Critical process parameters of RMG ( RAPID MIXER GRANULATOR )

 In pharmaceutical manufacturing, particularly in the **Rapid Mixer Granulator (RMG)**, several **Critical Process Parameters (CPPs)** must be closely controlled to ensure the granulation process is consistent, reproducible, and results in a high-quality product. These parameters directly influence the granule properties such as size, density, and uniformity, which in turn affect the drug's dissolution, bioavailability, and stability.

### Key Critical Process Parameters (CPPs) in RMG:

1. **Impeller Speed (Mixing Speed)**:

   - **Impact**: The impeller speed determines the shear and intensity of the mixing action. Too low a speed may lead to inadequate mixing, while too high can result in excessive shearing and over-granulation, which can cause poor flowability and excessive fines.

   - **Control**: Typically adjusted based on the formulation requirements, with optimal speeds being set for different stages of granulation.

2. **Chopper Speed**:

   - **Impact**: The chopper assists in breaking down large agglomerates and controlling the granule size distribution. A high chopper speed may lead to smaller granules with improved uniformity but can generate excess heat, affecting sensitive APIs.

   - **Control**: Set based on the desired granule size and mixing characteristics.

3. **Binder Solution Addition Rate**:

   - **Impact**: The rate at which binder solution is added influences the granule porosity, size, and strength. Too rapid or too slow addition can result in uneven granulation, causing inconsistencies in final product quality.

   - **Control**: Controlled by the pump speed or manual addition, typically linked to the impeller speed.

4. **Binder Concentration**:

   - **Impact**: The concentration of the binder solution plays a critical role in the formation of granules. Higher binder concentration may lead to more robust granules, while lower concentration may result in poor binding and granulation.

   - **Control**: Optimized based on the formulation’s needs, especially for ensuring good tablet compaction and uniformity.

5. **Granulation Time**:

   - **Impact**: Granulation time influences the final granule size and uniformity. Too short a granulation time may lead to under-processed granules, while too long can result in over-granulation.

   - **Control**: Typically set based on the desired endpoint of granule formation, which is often indicated by granule consistency and uniformity.

6. **Granule Moisture Content**:

   - **Impact**: The moisture content of the granules directly affects their compressibility, flowability, and drying behavior. Too much moisture may cause clumping, while too little can result in poor granulation.

   - **Control**: Monitored by moisture sensors or checked periodically by sampling to adjust binder addition or granulation time.

7. **Temperature**:

   - **Impact**: Heat generated during the granulation process can affect the physical properties of the granules, especially if the formulation is sensitive to temperature. Excessive heat may cause degradation of the API.

   - **Control**: Temperature is controlled by adjusting the mixer speed, binder addition rate, and managing any external heating or cooling systems.

8. **Granule Size Distribution**:

   - **Impact**: The particle size distribution affects the flowability, compressibility, and uniformity of the powder for tableting. Narrow size distribution is often desirable for better tablet uniformity and content uniformity.

   - **Control**: Achieved by controlling the mixing speed, chopper speed, binder addition rate, and granulation time. Particle size can also be adjusted through sieve analysis or in-line size measurement techniques.

9. **Mixing Uniformity**:

   - **Impact**: Uniformity of mixing ensures that the API and excipients are evenly distributed within the granules. Poor mixing can lead to content uniformity problems and variations in drug release.

   - **Control**: Controlled by impeller speed, chopper speed, and the duration of mixing.

10. **End-Point Monitoring (Granulation Consistency)**:

   - **Impact**: The granulation process should be monitored for the endpoint, often determined by granule consistency (moisture content, size, and flow). Stopping the process too early or too late can affect granule quality.

   - **Control**: End-point monitoring is typically based on visual assessment, moisture sensors, or sampling for granule size and uniformity.

11. **Powder Flowability Before Granulation**:

   - **Impact**: The flow properties of the powder blend before granulation (such as bulk density and Carr’s index) affect the granulation process and the final granule quality. Poor flowability may result in inconsistent mixing or granule formation.

   - **Control**: Powder flowability can be improved with the proper selection of excipients, pre-mixing, or addition of flow agents.

### Additional Considerations:

- **Mixing Profile**: The mixing behavior (whether the granules exhibit uniformity or clumping) during the initial and final stages of granulation can also be critical. It may require careful monitoring and adjustments in speed or binder addition rates.

  

- **Process Scale-Up**: The control of these parameters becomes even more critical when scaling up from pilot to production batches, as slight changes in parameters can have a significant impact on the batch quality.

### Monitoring and Automation:

Many RMGs in modern pharmaceutical production are equipped with advanced process analytical technologies (PAT) to continuously monitor these critical parameters. These technologies provide real-time data and enable better control, thus reducing the risk of deviations and ensuring consistent product quality.

Effective control of these parameters ensures that the granulation process produces consistent, high-quality granules with the right properties for downstream processing (e.g., tableting or capsule filling), meeting regulatory and quality standards.

Basics and use of HVAC system in pharma

HVAC is an essential aspect in pharmaceutical industry as factors like temperature, relative humidity and ventilation have a direct impact on the quality of the pharmaceutical product. The designing of the HVAC should be sorted out while design concept of facility is in progress as it is linked to the architectural layouts like air locks, doorways and lobbies. Once the HVAC system is properly designed and installed it not only helps to create the required room pressure differential cascades but also prevents the cross contamination. Basically an HVAC system works by transferring the heat and moisture into and out of the air and controls the level of the air pollutant either by removing them or diluting them to a particular level.

TECHNOLOGY OVERVIEW:

HVAC system varies according to the size and installation capacity within a facility but the basic components remain almost the same.

LAYOUT OF A TYPICAL BASIC HVAC SYSTEM
HEATING SYSTEM:

The heat source is either a furnace or another popular choice is boilers that heat water for steam radiators, or forced-water systems with baseboard radiators, electric heat, and heat pumps. A furnace will generally operate on natural gas or propane, while a boiler will use gas or oil to heat the water. Furnaces are generally installed with central air conditioners. Heat pumps provide both heating and cooling. Some heating systems have an integrated water heating system. Another option is a hydronic heating system also called as radiant floor. These use piping under a floor, and are made up of flexible tubes that are filled with water or a glycol solution.

COOLING SYSTEM:

The purpose of cooling equipment is to chill the water for pumping to cooling coils. From one end the treated air is then blown over the chilled water coils into the space to be cooled through the ventilation system. As part of the refrigeration cycle in the chiller, heat must also be rejected from the system via a cooling tower or condenser.

DUCT LINES AND VENTILATION:

The ducts are used within the system to circulate both hot and chilled water in the building to the required areas. The stale air is expelled by using a separate duct line. The installation of duct lines is an important part therefore location and  material type is considered at the time of designing of the HVAC system.

THERMOSTAT:

The thermostat (HVAC Controller) is installed to turn equipment on or off and to adjust the chillers and boilers, air and water flow rates, temperature and pressures. This also make the components work efficiently through the means of regulation of required conditions. A controller incorporating one or more temperature sensors inside the workspace sends a signal to the heating or cooling coils to activate.If there is a demand for heating or cooling then the controls may also send a signal to the chiller and boiler to operate as required. There are often other control panels on the chiller or boiler too, allowing users to have greater control.

Walkin for various post at mankind pharma on 29th Oct

Types of granulation in tablet formulation

TYPES OF GRANULATION
Granulation can be achieved by three method as follows :-
1. Direct compression   
      Crystalline substance like sodium chloride, sodium bromide may be compressed directly. The vast majority of medicinal agents are rarely so easy to tablet, direct compression material should posses good flow and compresibility and must be inert, tasteless, able to disintegrate and inexpensive.
Method
(Drug + filler + disintegrant + lubricant + glidant ) all are blend directly after sifting through Viber sifter and compressed


2. Dry Granulation
   It is used in situations where effective dose of a drug is too high for direct compaction and the drug is sensitive to heat, moisture, or both which preclude wet granulation. This is also called slugging method.
Method
A.      (Drug + filler + lubricant) All are.       blend then precompression done and     after that   comminution done
 
 B.  (glidant + lubricant + disintigrant)  sizing then blend with A

3. Wet Granulation
  Wet granulation forms the granules by binding the powders together with an adhesive, instead of by compaction. Liquid bridge are developed between particles, and the tensile strength of these bond increase as the amount of liquid binder added is increased. A drying process is required in all wet granulation to remove the solvent and to reduce the moisture content. After drying granulation is screened again, followed by compression.

Schematic drawing of All types granulation

METHOD FOR PREPARATION OF LIPSTICK

Formulation and manufacturing of Lipstick
Lipstick:-
Lipstick is a cosmetic product containing pigments, oils, waxes, and emollients that apply color, texture, and protection to the lips.
Lipstick Raw Materials 
Before making lipstick, ingredients must be chosen. The primary ingredients of every lipstick are waxes, oils, and pigments, but many other substances can be introduced into the mix that will enhance certain parts of the final product and add it some specific new features such as fragrance, longevity and gloss.

The wax used usually involves some combination of three types : beeswax, candelilla wax or the more expensive carnauba. Wax enables the mixture to be formed into the easily recognized shape of the cosmetic. Oils such as mineral, caster, lanolin, or vegetable are added to the wax.

Some of the most common secondary ingredients are preservatives (to ensure longer shelf life), alcohol (solvent for other substances), fragrance (oils and waxes can sometimes have their own smell and taste, which needs to be eliminated), antioxidant and others wide vaiety of other ingredients can also be included to make the substance smoother or glossy or to moisten the lips.

Lipstick tube
The tubes that hold lipstick range from inexpensive plastic dispensers for lip balms to ornate metal for lipsticks. Sizes are not uniform, but generally lipstick is sold in a tube 3 inches (7.6 cm) in length and about .50 inch (1.3 cm) in diameter. The tube has two parts, a cover and a base. The base is made up of two components, the twisting or sliding of which will push the lipstick up for application.

Description of Machinery in Lipstick Manufacturing 

1. Mixing Machine
2. Seizing Machine
3. Grinding Machine: Tri-Roller Rolling Machine and Successive High speed Moleculized Instrument – wet model 
4. Heating Mixing Machine for pearl ointment 
5. Mold Sets 
6. Filling Machine: Basic Type(conventional), Plate Type. Semi-Automatic Type, Fully Automatic Type 
7. Mold Releasing Machine By Air Blowing Machine 
8. Box Folding Machine 
9. Cartoning Machine 
10. Carton Tapping Machine 

Lipstick Manufacturing Process
In general, wax and oil make up about 60% of the lipstick (by weight), with alcohol and pigment accounting for another 25% (by weight). Fragrance is always added to lipstick, but accounts for 1% or less of the mixture.

The most common lipstick manufacturing procedure is done in four stages.

1. Pigment milling, in which you chose desired pigment, or the combination of pigment and then carefully mix them. Then, pigment is melt with oils or other fat good. The granule uniformity and particle distribution will be grinding by grinder to get optimization. The formula put through three-roll mill which grind ever particle usually to the size of 20 microns. Common ration of oil and pigment is 2 to 1 particles. 
2. Combination of pigment phase into base wax is done with simple mixing of those liquids in a steam-jacketed kettle that is equipped with one propeller agitator. After successful mixing, resulting liquid is again put through three-roll mill and usually grinded down to particle sizes of 20 microns. Perfume will be mixed within the paste phase under certain temperature and continuous agitating. 
3. Molding. Once the lipstick mass is mixed and free of air, it is ready to be poured into the tube. Molding is done at specific temperatures to eliminate certain unwanted products of fast cooling. Lipsticks liquid that is heated to around 80 C is poured into vertical split molds that are kept at temperature of around 35 C. To prevent formation of air bubbles in the molds, manufacturers often use slightly tilted molds or use vacuuming to forcefully extract any air. A variety of machine setups are used, depending on the equipment that the manufacturer has, but high volume batches are generally run through a melter that agitated the lipstick mass and maintains it as a liquid. For a smaller, manually run batches, the mass is maintained at the desired mix temperature, with agitation, in a melter controlled by an operator. 
4.  Resulting lipstick is cooled down, extracted from the molds and prepared for flaming (passing of the sticks near one or several open flame torches or flaming cabinet that will meltsmall layer of gloss around lipsticks). This procedure will ensure better visual appearance of the lipstick, and protection from outside air and influences (lipsticks can become rancid after prolonged exposure to air, moisture and heat). 
5. Packaging and labeling is done with the requirements of the manufacturers of brand owner. After the lipstick is retracted and the tube is capped, the lipstick is ready for labeling and packaging. Labels identify the batch and are applied as part of the automated operation. There are a variety of packaging options available, ranging from bulk packs, and including packaging as a component in a makeup kit or special promotion offering. Packaging for lipstick varied, depending on what will happen at the point of sale in the retail outlet. Packaging may or may not be highly automated, and the package used depends on the end use of the product rather than on the manufacturing process. 

PIC (Process in Control) 

Air Bulb removing, There are many chances to crease air bulb within the paste during melting, mixing, and agitating.

The method of de-gas from the paste is set the paste without moving for certain time for enable the light weight air bulb floating up to the surface of paste form material.

Therefore, the bottom portion of the paste material will be applied as material to fill the lipstick molds. However, please care of the powder, color agent or particle sediment from the paste.

Quality Control in Lipstick Manufactruring

Lipstick product must meet FDA standards. Lipstick is the only cosmetic ingested, and because of this strict controls on ingredients, as well as the manufacturing processes, are imposed. Lipstick is mixed and processed in a controlled environment so it will be free of contamination. Incoming material is tested to ensure that it meets required specifications. Samples of every batch produced are saved and stored at room temperature for the life of the product to maintain a control on the batch.

Color control of lipstick is critical. The dispersion of the pigment is checked stringently when a new batch is manufactured, and the color must be carefully controlled when the lipstick mass is reheated. The color of the lipstick mass will bleed over time, and each time a batch is reheated, the color may be altered. Colorimetric equipment is used to provide some numerical way to control the shades of lipstick.

There are two special test for lipstick :

1. The Heat Test. Lipstick is placed in the extended position in a holder and left in a constant temperature oven of over 130 degrees Fahrenheit (54 degrees Celsius) for 24 hours. There should be no dropping or distortion of the lipstick.
2. The Rupture Test.  Lipstick is place in two holders, in the extended position. Weight is added to the holder on the lipstick potion at 30-second intervals until the lipstick ruptures. The pressure required to rupture the lipstick is then checked against the manufacturer’s standards.

Preparation Process for Water for Injection (WFI) in Pharmaceuticals

There are basically two types of water preparation in pharmaceuticals.Water for Injection (WFI) preparation process and Purified Water preparation process. The analytical standards for the two water are almost very similar, the only difference is that Water for Injection (WFI) system in pharmaceuticals has stricter bacterial control standards than purified water process and has to pass the bacterial endotoxin test. Preparation methods are very similar to a particular point, however, Water for Injection (WFI) preparation process in pharmaceuticals must include distillation or double pass reverse osmosis techniques.

Water for Injection (WFI) preparation process in pharmaceuticals systems, involves several steps and processes this includes; dechlorination, ion reduction, bacterial control, and removal of specific impurities.

Dechlorination:
This refers to the removal of chlorine from the water. There are several ways of dechlorination.This include injection of a reducing agent like sodium metabisulfite and exposure to a high dosage of UV rays can dechlorinate. However, the most common one is filtration through activated carbon media. Water for Injection (WFI) preparation process in pharmaceuticals is dechlorinated by carbon. Carbon dechlorinates by chemically reacting with the free chlorine in water to form hydrochloric acid and carbon monoxide or dioxide. High doses of UV light rays are widely used in water purification systems for both disinfection and TOC reduction. Another use of UV is dechlorination though it is a relatively new process.


Ion removal:
 There are basically three types of ion reduction processes these include membrane processes, ion exchange processes, and distillation processes. Membranes are used in water purification systems to remove ions, remove particulate, remove organic compounds, and remove living organisms. Membranes are different from one another in terms of pore size, molecular weight, and even on ion rejection. Ion removal membranes include membranes such as reverse osmosis membranes and nanofiltration membranes. These are used in ion reduction processes. The ion exchange systems provide additional ion reduction process, making the water much lower in conductivity than required and it also provides a back up for membrane process. Distillation can also be used to remove ion, however, it is very expensive.

Bacterial control:
In bacteria control, one has to be careful to ensure that bacteria does not pass to pharmaceutical water for injection. Bacteria control includes both procedures and equipment. Equipment utilized are ultraviolet (UV) lights, ozone generation systems for production of ozone, heating systems for thermal treatment, and chemical injection and recirculation systems. Procedures in this process include periodic sanitizations and also general operational techniques to avoid intrusion of bacteria. Bacterial control is usually applied during processing, storage and even distribution. UV light is an excellent non-chemical method of disinfecting Water for Injection (WFI). Thermal sanitization involves the use of heat to kill the bacteria. Ozone can also be used since it is a very strong oxidizing agent it can, therefore, oxidize bacteria. Chemicals can also be used to kill bacteria as a means of bacteria control.

Removal of specific impurities:
There are various different sources of water for Injection (WFI) used during preparation process in pharmaceuticals. Every source is different and therefore the possibilities of specific contaminant problem are possible. These contaminants include Iron, manganese, hydrogen sulfide, hardness ions, particulate matter, high conductivity. Filtration can be used to remove any heavy loads. Cartridge filters are also used to remove essentially any sized particles. However, they are expensive.

The last stage is storage. Care and hygiene must be maintained during storage of WFI. Bacteria control must also be incorporated at this stage.

Disintegration Time for tablets as per IP, BP and USP

Disintegration Time:-
Uncoated Tablet
NMT 15 min, in water with Disc 37⁰C ± 2⁰C
Coated Tablet
NMT 30 min, In water with Disc for Film Coated Tab, and NMT 60 min Other than Film coated tablet
Enteric Coated Tab
Intact for 2 hr in 0.1 N HCl & disintegrate within 1 hr in Mixed 6.8 Phosphate buffer. According to USP 2 hr in Simulated gastric fluid, then in Simulated Intestinal Fluid.
Dispersible/Soluble
Within 3 min in water at 25⁰C ± 1⁰C (IP) & 15 – 25⁰C (BP)
Orodispersible
Within 1 min
Effervescent Tab
5 min in 250 ml water at 20 – 30⁰C (IP) & 5  min in 200 ml water at 15-25⁰C (BP)
Buccal & Sublingual
Not Applicable but dissolve within 15 – 30 min.

DT Apparatus:- Mesh Apperture:- 2mm (#10), Cycles:- 28 – 32 cycles/min, 50 – 60 mm distance from bottom & top, Temp of water 37⁰C ± 2⁰C. If 1 or 2 tabs fail, repeat for 12 tabs.

Weight variation limit for tablet and capsule.

Weight Variation Limits:-
1) For Tablets 
IP/BP.                          Limit.                         USP
80 mg or less.            10%                    130mg or less
 80 mg to 250mg.      7.5%              130mg to 324mg

250mg or more.         5%              More than 324mg

2) For Capsule:-
IP
Limit
Less than 300mg
10%
300mg or More
7.5%

ABBREVIATION USED IN PHARMACEUTICALS

ABBREVIATION:  Abbreviation is an shortened form of an word, the most commonly used abbreviations in pharmaceutical company                                               AADA: Abbreviated antibiotic drug application

ADE: Adverse drug event

ADME: Absorption, distribution, metabolism, and excretion

AHU: Air Handling Unit

ANDA: Abbreviated new drug application

ANVISA: Agência Nacional de Vigilância Sanitária (National Health Surveillance Agency Brazil)

AP: Applicants Part (of EDMF)

API: Active pharmaceutical ingredient

APR: Annual product review (APQR – Annual product quality          review)

AQL: Acceptable quality level

AR: Analytical Reagent

ASHRAE: American Society of heating, Refrgeration and  Air Conditioning Engineers

ASM: Active Substance Manufacturer

ASMF: Active Substance Master File

AST: Accelerated stability testing

ASTM: American Society for Testing and Materials

BA/BE: Bioavailability/bioequivalence

BCS: Biopharmaceutical classification system BDR: Batch Distribution Record

BET: Bacterial Endotoxin Test

BFS: Blow Fill Seal

BI: Biological Indicator

BMR: Batch Manufacturing/Processing Record

BOD: Biological Oxygen Demand

BOM: Bill of Materials

BOPP: Biaxially Oriented Polypropylene

BP: British Pharmacopoeia

BPR:  Batch Packaging Record

BRMS: Biologics Regulatory Management System

BSE: Bovine spongiform encephalopathy (mad cow disease)

CAPA: Corrective and preventive action

CBE: Changes being effected

CBER: Center for Biologics Evaluation and Research (FDA)

CCIT: Container closure integrity test

CDER: Center for Drug Evaluation and Research (FDA)

CDSCO: Central drug standard control organization (India)

CEP: Certification of suitability of European Pharmacopoeia monographs

CFR: Code of Federal Regulations CFM: Cubic Feet Per Minute

CFU: Colony Forming Unit

cGMP: Current Good Manufacturing Practices

CIP: Clean in place

CMC: Chemistry, manufacturing and controls

CMS: Continuous monitoring system

COA: Certificate of analysis

COS: Certificate of suitability

COPP: Certificate of Pharmaceutical Products

CPP: Critical Process Parameter

CQA: Critical Quality Attribute

CTD: Common technical document DCP: Di-Basic Calcium Phosphate DHA: Decosahexanoic Acid

DMF: Drug master file

DOP: Dioctyl Phthalate

DQ: Design Qualification

EDMF: European drug master file

EDQM: European Directorate for the Quality of Medicines

EH&S: Environmental health and safety

EIR: establishment inspection report (FDA)

EMEA: European Medicines Agency (formerly European Medicines Evaluation Agency)

EP: European Pharmacopoeia

EPS: Expanded polystyrene

ETP: Effluent Treatment Plant

EU: Endotoxin unit

EU: European Union

FAT: Factory Acceptance Testing

FBD: Fluid-bed dryer

FDA: Food and Drug Administration, United States FDAP: Food and Drugs Administration, Philippines

FDC: Fixed Dose Combination

FEFO: First expiry first out

FG: Finished Goods

FIFO: First in first out

FMEA: Failure modes and effect analysis

FOI: Freedom of information

GAMP: Good automated manufacturing practice

GC: Gas Chromatography

GCLP: Good clinical laboratory practice

GCP: Good clinical practice

GDP: Good distribution practice

GEP: Good engineering practice

GGP: good guidance practice

GIT: Gastrointestinal Tract

GLP: Good laboratory practice

GMO: Genetically modified organism

GMP: Good manufacturing practice

GPT: Growth Promotion Test

GRAS/E: Generally recognized as safe and effective

GRP: Good review practice

HACCP: Hazard analysis critical control point

HDPE: High Density Polyethylene

HEPA: High efficiency particulate air (filter) HLV: Hand Level Valve HMI: Human Machine Interface

HPLC: High performance liquid chromatography

HSA: Health Sciences Authority, Singapore

HVAC: Heating, ventilating, and air conditioning

ICH: International Conference on Harmonization

IH: In house

IM: Intramuscular

IND: Investigational new drug

INDA: Investigational new drug application

IP: Indian Pharmacopeia

IPA: Isopropyl Alcohol

IPS: In process control

IQ: Installation qualification

IR: Immediate release

ISO: International Organization for Standardization

ISPE: International Society for Pharmaceutical Engineering

IV: Intravenous

JP: Japanese Pharmacopoeia

KOS: Knowledge organization system

LAF: Laminar air flow

LAL:  Limulus Amoebocyte  Lysate

LD: Lethal dose

LD50: Lethal dose where 50% of the animal population die

LDPE: Low Density Polyethylene

LIMS: Laboratory Information Management System

LIR:  Laboratory Investigation Report

LOD: Loss on drying

LOD: Limit of detection

LOQ: Limit of quantification

LR: Laboratory Reagent

LVPs: Large Volume Parenterals

MA: Marketing Authorisation

MAA: Marketing Authorisation Application

MAC: Maximum Allowable Carryover

MCC: Medicines control council (South Africa)

MDD: Maximum daily dose

MFR: Master Formula Record

MEDSAFE: Medicines and medicinal devices safety authority (New zealand)

MHRA: Medicines and Healthcare products Regulatory Agency (UK)

MOA: Method Of Analysis MRP: Maximum Retail Price

MSDS: Material Safety Data Sheets

NCE: New chemical entity

NDA: New Drug Application

NF: National Formulary

NIR: Near Infra Red Spectroscopy NSF: National sanitation foundation

NON: Notice of non-compliance (Canada)

ODI: Orally Disintegrating Tablet

OQ: Operation Qualification

OSD: Oral Solid Dosage

OSHA: Occupational Safety And Health Administration

OTC: Over-the-counter

OOS: Out of specification

OOT: Out of trend

PAC: Post-approval changes

PAO: Poly alpha olefin

PAT: Process Analytical technology

PET: Preservative efficacy test

PET: Polyethylene

PIC/S:  Pharmaceutical Inspection Co-operation Scheme PIS: Product Information Sheet

PLC:  Programmable Logic Control PLM: Planetary Mixer

PQ: Performance Qualification PSI:  Pound per Square Inch

PVC: Polyvinyl Chloride

PVDC: Polyvinylidene Chloride

PW: Purified Water

QA :  Quality Assurance

QC:  Quality Control

QbD: Quality by design

QM: Quality Manual

QSD:  Quality System Dossier

QSM : Quality System Management

QMS: Quality Management System

RH: Relative humidity

RLAF: Reverse laminar air flow

RLD: Reference listed drug

RM: Raw material

RO: Reverse Osmosis

ROPP: Roll On Pilfer Proof

RS: Related Substance

SAL: Sterility Assurance Level

SAT: Site Acceptance Testing

SDN: Screening Deficiency Notice (Canada)

SIP: Sterilization in place/Steam in place

SLS: Sodium Lauryl Sulphate SPP: Sodium Propyl Paraben SSG: Sodium Starch Glycolate

SMF: Site master file

SOP: Standard operating procedure

SPE:  Society for Pharmaceutical Engineering

SUPAC: Scale-up and post approval changes

SVP:  Small Volume Parenteral

TC: Thermocouple

TDS: Total Dissolved Solids

TGA: Therapeutics goods administration (Australia)

TOC: Total organic carbon

TSE: Transmissible spongiform encephalopathy

USFDA: United states foods and drugs administration

USP: United States Pharmacopeia

USP-NF: United States Pharmacopeia-National Formulary

URS: User Requirement Specification

VAI: Voluntary action indicated

VMP: Validation Master Plan

WFI: Water for injection

WHO: World Health Organisation

WL: Warning letter