Line Clearance System

 Line Clearance: is a process which provide a high degree of confidence that

the said line is free from any unwanted residue or left over of previous
processing’s before proceeding for next process.

 Objective is to avoid cross contamination or mix up in the production,

which may led to serious issues such as complaints and product failure
which affects quality of the product and indirectly status of the company.
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 Following of the questions arises regarding this issues,

1. Does line clearance is mandatory?

2. Is it have any separate guidelines with respect to any regulatory

authority?

3. Does line clearance require any written procedure for this? If yes then
what are the criteria of checks? – area wise checklist?

4. Who is authorized to check ?

5. Why there should be third person check for the line clearance?

6. What are the importance of line clearance?

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 Regulatory Guideline : USFDA- PART 211

In USFDA-Part 211- Current good manufacturing practice for finished
pharmaceuticals point No.:211.130 Packaging and labeling operations:

There shall be written procedure designed to assure that correct labels,

labeling, and packaging materials are used for drug products; such
written procedures shall be followed.
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 Regulatory Guideline : USFDA- PART 211
These procedure shall incorporate the following features:

a) Identification and handling of filled drug product containers that

are set aside and held in unlabeled condition for future labeling
operation to preclude mislabeling of individual containers, lots, or
portions of lots. Identification need not be applied to each
individual container but shall be sufficient to determine name,
strength, quantity of contents, and lot or control number of each
container.
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b) Prevention of mix-ups and cross-contamination by physical or

spatial separation from operations on other drug products.

c) Identification of the drug product with a lot or control number that

permits determination of the history of the manufacture and
control of the batch.

d) Examination of packaging and labeling materials for suitability

and correctness before packaging operations and documentation
of such examination in the batch production record.
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e) Inspection of the packaging and labeling facilities immediately

before use to assure that all drug products have been removed
from previous operations. Inspection shall also be made to assure
that packaging and labeling materials not suitable for subsequent
operations have been removed. Results of inspection shall be
documented in the batch production records.
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 Schedule M:
8.2. Precautions against mix-up and cross contamination-

8.2.3.To prevent mix ups during production stages, material under-process shall be
conspicuously labeled to demonstrate their status. All equipment used for production
shall be labeled with their current status.

8.2.4.Packaging lines shall be independent and adequately segregated. It shall be

ensured that all left over of the previous packaging operations, including labels,
cartons & caps are cleared before the closing hour.

8.2.5.Before packaging operations are begun, steps shall be taken to ensure that the
work area, packaging lines, printing machines, and other equipment are clean and
free from any products, materials and spillages. The line clearance shall be
performed according to an appropriate checklist & records.
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8.2.6.The correct details of any printing (for example of batch numbers or

expiry dates) done separately or in the course of the packaging shall be
re-checked at the regular intervals. All printing and overprinting shall be
authorized in writing.

8.2.7.The manufacturing environment shall be maintained at the required

levels of temperature, humidity and cleanliness.

8.2.8. Authorized persons shall ensure change-over into specific uniforms

before undertaking any manufacturing operations, including packaging.
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 Regulatory Guidelines-EU and PIC Guidelines-Chapter 5:

Production
Processing operations : Intermediate and bulk products-

5.35 Before any processing operation is started, steps should be taken to

ensure that the work area and equipment are clean and free from any
starting materials,products, product residues or documents not required for
the current operation.
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Packaging operations

5.44 When setting up a program for the packaging operations, particular attention
should be given to minimizing the risk of cross contamination, mix-ups or
substitutions. Different products should not be packaged in close proximity
unless there is physical segregation.

5.45 Before packaging operations are begun, steps should be taken to ensure that
the work area, packaging lines, printing machines and other equipment are
clean and free from any products, materials or documents previously used, if
these are not required for the current operation. The line clearance should be
performed according to an appropriate checklist.
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Line clearance – Standard Procedure
Hence as per all above guidelines it is necessary to have a written procedure called as
SOP for Line Clearance.
1. SOP should cover all parameters such as responsibility, procedure, type of
changeovers and area wise checklist to ease the process.
2. It is required to have practice of line clearance in all the processing area, which can
be divided into three parts,
a. Dispensing Area.
b. Manufacturing Area
c. Packing Area.
3. In all this three areas change over can be identified in two types,
a. Minor
b. Critical
4. A minor change over is a change over between,
1. Batches of same product.
2. Batches of same product and same strength.
3. Batches of ascending strength of same product.
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5. As minor change over will not cause any serious contamination the line
clearance can be given by responsible person of the said department after
checking all the points as per checklist.
6. A Critical change over can be identified as change over between,
1.Batches of different product
2.Batches of descending strength of same product.
3.Batches of descending / ascending strength with different color.
7. A contamination caused by such critical change over can be more serious
effect on the product. So that clearance during such changeovers can be
given by concerned person ( production officer) as a primary check, which
must be again verified by (re inspected by) authorized person(QA person)as
a secondary check.
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Reasons for failure of line clearance
1. Inadequate Procedure-
It is important to have a very clear & adequate written procedure for
line clearance.
Procedure should understandable to the person who follows it.
Hard to clean areas, where product may be remain after cleaning should be
identified and clearly mentioned in the SOP.
2. Personnel-
80% failure of line clearance is due to personnel negligence and illiteracy
regarding the subject.
For this, persons should be trained properly to do their assign job.
They should know the importance of subject and also why, when, what and how
to clean the area.
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3. Each area should have a picture/ outline sketch to describe the types of problem &
effective way of doing the line clearance.

4. During on job training, demonstrate the line clearance activity practically which
will be easy to understand for the packers.

5. Area Specific detailed checklists should be in place considering the nature of

problems, significance and impact.

6. Periodic meetings should be conducted to share with other colleagues ‘ The system
–failure experiences/failure incident along with CAPA taken-to avoid repeat
incidences in remaining areas’.

7. For repeated problems, review the situation and resolve the problem with cross
functional dept. e.g. use removable panels.