Showing posts with label Quality Assurance. Show all posts
Showing posts with label Quality Assurance. Show all posts

Tuesday, November 13, 2018

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.

Monday, August 20, 2018

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

Tuesday, December 5, 2017

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.

Tuesday, August 15, 2017

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%

Saturday, August 5, 2017

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
NIRNear 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