GMP & Quality Assurance :

Production of Sera

Adhiny Disti Helmi 1511014024

 Processing Requirements

• Production should be carried out in a clean area class

C.
• Walls and floors should be cleaned periodically with
disinfectant according to an authorized protocol for
cleaning which should be validated
• Personnel shall be trained, educated and experienced
for the job they are required to do.
• Training shall be in the particular operations that the
employee performs and current good manufacturing
practice as they relate to the employee’s function
(DSSFDA, 2010 : 17)
• Contact parts of containers should be of stainless
steel of pharmaceutical grade (316L) or higher, easily
cleaned in place (CIP) and validated to be used for
plasma processing
• Water used should be of water for injection grade
(WFI). Water supply should be controlled to decrease
bioburden.
• WFI used in processing should be maintained at a
high temperature (70-80°C) at all times to prevent
contamination and decrease of bioburden.

(DSSFDA, 2010 : 17)

• Heat exchangers for cooling at the points of use or
alternatively depyrogenating and bacterial filters
should be fixed at the point of use
• Equipment in the processing area must be
maintained, cleaned, calibrated or validated
periodically as needed

(DSSFDA, 2010 : 18)

 Filling Requirements

• Sterile areas class A & B must be designed according

to the assigned procedure.
• Differential pressure between areas of different
classes must be maintained by positive pressure
between high-pressure areas to low- pressure areas.
• Environmental control must be carried out
periodically according to an authorized and validated
schedule to prevent contamination.
Environmental control includes:
– control of viable matters (microbiology tests),
– control of non viable matters (particle count control).
(DSSFDA, 2010 : 18)
• Sterilization of equipment (including filling pumps,
containers, stainless steel tanks and glass containers)
& depyrogenating of final containers if glass,
according to authorized and validated procedures.
• Validation of sterilizing equipment (autoclave) and
depyrogenating equipment (ovens or tunnel
sterilizer) which must be validated periodically
according to an authorized protocol.

(DSSFDA, 2010 : 18)

• Filling process validation by media fill must be carried
out periodically to ensure maintenance of sterility
conditions

(DSSFDA, 2010 : 18)

 Batch Record

• There shall be written procedures for production and

process control designed to ensure that the drug
products have the identity, strength, quality, and
purity they have or are presented to process.
• Such procedures shall include all requirements.
• Records shall be permanent and clearly indicate all
steps in processing, testing, filling and distribution.
• Written records shall be kept of all tests irrespective
of their results. The records shall be of a type
approved by the SFDA.
(DSSFDA, 2010 : 19)
• They shall be retained throughout the dating period
of a lot or batch of a biological product and be
available at all times for inspection by the SFDA.
• Records must make it possible to trace all steps in the
manufacture and testing of a batch, and should
include records of sterilization of all apparatus and
materials used in its manufacture.
• Distribution records must be kept in a manner that
permits rapid recall of any particular batch if
necessary

(DSSFDA, 2010 : 19)

 Sampling Procedure

• There should be written procedures for sampling,

which include the person(s) authorized to take
samples, the methods and equipment to be used, the
amount to be taken and any precautions to be
observed to avoid contamination of the material or
any deterioration in its quality.
• It is not sufficient to sample and test only the end
product. In-process sampling and testing must be
conducted.
• Samples should be withdrawn and tested at several
steps along the way.
(DSSFDA, 2010 : 19)
• The samples must be of sufficient number, size and
selection to be statistically representative.
• Criteria or specifications for allowable variation must
be sufficiently strict to assure that desirable quality is
assured. Sampling and evaluation should be
thoroughly documented at every stage.
• Protocols are commonly used to assure that this is
controlled

(DSSFDA, 2010 : 19)

 Stability

• The stability studies must be done according to recent ICH

guidelines for the biological products.
• It is extremely important that the manufacturer conducts
the stability tests of:
• raw materials,
• intermediate stages if stored for long time,
• finished products.
• Extreme conditions of storage should be taken into
consideration.
• Major factors which affect stability are:
− temperature and relative humidity,
− light.
(DSSFDA, 2010 : 20)
• A protocol for stability study has to be implemented to provide evidence
that the antisera are stable, i.e. remain within specification during the re-
test period when stored under the recommended environmental
conditions.
• The stability program should extend not only to the end of the shelf life
period but also in addition to accelerated study and should include, but
not be limited to, the following
• parameters:
• number of batches,
• relevant physical, chemical, microbial and biological test method,
• acceptance criteria,
• reference to test method,
• description of the container closure system(s),
• testing interval,
• description of the conditions of storage.
(DSSFDA, 2010 : 20)
 Validation

• Validation studies should reinforce Good Manufacturing Practice

and be conducted in accordance with defined procedures.
Results and conclusions should be recorded.
• When any new manufacturing formula or method of preparation
is adopted, steps should be taken to demonstrate its suitability
for routine processing.
• The defined process, using the materials and equipment
specified, should be shown to yield a product consistently of the
required quality.
• Significant amendments to the manufacturing process, including
any change in equipment or materials which may affect product
quality and/or the reproducibility of the process, should be
validated.
(DSSFDA, 2010 : 21)
• Processes and procedures should undergo periodic critical
revalidation to ensure that they remain capable of
achieving the intended results.
• Each material, each item of equipment and each step of
manufacturing is validated before
• the product is produced for distribution:
• e.g. for processing validation: media fill has to be done to
simulate all stages of processing and filling.
• e.g. for equipment: temperature mapping for autoclave, and
depyrogenation for ovens or tunnel sterilizer.
• e.g. validation methods used to ensure freedom from viruses
(DSSFDA, 2010 : 21)
 Complaints and Product Recall

• All complaints and other information concerning

potentially defective products must be carefully
reviewed according to written procedures.
• In order to provide for all contingencies, a system
should be designed to promptly and effectively recall,
if necessary, products known or suspected to be
defective from the market.

(DSSFDA, 2010 : 22)

 Reference

• Drug Sector Saudi Food & Drug Authority. 2010.

Guidelines for Production and Quality Control of
Antisera version 2.1. Saudi Arabia : DSSFDA. http://
www.sfda.gov.sa/En/Drug