Guidance for Industry:

Hong Kong Guide to

GMP for the Secondary
Packaging of Pharmaceutical
Products
Version 1.3

Drug Office, Department of Health

 Contents list

PURPOSE OF THIS GUIDANCE................................................................................................. 3

DEFINITION............................................................................................................................. 3
SCOPE ...................................................................................................................................... 3
GUIDANCE FOR INDUSTRY...................................................................................................... 4
RELATED DOCUMENTS .......................................................................................................... 13

Guidance for Industry: HK Guide to GMP of Secondary Packaging of Pharmaceutical Products Page 2
 PURPOSE OF THIS GUIDANCE
This document provides guidance to industry on how to achieve compliance with specific
sections of the Hong Kong Guide to GMP for Secondary Packaging and how specific sections will
be interpreted by GMP inspectors of the Department of Health.
It is intended that this document will be amended from time to time to include additional
guidance arising from discussions with industry associations and individual companies and from
on-site inspections by GMP inspectors of the Hong Kong Department of Health.

DEFINITION
Secondary packaging is a manufacturing step involving the labelling, relabelling, cartoning, re-
cartoning or adding additional information (including inserts) to pharmaceutical products which
are already enclosed in the container in which they are to be sold or supplied.

SCOPE
The Hong Kong GMP Guide for Secondary Packaging applies to any company carrying out the
secondary packaging of pharmaceutical products in Hong Kong.
Secondary packaging operations involving the application of a supplementary label that does
not obliterate, change or display information relating to the original name, list of ingredients,
dosage instructions, batch number or expiry date of the pharmaceutical products are exempted
from the requirements of the Hong Kong Guide to GMP for the Secondary Packaging of
Pharmaceutical Products.
Full compliance with the Hong Kong GMP Guidelines for Pharmaceutical Products applies to
packaging of a bulk product to become a finished product which involves the use of primary
packaging materials. Primary packaging materials are packaging materials that are intended to
be in direct contact with the products.

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 GUIDANCE FOR INDUSTRY
Although the Hong Kong Guide to GMP for Secondary Packaging of Pharmaceutical
Products is intended to be self-explanatory, this document provides additional
information in the form of guidance on specific sections of the Hong Kong Guide to GMP
for the Secondary Packaging of Pharmaceutical Products.

Section Requirement Guidance

No.

1.1 Quality Systems In a GMP environment, Quality Management Systems (QMS) refers to a
collection of documents that defines how the GMP aspects of the business
functions are going to operate, including processes such as:
• Managing and controlling documents and records
• Change control
• Corrective and preventative actions (CAPA)
• Training
• Customer complaints
• Deviation management

1.2 Monitoring QMS The effectiveness of QMS processes needs to be monitored. The
monitoring can be done through various methods and the monitoring
approach should be documented in a written procedure.
Consider measuring various aspects associated with each of the systems,
for example:
• the number of items still outstanding and their importance,
• how long they have been an issue,
• the number of items relating to a particular area, and whether these
relate to the facility, packaging operations or training of staff.
Example:

Quality system Example

Managing and Ensure all standard operation procedures for packaging

controlling operations are in place.
documents and
Measure how many documents have past their due date to be
records
reviewed; measure the number of documents that are in-
progress to being updated.

Change control How many change requests are opened; how many have
been closed; what areas of the business did they relate to.

CAPA How many open CAPA items are currently in the system; how
many have been closed; what areas of the business did they
relate to.

Customer How many open customer complaint items are currently in

complaints the system; how many have been closed; what areas of the
business did they relate to; are there reoccurring issues.

Deviation How many open deviation items are currently in the system;
management how many have been closed; what areas of the business to
which they relate.

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 Section Requirement Guidance
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1.5 Change control Changes to processes that may affect the quality of the product need to be
managed through a change control procedure.
Example:
If the refrigerator used to store product breaks down and needs to be
replaced, a change control request has to be raised to ensure that the
purchase, assessment of quality, validation requirements, capacity, and
documentation required for maintenance/calibration and specifications of
the new refrigerator meet the temperature range of the products to be
held in the refrigerator.

CAPA Corrective and preventative actions (CAPA) are the planned actions
resulting from an issue.
Example:

The issue A customer complaint was received that the batch number
printed on the product container was difficult to read and not
printed properly. The complaint was documented.

Investigation The printing and inspection processes were reviewed. Several

issues were identified and the investigation was documented.

Findings The batch number printer loses quality of print. The finding was
documented.

Corrective Corrective: As there was no checking of the printing process

and during manufacture, a print inspection process to check that
preventative quality print is maintained throughout the printing process and
actions this corrective action was documented.
Preventative: Improve the maintenance program for the
printer to help prevent similar occurrences, and this
preventative action was documented.

2.4 & Qualifications of The minimum requirements for academic qualifications and working
Key Personnel experience for Key Personnel (Quality Assurance Officer and Person in
2.5
charge of secondary packaging operations) involved in the secondary
packaging of pharmaceutical products are as follows:
a) Post-secondary qualification with:

• 1 year of experience in secondary packaging and/or manufacture

of pharmaceutical products in a GMP manufacturer; or
• 6 months of experience in secondary packaging and/or
manufacture of pharmaceutical products in a GMP manufacturer
with certified GMP training.

b) Secondary qualification (HKCEE or HKDSEE or equivalent)

with:

• 2 years of experience in secondary packaging and/or manufacture

of pharmaceutical products in a GMP manufacturer; or

• 1 year of experience in secondary packaging and/or manufacture

of pharmaceutical products in a GMP manufacturer with certified
GMP training.
HKCEE = Hong Kong Certificate of Education Examination
HKDSEE = Hong Kong Diploma of Secondary Education Examination

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 Section Requirement Guidance
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2.6 Training All personnel (including company employees and contractors) whose
activities could affect the quality of the final product need to be trained in
both general GMP as well as any procedures relevant to the tasks they are
to perform. Furthermore, they should be assessed for their ability to
perform the tasks assigned to them.
Procedures that require personnel to assess, measure and set up
equipment or perform a test will also require competency training to
ensure that they can complete these activities in the correct manner and
obtain the correct result.
Example:
A cleaner who cleans in the secondary packaging area may need to be
trained. This cleaner may also need to be assessed to make sure they
understand the cleaning procedure (e.g. what tools and cleaning agents to
use and how to perform the cleaning.
The assessment may include knowledge of the procedure and a review of
their cleaning technique to perform the task, by previously trained and
experienced or knowledgeable personnel. This training should be
documented in their individual training record.

3.2 Working area(s) The working area where secondary packaging operations are carried out
and prevention should be designed and arranged in a manner to avoid confusion and to
of mix-ups minimize the risk of mix-up between different products that are subject to
secondary packaging as well as between different materials and
components used in secondary packaging operations. This should include:
• Designation and labelling of the packaging lines with the name and
batch number of the product that is subject to secondary packaging;
• Handling only one batch of product at a time in the same packaging
line;
• Physical barriers such as partitions between different packaging lines;
• Use of closed containers for the storage and transfer of any printed
packaging materials such as labels to be used in secondary packaging
operations;
• Use of formal line clearance checks for each packaging line prior to
the commencement of each secondary packaging operation. This
line clearance should be recorded in the batch packaging record and
ensure that there is no other product or packaging material in the
area and that the area is clean and suitable for use.

3.3 Secondary Products to be subject to secondary packaging must remain in closed

Packaging containers at all times, the areas to be used for secondary packaging
Environment operations do not need to be classified, but they should be controlled to at
least the following conditions:

Design Risks of errors, omissions and mix-ups can be

mitigated by designing and creating a visual, thermal
and acoustic environment conducive to operator
comfort. This should include mitigating heat gains from
equipment such as shrink wrappers.

Lighting The lighting level should be greater than 300 lux in the
level packaging area in order to help prevent operator
errors when reading documents and other written

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 Section Requirement Guidance
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material.
Lux is a standard measurement of light and can be
measured by a lux meter.
Note: It is important to use a lighting level that
ensures operators can perform their job without error.

Temperature 17 – 25oC
Note: Temperature levels must be maintained whilst
product is stored or packed in the area.

Relative Not more than 65%

Humidity
Note: Humidity levels must be maintained whilst
product is stored or packed in the area.

Air supply • As a minimum, air within secondary packaging

areas should be filtered through filters rated as G4
according to EN 779:2012 or filters providing an
equivalent particulate arrestance in order to
maintain an adequate level of internal cleanliness.
More information on filters can be found at
www.ashrae.org.
• The secondary packaging manufacturer should
retain evidence from the supplier that the filters
purchased and installed meet the relevant
requirement.
• Where air is filtered by fitting G4 filters through the
wall, window or split system type air conditioners,
the secondary packaging manufacturer should
ensure that the resistance of the filter does not
reduce the volume of air being filtered to a level
that is ineffective for maintaining cleanliness.
• Portable air purifiers fitted with HEPA filter that can
provide sufficient air filtration coverage to that area
could be acceptable provided the unit is fixed in
place. Temperature and humidity must also be
maintained as per the standard.
• Secondary packaging manufacturers should
establish and maintain SOPs for operating and
maintaining the air handling system(s). Records of
maintenance (e.g. filter changes) should be kept.
Note: The frequency of filter changes must be
determined by the manufacturer’s specifications
and the maintenance schedule. The maintenance
schedule should require an inspection of the system
at minimum every 6 month.
• For large secondary packaging areas or an area
involving several packaging lines, a central AHU (air
handling unit) with recirculation and make-up fresh
air to maintain a positive room pressure, and
filtration through at least M6 filters and G4 pre-
filters should be considered. This will provide
additional protection to the secondary packaging
environment by preventing the ingress of
particulate matter from the exterior and will help
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 Section Requirement Guidance
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protect any ducting from internal dust build-up.

• An alternative to M6 filter is any filter that meets
99% arrestance and efficiency 70%-80%.
• The AHU should be visually inspected every 3
months and the filters checked according to the
manufactures specifications every 6-12 months at
minimum. These checks should be recorded.

Monitoring Temperature and humidity in secondary packaging

areas and associated storage areas should be
monitored at the worst case location and time of day,
which is determined by temperature and humidity
mapping. Results must be documented in a logbook.
Monitoring and trend review can be performed using
data loggers with the results recorded in a logbook.
Data loggers must be calibrated and validated at the
frequency specified by the supplier, typically 12-24
months dependent on the unit and the procedures.

4.2 Labelling of For each delivery of pharmaceutical product for secondary packaging
stored materials containers must be checked as per sections 4.1 and 6.2 of the Guide to
GMP for Secondary Packaging to assure the identity of the content.
Once the product quality specifications are confirmed, the checked product
should be appropriately labelled to indicate the identity of the product
during storage. The area in which the product is located should be clearly
identified so that the product can be easily tracked in the storage area.

4.6 Supplier Mis-labelling (application of the wrong label or label with incorrect text) is
approval recognised as a risk for any packaging operation, in particular where cut
labels are used. This also applies to e.g. printed outer unit cartons and
package inserts.
Mix-ups or other errors by the printer should be minimised by sourcing
these materials from suppliers (printers) that have been assessed and
approved.
Assessing supplier:
The amount of assessment required to approve supplier is based on the
level of risk associated with the criticality of the printed matter they are
supplying. Various assessing methods are available, such as on-site audits,
evidence of compliance with ISO9000 series standard, supplier to complete
questionnaire, etc.
Supplier audits
Suppliers of critical printed packaging materials should be approved by on-
site audit, this audit should be documented and as a minimum establish
that suppliers:

Premise Have suitable premises with adequate space and

segregation to minimise the likelihood of mix-ups.

Procedures Have written procedures for printing pharmaceutical

packaging materials and maintain records for each
lot printed. The procedures should include a line
clearance check before starting printing to ensure

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 Section Requirement Guidance
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that the area is clear of other printed materials and

have instructions for controlling start-up, damaged,
reject, QC samples and excess printed materials.

Quality Conduct QC checks at the start, during and the end

Control of each printing run. These checks should be
checks recorded. Samples removed for checking should not
be returned to the batch and should be destroyed. A
sample of all printed material associated with the
specific batch should be attached to the batch
documentation.

Specifications Have control over specifications to ensure that only

the correct specification is used.

Printing Have control over printing plates (if applicable) to

plates ensure that they are correct before use and that
redundant plates are destroyed or defaced to
prevent future use.

Labelling Securely package and properly label each lot of

printed packaging material, including with a unique
lot number for traceability.

Excess labels Do not keep excess printed packaging materials for

incorporation into the next lot produced. Excess
labels should be destroyed or sent to the customer.

Restricted Store printed packaging materials before delivery to

access the customer in a secure area with restricted access.

4.7 Reference Each delivery or batch of incoming material (e.g. labels and printed
numbers for packaging materials) received should be examined and approved by the
label and Quality Assurance Officer, and given a unique reference number for
printed traceability purposes. This is a different number to the batch number and
packaging allows for traceability of printed material during the process. This process
material is described in an incoming goods or stock management procedure.
This reference number can be recorded on the batch packaging record as a
way of confirming the identity and unique lot labels that have been used
on the appropriate product.
Example:
Example of reference numbering approaches could be in the format of
“year/month day/delivery lot for the day” e.g. 130301-01 refers to the
delivery came in on the 1st of March 2013 and was the 1st delivery for the
day. The second delivery on the day would be 130301-02, and so on.

4.8 Access control Adequately secure storage conditions for printed material include locked
of printed cupboards or separate areas with keys that are only issued to authorised
materials people according to an approved and documented procedure. A register
must be kept.

5.3 Special care for Special care should be taken when using cut-labels and when over-printing
cut labels and is carried out off-line. These would include additional line clearance checks
off-line printing for loose printed materials, greater use of segregated work areas and label
reconciliation at the completion of packaging.

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5.6 Line clearance How to perform a line clearance is defined by individual working area.
Conduct a risk assessment to identify where product and packaging
materials from previous operations may get stuck, fall or be stored. Draw
up an SOP for line clearance for operators to follow. When conducting line
clearance, the SOP must be strictly followed to ensure all of these locations
are checked to be clear before the next operation commences. Line
clearance should be carried out by two people (one is responsible for
checking while the other one is responsible for cross checking) and both
will sign the line clearance section on the batch packaging record.
Example:
For operations involving the use of sophisticated equipment such as a
conveyor belt packaging materials, particularly labels, can get stuck
between the conveyor belts. Therefore, the belts must be checked before
each new operation.

5.8 Checking of The correct performance of any printing operation should be checked and
printing recorded. In case, the printing operation (e.g. batch number coding and
operations expiry dating) is carried out by hand, the accuracy of the printed materials
should be re-checked at regular intervals.
These regular intervals should be documented in a procedure and record
should be made on the batch packaging record that the re-checking has
done.
Experience with the process will help defining the frequency of the
checking. Initially, checking every 15 or 30 minutes should be considered.
Frequency can be reduced or increased based on the error rate. The start
and the end of the batch processing event must always be checked.

6.4 Representative The standard to assess how many samples would be required as a
sample representative sample number is described in ISO 2859 Sampling
Procedures For Inspection By Attributes. This document provides guidance
based on the criticality of the attribute and the batch size.
• The method of sampling will depend on the material to be sampled.
• Ensure that the sampling activity do not contaminate, compromise or
affect the material.
Note: To determine the quantity or number of items to be sampled the
square roots plus 1 is still used in industry).

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Samples are retained to fulfil two purposes; firstly to provide a sample for
6.7 & Reference
analytical testing and secondly to provide a specimen of the fully finished
6.8 samples and
product. Samples may therefore fall into two categories:
Retention
samples • Reference sample means a sample of a batch of starting material,
packaging material or finished product which is stored for the purpose
of being analysed should the need arise during the shelf life of the
batch concerned. Each packaging site should keep reference samples of
each batch of printed packaging materials. Availability of printed
materials as part of the reference and/or retention sample of the
finished product can be accepted.
• Retention sample means sample of a fully packaged unit from a
batch of finished product. It is stored for identification purposes. For
example, presentation, packaging, labelling, patient information leaflet,
batch number, expiry date should the need arise during the shelf life of
the batch concerned.
For finished products, in many instances the reference and retention
samples will be presented identically, i.e. as fully packaged units. In such
circumstances, reference and retention samples may be regarded as
interchangeable.
Provided evidence or information is available that the manufacturer of the
product (or from the party carrying out the primary packaging of the
product) has retained a suitable number of reference samples to enable at
least a full re-examination (to properly investigate serious complaints or
adverse events), it is sufficient for the secondary packaging manufacturer
to retain one sample of finished product from each secondary packaging
run. For example, the secondary packaging manufacturer can ensure the
primary manufacturer has a proper Reference and Retention sample
procedure and there is a formal contract agreement in place with the
primary manufacturer identifying responsibilities, including the keeping of a
suitable number of reference samples.
If the primary manufacturer cannot provide this assurance, sufficient
number of reference samples (to permit at least a full re-examination) and
retention sample (from each packaging run) of finished product should be
kept by the secondary packaging manufacturer.

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 Section Requirement Guidance
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6.9 Calibration Measuring, weighing, recording and control equipment should be calibrated
frequency and checked at defined intervals by methods appropriate to the equipment
being calibrated.
Below are examples of calibration checks and intervals for different types
of equipment.

Type of Requirements Suggested frequency

equipment

Reference Full traceable recalibration Every three years

thermometers
(liquid in glass) Single point e.g. ice-point check Annually

Reference Full traceable recalibration Every three years

thermocouples
Check against reference Annually
thermometer

Calibration weights Full traceable calibration Annually

Hygrometers Traceable calibration Annually

12 Self-inspection Self-inspections can be conducted by staff from another department and

do not need to be performed by an external party. However, it is
recommended that at least one external audit by an auditor experienced in
conducting audits to PIC/S standards should be conducted when the QMS
has been implemented as this will assist in establishing that core
requirements are covered.
The self-inspection process, areas to be reviewed and frequency must be
documented in a self-inspection procedure. Typically, companies could
have at least one area undergoing self-inspection every one or two
months. This would break up the process into manageable blocks and
perform the smaller self-inspections. This would be in preference to one
large self-inspection that covers the whole manufacturing process, facility
and QMS.
Note:
If many quality issues are identified, self-inspections should be conducted
more frequently to help identify and address the root cause of these
problems, and provide the opportunity of continuous improvement.

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 RELATED DOCUMENTS

Doc. No. Document Title

AS 1680 Interior lighting

EN 779:2012 European Standard for General Ventilation Filters

ISO 2859 Sampling Procedures For Inspection By Attributes

ISO 9001:2008 Quality Management Systems

ISO 91.160.10 Interior lighting

- ISPE Good Practice Guide on HVAC

- ISPE Good Practice Guide, Packaging, labelling and Warehouse Facilities

PE 009-10 Jan 2013 PIC/S Guide to GMP for Medicinal Products

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