MODULE 5│PHARMACEUTICS 2
MANUFACTURING PHARMACY
MANUFACTURING PHARMACY Drug Manufacturer
I. INTRODUCTION TO MANUFACTURING 1. Manufacturer – involved in production of drugs products
(preparatory processing, compounding, formulating, filling,
A. MANUFACTUIRNG packaging, repackaging, altering, ornamenting, finishing, labeling)
• large-scale production of drug products’ preparation, 2. Packer – involved in packaging of bulk drug product to its
processing, packaging, labeling, repacking, changing immediate container
wrapper, label or container of any drug products
3. Repacker – involved in repackaging of finished product into
Stages of Manufacturing smaller quantities in a separate container and/ or secondary
packaging
1 2 4 Trader – Registered owner of drug product and formulation but
Dispensing Processing 3 Packaging subcontracts manufacturing
of Raw of Dosage Filling & - Procures RM and PM
Materials Forms Repacking
- Provides monographs and QC protocols
Drug Distributor
Manufacturing Activities
1. Importer – imports RM, API, and/or finished products for
Primary Manufacturing – manufacture of raw material (APIs and wholesale distribution to other licensed established
Excipients)
2. Exporter – exports RM, API, and/ or finished products for
Secondary Manufacturing – manufacture of finished dosage form wholesale distribution to establishments outside the country
Tertiary Manufacturing – packaging, labeling, and repacking of 3. Wholesaler – procures RM, API, and/ or finished
bulk finished product products from a local licensed establishment for local
distribution in wholesale basis
Toll Manufacturing – an arrangement whereby a
competent company manufactures products for another C. DEPARMENTS IN MANUFACTURING COMPANY
company
1. Research and Development Department
B. TYPES OF DRUG ESTABLISHMENTS • formulates new products
• Stages of Drug Development
AO 56 s.1989 1) Discovery and Development
• Revised Regulations for the Licensing of Drug 2) Preclinical Research
Establishments and outlets 3) Clinical Research
4) FDA Review
Drug
Establishments 5) Post-market Surveillance
• involved in process development and scale-up
• prepares Master formula
Drug Drug
Drug Trader Drug Importer Drug Exporter
Manufacturer Wholesaler
Master formula – contains the formulation,
specifications, manufacturing procedures, QA
AO 2014-0034 requirements, and labeling of a finished product
• Rules and Regulations on the Licensing of Establishments
Engaged in the Manufacture, Conduct of Clinical Trial, • justifies overages in the formula
Distribution, Importation, Exportation, and Retailing of Drug
Products, and Issuance of Other Related Authorization Overages – addition of an excess amount of API in
an unstable preparation
Manufacturer
• improves existing products
Packer
Drug 2. Production Department
Manfacturer • deals with all stages of manufacturing batches of finished
Repacker drug products
Trader Batch – specific quantity of product intended to have
uniform character and quality, produced during the
Drug Establishments
Importer same single cycle of manufacture
Drug Distributor Exporter Lot – specific identified portion of a batch
Drugstore Wholesaler • Plans the production according to MO
RONPD
Manufacturing Order (MO) – gives instructions to
manufacture a product
Sponsor
• accomplish the BMR to ensure that batches were properly
made and tests were conducted
CRO
Batch Manufacturing Record (BMR) – document
containing the details of the manufacture of each
batch
Module 5 – Manufacturing Pharmacy Page 1 of 9 RJAV 2022
, 3. Warehouse Department f. Mannitol and xylitol
• stores materials and finished products • Used in chewable tablets
• holds incoming components in the quarantine area • Negative heat of solution
Quarantine – status of materials which are isolated 2. Binder
physically while a decision is awaited on their release, • Imparts cohesiveness to powders causing them to from
rejection, or reprocessing granules
• involved in purchasing and logistics Inadequate binder Too much binder
4. Quality Assurance Department • Soft granules • Too hard granules
• assures that all operations meet required standards for • Too much fines • Difficulty in screening
safety and efficacy, ensures compliance to cGMP • Inadequately hard tablets • Hampered disintegration &
• conducts quality audit and monitoring dissolution (↓ BA)
• prepares SOPs
a. Starch paste
Standard Operating Procedures (SOP) – step-by- • Binder of choice for wet gran
step instructions for performing operational tasks or
activities b. Acacia & Tragacanth
• Natural guns
5. Quality Control Department c. Gelatin
• tests compliance of raw materials, packaging materials, and • Protein substance
finished products to specifications
• conducts sampling of materials to be tested d. Sucrose
• performs IPQC and environmental testing • Can be used as powder or syrup
6. Marketing Department e. Cellulose Derivatives
• studies current market trends, consumer behavior and • Methyl cellulose
product status in market • Ethyl cellulose
• promote and advertisement • Carboxymethyl cellulose
• Hydroxypropyl methyl cellulose
7. Regulatory Department
• ensures compliance of company and its products with all f. PVP
pertinent regulations and laws about drugs and their • Binder for chewable tablets
marketing
3. Disintegrant
8. Engineering Department • Facilitates the breakup of a tablet when in contact with
• installs, maintains and repairs of equipment and premises aqueous medium
• conducts validation and qualification
Validation – action of proving and documenting that
any process, procedure or method actually and
consistently leads to the expected results
Qualification – action of proving that premises,
systems or equipment work correctly and actually
lead to expected results • MOA:
• Swelling – starch paste
• ensures safety • Wicking – MCC
• Release of gas – effervescent tablets
9. Medical Department
• concerned with physical examination and medical treatment 4. Superdisintegrant
of employees • Newer class of disintegrants which are effective at much
• performs clinical studies lower levels
• publishes house organ/paper • Hydroscopic
II. MANUFACTURING OF SOLID DOSAGE FORMS a. Sodium Starch Glycolate (Explotab®, Primojel®)
• Cross link starch polymer
A. FORMULATION COMPONENTS
b. Crospovidone
1. Diluent (Filler/ Bulking Agent) • Cross link polyvinylpyrrolidone
• inert substance added to increase tablet size or fill the
capsule body c. Croscarmellose Na
• Cross link cellulose derivative
a. Lactose
• Most common 5. Antifrictional Agents (Flow Activators)
• No reaction with most drugs • Fine powders added prior to compression to reduce friction
• Monohydrate, anhydrous, and spray-dried and improve flow properties
• Mostly hydrophobic and added at low concentration
b. Sucrose and Dextrose
• Used as sweetener Lubricant Antiadherent Glidant
Reduces friction Reduces sticking to Reduces friction
c. Microcrystalline Cellulose (Avicel®) between the tablet die walls and picking among particles to
and die wall to by punches enhance the flow
• Good flow and very compressible
facilitate ejection from
• Disintegrates rapidly in water die cavity
d. Starch a. Stearates (Mg, Ca, Na)
• Used as diluent, binder and disintegrant • lubricant, antiadherent and glidant
• Modified Starch: Sta-Rx 1500®, Cellutab®
b. Purified Talc
e. Dibasic calcium Phosphate • lubricant and antiadherent
• Only inorganic salt used as diluent
Module 5 – Manufacturing Pharmacy Page 2 of 9 RJAV 2022
MANUFACTURING PHARMACY
MANUFACTURING PHARMACY Drug Manufacturer
I. INTRODUCTION TO MANUFACTURING 1. Manufacturer – involved in production of drugs products
(preparatory processing, compounding, formulating, filling,
A. MANUFACTUIRNG packaging, repackaging, altering, ornamenting, finishing, labeling)
• large-scale production of drug products’ preparation, 2. Packer – involved in packaging of bulk drug product to its
processing, packaging, labeling, repacking, changing immediate container
wrapper, label or container of any drug products
3. Repacker – involved in repackaging of finished product into
Stages of Manufacturing smaller quantities in a separate container and/ or secondary
packaging
1 2 4 Trader – Registered owner of drug product and formulation but
Dispensing Processing 3 Packaging subcontracts manufacturing
of Raw of Dosage Filling & - Procures RM and PM
Materials Forms Repacking
- Provides monographs and QC protocols
Drug Distributor
Manufacturing Activities
1. Importer – imports RM, API, and/or finished products for
Primary Manufacturing – manufacture of raw material (APIs and wholesale distribution to other licensed established
Excipients)
2. Exporter – exports RM, API, and/ or finished products for
Secondary Manufacturing – manufacture of finished dosage form wholesale distribution to establishments outside the country
Tertiary Manufacturing – packaging, labeling, and repacking of 3. Wholesaler – procures RM, API, and/ or finished
bulk finished product products from a local licensed establishment for local
distribution in wholesale basis
Toll Manufacturing – an arrangement whereby a
competent company manufactures products for another C. DEPARMENTS IN MANUFACTURING COMPANY
company
1. Research and Development Department
B. TYPES OF DRUG ESTABLISHMENTS • formulates new products
• Stages of Drug Development
AO 56 s.1989 1) Discovery and Development
• Revised Regulations for the Licensing of Drug 2) Preclinical Research
Establishments and outlets 3) Clinical Research
4) FDA Review
Drug
Establishments 5) Post-market Surveillance
• involved in process development and scale-up
• prepares Master formula
Drug Drug
Drug Trader Drug Importer Drug Exporter
Manufacturer Wholesaler
Master formula – contains the formulation,
specifications, manufacturing procedures, QA
AO 2014-0034 requirements, and labeling of a finished product
• Rules and Regulations on the Licensing of Establishments
Engaged in the Manufacture, Conduct of Clinical Trial, • justifies overages in the formula
Distribution, Importation, Exportation, and Retailing of Drug
Products, and Issuance of Other Related Authorization Overages – addition of an excess amount of API in
an unstable preparation
Manufacturer
• improves existing products
Packer
Drug 2. Production Department
Manfacturer • deals with all stages of manufacturing batches of finished
Repacker drug products
Trader Batch – specific quantity of product intended to have
uniform character and quality, produced during the
Drug Establishments
Importer same single cycle of manufacture
Drug Distributor Exporter Lot – specific identified portion of a batch
Drugstore Wholesaler • Plans the production according to MO
RONPD
Manufacturing Order (MO) – gives instructions to
manufacture a product
Sponsor
• accomplish the BMR to ensure that batches were properly
made and tests were conducted
CRO
Batch Manufacturing Record (BMR) – document
containing the details of the manufacture of each
batch
Module 5 – Manufacturing Pharmacy Page 1 of 9 RJAV 2022
, 3. Warehouse Department f. Mannitol and xylitol
• stores materials and finished products • Used in chewable tablets
• holds incoming components in the quarantine area • Negative heat of solution
Quarantine – status of materials which are isolated 2. Binder
physically while a decision is awaited on their release, • Imparts cohesiveness to powders causing them to from
rejection, or reprocessing granules
• involved in purchasing and logistics Inadequate binder Too much binder
4. Quality Assurance Department • Soft granules • Too hard granules
• assures that all operations meet required standards for • Too much fines • Difficulty in screening
safety and efficacy, ensures compliance to cGMP • Inadequately hard tablets • Hampered disintegration &
• conducts quality audit and monitoring dissolution (↓ BA)
• prepares SOPs
a. Starch paste
Standard Operating Procedures (SOP) – step-by- • Binder of choice for wet gran
step instructions for performing operational tasks or
activities b. Acacia & Tragacanth
• Natural guns
5. Quality Control Department c. Gelatin
• tests compliance of raw materials, packaging materials, and • Protein substance
finished products to specifications
• conducts sampling of materials to be tested d. Sucrose
• performs IPQC and environmental testing • Can be used as powder or syrup
6. Marketing Department e. Cellulose Derivatives
• studies current market trends, consumer behavior and • Methyl cellulose
product status in market • Ethyl cellulose
• promote and advertisement • Carboxymethyl cellulose
• Hydroxypropyl methyl cellulose
7. Regulatory Department
• ensures compliance of company and its products with all f. PVP
pertinent regulations and laws about drugs and their • Binder for chewable tablets
marketing
3. Disintegrant
8. Engineering Department • Facilitates the breakup of a tablet when in contact with
• installs, maintains and repairs of equipment and premises aqueous medium
• conducts validation and qualification
Validation – action of proving and documenting that
any process, procedure or method actually and
consistently leads to the expected results
Qualification – action of proving that premises,
systems or equipment work correctly and actually
lead to expected results • MOA:
• Swelling – starch paste
• ensures safety • Wicking – MCC
• Release of gas – effervescent tablets
9. Medical Department
• concerned with physical examination and medical treatment 4. Superdisintegrant
of employees • Newer class of disintegrants which are effective at much
• performs clinical studies lower levels
• publishes house organ/paper • Hydroscopic
II. MANUFACTURING OF SOLID DOSAGE FORMS a. Sodium Starch Glycolate (Explotab®, Primojel®)
• Cross link starch polymer
A. FORMULATION COMPONENTS
b. Crospovidone
1. Diluent (Filler/ Bulking Agent) • Cross link polyvinylpyrrolidone
• inert substance added to increase tablet size or fill the
capsule body c. Croscarmellose Na
• Cross link cellulose derivative
a. Lactose
• Most common 5. Antifrictional Agents (Flow Activators)
• No reaction with most drugs • Fine powders added prior to compression to reduce friction
• Monohydrate, anhydrous, and spray-dried and improve flow properties
• Mostly hydrophobic and added at low concentration
b. Sucrose and Dextrose
• Used as sweetener Lubricant Antiadherent Glidant
Reduces friction Reduces sticking to Reduces friction
c. Microcrystalline Cellulose (Avicel®) between the tablet die walls and picking among particles to
and die wall to by punches enhance the flow
• Good flow and very compressible
facilitate ejection from
• Disintegrates rapidly in water die cavity
d. Starch a. Stearates (Mg, Ca, Na)
• Used as diluent, binder and disintegrant • lubricant, antiadherent and glidant
• Modified Starch: Sta-Rx 1500®, Cellutab®
b. Purified Talc
e. Dibasic calcium Phosphate • lubricant and antiadherent
• Only inorganic salt used as diluent
Module 5 – Manufacturing Pharmacy Page 2 of 9 RJAV 2022
