Prevention Of Contamination And Cross

– Contamination In Pharmaceutical
Dosage Forms

The current Good Manufacturing Practice (cGMP) regulation recognizes that

Contamination and Cross-Contamination of pharmaceutical products must not occur. The
control of cross-contamination plays a very important role in maintaining the quality of
product.

The manufacturing of pharmaceutical products involves series of processing steps and

use of various equipments. Equipments and ancillary systems may be used for
manufacturing multiple products or single dedicated product. The inadequate cleaning
process may leads to the fact that, residue may get carried forward as contaminant in the
next batch to be manufactured in the same equipment.

In this article we have concentrated mainly on the prevention of cross-contamination,

beginning with the definitions of contaminant, contamination and cross-contamination.

Contaminant – An impurity or any substance or material that causes contamination or

spoilage.

Contamination – The undesired introduction of impurities of a chemical or

microbiological nature or of foreign matter, into or on to a starting material or
intermediate during production, sampling, packaging, repacking, storage and transport.

Cross-Contamination – Contamination of a starting material, intermediate product,

finished product with another starting material or a product.
The most typical sources of contamination are – Premises and design of building, People,
HVAC system, Manufacturing Operations, Clothing, Utilities and Services. We hope, all
the pharmaceutical manufacturers of different dosage forms follow cGMP Guidelines
but, even there is possibility of ignoring these points. We have briefly highlighted the
preventive measures of cross-contamination on the above mentioned points.

Premises and Design of Building

Eliminate risk of the entry of insects and pests inside the manufacturing area by good
design of facilities and services equipped with maximum protection. Entry of
unauthorized person should be prevented in production, packing and quality control
areas. Persons who do not work in these areas should not use them as passage way.
Interior surfaces of walls, floor and ceiling should be smooth, free from cracks and open
joints, should not shed paint particulate matter and should permit easy and effective
cleaning. Ventilation and light points should be designed to avoid creation of recesses
which are difficult to clean.

Equipment
Should have smooth surfaces free from pitting. Contact surfaces should be inert, should
not be additive or absorptive. Use dedicated equipments which are difficult to clean.
Equipment cleaning aids like bristles, brushes, shedding clothes, etc. that raise dust or
generate contamination should not be used. Manufacturer must ensure that all materials
of previous product manufactured are removed and after cleaning there should be no
residual cleaning agent left behind. Repair and maintenance operations should not present
any hazard to the quality of the product. Wrap the cleaned equipment with polythene
bags until use.

People
All personnel prior to and during employment as appropriate should undergo health
examination. Personnel should wear clean body coverings appropriate to the duties they
perform. Direct contact should be avoided between the operator’s hand and starting
materials, primary packing materials and intermediate and finished products. Appropriate
personnel protective equipments (PPE’s) should be used wherever applicable.

Heating Ventilation and Air Conditioning

(HVAC) System
Install dedicated and validated HVAC system with appropriate filters in all
manufacturing areas with suitable air locks and pressure differentials. Air supply and
extraction points should not be so close or so disposed, that it restricts the supply of clean
air to manufacturing areas or sweeps dust or contaminants away from working area. Risk
of contaminants caused by recirculation/re entry of untreated/insufficiently treated air
should be minimized. Clean dust extraction and associated pipes during every product
changeover. Maintain separate area for cleaning of filters away from AHU.

Manufacturing
At every stage of processing, raw material, intermediate or printing material should be
free from microbial and other contaminants. It is more scientific that by removing outer
wrapping of the packaging material in which they are delivered before being issued to the
shop floor reduces the bio burden and other contaminants.

Clothing and Foot Wear

Minimize exposed body surfaces. Clothes should not get contaminated by cleaning agents
and capable of repeated wear, laundering without deterioration. The operator should
ensure that, clothes are changed and are clean during product change over process.
Personal footwear should not be allowed inside the manufacturing area. The company
should provide appropriate foot wear to the personnel functioning in particular areas.
Procedure for cleaning foot wear should be in practice.

The most important factor is monitoring, training and inculcating of these modules and
the importance should be well understood.

Conclusion
Validation of equipment cleaning procedures should be practiced in pharmaceutical
industries to prevent cross-contamination of drug products. The most important benefit of
conducting equipment cleaning validation is to identify and correct the potential
problems previously unsuspected which could compromise the safety, efficacy and
quality of subsequent batches of drug product produced within the equipment.

Consider what levels of residue can be tolerated in the equipment after cleaning. Toxicity
data can be useful in calculating permissible residue limits. Companies are required to
qualify the cleaning materials and to be sure that these materials are suitable and of
consistent quality. Failure to prevent cross-contamination may cause dire consequence on
the consumer and expensive materials to be scrapped as waste which invites regulatory
action if contamination issues are not thoroughly investigated and addressed.

References
 Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-
operation Scheme. Validation Master Plan Installation and Operational
Qualification: Non Sterile Process Validation Geneva, Switzerland. 2004.
 J A. Constance. “Why Some Dust Control Exhaust Systems Don’t Work”. Pharm.
Engineering. 1983.
 Ash Stevens. Cross-contamination is a major concern for pharmaceutical
manufacturers. Cleanroom Technology. March 2010.
 Gary A. Baker. A guide to designing cleaning procedures for CMO’s.
 Good Manufacturing Practice or Medicinal Products in the European Community.
Brussels, Commission of the European Communities. 1992.
 Quality Assurance of Pharmaceuticals. A compendium of guidelines and related
materials. Volume 2. Good Manufacturing Practices and Inspection. Geneva,
World Health Organization. 1999.