Current Good Manufacturing

Practices
For Ninth Semester
Pharmacy Students
By
Dr. Mohamed A. Attia , Ph.D.
Prof. of Pharmaceutics &
Pharmaceutical Technology
Winter 2009 / 2010
Second Lecture
 Head of the Quality Control Department
Responsibilities
1. To approve or reject starting materials, packaging materials ,etc.
2. To evaluate batch records
3. To ensure that all necessary testing carried out .
4. To approve sampling instructions, specifications, test methods
and other quality control procedures .
5. To approve & monitor analyses carried out under analyses .
6. To check the maintenance of the department, premises and
equipments .
7. To ensure that the appropriate validations, including those of
analytical procedures, and calibrations of control equipment are
done .
8. To ensure the required initial and continuing training of quality
control personnel is carried out and adapted according to need .
 Training
1. The manufacturer should provide training in accordance with a
written program for all the personnel whose duties take them into
production areas or into control laboratories and for other
personnel whose activities could affect the quality of the product .

2. Newly recruited personnel should receive training appropriate to

the duties assigned to them . Continuing training should be
periodically assessed . Training programs should be available ,
approved by the head of either production or quality control
manager .

3. Personnel working in areas where contamination is a hazard, e.g.

clean areas or areas where active, toxic, infectious materials are
handled should be given specific training .
 Personal Hygiene
1. All personnel prior and during employment, should undergo health
examinations .
2. All personnel should be trained in the practices of personal hygiene .
3. Any person show at any time to have an apparent illness or open
lesions that may adversely affect the quality of products should not
allowed to handle starting materials , packaging materials ..
4. Direct contact should be avoided between the operator’s hands and
any manufacturing materials .
4. To ensure protection of the product from contamination , personnel
should wear clean body coverings appropriate to the duties they
perform .
5. Smoking, eating, drinking, chewing and personal medicines should
not be permitted in production, laboratory, and storage areas .
 Premises
Premises must be located, designed, constructed to suit the
operations to be carried out . Their layout and design must aim to
minimize the risk of errors and permit effective cleaning and
maintenance in order to avoid cross-contamination, build-up of dust
or dirt .
Premises Requirements
1. Should be situated in an environment that presents minimum risk
of causing any contamination of materials or products .
2. Should be suitably designed and constructed to facilitate good
sanitation .
3. Should be cleaned and disinfected according to detailed written
procedures .
4. Should be designed and equipped so as to afford maximum
protection against the entry of insects or other animals .
 Ancillary Areas
1. Rest and refreshment rooms should be separated
from other areas .
2. Facilities for changing and storing cloths and for
washing and toilet purposes should be easily
accessible and appropriate for the number of
users . Toilets should not communicate directly
with production or storage areas .
3. Animal houses should be well isolated from other
areas, with separate entrance and air handing
facilities .
 Storage Areas
1. Should be of sufficient capacity to allow orderly storage of various
categories of materials and products .
2. Storage areas should be designed to ensure good storage conditions .
3. Receiving and dispatch bays should protect materials and products
from weather . Reception areas should be designed to allow containers
of incoming materials to be cleaned before storage .
4. There should be a sampling area for staring materials .
5. Segregation should be provided for storage of rejected, recalled, or
returned materials or products .
6. Highly active materials , narcotics , or other dangerous drugs should be
stored in safe and secure areas .
7. Printed packaging materials are considered critical and should be
stored in safe and secure place .
8. The weighing of starting materials should be carried out in separate
weighing area designed for that use .
 Production Area
1. In order to minimize the risk of cross-contamination
self-contained facilities must be available for the
production of particular pharmaceutical products e.g.
penicillins but certain other products e.g. Some
antibiotics, hormones, cytotoxic substances, should
not conducted in the same facilities .

2. Premises should be laid out in such a way as to allow

production to take place in areas connected in a
logical order corresponding to the sequence of the
operations .

3. The adequacy of the working and in-process storage

space to minimize the risk of confusion between
different products or their components and to avoid
cross-contamination .
 Production Area ( cont..)
4. Interior surfaces ( walls, floors, and ceilings )
should be smooth and free from cracks and
open joints .

5. Pipe work, light fittings, ventilation points, and

other services should be designed and sited to
avoid the creation of recesses that are difficult
to clean .

6. Drains should be of adequate size and

equipped to prevent back-flow .
 Production Area ( cont..)
7. Production area should be effectively
ventilated , with air control facilities (including
control of temperature , humidity , and
filtration .

8. Premises for packaging of pharmaceutical

products should be designed and laid-out so
as to avoid mix-up or cross contamination .

9. Production area should be well illuminate ,

where visual on-line controls are carried out .
 Quality Control Area
1. Quality control laboratories should be separated from
production areas. Areas where biological ,
microbiological test methods are used should be
separated from each other .
2. Sufficient space should be given to avoid mix-ups and
cross-contamination . There should be adequate
suitable storage space for examples, reference
standards and records .
3. The design of the laboratories should take in account
the suitability of construction materials , prevention of
fumes and ventilation . Separate air-handling units are
needed for biological , microbiological & radioisotope
laboratories .
 Equipment
1. The layout and design of equipment must aim to
minimize the risk of errors and permit effective
cleaning and maintenance in order to avoid cross-
contamination, build-up of dust or dirt, and any
adverse effect on the quality of products .
2. fixed pipe work should be clearly labeled to indicate
the contents and where the direction of flow .
3. Balances and other measuring equipment of an
appropriate range & precision should be available for
production and control operations and should be
calibrated on a scheduled basis .
4. Production equipment should be designed, located,
and maintained to serve its purpose .
 Equipment ( cont..)
5. Production equipment should be designed so that it
can be easily and thoroughly cleaned on a scheduled
basis .
6. Washing and cleaning equipment should be chosen
and used so as not to be a source of contamination .
7. Production equipment should not present any hazard
to the products . The parts of the production
equipment that come into contact with the product
must not be reactive to extent that would affect the
quality of the product .
8. Defective equipment should be remove from
production and quality control areas or be labeled as
defective .
 Materials
The main objective of a pharmaceutical plant is to
produce finished products for patient’s use from a
combination of materials e.g. active, auxiliary, packaging
Starting Materials
1. The purchase of the staring materials should be done by
staff who have knowledge of products and suppliers .
2. Starting materials should be purchase from suppliers
according to specified specifications .
3. For each consignment the containers should be checked
for integrity of package and seal .
4. All incoming materials should be checked to ensure that
the consignment corresponding to the order . Containers
should be cleaned and labeled with prescribed data .
 Materials ( cont.. )
5. Damage to containers should be recorded and reported
to the quality control department and investigated .
6. If one delivery of material is made up of different batches
each batch must be considered as separate for sampling,
testing and release .
7. Starting materials in the storage area should be labeled .
Labels should carry the following information :
a. The designated name of the product and internal code reference .
b. The batch number given by supplier and by manufacturer .
c. The status of the contents e.g. on quarantine, on test , released.. .
d. Any expiry date or a date beyond which retesting is necessary .
 Materials ( cont.. )
8. There should be appropriate procedures to ensure the
identity of the contents of each container of starting
material .
9. Only staring materials released by the quality control
department and within their shelf-life should be used .
10. Starting materials should be dispensed only by
designated persons following written procedure, to
ensure that the correct materials are accurately
weighed into clean and properly labeled containers .
11. Each dispensed material and its weight should be
independently checked and the check recorded .
 Packaging Materials
1. They should be stored in secure conditions so as to
exclude the possibility of unauthorized access . Cut
labels and other loose printed materials should be
stored and transported in separate closed containers
so as to avoid mix-ups .
2. Packaging materials should be issued for use only by
designated personnel following an approved and
documented procedure .
3. Each delivery of printed or primary packaging material
should be given a specific reference number ,
4. All products and packaging materials to be used
should be checked on delivery to the packaging
department for quantity , identity, and conformity with
packaging instructions .
 Intermediate and Bulk Products
1. Intermediate and bulk products should be kept under
appropriate conditions
2. Intermediate and bulk products purchased as such
should be handled as were starting materials .

Finished Products

1. Finished products should be held in quarantine until

their final release .
2. The evaluation of finished products and documentation
necessary for release of a product for sale .
 Rejected and Recovered Materials
1. Rejected materials and products should be clearly
marked as such and stored separately in restricted
areas . They should either returned to the suppliers or
reprocessed or destroyed .
2. The reprocessing of the rejected products is permitted
only if the product quality is not affected i.e. if the
product specification is met .
Recalled Products
Recalled products should be identified and stored
separately in a secure area until a decision is taken on
their fate .
 Documentation
The documents required are :
1. Labels :
Labels applied to containers, equipment or premises should
be clear and in company’s agreed format . It is helpful in
addition to wording on the labels to use colors to indicate
status ( quarantined, accepted, rejected, or clean ) .
The label for finished product should bearing the following
information :
a. The name of the drug product
b. A list of active ingredients .
c. The batch number assigned by the manufacturer .
d. The expiry date in an uncooked form .
e. Any special storage conditions or handling precautions that necessary
f. Directions for use, and warnings and precautions that necessary .
g. The name and address of the manufacturer or company .
 Specifications and Testing Procedures
1. Testing procedures described in documents should be
validated before they are adopted for testing .
2. There should be appropriately authorized and dated
specifications including : tests on identity , content
uniformity , purity and quality for staring and
packaging materials and finished products . Also
specification for water , solvent , and reagents used in
production .
3. Each specification should be approved and maintained
by the quality control unit .
4. Periodic revisions of the specifications may be
necessary to comply with new editions of
Pharmacopoeia .
 Specifications for Starting and Packaging
materials
Specifications for starting and primary or printed
packaging materials should provide, a description of the
materials including :

a. The designated name and internal code reference .

b. The reference to a pharmacopoeia monograph .
c. Qualitative and quantitative requirements with
acceptance limits .
d. The supplier and the original producer of the materials
e. Directions for sampling and testing .
f. A specimen of the printed materials .
g. Storage conditions and precautions .
j. The maximum period of storage before re-examination
 Specifications For Finished Products
Specifications for finished products should include :
1. The designated name of the product and the code
reference where applicable .
2. The designated name of the active ingredients .
3. The formula or a reference to the formula .
4. A description of the dosage form and package details .
5. Directions of sampling and testing or a reference to
procedure .
6. The qualitative and quantitative requirements with
acceptance limits .
7. The storage conditions and precautions .
8. The shelf-life .
 Master Formulae
A formally authorized master formula should exist for
each product and batch size to be manufactured .
The master formula should include :
1. The name of the product .
2. A description of the dosage form, strength and batch size
3. A list of all starting materials to be used with the amount
of each .
4. A statement of the expected final yield with the acceptable
limits .
5. A statement of the processing location and the principle
equipment to be used .
6. The methods or the reference to the methods to be used
for preparing the critical equipment e.g. cleaning,
assembling, calibrating and sterilization .
 Master Formulae ( cont..)
7. Detailed stepwise processing instructions .
8. The instructions for any in-process controls with their
limits .
9. The requirements for storage of the products,
including the container, the labeling etc. .
10. Any special precautions to be observed .
 Packaging Instructions
Formally authorized packaging instructions should exist
for each product, pack size and type . These should
include the following :
1. The name of the product .
2. A description of its pharmaceutical form, its strength
and route of administration .
3. The pack size expressed in terms of the number,
weight, or volume of the product in the final container .
4. A complete list of all packaging materials required for a
standard batch size, including quantities, sizes, and
types with the code number relating to the
specifications for each packaging materials .
 Packaging Instructions ( cont.. )
5. Example of the printed packaging materials indicating
where the batch number and expiry date of the product
have been marked .
6. Special precautions to be observed including
examination of the packaging area and equipment in
order to ascertain the line clearance before operations
begin .
7. A description of the packaging operation and
equipment to be used .
8. Details of in-process controls with instructions for
sampling and acceptance limits .
 Batch Processing Records
1. A batch processing record should be kept for each
batch processed .
2. Before any processing begins a check should be made
that the equipment and work station are clear of
previous products, documents, or materials not
required for the process, and the equipment is clean
and suitable for use . This check should be recorded .
3. During the processing the following information
should be recorded at the time each action is taken :
i. The name of the product .
Ii. The number of the batch being manufactured .
Iii. Dates and times of the beginning of stages and
completion of production .
 Batch Processing Records ( cont.. )
iv. The name of the person responsible for each stage of
production .
v. The initials of the operator of different steps of
production and of person who checked each of these
operations .
vi. The batch number / control number and the quantity of
each starting material actually weighed .
vii. Any relevant processing operation and the major
equipment used .
viii. The in-process controls performed, and the results
obtained .
ix. The the yield of the product with explanations for
deviations from the expected yield .
 Batch Packaging Records
It should be based on the relevant parts of the packaging
instructions . It include the following information :
1. Before any packaging operation begins, checks should
be made that the equipment and workstation are clear .
2. The name of the product, the batch number, and the
quantity of bulk product to be packed, as well as the
quantity of the finished product that will be obtained .
3. The date and time of the packaging operations .
4. The name of the responsible person carrying out the
packaging operation .
5. The checks made for identity and conformity with the
packaging instructions including the in-process
controls .
 Batch Packaging Records ( cont.. )
vi. Details of the packaging operations carried out .

vii. Samples of the printed packaging materials used .

viii. Notes on any special problems including any

deviation from packaging instructions .

ix. The quantities of all printed materials and bulk

product issued, used, destroyed, or returned to the
stock and the quantities of the product obtained to
permit an adequate reconciliation .
 Standard Operating Procedures ( SOPs)
There should be standard operating procedures and
records for the receipt of each delivery of starting
material and primary and printed packaging material .
The records for the receipts should include :
1. The name of the material on the delivery note and the containers .
2. The “in house” name / code number of material
3. The date of the receipt
4. The supplier’s name and if possible the manufacturer’s name .
5. The manufacturer’s batch or reference number
6. The total quantity and the number of containers received .
7. Any relevant comment e.g. state of the containers .
 SOP for Sampling
The sampling instructions should include :
1. The method of sampling and the sampling plan .
2. The equipment to be used .
3. Any precautions to be observed to avoid
contamination of the material or any deterioration in its
quality .
4. The amounts of sample to be taken .
5. Instructions for any required subdivision of the sample
6. The type of sample containers to be used .
7. Any specific precautions to be observed specially in
regard to the sampling of sterile material .
 Good Practices in Production and Quality
Control
1. All handling of materials and products should be done
in accordance with written procedures or instructions .
2. Any deviation from instructions should be avoided and
if it occur they should be approved in writing by a
designated person .
3. Checks on yields and reconciliation of quantities
should be carried out to ensure there are no
discrepancies outside acceptable limits .
4. Operations on different products should not be carried
out simultaneously or consecutively in the same room
unless is no risk of mix-up or cross-contamination .
5. Access to production premises should be restricted to
authorized personnel .
 Good Practices in Production and Quality
Control ( cont.. )
6. At all the times during processing all materials, bulk
containers, equipment, and rooms used should be
labeled that the product or material being processed ,
its strength, the batch number and the stage of
production .

7. In-process controls are performed within the

production area .
 Prevention of Cross-Contamination and
Bacterial Contamination in Production
Cross-contamination can be avoided by technical or
organizational measures , for example :
1. Production in segregated areas or by campaign
followed by appropriate cleaning .
2. Providing appropriate airlocks, pressure differentials,
air extraction .
3. Wearing protective clothing in areas where products
with special risk of cross-contamination are processed
4. Using cleaning procedures of known effectiveness .
5. Using closing system of production .
6. Testing for residues .
7. Using cleanliness status labels on equipment .