2. Auditing of Microbiological
lab:
ⶠâA service involving an independent review of an organization's records,
operations and procedures to evaluate for efficiency, effectiveness,
compliance and the existence of adequate internal controls to mitigate risks
to the achievement of the organization's objectives.â
Objectives:
ⶠ1.Determine quality systems in place for microbiological control
ⶠ2.Determine level of knowledge and capabilities of audited site
ⶠ3.Determine if continuous improvement is part of culture
3. Six Principles of Efficient
Auditing
ï” â¶ Correct preparation
ï” â¶ Correct types and frequencies of QC protocols and procedures
ï” â¶ Correct documentation
ï” â¶ Adherence to method requirements
ï” â¶ Adherence to SOP procedures
ï” â¶ Initial and continuing proficiency demonstrations
4. WHAT ARE RAW MATERIALS ?
ⶠAll materials that used into the manufacturing of a finished bulk (even
though it may not be present in final product e.g. Certain solvents etc.)
and which are consumed by person using it are called as raw materials.
ⶠRaw materials can be either active drug or inactive substances.
ⶠE.g. Hard gelatin capsules: even though it is used to fill the blend of
medicine, it is not considered as package materials because it is
consumed by person using medicines.
5. AREAOF INTEREST IN BUILDING OF RAW MATERIAL:
1)Walls and Celling's:
ⶠMoulds are most commonly encountered microbes on walls cellingâs,
particularly when poor ventilation, temperature, and relative humidity
control lead to high level of moisture.
ⶠContamination may be excessive where damaged surfaces expose the
underlying plaster.
ⶠSurfaces should be smooth ,impervious and cleanable; damaged
surfaces should be repaired promptly.
6.
7. 3.DOORS ,WINDOWSAND FITTINGS :
ⶠThese should be flush-fitting whenever possible.
ⶠWood readily absorbs moisture and can generate high number of
moulds; where present, it should be sealed with a high âglass paint and
any surface damage repaired immediately.
4.EQUIPMENT:
ⶠThe ability of bacteria to attach to surfaces such as stainless steel and
plastic and survive should not be under estimate.
ⶠEvery piece of equipment has its own particular nooks and crannies
where microbiological contamination can reside; internal threads and
dead legs cause particular problem
8. 5.CLEANING OF EQUIPMENT:
ⶠCleaned equipment can be readily re-contaminated before use .
ⶠThe auditor should review :the quality water used in final rinsing stage
and how equipment is dried and stored to minimize the risk of
contamination by pseudomonas and other gram ânegative bacteria.
6.PIPELINES:
ⶠPipeline must be completely drainable to ensure that trapped fluid
does not provide a hospitable environment for growth of bacteria.
ⶠInternal surfaces should be smooth and polished to minimize pits
where microbes may lodge.
ⶠJoints and welds should be kept a minimum, since they may provide a
protective haven for a microorganism. Its sealed with lagging material.
ⶠIf the protective outer seal is damaged then it may provide a rich
source for contamination.
9. RA
W MATERIALS:
ⶠRaw materials pose a major contamination threat to the product and the
production environment, and warrant special attention from auditor.
ⶠUntreated raw material of natural origin contain an extensive and varied
microbial population ,including potentially pathogenic organisms, such as E.coli
and salmonella species,
ⶠIn case of excessively high bio-burden , pre-treatment may be needed to reduce
the bio-burden to an acceptable level , using process such as heat filtration,
irradiation ,recrystallization from a biocides or where compatible ,ethylene
oxide gas.
ⶠIrrespective of the type raw material used, the auditor should confirm that the
material is provided by an âapproved âsupplier.
10. ⶠConfidence in the supplier âs manufacturing process and their quality
system, which have been challenged through audit.
ⶠLikewise the sampling program used should be satisfactory ,based upon
the nature of the raw material(natural /synthetic),the history and
performance of the supplier ,and end use of raw material.
ⶠSampling procedure should be reviewed.
ⶠReduce the risk of contamination both sample and bulk.
ⶠSampling equipment should be dedicated and clean.
ⶠSamples should be properly trained in aseptic techniques.
ⶠWarehouse storage condition should also be reviewed: temperature
control should be satisfactory ;pest control should be effective; and
containers should be positioned so that they do not come into contact with
damp ,cold surfaces such as walls and floors.
11. Water:
ⶠWater is principle of raw material used in pharmaceutical industry.
ⶠWhen reviewing water systems usually as part of a âproduct based
audit', the auditor must establish quickly an understanding of the
system and how it performs.
ⶠKey facts to know include whether water is used directly manufacture
and which grades of water used.
ⶠManagement and operational issues include who owns the system, its
complexity(one or multiple plants).
ⶠAschematic diagram of system should be provided.
12. MICROBIOLOGICALRESULTS :
ⶠIn establishing whether an adequate system of control operates ,data
from samples taken from user points over the past 6 to 12 months
should be reviewed noting user points sampled , the range of results
and underlying trend ,whether action and alert limits are visible and
appropriate, and whether trend analysis has been applied to improve
interpretation and reporting of results.
ⶠThe time of monitoring should also be noted with reference to when
the system was sanitized.
ⶠEven in the event of zero counts, the microbiological sampling
practices and test procedures should be challenged .
13. ⶠPACKAGING MATERIALS:
ⶠCardboard ,paperboard and pulp board, unless sealed or treated, can
provide a rich source of contamination particularly moulds and gram
positive bacteria, often as resistant spores.
ⶠMaterials become moist through poor storage levels of water and
subsequently microbiological contamination can increase.
ⶠMaterial such as glass, synthetic rubbers, plastics and laminates have
minimal surface microbial counts.
ⶠHowever ,if stored with limited protection in dusty or damp
conditions and packed for transportation in cardboard boxes ,often on
damp ,dirty wooden pallets, they may contain moulds and bacterial
spores.
14. ESSENTIALDOCUMENTS:
ⶠValidation documents relating to design qualification ,installation
qualification ,operational qualification and performance qualification
(DQ,IQ,OQAND PQ) should be complete , available and current for
the water system concerned.
ⶠOnly when this has been thoroughly reviewed and approved may any
microbiological considerations be addressed.
ⶠProtocol should be prepared and approved.
ⶠFinal reports should have been completed, reviewed and approved
highlighting areas of non compliance together with justifications and
recommendations for corrective action.
15. EFFECTIVE VENTILATION:
ⶠThe aerial route of contamination is common and can be
significantly reduced by an effective heating ventilation and air
conditioning system.
ⶠHumidity and Temperature control is important , since this not only
provides a pleasant working environment ,but also reduces the risk
of mould contamination.
16. CLEANINGAND DISINFECTION:
ⶠAlthough routine sanitization of surfaces is key to controlling environmental
contamination ,its importance is often over looked.
ⶠThe sanitization program and procedure should be reviewed to confirm the
frequency and precise method of cleaning and their scientific basis.
ⶠThe cleaning records should confirm procedural compliance (when, where and by
whom).
ⶠThe activity of any disinfectant used should be appropriate for the wide range of
environmental contaminants likely to be present.
ⶠThe manufacturers instructions should be followed and fresh disinfectant solutions
should be made up before use.
ⶠMops, sponges and cloths can provide an ideal environment for rapid and extensive
growth of water âbone organisms such as pseudomonas species.
ⶠInadequately stored and maintained cleaning equipment can be highly efficient
vehicles for spreading micro-organisms throughout the environment.