DECEMBER 2023

GUIDANCE NOTES ON GOOD

DISTRIBUTION PRACTICE
GUIDANCE NOTES ON GOOD DISTRIBUTION PRACTICE DECEMBER 2023

Introduction

This guide is intended for those involved in the storage, transportation and
distribution of Active Ingredients, Therapeutic Products, Chinese Proprietary
Medicines, Cell, Tissue and Gene Therapy Products (CTGTP) and CTGTP
starting materials and health products which are used as clinical research
materials, collectively referred to herein as “products”. This guide applies to all
steps in the distribution/supply chain.

The objective of the guide is to ensure that the quality and integrity of the
products are maintained throughout the distribution chain. The manufacturers,
importers and distributors share important and distinctive roles and
responsibilities to ensure that products are of the required quality for their
intended use.

This guide aims to describe the critical and important controls appropriate for the
storage and distribution of these products. Not all of the controls described will be
relevant to every situation. It is recognized that some of the controls are not
applicable to certain companies or environments. The controls should be
adapted to meet individual company’s needs where necessary. The relevance of
any control should be determined taking into consideration the specific risks the
company is facing such that the desired standards of quality are achieved.

For cold chain products, both the requirements as stipulated in this guide and
Annex 1 will be applicable.

Principle

The licensee has the ultimate responsibility to ensure an effective quality

management system (QMS) is in place to manage the GDP activities. The
system should be fully documented, monitored for effectiveness, and supported
by competent personnel and suitable facilities. The QMS should also extend to
outsourced activities. Where appropriate, risk-based approach should be applied
in the implementation of the QMS.

1 PERSONNEL

1.1 There should be an adequate number of trained personnel involved

in all stages of the distribution/supply chain. The number of
personnel required will depend on the volume and scope of
activities.

1.2 All personnel should be competent and possessing appropriate

knowledge and experience, and where applicable, the relevant
professional and technical qualifications for the tasks assigned to
them.
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1.3 All personnel should receive initial and continuing training in

relation to Good Distribution Practice (GDP) standards, operating
procedures and safety issues, in accordance with a written training
procedure. Special training, including the need for Personnel
Protective Equipment (if necessary), should be provided to
personnel when dealing with special categories of products such as
cytotoxic, infectious or sensitizing products, products presenting
special risks of abuse (including narcotic and psychotropic
substances), CTGTP and cold chain products. Training records
should be maintained.

2 PREMISES AND EQUIPMENT

2.1 Premises should be designed or adapted to ensure that the

required storage conditions are maintained. Premises should also
have sufficient security to prevent unauthorized access and
misappropriation of the products.

2.2 Receiving and dispatch bays should protect products from the
weather. The receiving area should be designed and equipped to
allow cleaning of the containers of incoming materials, if necessary,
before storage.

2.3 Storage areas should be of sufficient capacity to allow orderly and

segregated storage of the various categories of products: those in
quarantine and released, rejected, returned or recalled products.
These designated storage areas should be clearly marked and the
access to the products in quarantine and those that are rejected,
returned or recalled should be restricted to authorized personnel.
Any system (e.g. computerized and bar coding system) replacing
the physical separation should give equivalent assurance in
segregation and restriction in accessibility.

2.4 The storage areas should have adequate lighting and ventilation to
enable all operations to be carried out accurately and safely.
Premises should be carefully maintained, ensuring that repair and
maintenance operations do not present any hazard to the quality of
the products.

2.5 Premises should be dry, clean and free of accumulated waste and
dust. A written cleaning procedure should be available indicating
the frequency and methods to be used to clean the premises.
Cleaning should be conducted so as not to present a source of
contamination. Cleaning records should be maintained. For
cytotoxic, infectious, sensitizing products or CTGTP, there should
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be appropriate procedures for the cleaning up of any spillage to

ensure complete removal of any risk of contamination.

2.6 Products should be stored off the ground and suitably spaced to
permit cleaning and inspection. Pallets should be well maintained
and kept in a good state of cleanliness.

2.7 Storage conditions for products should be in compliance with the

instructions on the product label. All equipment impacting on
storage and distribution of products should be designed, located,
maintained and cleaned to a standard which suits its intended
purpose. The storage areas should be equipped with recorders or
devices that will continuously monitor the storage conditions and
record the relevant readings such as maximum and minimum
temperature and humidity of the day. Such records should be
reviewed regularly. Appropriate actions on the premises, equipment
and/or products should be taken when the storage conditions are
not met and these actions taken should be recorded.

2.8 The recorders and devices for monitoring the storage conditions
should be located in areas that are most likely to show fluctuations
and/or the hottest and coldest locations where appropriate. These
measuring equipment should be calibrated for the required
operating range at defined intervals. Calibration of these measuring
equipment should be traceable to national or international standard
and such calibration records should be maintained.

2.9 Appropriate and suitable storage conditions should be provided for

hazardous, sensitive and dangerous products such as combustible
liquids and solids, pressurised gases, highly toxic substances,
CTGTP and radioactive products.

2.10 Premises should be designed and equipped to prevent the entry of

insects, rodents and other pests/animals. There should also be a
pest control programme to identify and prevent pest infestation.
Appropriate records should be maintained.

2.11 The presence of food, drink, smoking material or medicinal

products for personal use should be prohibited in the storage areas.

3 STOCK HANDLING, STOCK CONTROL AND DELIVERIES

3.1 Upon receipt, each incoming delivery should be checked for

tampering and damage. Label description, type and quantity of the
incoming products should also be physically verified against the
relevant purchase order information. If necessary, any container or
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the entire delivery should be quarantined or set aside for further

investigation. The type and nature of checks should be stated in a
written procedure.

3.2 Products subject to specific storage requirements (e.g. narcotics,

cold-chain products) should be immediately identified and stored in
accordance with the written procedure. Incoming containers should
be cleaned if necessary, before storage. Any activities performed
on the incoming goods should not impact on the quality of the
products.

3.3 Products in cartons/bulk packs should be adequately labeled with at

least the product name, the batch number and the expiry date or
retest date. The labels should be clear, unambiguous, and should
be in accordance with the national legislative and regulatory
requirements.

3.4 Products with broken seals, damaged packaging or suspected of

possible tampering/contamination should be quarantined either
physically or using an equivalent electronic system and the cause of
the issue investigated. These products must not be sold or
supplied.

3.5 Periodic stock reconciliation should be performed, at least for

quantity, overall condition, expiry date and retest date (for Active
Ingredients). All significant stock discrepancies should be
investigated to check for inadvertent mix-ups and wrong issuance of
stocks.

3.6 Products bearing an expiry date must not be received or supplied

after their expiry date or so close to their expiry date that this date is
likely to occur before the products are being used by the consumer.

3.7 A system should be in place to ensure proper stock rotation e.g.

first expiry, first out (FEFO) or for Active Ingredients, first expiry or
retest date, first out. This system should be checked regularly to
ensure that the system is operating correctly. Deviations may,
however, be permitted in exceptional cases where such deviation is
appropriate and justified.

3.8 Deliveries should be made only to wholesale dealers or persons

who are authorized to supply the products.

3.9 A written procedure on the delivery of the products to customers

should be available.

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3.10 Products should be transported in such a way that:

a) their identification is not lost;
b) they do not contaminate, and are not contaminated by, other
products or materials;
c) adequate precautions and measures are taken against spillage,
damage or theft;
d) they are secure and not subject to unacceptable degrees of heat,
cold, light, moisture or other adverse influence, nor to be
attacked by microorganisms or pests.

3.11 The vehicle/mode of transportation should not be used as a store

for the products.

4 DISPOSAL OF PRODUCTS

4.1 Products intended for destruction should be appropriately identified,

held separately, and handled in accordance with a written
procedure.

4.2 Destruction of products should be carried out in accordance with

the national legislative and regulatory requirements and with due
consideration to protect the environment.

4.3 Records of all disposed products should be retained for a defined

period.

5 DOCUMENTATION

5.1 The documentation system should include the specifications of

products (applicable mainly to importers), procedures, instructions,
protocols, contract, records, Certificate of Analysis, storage and
handling information, safety data sheets and other relevant data, in
paper or in electronic form. These documents should be made
available for audit and upon request by the licensing authority.

5.2 Written procedures should be available to describe the different

operations which may affect the quality of the products or of the
distribution activities: personnel training, receipt and checking of
incoming products, storage, deliveries, cleaning and maintenance
of premises, pest control, monitoring and recording of the storage
conditions, security of stocks on site, withdrawal of saleable stock,
returned products, complaints, recalls, self-inspection, audit and
assessment of contract acceptor, etc. The associated records of
actions taken or conclusions reached should be maintained.

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5.3 The title, nature and purpose of each document should be clearly
stated. Documents should be uniquely identifiable and the effective
date should be defined. The contents of documents should be clear
and unambiguous. All documents should be approved, signed and
dated by an appropriate authorized person(s) and should not be
changed without the necessary authorization.

5.4 Documents should be reviewed regularly and kept up to date.

When a document has been revised, a system should exist to
prevent inadvertent use of the superseded version.

5.5 Records should be made or completed at the time each action is

taken in such a way that all significant activities or events are
traceable. Handwritten data entry should be made in a clear, legible
and indelible way. Any alteration made to the entry should be
signed and dated, and the alteration should permit the reading of
the original information.

5.6 A record of receipt and distribution of the products shall be kept,

stating the product name, date of transaction, invoice/delivery order
number, name and address of purchaser/supplier, batch number,
expiry date, quantity received/sold and stock balance. Relevant
documents for the distribution (including records for samples)
should be maintained.

5.7 Documents should be retained for a duration as in accordance with

the legal requirements and be readily retrievable.

5.8 Each employee should have ready access to all necessary

documentation for the tasks executed.

5.9 Data may be recorded by an electronic data processing system but

detailed procedures relating to the system in use should be
available and the accuracy of the records should be checked. Only
authorized persons should be able to enter or modify data in the
computer and there should be a record of changes and deletions
(i.e. audit trail); access should be restricted by password or other
means. It is particularly important that the data, including audit trail,
are readily available throughout the period of retention. These data
should also be protected by back-up transfer on separate hard disc,
paper or other means.

6 PRODUCT COMPLAINTS

6.1 There should be a written procedure describing the actions to be

taken in the handling of all written and oral complaints regarding a
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possible product defect. There should be a record for each

individual product complaint.

6.2 The procedure for handling product complaints shall ensure that the
complaints received are investigated and followed through, and that
corrective actions are taken to prevent recurring problems. All
original details of the product complaint, investigations and
subsequent corrective and preventive actions taken, including
product recall should be documented in the product complaint
record.

6.3 Within the company, a person shall be designated to handle

product complaints. This person must have the authority to initiate
investigations.

6.4 If a product defect is discovered or suspected in a batch,

consideration should be given to determine whether other batches
are also affected.

6.5 Product complaint records should be retained and periodically

reviewed to evaluate trends, product related frequencies, and
severity with a view to taking additional, and if appropriate,
immediate corrective action.

7 PRODUCT RECALL

7.1 An emergency plan for urgent recalls and a non-urgent product

recalls procedure should be described in writing.

7.2 A person or committee should be designated for the co-ordination

and execution of all product recalls.

7.3 In the event of a product recall, all customers to whom the product
has been distributed shall be informed with the appropriate degree
of urgency. The recall message should indicate whether the recall
should be carried out at the retail level, and whether there is a need
to remove all recalled products immediately from the shelves and
prevent their mixing with other saleable stocks.

7.4 The local regulatory authority should be informed of all product

recalls. If the product is exported, the overseas counterparts and/or
regulatory authorities must be informed of the recall.

7.5 Where product recall affects a particular batch, consideration

should also be given to determine whether other batches are also
affected.
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7.6 All actions taken in connection with the product recall must be
approved by the company and/or regulatory authorities and
recorded.

7.7 The progress of recall process should be recorded and a final

report issued, which includes reconciliation made between
delivered and recovered quantities of products.

7.8 The effectiveness of the arrangements for product recall should be

evaluated regularly.

8 RETURNED PRODUCTS

8.1 There should be a written procedure describing the handling of

returned products and the corresponding records of all returned
products should be kept.

8.2 All returned products should be kept apart from saleable stock to
prevent redistribution until a decision has been reached regarding
their disposition.

8.3 Returned products should only be returned to saleable stock if all of

the following are confirmed:
a) the products are in their original unopened and undamaged
secondary packaging and are in good condition. If there are
original security seals, these seals must be present and intact.
b) it is known that the products have been transported, stored and
handled under proper conditions;
c) the remaining shelf life period is acceptable; and
d) the products have been examined and assessed by appropriate
and qualified personnel. This assessment should take into
account the nature of the product, any special storage
conditions required, and the time which had elapsed since it
was distributed. Special attention should be given to thermo-
labile products. Advice should be sought from the marketing
authorization (product licence) holder or manufacturer as
necessary.

Where any doubt arises over the quality of the product, it should
not be considered suitable to be returned to saleable stock.

8.4 The responsible person or nominated designee should decide on

the disposition of the returned goods following a satisfactory quality
re-evaluation. Corrective and preventive actions should be taken
where appropriate.
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8.5 Products returned to saleable stock should be placed in

accordance with the FEFO system.

9 COUNTERFEIT PRODUCTS

9.1 The sale and distribution of a suspected counterfeit product should

be suspended immediately.

9.2 Any counterfeit products found in the supply chain should be

physically segregated from other materials to avoid any confusion.
They should be clearly labeled as “Not for Sale” or with other
similar phrases/words. All relevant activities in relation to such
products should be documented and records retained.

9.3 The regulatory authority and the holder of the marketing

authorisation of the original product should be informed
immediately.

9.4 Upon confirmation as a counterfeit product, a formal decision

should be taken on removal of such product from the market,
ensuring that it does not re-enter the supply chain, including
retention of any samples necessary for public health, regulatory, or
legal needs and arrangements for its disposal. All related decisions
should be appropriately documented.

10 SELF-INSPECTION

10.1 Self inspections should be conducted to monitor the implementation

and compliance with this GDP standard and to propose necessary
corrective and preventive measures.

10.2 Self-inspections should be conducted in an impartial and detailed

way by designated, competent personnel. There should be a
written procedure on self-inspection stating the persons involved in
self-inspection, the frequency of self-inspection and the inspection
criteria.

10.3 All self-inspections should be recorded. This record should include

all observations made during the inspection. In the event that
irregularities and/or deficiencies are observed, their cause should
be determined and the corrective and preventive actions (CAPA)
should be documented and followed up.

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11 CONTRACT ACTIVITIES

11.1 Any activity covered by the GDP Guide that is outsourced should
be defined, agreed and controlled in order to avoid ambiguity,
which could affect the quality of the product. There must be a
written contract between the contract giver and the contract
acceptor which clearly establishes the roles and responsibilities of
each party, including compliance with this standard.

11.2 The contract giver is responsible for assessing the competence of

the contract acceptor to successfully carry out the work required
and for ensuring by means of the contract and through audits that
the principles and guidelines of GDP are followed. An assessment
of the contract acceptor should be performed before
commencement of, and whenever there has been a change to, the
outsourced activities. Any contract acceptor should be audited
periodically by the contract giver. The requirement for audit and the
frequency for audit should be defined based on risk depending on
the nature of the outsourced activities. Audits by the contract giver
should be permitted at any time.

11.3 The contract giver should provide the contract acceptor with all the
information necessary to carry out the outsourced operations in
accordance with the specific product requirements and any other
relevant requirements.

11.4 The contract acceptor should have adequate premises and

equipment, procedures, knowledge and experience, and competent
personnel to carry out the work ordered by the contract giver.

11.5 The contract acceptor should not pass to a third party any of the
work entrusted to him under the contract without the contract giver’s
prior evaluation and approval of the arrangements. Such
arrangements should ensure that the wholesale distribution
information is made available in the same way as between the
original contract giver and contract acceptor.

11.6 The contract acceptor should refrain from any activity which may
adversely affect the quality of the product(s) handled for the
contract giver.

11.7 The contract acceptor must forward any information that can
influence the quality of the product(s) to the contract giver in
accordance with the requirement of the contract.

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12 HANDLING OF CELL, TISSUE AND GENE THERAPY PRODUCTS

(CTGTP) AND STARTING MATERIALS OF CTGTP

12.1 There must be an effective, risk-based QMS which adequately

assesses the risks that impacts product quality; considers the
proper controls and mitigation measures; as well as putting in place
the appropriate communications and active process reviews, to
ensure maintenance of appropriate storage and distribution
conditions for the CTGTP and its starting materials (hereinafter
known as “products” in this section). The level of effort, formality
and documentation should commensurate with the level of product
quality-related risks in the handling of the products, and is fit for its
purpose to the protection of the patient.

The active substance of a cell or tissue therapy product is

composed of the engineered (manipulated) cells and/or tissues.
The active substance of gene therapy product is the nucleic acid
sequence(s), or genetically modified microorganism(s), virus(es) or
cells. The active substance is manufactured from Starting Materials
such as cells, tissues, gene of interest, expression plasmid, cell
banks and virus stocks or non-viral vector.

12.2 The appropriate use of risk-based processes and documentation

should demonstrate the company’s obligation and compliance with
regulatory requirements, through appropriate communications of
these documented evidences between the company and the
regulatory authority.

12.3 The established infrastructure should build in relevant

capability(ies) that permit real-time monitoring of the conditions,
appropriate alert mechanisms, and accurate track-and-trace of the
products through storage, transport and delivery in the supply
chain. All these tasks should be carried out by trained personnel.

12.4 The system should ensure that traceability data may be accessed
rapidly in case of an adverse reaction from the patient.

12.5 The traceability data are to be retained for a minimum of 30 years

after the expiry date of the product, or any other period provided for
in the product registration.

12.6 Storage containers should be sealed, clearly labelled and kept at an

appropriate temperature. When liquid nitrogen is used, liquid-
nitrogen vapour phase storage may be associated with vertical
temperature gradients. Temperature gradients should be monitored
and vertical temperature gradients should be minimised. The liquid
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nitrogen level should be monitored. Deviation from set limits and

corrective and preventive action taken should be recorded. A stock
inventory and the relevant monitoring records must be kept.

12.7 There should be written procedures established to ensure that

adequate conditions have been maintained and will not compromise
the product quality if products need to be removed from the storage
area. All relevant activities in relation to such products should be
documented and records retained.

12.8 There should be written procedures and documentation in place for

the secured handling and storage of products with positive
serological markers (e.g. bacterial and viral infections) or viral
vector products. This should describe the storage arrangements,
such as the type of storage chamber, placement and retrieval
process, as well as the cleaning processes to minimise the risk of
cross-contamination, while maintaining the quality of the products
and facilitate accurate product retrieval.

12.9 Particular attention should be paid to implementing appropriate

measures and labelling to prevent mix-ups of products (e.g.
autologous products).

12.10 There should be an emergency plan for dealing with accidental

spillage of viable organisms. This should consider the methods and
procedures for containment, protection of personnel, cleaning,
decontamination, waste management and safe return to use.

12.11 CTGTP should be transported in accordance with the conditions

defined in the product registration or clinical trial authorisation
(where applicable).

12.12 The conditions during distribution and delivery of CTGTP (e.g.

transportation routes, temperature, time limit, type of container)
should be clearly defined and validated. All containers and
packages need to be validated and suitable for the intended
purpose.

13 HANDLING OF ACTIVE INGREDIENTS

13.1 This section are additional requirements which are relevant to

agents, brokers, traders or distributors, generally referred to as
“dealer” who may trade and/or take possession, distribute or store
an Active Ingredient.

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13.2 Active Ingredients should be purchased from approved suppliers in

accordance with the established specifications. Deliveries should be
examined at receipt in order to check that all security seals are
present with no sign of tampering.

13.3 The dealers should maintain complete traceability of Active

Ingredients that they distribute. Documents that provides traceability
includes identity and address of the original manufacturer, purchase
orders, transportation documentation, manufacturer’s batch number,
transportation and distribution records as well as authentic
Certificates of Analysis (COA).

13.4 Original COA issued by the manufacturer or authenticated copies of

the original COA should be provided for each batch of Active
Ingredients on request by the customers.

13.5 Information on the COA should include at least the name of the
Active Ingredient including where appropriate its grade, the batch
number, and the date of release. For Active Ingredient with an
expiry date, the expiry date should be provided on the label and
COA. For Active Ingredient with a retest date, the retest date should
be indicated on the label and/or COA. The COA should list each
test performed in accordance with compendial or customer
requirements, including the acceptance limits, and the numerical
results obtained (if test results are numerical). COA should be dated
and signed by authorised personnel of the quality unit(s) and should
show the name, address and telephone number of the original
manufacturer.

13.6 The dealers should provide the identity of the original Active
Ingredient manufacturer to licensing authority upon request. The
original manufacturer can respond to the licensing authority directly
or through its authorised agents.

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14 GLOSSARY

Term Definition
Batch number A unique combination of numbers, letters and/or
symbols that identifies a batch (or lot) and from which
the production and distribution history can be
determined.
Calibration The demonstration that a particular instrument or
device produces results within specified limits by
comparison with those produced by a reference or
traceable standard over an appropriate range of
measurements.
Contamination The undesired introduction of impurities of a chemical
or microbiological nature, or of foreign matter, into or
onto the product during storage or transport.
Contract Acceptor The company who is contracted to conduct an activity
covered by GDP by the contract giver.
Contract Giver The company who is contracting out any activity
covered by GDP to another legal entity.
Cold Chain Products Products requiring storage condition of not more than
8°C.
Expiry Date The date placed on the container/labels of product
designating the time during which the product is
expected to remain within established shelf-life
specifications if stored under defined conditions and
after which it should not be used.
Licensee A licensed importer, wholesaler and/or GDP-certified
companies.
Procedure A documented description of the operations to be
performed, the precautions to be taken and measures
to be applied directly or indirectly related to the
distribution of a product.
Quality management The sum of all aspects of a system that implements
system quality policy, processes, procedures, and resources
that an organisation uses to ensure that quality
objectives in Good Distribution Practice standards are
met.
Quarantine The status of products isolated physically or by other
effective means pending a decision on the subsequent
approval or rejection.
Record Evidence of various actions taken to demonstrate
compliance with instructions, e.g. activities, events and
investigations.
Retest Date The date when an Active Ingredient should be re-
examined to ensure that it is still suitable for use.

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15 REFERENCES

15.1 HSA Guidelines on Good Manufacturing Practice for Cell, Tissue

and Gene Therapy Products, 01 March 2021.

15.2 Pharmaceutical Inspection Co-operation Scheme (PIC/S) Guide to

Good Distribution Practice (GDP) for Medicinal Products (PE 011-1,
1 June 2014).

15.3 Pharmaceutical Inspection Co-operation Scheme (PIC/S)

Guidelines on the Principles of Good Distribution Practice of Active
Substances for Medicinal products for Human Use (PI 047-1 Annex,
1 Jul 2018)

15.4 USP <1044> Cryopreservation of Cells, 27 Sep 2018

15.5 World Health Organization (WHO) Good Storage and Distribution

Practices for Medical Products. WHO Technical Report Series, No.
1025, 2020.

15.6 World Health Organization (WHO) Good Trade and Distribution

Practices for Pharmaceutical Starting Materials. WHO Technical
Report Series No. 996, 2016.

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Annex 1

COLD CHAIN PRODUCTS

1. There should be written procedures established to ensure that incoming

cold chain products are delivered under the storage conditions in
compliance with the instructions on the product label, which are based on
the results of stability testing. Companies may make use of temperature
data loggers or other temperature recording instruments to verify that the
desired temperature has been maintained during delivery for each
consignment received. Alternatively, there should be a simulation study
carried out to validate the delivery conditions, taking into consideration the
possible worst-case situation. This aforementioned requirement should
also be applicable to the outbound deliveries.

2. The list of cold chain products should be made available for reference by
staff handling the receipt of such goods and other relevant store
personnel.

3. Cold chain products should be immediately identified upon receipt and

stored under the storage conditions in compliance with the instructions on
the product label. This should be carried out in accordance with the written
procedure.

4. The subsequent checking for signs of tampering, damage and non-

compliance with cold chain storage condition, as well as physically
verifying the label description, and product quantity, against the relevant
information in the purchase order should be carried out under the storage
conditions as recommended on the product label unless otherwise
justified.

5. All cold chain products (e.g. released, quarantined) must be stored under
the storage conditions as indicated on the product label other than
products to be disposed.

6. The cold room, which is used for storage of cold chain products, should be
subject to temperature mapping studies, under representative conditions
in order to identify the suitable locations for placing the temperature
probes. The mapping exercise should be repeated accordingly if there are
significant changes.

7. The temperature conditions of the cold room or refrigerator should be

monitored and recorded on a continuous basis. The temperature probes
should also be subject to periodic calibration for the required operating
range. A regular maintenance programme should be established and
carried out for the air conditioning system of the cold room and
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refrigerator. For storage units that has an auto-defrost facility,

precautionary steps should be taken to ensure that the storage
temperature is not affected during the defrost cycles.

8. The cold room or refrigerator should be installed with an alarm system to

alert the staff to any temperature excursions. Action and alert limits should
be established. The function of the alarm system should be subject to
periodic testing.

9. Backup power should be available for the cold room to ensure that storage
temperature conditions will be maintained and temperature probes and
recording devices will continue to function in the event of a power failure.
Any backup generators used should be subject to periodic testing.
Alternative back-up plans that provide equivalent storage temperature
conditions and monitoring system can be considered in the absence of
backup generator.

10. There should be written procedures to describe the packing materials

required, the packing configuration of transportation containers of cold
chain products and labeling requirements that easily identify these
products as products that require special delivery/storage conditions. The
packing operation for the cold chain products should be recorded and
there should be an independent check to ensure that the packing
operation is carried out in accordance with the written procedure. The
individual who carried out this independent check should initial in the
packing records.

11. Refrigerated vehicles or transportation containers for cold chain products

should be mapped and monitored if they provide the primary means for
environmental control. However, this is not necessary if a
qualified/validated insulated container is used for this purpose. Special
care should be exercised when using dry ice during transportation.
Products should not come into contact with dry ice as this may cause
freezing of the product.

12. There should be written procedures available for the delivery of cold chain
products. The planning of the delivery route should be taken into
consideration.

13. There should be procedures established for handling temperature

excursions that may occur during receiving, storage and delivery.
14. There should be procedures established to describe how product return
requests should be handled and the disposition of such products.

15. Written contract(s) should be established to describe arrangements and

responsibilities between the contract giver and contract acceptor with
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respect to contract warehousing and transportation of cold chain products.

The contract should provide all the necessary information and define the
conditions required for the contracted operations to be carried out, as well
as the responsibilities of each party.

16. There should be written procedures available and appropriate training

provided for all staff involved in the handling, receipt, storage, packing and
delivery operations that may affect the quality of cold chain products.

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Annex 2
General points to consider for auditor and auditee
• General Information • Self-Inspection
- Any contract warehouse(s) - SOP and records
- Approval available for the use of the warehouse
• Contract Activities
• Personnel - Contract
- Name and designation of personnel - Content defines responsibilities and requirements
- Training programme and records
• Poisons & CD Requirements
• Premises and Equipment - Sample control record
- Floor area - Signed orders/invoices/other supporting documents
- Layout plan - CD register
- Store approval
- Prevent unauthorized access • Cytotoxic Products
- Adequate storage area with segregations - Labels for identification and warning
- Appropriate for the products - Appropriate training
- Lights/ventilation - Procedure for dealing with spillage incident
- Dry and clean - Cytotoxic spillage control kit
- Cleaning procedure
- Cleaning records • Cell, Tissue and Gene Therapy Products
- Storage off ground - Quality risk management
- Storage – Sunlight - Real-time monitoring of storage, transport and
- Thermometer / hygrometer and records delivery conditions
- Warehouse design prevents pest entry - Track-and-trace of CTGTP
- Appropriate pest control programme - Rapid access to traceability data
- Data retention period
• Stock Handling, Stock Control And Deliveries - Handling of storage containers
- Receiving procedure - Procedures for return of CTGTP back to storage
- Appropriate types of checks conducted - Procedures for handling of CTGTP with positive
- Labelling of goods serological markers or viral vector products
- first expiry (retest date), first out (FEFO) - Prevention of mix-ups
- Periodic stock reconciliation - Emergency plan for dealing with spillage
- Procedure for delivery of products - Defined transportation conditions
- Validated containers and packages used for
• Disposal delivery
- Written procedure and records
• Active Ingredients
• Documentation - Purchase AI from approved supplier
- Procedure for stock handling and labeling and - Checking of security seals upon receipt
monitoring of storage conditions - Complete traceability to the original manufacturer
- SOP signed and formalized - COA format requirements
- Content of SOP clear and kept up to date
- System to prevent inadvertent use of obsolete • Cold Chain Products
procedures - Receiving and incoming checks
- Receiving and distribution records, invoices and - Labels/means to identify cold chain products
delivery orders - Temperature mapping
- Record retention - Thermometer and records
- Computerized record – restricted access, audit trail - Maintenance programme
and back-up - Alarm system for temperature excursion
- Backup generator/plan
• Product Complaints - Packing procedure and records, and independent
- SOP and records check
- System for investigation and review - Temperature mapping for vehicles or
qualified/validated containers
• Product Recall - Monitoring of storage conditions during
- SOP and records transportation or simulation study
- Designated person - Delivery procedure
- Level of recall established - Procedure to handle temperature excursion
- Procedure for handling returned products
• Returned Products - Contracts
- SOP and records - Training programme and records
- Assessment criteria
- Authorization for re-sale

END OF DOCUMENT
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Contact:

GDP Unit
Audits Branch
Audit & Licensing Division
Health Products Regulation Group
Health Sciences Authority

11 Biopolis Way, #11-01, Helios

Singapore 138667
www.hsa.gov.sg
Email: [email protected]