A Seminar on

AUDIT OF STERILE PRODUCTION AND PACKAGING

Subject Name: AUDIT AND REGULATORY COMPLIANCE
Subject Code: MQA203T

Name of Student: ODIYA ANKUR

Roll No: 20QA02
Semester: 2
Course: M. Pharm (Pharmaceutical Quality Assurance)

Seminar Mentor: Dr. S. J. PARMAR

Designation: Assistant professor

D E PA R T M E N T O F P H A R M A C E U T I C A L S C I E N C E S
S A R D A R PAT E L U N I V E R S I T Y
VA L L A B H V I D YA N A G A R

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Contents…….

1. Auditing an Aseptic Sterile Area & goals

2. Definitions
3. Auditing an Aseptic Sterile Area
4. Sterile Production and packaging
5. Visual inspection
6. Auditing an Aseptic Sterile Area
7. CONCLUSION

Continue…

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Auditing an Aseptic Sterile Area

When you have completed this unit, you should be

able to:

Perform an audit of an aseptic/sterile processing area

Access and understand aseptic/sterile manufacturing
requirements

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 Goals
 The simple goal of this complex process is to evaluate existing
activities and documentation and determine if they meet the
established standards.
 An audit will evaluate the strengths and weaknesses of quality
control and quality assurance processes, the results of which
will help us to improve processes and build a better system for
the benefit of the company.
 Every product manufactured by a pharmaceutical company has
characteristics that must be quantified or qualified by
laboratory tests. Quality control and quality assurance are the
necessary processes that play the role of control and balance
system in pharmaceutical industry.
 With proper preparation and planning, the audit itself must
easily achieve the intended purpose. Effective auditing and
proper compliance with standards will help build brand
reputation and avoid the negative effects of non-compliance,
such as fines, bad public relations and court proceedings.

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Definitions
 Action levels: established microbial or particle levels that,
when exceeded, should trigger an appropriate investigation
and corrective action based on the investigation.

 Air Lock: a small room with interlocked doors, constructed

to maintain air pressure control between adjoining rooms
(generally with different air cleanliness standards). The
intent of an air lock is to preclude ingress of particulate
matter and microorganism contamination from a lesser
controlled area.

 Alert levels: established static and operational microbial or

particulate levels giving early warning of potential drift
from normal operating conditions which are not
necessarily grounds for definitive corrective action but
which require follow-up investigation.
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 Aseptic filling: a process by which the drug or biological
product, container, and closure are sterilized separately
then assembled under strict environmental conditions.

 Bio burden: the total number of microorganisms

associated with a specific item prior to sterilization.

 Clean room: a room designed, maintained, and controlled

to prevent particle and microbiological contamination of
drug products using high efficiency particulate air filters
(HEPA). Air from the filters may either flow down
(vertical) or across (horizontal) the surface to be kept
clean.

 Compounding: a process in which one bulk drug

substance is combined with another bulk drug substance
and/or one or more excipients to produce a drug product.
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 Auditing an Aseptic Sterile Area
Aseptically produced products

o The bulk solution is then filtered both to remove particles and

to remove all microorganisms to render the product sterile.
o The sterile bulk solution is filled into washed, sterilised
containers under conditions that minimise the potential for
microbial contamination of the product. The environment
standards of cleanliness are required to be higher for aseptic
manufacturing than for products to be terminally sterilised.
o As the actual sterilisation step is the filtration step the bio
burden must be kept to an absolute minimum and there must
be a good understanding of the types of microorganisms
present.
o Solutions should be protected from contamination and
holding times kept to a minimum.
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 Container Integrity
o The consequences of a problem in the quality of sterile
products are so significant that 100% inspection is necessary.
The EU GMP guide requires 100% leak testing of containers
closed by fusion and 100% inspection of parenteral products
for particulate contamination.
o Leak testing is usually performed by methods of dye batch
testing and/or electrostatic testing, the later is preferred. Such
a non-destructive high voltage inspection method allows
defects as pinholes

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Sterile Production
 What is Sterile Production?
 In sterile production, aseptic, terminally sterilised products
are produced under aseptic conditions. These conditions
are maintained by the use of equipment such as special air
filters and the regular disinfection of the premises.

DATE OF
AUDIT

PURPOSE SPECIFICIT
OF AUDIT Y

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A. Documents Reviewed:
1. SOP
2. Personnel

B. Data Reviewed:
1.Facilities
2.Batch records
3.Monitoring

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A. Documents Reviewed:
1. SOP
› Is a complete index and a complete set of application sop
available in the department.
› Are the index and the SOP current.
› Is the set of SOP correctly organized according to the index.
2. Personnel
› Select three employees working in the department. Are their
training records up-to-date.
› Have the employees undergone training in the following area
during the last year.
› 1. GMP
› 2. SOP
› 3. sterile manufacturing techniques
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B. Data Reviewed:
1. Facilities
› Is the department maintained in a good state of repair.
› Is the department neat and orderly with sufficient space for
equipment and operation.
› Are the cleaning and sanitizing solution labeled with an
expiration date according to the relevant SOP.
2. Monitoring
› Is there a valid calibration label affixed to monitoring
sensors for pressure , temperature , and relative humidity.
› Are records according to the relevant SOP.

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3. Batch records:
› These documents are typically used and completed by
the manufacturing department. ... Specifications:
Documents that list the requirements that a supply,
material, or product must meet before being released for
use or sale.

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Sterile Packaging
Edition no

Approved

Effective Date Department Dry production :

packaging

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 DATE OF AUDIT

PURPOSE OF SPECIFICITY
AUDIT

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 What is sterile packaging?
 The package must protect sterilized items against
microbial contamination during removal from the
sterilising chamber, and during storage or transport until
use. ... Sterilization packaging must conform to standards.
There are not Polish standards for sterile packaging of
medical devices.
A. Documents Reviewed:
1. SOP
2. Personnel
B. Data Reviewed:
1. Facilities
2. Cleaning procedures
3. In-process control

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A. Documents Reviewed:
1. SOP
› Is a complete index and a complete set of application sop
available in the department.
› Are the index and the SOP current.
› Is the set of SOP correctly organized according to the index.
2. Personnel
› Select three employees working in the department. Are their
training records up-to-date.
› Have the employees undergone training in the following area
during the last year.
› 1. GMP
› 2. SOP
› 3. Packaging techniques
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B. Data Reviewed:
1. Facilities
› Is the department maintained in a good state of repair.
› Is the department neat and orderly with sufficient space for
equipment and operation.

› Are all work areas clearly labeled with the name and the
batch number of the product being processed.
2. Cleaning procedures
› Is there a written procedure for the cleaning of the
packaging facility.
› Is there documented evidence that the cleaning procedure
is being followed.
› The procedure specific to a particular machine.
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Visual inspection:-
› Visual inspection of parenterals may be performed
manually or automatically using camera vision systems.
Pharmacopoeias provide information on how viewing units
should be designed when performing manual inspections.

› Personnel should undergo frequent eyesight checks and be

trained in identification of defect types and the expected
standards. Frequent breaks and rotation of tasks should be
allowed.
› The premises used must be quiet and allow personnel to
work separate from pass ways and noisy production areas.
Appropriate lighting should be provided.

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Auditing an Aseptic Sterile Area

› Inspect the component preparation area.

› Inspect the microbiology laboratory.
› Review the Media Fill Procedure.
› Review the Environmental Monitoring Program.

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CONCLUSIONS:-
› Audits to be conducted at planned intervals to evaluate
effective implementation and maintenance of the quality
system and to determine if processes and products meet
established parameters and specifications.
› An audit performed by a well trained and thoroughly
prepared auditor can be highly beneficial by identifying
areas for genuine improvement.
› Auditing in the pharmaceutical sector serves two different
categories: regulatory compliance and business needs.

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 REFERENCES:-
› https://www.who.int/medicines/areas/quality_safety/
quality_assurance/
GMPSterilePharmaceuticalProductsTRS961Annex6.pdf
assets on date (15,04,2021) on audit of sterile production
and packaging.

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