In ancient times people use plants or animals matter to cure some sort of ailment or diseases by using home remedies. But now day’s medicine manufacturing is performed by chemical processing. Scientists first finds chemicals in plants or animals with their years of research and knowledge, then isolate these chemicals and try to make artificial chemical like original source chemical taken from plant or animals. After getting succeeded in making artificial synthetic chemical that cure targeted ailment or diseases, scientists start making medicines.
Now question is what a medicine contains? So medicines contain active drug called API (Active Pharmaceutical Ingredients) and excipient. API is active drug in any medicine which has therapeutic action to cure targeted ailment or diseases or disorder. While excipient is the non-active ingredient to support and enhance activity of drug product.
Where these medicines are manufactured?
Medicines are manufactured in Pharmaceutical manufacturing companies like Cipla, Glenmark, Lupin, Wockhardt, Alembic, Zydus, Mylan etc. First drug API is manufactured in API processing plants and then medicines are manufactured in Formulation plants by using API drugs and excipients. Medicines are manufactured in different dosage forms like OSD (Oral Solid Dosage) tablets, capsules, Liquid Syrups, Injectable etc. Means you get medicines prescribed by your doctor in forms like tablets, capsules, liquid syrups, injections. These medicines are manufactured under GMP (Good Manufacturing Practices) controlled environment. During medicines manufacturing temperature, humidity and air pressure is maintained by AHU (Air Handling Unit) to provide controlled environment and also to prevent cross contamination.
API Manufacturing Plant
API plants have different departments for dedicated function like Warehouse Department for storage receive, dispensing and dispatch of materials. Production Department or API Plant where batch (Batch is a specific quantity of a drug or other material that is intended to have a uniform character and quality, within specified limits, and is produced according to a single manufacturing order during the same cycle of manufacturing.) processing happen, means chemical reactions are performed as per Batch Records and SOPs (Standard Operating Procedure) in chemical reactors.
Quality Control Department or QC Lab where testing of samples is performed. QC Sampling is a process of abstraction of a portion of material from a lot or a batch in such a way that the withdrawn sample is representative of that whole lot or batch. QC person perform testing by taking samples at different stages of API manufacturing. Quality Assurance Department for taking assurance of quality of manufactured API during processing. HR, Admin, IT, Finance, RA, CQA are other supporting departments.
Formulation Plant
Formulation plants also have different departments just like API manufacturing plants. Warehouse for storage, control, dispense and dispatch of materials and products. Production Department where medicines are produced, Different type of machines are used in production plants to make medicines like Isolators, Blending machine, compression machine, coating machine, granulation machine, capsule filling machine, inspection machine etc. are used to make medicines.
Packing Department where packaging of medicines is performed with the help of different machines. Blister machine, Bottle filling Counter machine, checkweigher, Unscrambler, Desiccant Sachet inserter, Cottoner, Capper Sealer, Labeller, CAM cartonator, Printer, Shipper Sealer are some machine used in packing department.
Quality Control Department or QC Lab where testing of samples is performed. QC person take sample during batch processing from different stages of manufacturing and analyse these sample in chemical labs using HPLC, GC, distillation, chromatography, titration and many more advance testing methods. Quality Assurance Department for taking assurance of quality of manufactured medicines. Safety Department to take care about safety of property building and peoples working in pharma industry
Drug development: journey of a Medicine manufacturing
During manufacturing medicines goes through different stages to become finished goods. First API and Excipient is dispensed by warehouse to production. Then these are mixed filtered and processed to produce intermediate product (A partly processed material, which undergoes further processing before it becomes a finished product). Then this intermediate product is processed further to produce finished product.
Finished product is a product that has completed all stages of manufacturing, and now this finish product is ready for packing. Now packing department perform packaging of finish product into finished goods. Finished goods are products that has completed all packing stages and packed into the final pack, as a result now ready for dispatch.
Dispatched finished goods are now become medicine after several processing testing manufacturing and packaging stages. Manufacturing of medicines is regulated by Regulatory Bodies around the world like USFDA (Unites States Food and Drug Administration from United States), WHO (World Health Organization), MHRA (Medicines and Healthcare Products Regulatory Agency from United Kingdom), CDSCO (Central Drug Standard Control Organization from India), TGA (Therapeutic Goods Administration from Australia), TPD (Therapeutic Product Directorate from Canada), EMA (European Medicines Agency from Europe) etc. Every manufactured medicine has manufacturing date, expiry date and shelf life. So now we understand these terms more clearly means what is manufacturing date, expiry date and shelf life.
What is Manufacturing Date?
Manufacturing date of the batch is the date on which actual batch activity is started so dispensing is always the first activity during any batch processing. So date of dispensing is considered as the manufacturing date.
What is Expiry Date?
Expiry date is the date till which a drug product is expected to remain within its approved specification. Or simply it is the date up to which the medicine is useful for its intended action.
What is Shelf Life?
Shelf life of medicine is a period of time during which a medicinal product or medicine, when stored properly under environments defined on the label is expected to comply with established specification. Or simply it is the time period up to which the medicine is useful for its intended action.
So today we learn what is medicine and how it is manufactured at Chemistry Notes Info. In upcoming posts we learn more about medicine manufacturing. Do you know what is GMP and why it is necessary during medicine manufacturing.
Books to learn how pharma drug medicines are manufactured
cGMP Current Good Manufacturing Practices for Pharmaceuticals, 2nd Edition
Handbook of Pharmaceutical Manufacturing Formulations: Volume Three, Liquid Products
An Unfinished Agenda: My Life in the Pharmaceuticals Industry
Abbreviations used in Pharmaceutical Manufacturing
As we know pharmaceutical manufacturing products i.e. medicines, life saving drugs have very high importance in our life. Today we learn about various abbreviations used in pharmaceutical manufacturing process steps or simply in pharmaceutical manufacturing companies. These short forms are used in every pharmaceutical manufacturing companies like pharmaceutical industry in USA, pharmaceutical industry in India, pharmaceutical industry in France, pharmaceutical industry in Canada, pharmaceutical industry in China, pharmaceutical industry in Japan etc. These short forms are also asked in various pharma interviews. So learn these Pharmaceutical Manufacturing Abbreviations and also share with your science friends working in pharma companies or studying pharmacy.
GMP : Good Manufacturing Practices cGMP : Current Good Manufacturing Practices
PVP : Process Validation Protocol
PVR : Process Validation Report
CVP : Cleaning Validation Protocol
CVR : Cleaning Validation Report
GDP : Good Documentation Practices
MQRM : Monthly Quality Review Meeting
QRM : Quality Risk Management
UCL : Upper control Limit
LCL : Lower control Limit
IPQA : In process Quality Assurance
LLC : Live line clearance
API: Active pharmaceutical ingredient
APQR: Annual product Quality review
AQL: Acceptable quality level
ASM: Active Substance Manufacturer
ASMF: Active Substance Master File
AST: Accelerated stability testing
CRT : Controlled Room Temperature
ASTM: American Society for Testing and Materials
BA: Bioavailability
BE : Bioequivalence
BET: Bacterial Endotoxin Test
BMR: Batch Manufacturing Record
BOD: Biological Oxygen Demand
BOM: Bill of Materials
BOPP: Biaxially Oriented Polypropylene
BP: British Pharmacopoeia
BPR: Batch Packaging Record
BSE: Bovine spongiform encephalopathy (mad cow disease)
CAPA: Corrective and preventive action
FMEA : Failure mode & Effect Analysis
RCA : Root cause Analysis
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 monograph
GC : Gas Chromatography
HSA: Health Sciences Authority, Singapore
ANVISA: Agรชncia Nacional de Vigilรขncia Sanitรกria (National Health Surveillance Agency Brazil
TGA: Therapeutics goods administration (Australia) USFDA: United states foods and drugs administration
FDA: Food and Drug Administration, United States
WHO: World Health Organisation
JP: Japanese Pharmacopoeia
MHRA: Medicines and Healthcare products Regulatory Agency (UK)
MEDSAFE: Medicines & medicinal devices safety authority (New zealand)
CQA: Critical Quality Attribute
MACO : Maximum allowable Carry over
ADE: Adverse drug event
PDE : Permitted Daily Dosage Exposure
ACU: Air Cooling Unit
AHU: Air Handling Unit
ANDA: Abbreviated new drug application
NDA : New drug application
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
EP: European Pharmacopoeia
ETP: Effluent Treatment Plant
EU: Endotoxin unit
EU: European Union
URS: User Requirement Specification
FAT: Factory Acceptance Testing
SAT : Site Acceptance Test
IQ : Installation Qualification
DQ : Design Qualification
OQ : Operational Qualification
PQ: Performance Qualification
FBD: Fluid-bed dryer
FBP: Fluid-bed Processor
RMG : Rapid mixer Granulator
FDC: Fixed Dose Combination
FEFO: First expiry first out
RA: Regulatory Affairs
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
DOP: Dioctyl Phthalate
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)
HPLC: High performance liquid chromatography
DHS : Dry heat sterilization
HVAC: Heating, ventilating, and air conditioning
ICH: International Conference on Harmonisation
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
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
WL: Warning letter
MOA: Method Of Analysis
MSDS: Material Safety Data Sheets
NCE: New chemical entity
NDA: New Drug Application
NF: National Formulary
NIR: Near Infra Red Spectroscopy
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
PLC: Programmable Logical Control
PVC: Polyvinyl Chloride
PVDC: Polyvinylidene Chloride
PW: Purified Water
QBD : Quality by design
QM: Quality Manual
QMS: Quality Management System
RH: Relative humidity
RLAF: Reverse laminar air flow
RLD: Reference listed drug
RM: Raw material
RM: Packing material
FGS: Finished Goods Store
BSR: Bounded store Room
RO: Reverse Osmosis
RS: Related Substance
SAT: Site Acceptance Testing
SIP: Sterilization in place
SIP: Steam in place
SLS: Sodium Lauryl Sulphate
SMF: Site master file
SOP: Standard operating procedure
SPE: Society for Pharmaceutical Engineering
SUPAC: Scale-up and post approval changes
SVP: Small Volume Parenteral
TDS: Total Dissolved Solids
TOC: Total organic carbon
TSE: Transmissible spongiform encephalopathy
USP: United States Pharmacopoeia
USP-NF: United States Pharmacopoeia-National Formulary
API: Active Pharmaceutical Ingredients
VMP: Validation Master Plan
WFI: Water for injection
TRF : Test Request Form
CFR: Code of Federal Regulations
CFU: Colony Forming Unit
cGMP: Current Good Manufacturing Practices
CIP: Clean in place
COA: Certificate of analysis
MOA: Method of analysis
COS: Certificate of suitability
COPP: Certificate of Pharmaceutical Products
CPP: Critical Process Parameter
DMF: Drug master file
PMPS: Pharmaceutical Manufacturing Process Steps
MFP: Media Filling Process
SFG: Semi Finished Goods
PM: Preventive Maintenance
SFG: Semi Finished Goods
FG: Finished Goods
NPI: New Product Introduction
PDL: Packaging Development Laboratory
Do you know How medicines are manufactured ?
In ancient times people use plants or animals matter to cure some sort of ailment or diseases by using home remedies. But now day’s medicine manufacturing is performed by chemical processing. Learn more about How medicines are manufactured at given below article
The simple meaning of
humidity is ‘atmospheric moisture’ or ‘amount of water vapor in the atmosphere’.
Humidity is
the amount of water vapors present in the atmosphere (or air). Water vapors are
the gaseous state of water and are invisible.
Humidity can be measured by three ways that
are: absolute, relative and specific.
1.Absolute
humidity is the water content of air in the gram per cubic meter at
a given temperature.
2.Relative
humidity is expressed in percentage, and it measures the current
absolute humidity relative to
the maximum humidity for that temperature.
3.Specific
humidity is expressed as the ratio of the mass of the water vapors
to the total mass of moist air parcel.
What
is Absolute Humidity?
To
understand absolute humidity let’s assume you are standing in ground and you
collect some air. Now you check that air volume in your chemistry lab and get accurate
amount of water vapors in gram. If you collect 1 cubic meter of air volume and
it contains 30 gram water vapors than absolute humidity of that ground air is 30 grams
per cubic meter. So, now you answer this question i.e. what is absolute
humidity.
Absolute humidity (AH)
is defined as the total mass (in gram) of water vapor present in a given volume
(in cubic
meter) of air. Absolute Humidity changes
with changes in air temperature and pressure. Absolute humidity is the mass of
the water vapors( m H 2 O ) {\displaystyle
(m_{H_{2}O})} divided by the volume of the air and water vapor mixture.
AH
= m/V
Where,
AH = Absolute humidity,
m = mass of the water vapors( m H 2 O ) {\displaystyle (m_{H_{2}O})},
V = volume of the air and water
vapor mixture.
What
is Relative Humidity?
To
understand relative humidity let’s assume you are in a building where air
absolute humidity is 15 grams per cubic meter at 25 degree Celsius
temperature and at 25 degree Celsius temperature highest amount of water vapors
is 30 grams per cubic meter (saturated air with water vapors 15 grams
per cubic meter). So, now you can calculate relative humidity as follows:
Relative
humidity = (15 grams per cubic meter / 30 grams per cubic meter)x100
RH = 50%
So,
now you answer this question i.e. what is relative humidity.
Relative humidity (RH)
is defined as the
ratio of the partial pressure of water vapors to the equilibrium vapor pressure
of water at a given temperature. If temperature of the atmosphere is lower than
relative humidity is higher as cold air (air with low temperature) holds more
water vapors (moisture) but, If temperature of the atmosphere is higher than relative
humidity is lower as hot air (air with high temperature) holds less water
vapors (moisture).
What
is Specific Humidity?
To
understand specific humidity let’s assume you have an air parcel (air volume or
some amount of air) and this parcel contains 10 gram mass of water vapors and
total mass of air is 1 kg (including mass of all gases present in air and mass
of water vapors) than specific humidity is 10 gram per kilogram. So, now you
answer this question i.e. what is specific humidity.
Specific Humidity is defined as the ratio of the mass of water vapors in air to
the total mass of the mixture of air and water vapors.
Specific Humidity
= mass of water vapor/total mass of air
Difference
between Humidity and Relative Humidity
Before going to discuss
about “Difference between Humidity and Relative Humidity” we need to understand
that what is humidity and what is relative humidity. And to get answer of these
two questions just read above paragraph once again if you don’t understand.
Humidity is
the amount of water vapors present in the atmosphere (or air). Relative
humidity is expressed in percentage, and it measures the current absolute
humidity relative to the
maximum humidity for that temperature.
General Questions Answers asked during interview in pharmaceuticals manufacturing companies
Question: What is GMP?
Answer: GMP is a system for ensuring that products are consistently produced and controlled according to quality standards. It is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product.
Question: What is GDP?
Answer: Good documentation practice GDP is a systematic procedure of preparation, reviewing, approving, issuing, recording, storing and archival of any document.
Question: Importance of Visual inspection?
Answer: Visual inspection is an essential operation in parenteral drug production to ensure the safety of the drug product in its container.
Question: Type of defects?
Answer: Critical, major minor.
Critical- crack, missing stopper, particles inside container.
Major- Sealing defects, broken container, volume variation.
Minor- stain on container, scratch on container, cosmetic.
Question: Where you perform visual inspection?
Answer: At visual inspection hood in visual inspection area
Question: How you measure light intensity of hood light source?
Answer: Using lux meter.
Question: What is lux ?
Answer: The lux (lx) is the SI unit of illuminance and luminous emittance, measuring luminous flux per unit area. It is equal to one lumen per square metre.
Question: what Lux range used in pharmaceuticals inspection?
Answer: 2000-3750 Lux
Question: what is deviation?
Answer: Departure from standard stablish procedure is known as deviation.
Question: What is Media?
Answer: Substance which promotes growth of microorganisms like bacteria, viruses, fungus.
Extraction of Essential Oil by Steam Distillation of Tulsi (Ocimum Basillicum)
Essential
oils are insoluble in water and evaporate easily. We can obtain
essential oil from plant tissues by distillation or extraction
processes. Generally essential oils are obtain from every part of plant
like stem, root, leaves, flowers, seed, branches etc. And these
essential oils are used in the preparation of drugs, cosmetics and
perfumes.
Ocimum
Basillicum means Tulsi is an aromatic plant. Ocimum Basillicum is used
to obtain essential oil useful for different application. This oil
evaporates within 24 hours after applying it to our body. This essential
oil helps in cure of digestion problem, strained muscles, headaches and
nervous breakdowns. Due to its good medicinal properties and aroma its
demand is very high in many countries. A person or company can build a
small or large scale industry for the extraction of essential oil from
Ocimum Basillicum (Tulsi).
Top 10 General qualitative properties of Ocimum Basillicum essential oil are given below-
1.Appearance : Transparent fluid
2.Color : Pale yellow
3.Fragrance : Ocimum Basillicum’s distinctive flavor and fragrance
4.Refractive Index on 20°C : 1.51200 to1.51900
5.Specific Gravity on 25°C : 0.95200 to 0.97300
6.Optical gyration on 25°C : [-] 8.85ยบ to [-] 11.85ยบ
7.Well mixed with Hydroxycitronellal
8.Insoluble in water
9.Dissolved in paraffin oil
How to obtain oil from holi Tulsi plant?
The
extraction of essential oil by steam distillation of ocimum basillicum
(Tulsi) is a solid-liquid extraction process. This process completes in
following steps-
1.Collect plant material and dry it if required.
2.Fill this plant material in distillation vessel.
3.Add water or solvent (like Ethanol, n-Hexane) in distillation vessel.
4.Heat the mixture in well-equipped distillation vessel in control environment and controlled temperature, then
5.Diffusion of essential oil from inside of solid material of plant to its surface occurs, then
6.Transfer of mass from surface of plant solid material to surrounding liquid occurs, then
7.This liquid contains essential oil which is obtained by reverse cooler.
8.Then
the collection of above liquid obtained from reverse cooler is put to
stand for some time then essential oil come over water, then
9.We perform layer separation to separate out essential oil from water, then
10.Store this essential oil in dark, closed vessel for future use.
The
experimental results proves that yield of essential oil of Tulsi
(Ocimum-Basillicum) from only leaves of plant is slightly higher than
from the mixture of leaves and stems (means plant crush).
MAIN REGULATORY BODIES
AROUND THE WORLD FOR PHARMACEUTICAL PRODUCTS
Medicines are chemical
or natural products used for healing, diagnosing, treating and improving
health. These medicines contain API and Excipient. API is the main active drug
which provide therapeutic effect and biologically active. Excipient is non-active ingredient added in
formulation along with API in medicine formulation.
Drugs or Medicines are
very high importance as these are life saving, health improving, biologically
active, provide therapeutic effect.Drugs or Medicines provide adverse effect or
lead to death if they are not manufactured with care and not manufactured in
GMP (Good Manufacturing Practices) environment. Due to high risk, every country
has its own regulatory body or regulatory authority. These regulatory bodies or
regulatory authorities make and enforce rules and regulations and also prepare and
issue guidelines for drugs or medicines manufacturing, licensing, registration,
marketing, labeling and packaging of pharmaceutical products like tablets,
injections, syrups, eye drops, ointment cream, spray, inhalers, liquid and
OSD(oral solid dosage) etc.
List of Main Regulatory
Authority around the World
Country
Name of Regulatory Authority (Full and Short Form of Name)
USA
USFDA – Unites States Food and Drug Administration
UK
MHRA - Medicines and Healthcare Products Regulatory Agency
Australia
TGA - Therapeutic Goods Administration (TGA)
India
CDSCO - Central Drug Standard Control Organization (CDSCO)
Canada
TPD – Therapeutic Product Directorate
HPFBI – Health Product & Food Branches Inspectorate
Europe
EMA - European Medicines Agency
New Zealand
Medsafe - Medicines and Medical Devices Safety Authority
ANZTPA – New Zealand Therapeutic Product Authority
China
CFDA - China Food and Drug Administration
South Africa
MCC - Medicines Control Council
Sri Lanka
SPC – State Pharmaceutical Corporation, Ministry of Health
Brazil
ANVISA - Agencia Nacional de Vigiloncia Sanitaria
Vietnam
MOH - Ministry of Health
Malaysia
DCA – Drug Control Authority
Along with these Regulatory Bodies there are
some international organizations also to control these pharmaceutical products
like WHO (World Health Organization) and ICH (International Conference on
Harmonization).
