AUDITING OF VENDORS AND
PRODUCTION DEPARTMENT
DRY PRODUCTION OF CAPSULES
BY
PRACHI KRISHNANATH PARSEKAR
M.PHARM ( PHARMACEUTICAL QUALITY ASSURANCE )
ROLL NO 16
VENDOR AUDIT
A method to inspect and evaluate a vendor's quality management
system, as well as its overriding practices, product handling and data
integrity of all relevant documentation.
✔ Provides assurance that system is operating effectively and efficiently in
the recording and payment of goods/services of appropriate quality,
✔ At the right time, in sufficient quantity and at an acceptable price.
• Auditor is a neutral body, commissioned to find a specific set of results so
that vendor meets desired criteria and standards.
• They are expected to deliver a comprehensive report on their findings,
with specific recommendations and actions.
CAPSULES
Solid pharmaceutical dosage forms in which the drug or a mixture of
drugs is enclosed in a gelatin shell or any other suitable material to form
various shapes.
Manufacturing of capsules
Hard gelatin capsules
• Hard gelatin capsule shell is composed largely of gelatin.
• Also may contain plasticizer, colourants, opacifying agents, and
preservatives which either enable capsule formation or improve their
performance.
• 12-16% water, but the water content can vary, depending on storage
conditions.
Step 1: Preparation of gelatin solution (dipping solution)
• Concentrated solution of gelatin is prepared by dissolving gelatin in
demineralized water (heated to 60-70°C) in jacketed pressure vessels.
• This solution contains 30-40% w/w of gelatin and is highly viscous.
• Colourants and pigments are added to attain desired final capsule appearance.
Step 2: Dip-coating gelatin solution on to metal pins (moulds)
• Capsule shells are manufactured under strict climatic conditions by dipping
pairs (body and cap) of standardized steel pins arranged in rows on metal bars
into an aqueous gelatin solution (25-30% w/w) maintained at about 50° C in a
jacketed heating pan.
• As moulds are below gelling temperature, gelatin begins to form a thin gelatin
layer or film on the moulds.
Step 3: Rotation of dip-coated pins
• Following adsorption of gelatin solution on to surface of pins, bar containing the pins
is removed and rotated to evenly distribute the solution around the pins.
Step 4: Drying of the gelatin-coated pins
• Blast of cool air is used to set gelatin on the mould.
Step 5: Stripping and trimming
• Capsule is stripped off the mould and trimmed to proper length.
Step 6: Joining of trimmed capsule shell
• Two halves (cap and body) are joined to pre-closed position using a pre-lock
mechanism. Printing is done if needed before packing in cartons for shipping.
Filling of hard gelatin capsules
• An established technology, with
equipment available ranging from
✔ very small-scale manual filling
(e.g., Feton capsule filling
machine)
✔ intermediate-scale
semi-automatic filling
✔ large-scale fully automatic filling.
• Can also be hand-filled one at a
time.
BASIC STEPS IN FILLING HARD
GELATIN CAPSULES
1. Rectification of capsules
Placing empty gelatin capsules on the removable plate with bodies facing
downward.
2. Separation of caps from bodies.
3. Dosing of fill material
The body is filled with the formulation manually using a plastic spatula,
the excess powder is removed.
4. Replacement of caps/ closing capsule shells
5. Ejection of filled capsules
SOFT GELATIN CAPSULES
Components of the soft gelatin capsule shell
✔ Gelatin
✔ Plasticizing agent
✔ Water
✔ Preservatives
✔ Colorants
✔ Other excipients
METHODS OF MANUFACTURING SOFT GELATIN
CAPSULES
PLATE PROCESS
• Warmed sheet of plain or coloured plasticized gelatin is placed over die plate
having a number of depression or moulds or die pockets.
• By applying vacuum, sheet is drawn into depressions or pockets to form
capsule wells.
• Capsule wells are filled with medication-containing liquid.
• A second sheet of gelatin is carefully placed on top of filled wells followed by
top plate of the mould.
• Pressure is then applied to combined plate to form, seal and cut capsules into
individual units.
ROTARY DIE PROCESS
1. Two plasticized gelatin ribbons are prepared in rotary-die machine.
2. They are continuously and simultaneously fed with liquid, semiliquid or paste
fill between the rollers of rotary die mechanism.
3. Forced injection of feed material between two ribbons causes gelatin to swell
into die pockets
4. This governs size and shape of softgels as they converge.
5. As die rolls rotate, convergence of matching dies pockets hermetically seals
and cuts out filled capsules.
RECIPROCATING DIE PROCESS
1. Gelatin ribbons are fed between a set of vertical dies that continually open
and close to form rows of pockets in gelatin ribbons.
2. Pockets are filled with medication and are sealed, shaped, and cut out of the
film as they progress through machinery.
3. As capsules are cut from ribbons, they fall into a cooled solvent bath that
prevents capsules from adhering to one another.
ACCOGEL PROCESS
1. Involves a measuring roll that holds fill formulation in its cavities under
vacuum and rotates directly above elasticized sheet of gelatin ribbon.
2. Ribbon is drawn into capsule cavities of capsule die roll by vacuum.
3. Measuring rolls empty the fill material into capsule-shaped gelatin cavities on
die roll.
4. Die roll converges with rotating sealing roll covered with another sheet of
elasticized gelatin.
5. Convergence of two rotary rolls creates pressure to seal and cut the formed
capsules.
SEAMLESS PROCESS
1. Molten gelatin stream flows though outer nozzle of a concentric tube at a
constant rate
2. Medicated liquid formulation is dispensed through inner orifice by means of a
precision metering pump.
3. Emerging stream is broken up into an intermittent but steady flow of
uniform-sized by a pulsating mechanism
4. Leading to the formation of droplets enveloped in molten gelatin.
5. Formed capsules are quickly removed from nozzle, slowly congealed and
automatically ejected from system.
CHECKLIST FOR CAPSULE
The followings are the most critical parameters which need to be checked before
placing order:
1. What is the source of gelatin?
2. Is it GMP Compliant or Not?
3. If the quality control/ quality assurance facilities are adequate or not?
4. If all the sizes and all types of printing facility available?
5. If inspection, packaging, storage and transportation of the product is adequate to
retain the quality of the capsules?
6. If the product is readily available for recall?
Sr. Audit item Yes No Observatio Correctiv
no n e action
Gelatin Source
1 Check If Gelatin confirming to USP or B.P.
2 Check if the supplier has filed DMF Type III.
3 Check if by chance Commercial Grade,
Industrial Grade or Food Grade gelatin has been
employed for capsule manufacturing, which
should otherwise be avoided.
4 Check if the Gelatin, Colors and Pigments
source is well reputed.
5 The gelatin shall be good enough to make the
surface of the capsule smooth evenness of the
thickness and smooth incision.
Sr. Audit item Yes No Observatio Correctiv
no n e action
Quality Control Facility
1 Well equipped QC Laboratory
2 Disintegration tester
3 Gas chromatographer
4 Atomic absorption
5 Graphite oven
6 Chlorohydrins and Ethylene oxide detector
7 Fast Measure Moisture Meter
Sr. Audit item Yes No Observatio Correctiv
no n e action
Quality Control Facility
8 Glass Constant temperature water bath
9 UV Spectrophotometer
10 Dedicated Micro Lab
11 Dedicated Physiochemical testing Wet lab
12 Special facility for Testing Packaging Materials
Sr. Audit item Yes No Observatio Correctiv
no n e action
Quality Assurance Facility
1 Manufactured under controlled continuous
production environments under strict GMP
guidelines
2 Samples are regularly tested for physical defect,
length, dome, double, wall thickness, moisture
content, colorshades, weight variation and other
relevant parameters
3 Quality built into the process from vendor site
to buyer site or not
4 All manufacturing processes and quality
management procedures are qualified and
validated in compliance with CGMP and other
international standards.
Sr. Audit item Yes No Observatio Correctiv
no n e action
Quality Assurance Facility
5 All batch records are well documented or not
6 Strict process monitoring and Quality inspection
7 Strict control on viscosity of the gelatin solution
8 Uniformity in capsule colors
9 Precise printing on capsules.
10 Strict control on humidity and temperature
11 Pesticide Residues Shall be absent
12 Linear printing, Circular printing or Customized
as per need.
13 Facility for precise control of temperature and
humidity
Sr. Audit item Yes No Observatio Correctiv
no n e action
Specifications for Finished products
1 Viscosity 260mm^2 /s
2 Arsenic ≤1ppm
3 Ash for transparent capsules ≤2.0%
4 Ash for translucent capsules ≤3.0% ~4.0%
5 Ash for opaque capsules ≤5.0%
6 Disintegration $10min
7 Heavy Metals $50ppm
8 Chlorohydrins shall be absent
9 Loss On Drying 12.5% 17.5%
10 Suitable for Dry Powder/Granules filling
Sr. Audit item Yes No Observatio Correctiv
no n e action
Specifications for Finished products
11 Uniform color and glossy.
12 Separated incisions not allowed
13 Significant deformation not allowed.
14 Bubbles more than 0.3mm in diameter not
allowed.
15 Clear shrunken and thin head not allow
16 Black spots more than 0.3mm in diameter not
allowed.
17 There shall be no intra batch and batch to batch
variation in color of the capsules.
18 The incision is very smooth to prevent the small
medicinal powder leaking out of the depart.
Sr. Audit item Yes No Observatio Correctiv
no n e action
Packaging and Storage
1 Check if the Packaging System is robust
2 PE bag/Aluminum foil bag + Styrofoam board
lined in
3 Bursting Strength Suitable
4 The packaging shall be suitable for heat and cold
shocks
6 Check that Storage for Gelatin capsules are
appropriate
Temperature: between 15° C to 25° C
Humidity: between 35% and 65%
7 Heat sources such as space heaters or sunlight
through windows are avoided.
REFERENCES
1. 50 STEPS FOR SUCCESS IN SOURCING OF HARD GELATIN CAPSULES
FOR PHARMACEUTICAL USE By Rajkumar Gupta, Managing Director Perfect
Pharmaceutical Consultant Pvt. Ltd
2. https://www.pharmaguideline.com/2017/02/vendor-audits-checklist-pharmaceutical
s.html
3. www.pharmapproach.com/manufacture-of-hard-gelatin-capsules
