cGMP

Current Good Manufacturing Practice

 GOOD MANUFACTURING
PRACTICES (GMPs)
• GMPs are regulations developed by the FDA.
• GMPs are minimum requirement that the industry
must meet when manufacturing, processing, packing,
or holding human and veterinary drugs.
• These regulations. Also known as cGMPs,
establish criteria for personnel, facilities, and
manufacturing processes to ensure that the
finished drug product has the correct identity,
strength, quality, and purity characteristics
 QUALITY CONTROL
• Group within the manufacturer that is responsible for
establishing process and product specifications.
• Specif ications: criteria to which a drug product should
conform to be considered acceptable quality for its
intended use.
• The QC unit tests the product and verifies that the
specifications are met .
• QC testing includes the acceptance and rejection of
the incoming raw materials, packaging components,
drug products, water system, and environmental
conditions that exist during the manufacturing
process.
 QUALITY ASSURANCE
• is the group within the manufacturer that determines
that the systems and facilities are adequate, and that
the written procedures are followed to ensure that the
finished drug product meets the applicable
specifications for quality.
 Good Manufacturing Practice
• Ensures that products are
consistently produced. The standard
of quality must be suitable for use.
 Current Good Manufacturing Practice
I. Regulatory Aspects of CGMP
Guidelines promulgated by the US-
FDA, Administrative Order no. 220 s. 1974
on current good manufacturing practice.
This administrative order was patterned after
the guidelines developed in 1963 by the US-
FDA with the participation of drug
companies.
Good Manufacturing Practices (GMP) is a
responsibility of:
1) Quality control
2) Production control
 Functions of the QUALITY CONTROL in
the GMP:
• To audit or to inspect periodically
the procedures, equipment, and facilities
employed by the various areas engaged
in research development, production,
control, purchasing, distribution and sale
of the product.
• To detect non compliance to
cGMP and to correct them.
 Areas of Concern
A. Contamination
B. Personnel
C. Buildings
D. Equipment
 A. Contamination
In addition, non-compliance to cGMP could
result in the ff:
• Quality variation
• Contamination (from people and
environment)
• Mix-ups and errors
• Product recalls
The ff. are the disadvantages of product
recalls:
• Causes financial losses.
• Bad publicity
• Harmful publicity which can have a
negative effect on sales.
• Causes adverse psychological
effects on the employees.
 Objective of cGMP
• To produce a product that is safe,
pure and effective.

*NOTE: for drug firms manufacturing both

penicillin and non-penicillin products, use of
the same area/premises, same equipment
and personnel is conductive to cross-
contamination!
 Contamination
A. PEOPLE
Sources:
1. Unclean clothing
2. Clothes that shed lint and particles.
3. Objects falling out of one’s pockets
4. Not following SOP’s
 Prevention
1. Always wear clean clothing and uniform.
2. Avoid wearing clothes that shed lint or
particles.
3. Wear head coverings, gloves, hair
covering, masks, protective gear.
4. Do not use breast pocket.
5. Follow SOP’s that relate to proper
cleaning of equipment.
 II. Cross-contamination
SOURCES:
1. Airborne particles within storage area and
thru ventilation system.
2. Packaging machines not cleared out prior
to a new packaging run
3. Improper dispensing of components
4. Inaccuracies and mix-ups in record-
keeping.
 PREVENTION:
1. Keep containers tightly closed and in
separate rooms.
2. Follow specific SOP’s on cleaning
equipments and proper labeling and
packaging procedures.
3. Follow SOP’s on correct dispensing of
components.
4. Follow SOP’s in accurate record-keeping.
 III. MICROBIAL
SOURCES:
1. People
2. SOP’s not being followed.
3. Environment.
 PREVENTION
1. Good personal hygiene.
2. Report all injuries and illnesses.
3. Follow SOP’s on handling, storage,
cleaning and sterilization.
4. Monitor microbial level of
environment.
 B. Personnel
The qualified personnel should posses
the ff:
• Proper education
• Proper training and experience to
execute technological assignments.
• Personnel having direct contact with
drugs and cosmetics should:
• Periodic health check-ups.
 B. Personnel
• Free from communicable diseases and
open lesions on the exposed surface of
the body.
• Have an awareness of the importance of
good personal hygiene.
• Wear clean outer garments
• Maintain a high degree of personal
cleanliness
• Should conform to hygienic practices.
 C. Buildings
• Buildings must be planned for easy
cleaning, maintenance and freedom
from congestion and traffic. Buildings
should provide for the ff.:
• Adequate space for proper operation
of manufacturing, processing,
packaging, control and storage of
products and their components.
• Adequate lighting and ventilation.
• Adequate locker facilities, hot and cold
washing facilities
• Adequate supply of potable water under
continuous positive pressure, plumbing
system free from defects or
contamination.
• Suitable housing and space for the care of
all laboratory animals.
• Safe and sanitary disposal of sewage,
trash, and other refuse within and from the
buildings and immediate premises.
 D. Equipment
• Equipment used for the manufacture,
processing, packaging, holding, testing or
control of drugs and cosmetics should be:
• Maintained in a clean and orderly manner.
• Of suitable design, size, construction and
location in relation to surroundings to
facilitate maintenance and operation for its
intended uses.
The equipment should have the ff. properties:

• Its surface should not be reactive,

additive or absorptive
• It should facilitate adjustment,
disassemble, cleaning and
maintenance as necessary
• It should be of suitable type, size and
accuracy intended for testing,
measuring, mixing, weighing or other
processing or storage operations.
NOTE. Each piece of equipment should have its own logbook
and identification number.
• Entries in the equipment logbook should
contain the ff.:
1) Date when the equipment was used.
2) Name of the product where the
equipment was used.
3) Date when it was cleaned.
4) Personnel responsible for cleaning it.
5) Date when the equipment was validated.
6) Result of validation.
 Administrative Order No. 220 s. 1974
Subject: CGMP in Manufacture, Processing, Packaging
and Holding
• The score of this regulation is as follows:
1)Definitions
2)CGMP
3)Buildings
4)Equipment
5)Personnel
6)Components (Raw materials)
7) Master formula and Batch
Production records
8) Production and Control procedures
9) Product containers
10)Packaging and labeling
11)Laboratory controls
12)Finished Goods Warehouse
Distribution records
13)Stability
14)Complaint Files
• Component (raw material)
- means any ingredient intended for use in the
manufacturing of drugs, including those that may
not appear in the finished product.
• Batch
- means a specific homogenous quantity of a
drug or in case of drug produced according to
single manufacturing order during the same
cycle of manufacture.
–Lot – means a batch or any portion of
a batch of a drug, produced by a
continuous process
– Lot number or control number –
means any distinctive combination of
letters and/or numbers, or both, by
which the complete history of the
manufacture, control, packaging and
distribution of a batch or lot of a drug is
determined.
– Active Ingredient – means any
substance of a drug, which is
intended to furnish
pharmacological activity
– Inactive Ingredient – means any
substance other than “Active
Ingredient” present in the drug
formulation.
– Materials Approval Unit – means any
organizational element having the
authority and responsibility to approve
or reject raw materials, in-process
materials, packaging components and
final products.
– Strength – means (a) the concentration
of a known active drug substance in the
formulation (b) potency, that is, the
specific ability or capacity of the product
as indicated by appropriate lab.
Control of components shall include the
ff:
• Each container of components shall
be examined visually for damage
contamination in transit,
• An adequate number of samples
shall be subjected to one or more
identity tests, including at least one
laboratory test for identity.
 Preservation: Samples and records
• At least twice the quantity necessary for
all the required tests of identity, purity and
strength
• Complete records related to the control,
use, production, distribution and complaint
are maintained to permit reconstruction of
the history of the product.
• In general, records and samples are
retained for a period of 5 years.
 BFAD recommends the following retention
periods:
• For Components:
– At least 2 years after the distribution of
the last lot of the product incorporating
the components has been completed
or;
– One year after the expiration date of
this last lot incorporating the
components.
 For Finished Products:
– At least 2 years after lot distribution is
completed or;
– One year after the expiration date of the
product.

For Records:
– Drugs: same as above.
– Cosmetics: at least 3 years after the
manufacture is completed.
• Representative samples of components
particularly liable to contamination with
highly toxic substances (like heavy
metals)
• Representative samples of all
components shall be appropriately
examined by microscopic examination for
evidence of filth, insect infestation, or
other extraneous contamination.
• Representative samples of components
subject to be used as active ingredients
shall be tested to determine their strength
per unit of weight
• Representative samples of components
subject to microbial contamination (those
of animal and plants origin drugs) shall be
subjected to microbiological tests.
• Approved components shall be
appropriately marked and re-tested
as necessary to assure that they
conform to appropriate specifications
of identity, strength, quality, and
purity at the time of use
• A reserved sample of all active ingredients
consisting of at least twice the quantity
necessary for all the required tests of
identity, quality, purity and strength shall
be retained for at least 2 years after the
distribution of the last drug lot
incorporating the active ingredient has
been completed; or 1 year after the
expiration date of this last drug lot
incorporating the active ingredient, or
whichever is the shortest.
 Master Formula and
Batch Production Records
• A Master formula records shall be
retained for a period of at least 2
years after the distribution of the
last drug batch produced using the
master-formula records; or 1 year
after the expiration date of the
drug’s last batch, or whichever is
the shortest.
 I. The master formula record include:
1) The name of the product, a
description of its dosage form.
Including a specimen copy of the
label and other labeling contained in
the retail package of the drug.
2) The name and weight measure of
each ingredient per dosage unit or
per weight measure of the finished
drug.
3) Complete list of ingredients
designated by names/codes.
Accurate weight or measure of each
ingredient.
4) Theoretical weight or measure at
various stages of processing.
5) Theoretical yield.
II. The Batch Production Records shall include:
1)Accurate reproduction of the M.F.
record checked and endorsed by
competent, responsible individual.
2)Records of each step in the
manufacture, processing, packaging,
labeling, testing and controlling of
the batch.
- in-process and laboratory control
results, endorsement/signatures of
the individual actively performing
and supervising the operation.
3) Batch number, lot number and/or
control numbers of all laboratory
control procedures.
4) A record of complete investigative
history of any mix-ups, errors,
unsatisfactory drug products found
during and after the operation of
the batch.
 Production and Control Procedures
• Include the ff. general scope;
– Assurance that the drugs
produced have the safety,
strength, quality and purity they
purport to possess
– The following processes should
be performed by a competent,
responsible individual, checked
by a second responsible,
competent individual;
– Selection, weighing and measuring
of components
– The addition of the active
ingredients during processing
– Weighing and measuring during
the various stages of processing
– Determination of the finished yield
– All containers, lines and equipment
used in the production of a batch
of drugs shall be distinctly labeled
at all times to identify accurately
and completely the ff. data;
– Its contents
– The stage of processing
– Batch number/ identification
 For equipment and lines, the placement of
identification shall include;
• input lines
• output lines
• operator controls

*Note: All equipment, containers and lines

shall be stored and handled in a manner
adequate to prevent mix-ups or
contamination with other drugs.
– Appropriate procedures shall be
taken to minimize the hazard of
microbial contamination with
microorganisms in the production
of parenterals, ophthalmic
solutions and other sterile drugs.
– To assure uniformity and integrity of
products, there shall be adequate in-
process controls such as;
1) Checking the weights and
disintegration time of tablets
2) The fill of liquids
3) The adequacy of mixing
4) The homogeneity of suspensions
5) The clarity of solutions
• Such in-process testing shall be
done at appropriate intervals during
each individual operations, using
readily accessible, adequate and
suitable equipment.
• A written record of all such tests shall be
maintained, which will include the ff. data;
• The date and time of each test
• The product name
• Batch number
• The quantity tested
• The results
• Initials of the person performing the
test
– In-process batches of drugs found
unacceptable to the firm shall be
held until a determination as to
their disposition has been made.
– Appropriate records shall be
maintained which contain the ff.;
• Reasons for unacceptability
• The ultimate disposition of the
material
– Certifiable antibiotics and insulin
are to be withheld from distribution
until the letter of certification is
received.
– Returned goods shall be so
identified and held. The returned
goods shall be either destroyed or
subjected to complete protocol of
testing.
 Product Containers
• Suitable specifications, test
methods, cleaning procedures and
sterilization procedures shall be
used to assure those containers,
closures and other component
parts of drug packages.
• The container shall comply with
applicable compendia requirements
when used for an official product.
Packing and labeling operations shall include
the ff.:
• Be separated from operations on
any other drugs in a manner
adequate to avoid mix-ups.
• Provide for an inspection of the
facilities prior to use to assure
that all other drugs and
previously used labeling have
been removed.
– Provide strict control of the package
labeling issued for use with the drug.
Such issuance shall be carefully
checked by a competent, responsible
person
– Provide for adequate examination and
laboratory testing of an adequate
number of representative samples of
finished products after packaging and
labeling
–A labeled sample package of
the drug is shipped by the
manufacturer to the repacker
for comparison with the
appearance and labeling of the
article in the bulk container.
• Prior to repacking, a visual
comparison is conducted by a
competent, responsible individual
to assure that the drug to be
repacked from the bulk is identical
to the appearance to that in the
sample package and the labeling of
the bulk package, as well as the
sample package show the same
drug identity and composition.
• The repacked labels of the drug
with suitable expiration date to
assure that the drug meets
appropriate standards of identity,
strength, quality and purity at the
time of use.
• The label of the repacked drug
bears a lot or control number and
the repacker maintains record for at
least 2 years after the distribution of
the drug has been completed; or 1
year after the drug’s expiration
date, whichever is the shortest.
• Gang printing of cut labels or
cartons should be avoided.
Especially when labels of cartons
for different products or different
strengths of the same product are
of the same size and have identical
format and/or color combinations.
 Laboratory Controls
Include:
• Establishment of scientifically sound and
appropriate specifications, standards
and test procedures
• To assure that the components, drug
preparations in the course of processing
and finished products conform to
appropriate standards of identity,
strength, quality and purity.
 Finished Goods Warehouse Control
Distribution Records

• This provision of the CGMP shall

include the ff.:
– An adequate, perpetual inventory
control system
– System program for distribution of
finished goods in the warehouse
 Stability
• There shall be assurance of the
stability of components, drug
preparations in the course of
processing, and finished drugs.
• Stability shall be determined by;
Reliable, meaningful and
specific test methods
• On products in the containers in which
they are marketed to assure that the
container is not reactive, additive or
absorptive, so as not to affect the safety,
identity, strength, quality or purity of the
drug or its components beyond
specifications.
• On any solution of a drug which is to be
prepared as directed in its labeling, at the
time of dispensing.
• To assure that reasonable uniform
rates of absorption and biological
availability of the drug product
according to the specifications for
composition and physical
characteristics of the drug product.
• Expressed as expiration date with
related conditions of storage on the
drug label
• Maintenance of records of expiration
dates and periods used in the labeling of
each batch or lot of the drug. These
records shall be maintained for;
– At least 2 years after the
distribution of the drug has been
completed
– 1 year after the drug’s expiration
date
– Or whichever is the shortest
 Complaint Records
• It is the customer who performs the
final test on the product. A
dissatisfied consumer may write in or
phone in his complaint and the
company must review such
complaint. A decision is made
whether or not an investigation is
necessary.
Complaint records should contain the ff.:

• Name and address of the

complainant
• Product name, strength, and
control/lot number
• Nature of complaint
• Reply to the person complaining
• Results of the investigation and
follow-up action that was required
• If no investigation took place, the
record must indicate:
– why it was considered
unnecessary
– the name of the person
responsible for that decision