the average content. If a dose has
more than ±25% deviation, the batch is considered to fail.
 Example: If most units contain 100 mg of API, one unit should not have less than 85 mg
or more than 115 mg.
5. Uniformity of Mass
 Goal: Ensure each single-dose unit (e.g., a bottle) weighs consistently.
 Applies to: Single-dose forms like solutions, emulsions, and powders that will be mixed
into liquids.
 Method: Weigh each of 20 units and calculate the average mass.
 Criteria: No more than two units can differ by more than 10% of the average mass, and
none should differ by more than 20%.
 Why Important?: Ensures each dose provides the same amount of medication to the
patient.
6. Mass Variation
 Goal: Check for variations in the mass of liquid removed from each container.
 Method: Weigh the amount of liquid taken from 10 containers and calculate API content
for each.
 Criteria: The acceptance value must be ≤15%. If it’s higher, an additional 20 units are
tested.
 Outcome: Ensures patients receive the intended dose without significant variation in
mass or content.
7. Uniformity of Volume
 Goal: Make sure each container has the correct volume, especially important for viscous
(thick) liquids.
 Method:
o For viscous (thicker) liquids: Weigh 10 containers to confirm the actual volume by
converting weight to volume.
 o For non-viscous (watery) liquids: Pour out the contents of 10 containers into a
calibrated measure to verify volume.
 Criteria:
o If the average volume of the 10 containers is correct, they pass.
o If one container has less than 91% or more than 109% of the stated amount, or
fails other limits (see below), then test 10 more.
o Limits:
 Up to 50 mL: Can vary up to ±9%.
 More than 50–200 mL: Can vary up to ±4.5%.
 More than 200–300 mL: Can vary up to ±3%
Uniformity of Weight
 Purpose: To verify each container has the correct weight of powdered contents.
 Procedure:
1. Select 10 containers, clean, and weigh each one with its contents.
2. Remove the powder, clean, dry, and weigh the empty container.
3. The difference in weights gives the net content weight.
 Acceptance Criteria:
o Average net weight must meet or exceed the labeled amount.

o For weights:

 ≤ 50 g: Each container's net weight can vary by ±9%.

 50–100 g: Each container’s net weight can vary by ±4.5%.
o If this is not met, check another 10 containers; no more than one of 20 can be
outside the limits.
4.9 Dose and Uniformity of Dose
 Purpose: Applicable for oral drops, ensuring each dose has consistent mass or volume.
 Procedure:
1. Drop or measure out the usual prescribed dose into a cylinder.
2. Weigh and repeat until 10 doses are obtained.
  Acceptance Criteria:
o No dose should vary by more than 10% from the average dose mass.

o The total of 10 doses must not deviate by more than 15% from the labeled total
dose.
4.10 Uniformity of Mass of Delivered Doses
 Purpose: Ensures each dose from multi-dose containers (except oral drops) is uniform.
 Procedure: Weigh 20 doses randomly taken from the container.
 Acceptance Criteria:
o No more than two doses can differ by more than 10% from the average mass.
o None should deviate by more than 20% from the average.
4.11 Phase Separation
 Purpose: Checks stability of emulsions by identifying any separation of oil and water
phases.
 Procedure:
o Observe visually for signs of phase separation.
o If separation occurs, measure separated volume over time.
o Centrifuging at a low speed can accelerate separation for testing.
 Signs of Instability: Phase separation, creaming (layering), or coalescence (droplets
joining).
4.12 Droplet Size
 Purpose: For emulsions, checks if droplet sizes stay stable over time.
 Procedure:
o Measure droplet sizes using microscopy or electronic counters.
o Techniques like light scattering can help with very small droplets.
 Importance: Increased droplet size indicates instability and potential issues with
effectiveness.
4.13 Thermal Stress
 Purpose: Evaluates stability of emulsions under temperature changes.
  Procedure:
o Expose emulsion to high temperatures (60°C) and then to lower temperatures
(40°C) in cycles.
o Repeat multiple times and assess stability after each cycle.
 Outcome: Stability is confirmed if the emulsion remains intact without phase separation
or droplet growth after the cycles.
4.14 Sedimentation Volume
 Purpose: Measures how well particles in a suspension stay evenly distributed.
 Formula: F=VuVoF = \frac{V_u}{V_o}F=VoVu
o Where VuV_uVu = sediment volume, and VoV_oVo = total volume.
 Interpretation:
o F = 1: No clear liquid on top; all particles are evenly suspended.
o F = 0.5: Sediment takes up half the volume.
o F > 1: Sediment is larger than original volume (fluffy particles).
 Shaking Test: Ensures easy mixing; mechanical devices simulate shaking.
4.15 Degree of Flocculation
 Purpose: Checks particle clumping (flocculation) in suspensions.
 Formula: β=FF∞\beta = \frac{F}{F_{\infty}}β=F∞F
o Where FFF = sedimentation volume of the flocculated suspension, F∞F_{\
infty}F∞ = sedimentation volume of the deflocculated suspension.
 Value of β\betaβ: Should be at least 1, indicating flocculated sediment volume is equal
to or greater than deflocculated volume.
4.16 Redispersibility
 Purpose: Confirms suspension can be easily mixed back evenly after storage.
 Procedure: After storage, a cylinder with the suspension is rotated to see how quickly
sediment clears and redisperses.
 Goal: Minimal shaking should be needed for uniform distribution from first to last dose.
4.17 Zeta Potential
  Purpose: Assesses stability by measuring the charge on droplets or particles, predicting
flocculation.
 Procedure: An electric current moves particles; their speed helps measure stability.
4.18 Rheology
 Purpose: Determines the flow properties of emulsions and suspensions to predict
stability.
 Factors Affecting Stability: Globule size, emulsifier, phase volume, and viscosity.
 Testing: Use cone-plate viscometers or Brookfield viscometers for viscosity
measurements.
 Plastic/Pseudoplastic Characteristics: Important in suspensions for ease of redispersion.
4.19 Microbiological Test
 Purpose: Ensures the suspension is free from harmful microbes.
 Testing Methods: Membrane filtration, plate count, and most-probable-number for
bacteria and fungi.
 Limits (IP):
o Bacteria: ≤ 1000 bacteria per gram/mL.
o Fungi: ≤ 100 fungi per gram/mL.
o E. coli: Must be absent in 1 gram/mL.
4.20 Antimicrobial Effectiveness Testing
 Purpose: Ensures that oral products (especially with water bases) can inhibit microbial
growth over time, to prevent contamination and ensure product safety.
 Procedure:
1. Sample Selection: Choose 5 original product containers if enough volume is
available.
2. Inoculation: Add microorganisms (about 0.5-1% of the product volume), reaching
a final concentration of:
 For regular oral products: 1 × 10⁵ to 1 × 10⁶ CFU/mL.
 For antacids: 1 × 10³ to 1 × 10⁴ CFU/mL.
3. Incubation: Store containers at 22.5°C (±2.5) and take samples at set intervals for
microbial counts.
 Microbial Testing Conditions:
o Each microorganism uses a specific growth medium and incubation:

 E. coli, P. aeruginosa, S. aureus: 32.5°C, 18-24 hours for inoculum; 3-5

days for recovery.
 C. albicans: 22.5°C, 44-52 hours for inoculum; 3-5 days for recovery.
 A. niger: 22.5°C, 144-240 hours for inoculum; 3-7 days for recovery.
 Acceptance Criteria (USP-NF):
o For Bacteria (oral products other than antacids): At least a 1-log reduction from
initial counts by 14 days; no increase at 28 days.
o For Yeasts and Molds: No increase at both 14 and 28 days.

o For Antacid Products: No increase from the initial count at 14 days.