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QUALITY ASSURANCE OF PACKAGING MATERIAL

SPECIFICATIONS:

WHO Guidelines

Specifications for starting and primary or printed packaging materials should provide if
applicable, a description of the material, including,

 The designated name (if applicable International, Non-Proprietary Name) and

Internal code reference.
 The reference if any, to a pharmacopoeial monograph and
 Qualitative and quantitative requirements with acceptance limits.

Depending on the company’s practice other data may be added to the specification such
as,

 The supplier and the original producer of the materials,

 A specification of printed materials,
 Direction for sampling and testing, or a reference to procedure.
 Storage conditions and precautions.
 The maximum period of storage before examination.

Packaging materials should conform to specifications with emphasis placed on the

compatibility of the 1113th with the drug product it contains. The material should be exam
for official and major physical as well as for the correct of identity markings.

Documents describing testing procedures should state the required frequency for re-
assaying each starting material as determined by its stability (14.19).

RECEIPT:

1. Upon arrival of the vehicle with material, the security personnel check the delivery
documents and ensures that consignment is meant for pharmaceutical formulation
plant.
2. After confirmation of the address, the documents related to the consignment shall
be sent to warehouse office for verification before making entries into “Security
Register for Incoming RM/PM” Annexure-I.
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3. Warehouse Personnel shall collect the documents through window and check the
following in the delivery documents (delivery Challan / invoice).

 Appropriateness of company address on the delivery documents.

 The vendor is approved as per current version of Approved Manufacturer /
Supplier List, including address.
 Availability of Vendor Certificate of Analysis copy.
 Reference of Purchase Order number on the delivery documents.
 Description of the material (Material name, grade/ pharmacopeia status,
quantity) in purchase order tallies with that mentioned in delivery document.
4. In case of any discrepancies observed in the above-mentioned points, shall be
informed to HOD – Warehouse, and HOD – Purchase for corrective action, and
vehicle should not be allowed to enter if applicable.
5. After ensuring the adequacy of the received documents; the warehouse personnel
shall send back the documents to security personnel to make entries in the
“Security Register for Incoming RM/PM”.
6. Security personnel shall make entries in the “Security Register for Incoming
RM/PM” as per Annexure-I, after receiving the consignment documents from
warehouse.
7. After entering the required details, the security personnel shall stamp on the back
side of the Invoice / Delivery Challan with serial number as per “Security Register
for Incoming RM/PM”, and received date with signature.

 The following stamp format shall be used.

PHARMAPATHWAY

GATE ENTRY No. _____ BILL No. _____

VEHICLE No. _________ DATE _________

SIGN. OF SECURITY OFFICER

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8. “Gate Entry No” mentioned in the above stamp format, shall be in the form of serial
number i.e. 1, 2, 3, and so on.
9. Allow the vehicle to enter in to the plant premises.

TESTING:

After the materials have been sampled, the next activity is to test the material using
‘Standard Test Method’ against the approved material specification. The entire testing
activity can be divided into following parts, namely:

A. Pro-Testing Part

This will incorporate following points

 Responsibility of the persons for analysis, supervising the analytical work and the
person managing and taking quality control-related decisions.
 All material must have approved specifications against which the material will be
tested.
 Validated and calibrated instruments and other equipment. s Validated test
methods.
 Availability of well-equipped test laboratories for chemical. instrumental,
microbiological and animal testing.
 Standardized reagents, microbial media etc.

B. Testing Part

 Actual testing and supervising of the testing operations.

 Critical examination of calculations and other relevant experimental data
collected during analysis.
 Verification of I.P.Q.C. and environmental data collected during production
activities.
 Verification of Certificates of Analysis (COA) of manufacturers provided by them.

C. Post-testing Part

 Preparation of Test Reports.

 Checking and verification of Test Reports.
 Final decision of the Q.C. Manager.
 This is a brief description of various activities which are carried out during the
testing process.
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SAMPLING
The sampling plan for packaging materials should account at least the following:
 The quantity received,
 The quality required,
 The nature of the material (e. G. Primary packaging materials and/or printed
packaging materials),
 The production method, and
 The he knowledge of quality assurance system of the packaging materials
manufacturer based on audits.
The number of samples taken should be determined statistically and specified in a
sampling plan.

MCC South Africa guidelines

Samples should be taken in such a manner that they are representative of the batch of
material from which they are taken, in accordance with approved written
sampling procedures. These procedures should include:
 The method of sampling.
 The equipment to be used.
 The amount of sample to be taken.
 Instructions for any required sub - division of the sample.
 The type and condition of sample container to be used.
 Any special precautions to be observed, especially in regard to sampling of
sterile or noxious materials.
 Cleaning and storage of sampling equipment.

Any sampling by production personnel should only be done in accordance with

these approved procedures. (7. 5. 1)
 Each sample container should bear a label indicating its contents, with the batch or
lot number reference and the date of sampling. The sampler should initial on the
label and there should be an indication from which container the sample was taken.
It should also be possible to identify the bulk containers from which samples have
been drawn and which containers have been sampled. (7. 5. 2)
 Care should be taken to avoid contamination or deterioration whenever a material or
product is sampled. Sampled containers should be resealed in such a way so as to
prevent damage to, or contamination of, or by, the contents. (7. 5.3)
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 Retention samples from each batch of finished products should be kept in their final
packaging and stored under the recommended conditions. Samples of starting
materials (other than solvents, gases and water) should be retained until at least the
expiry date of the batch in which they are used.
 Reference samples of materials and products should be of a size sufficient to permit
at least one full re – examination

USFDA Guidelines
1. Each lot of components, drug product containers, and closures shall be withheld
from use until the lot has been sampled. tested, or examined, as appropriate, and
released for use by the quality control unit.
2. Representative samples of each shipment of each lot shall be collected for testing or
examination. The number of containers to be sampled, and the amount of material to
be taken from each container, shall be based upon appropriate criteria such as
statistical criteria for component variability, confidence levels, and degree of
precision desired, the past quality history of the supplier, and the quantity needed for
analysis and reserve where required by § 211. 170.
3. Samples shall be collected in accordance with the following procedures
 The containers of components selected shall be cleaned where necessary, by
appropriate means.
 The containers shall be opened, sampled, and resealed in a manner designed to
prevent contamination of their contents and contamination of other components,
drug product containers, or closures.
 Sterile equipment and aseptic sampling techniques shall be used when
necessary.
 If it is necessary to sample a component from the top, middle, and bottom of its
container, such sample sub - divisions shall not be composited for testing.
 Sample containers shall be identified so that the following information can be
determined: name of the material sampled, the lot number, the container from
which
the sample was taken, the date on which the sample was taken, and the name
of
the person who collected the sample.
 Containers from which samples have been taken shall be marked to show that
samples have been removed from them.
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Comments

When we critically evaluate the various points discussed in the regulatory text related to
sampling the following points come forward, which needs further comments. These
points should be considered in formulating the S.O.P. for sampling e.g. 8.0.P. on
sampling should cover minimum following points.

1. Trained Personnel:
Sampling should be classified as a critical operational activity and only those persons
(workers and supervisors) should be allowed to do sampling who are trained in all
aspects of sampling and certified as trained persons by quality assurance authorities.
These names may preferably be notified in the sampling area. The training should cover
minimum following points:
 Sampling plans, i.e. which sampling plan should be used for which materials.
 Written sampling procedures must be explained to all the sampling workers and their
supervisors, including various precautions to be taken before, during and after the
sampling activities.
 Technique and equipment used in sampling.
 Issue related to risk of cross contamination.
 Precautions to be taken with regard to unstable, (e.g. moisture, light or heat
sensitive products) and/or sterile substances.
 The importance of considering the visual appearance of material, containers and
labels.
 The importance of recording any unexpected or unusual circumstances. Regular
retraining and refresher training sessions may be conducted and evaluation made
and records of such activities should be maintained.

2. Environment
The sampling environment is of utmost importance. Normally special separate sampling
booths should be designed and used for active, inactive, critical active substances like
beta-lactam products, steroids, toxic or poisonous substances, sterile products etc.
Following points should also need to be considered :
 Temperature.
 Humidity.
 Working of laminar flow units.
 Direct exposure of sunlight.

3. Equipment

All equipment used for sampling should be cleaned, dried and where required sterilized.
Such pro-processed equipment should be stored in well protected manner, e.g. in clean
plastic wrapper and then kept in a clean 8.8. container till required for use. A provision
for washing and drying may be provided adjacent to sampling area. Equipment and
area cleaning procedures must be validated and records of such validation should be
maintained.
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4. Contamination Control
All precautions should be taken to avoid cross-contamination during sampling operation.
These should cover at least following points:
 Area cleaning and certifying before and after sampling.
 Handling only one product at a time.
 Proper way of opening and closing of containers to be sampled.
 Using clean hand gloves for each material being sampled.
 Proper dress-code followed during sampling, cg. use of nose and face masks,
head gear, feet cover, gloves and clean, neat and tidy cover all.
 Always use clean, dried, sanitized equipment and whenever required sterilized
equipment for sampling.
 Collection and transfer of used equipment for cleaning in a closed and protected
manner.
 Validated methods should be used for cleaning of weighing equipment whenever
used.

4. Methods Used

Different types of sampling plans may be used depending upon the availability of
validation data on the subject. E.g.:

1. 100% Sampling when not much data is available

2. Reduced Sampling when validated data is available about manufacturers.
3. Sterile Product Sampling: current practice is to sample in the aseptic areas of
production or if possible, in QC. Laboratory. But the latest thinking is to construct a
separate aseptic area for sampling purpose only, adjacent to the warehousing
facility. This should be a class 100/ 10,000 area with minimum 4 vestibules for entry
and exit of personnel, suitably pressurized, with a provision of dynamic pass box of
suitable size for transfer of material to and from the sampling area. The
environmental conditions of such rooms must be monitored, controlled and records
maintained.

6. Reference and Retained Samples

All samples collected should also cover the samples to be retained till at least one year
after the expiry of the product. The 8.0.P. should mention at least following points in this
regard.

 Quantity of sample to be retained (may be at least 2 full analysis equivalent).

 Container type to be used for retention.
 Labeling requirements on such retained container.
 Storage and retrieval procedures to be followed along with proper records thereof.
 Environmental conditions needed for storage of such samples.
 Detailed procedures of the reference samples of finished products to be collected
and stored must be written. They should clearly mention sample for stability studies
if they are kept from a particular batch.
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7. Labelling

Each sample contains should bear a label indicating,

 Name of the sampled material.

 Batch or lot number or the material.
 Number of containers from which the sample is taken.
 Initials signature of the person who has taken the sample.
 Date of Sampling.

The container from which the sample is taken should be marked to indicate that this
container was opened for sampling purpose.

8. Sealing of Sampled Containers

Very clear instructions should be provided about how to reseal the opened container,
e.g. remove all air from the plastic bags before closing the bag for sealing. The correct
way of sealing should also be described to avoid possibility of cross-contamination.

9. Records.

Following records should be maintained:

 Identity of material sampled, ca. name, batch and number etc.

 Chronological record of sampling, i.e. time and date of sampling.
 Record of environmental conditions e.g. temp. humidity during sampling.
 Names of workers and supervisors.
 Comments, if any, of the sampler and/or supervisor.
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CERTIFICATE OF ANALYSIS
 Name and address of lab performing
the tests
 Identification number of COA

 Name and address of originator of

request of analysis

 Registration number of samples

Quantity
 Date received received
 Name of the product(generic
name/brand name)

 Dosage form, strength, packaging

size(if applicable)
 Type of material of container(primary,
secondary)

 Batch number

 Date of manufacture

 Expiry / Retest date

 Phone Number
 Name and address of original
manufacturer

 Fax

 Email
 Name and address of repacker
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Test Method Specifications Result Compliance

Reference statement

COMMENTS:

 Date on which the tests were

completed
 Conclusion or compliance of the
sample with specifications
 Name and address of the head of
laboratory/authorized person
 Phone number

 Fax
 E-mail
 Signature