Transcript Company name DEPARTMENT Management of GMP Documentation

Good Distribution Practice
of Human and Veterinary
Medicinal Products and
Medical Devices
Overview
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Introduction (page 1)
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Scope (page 2)
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Quality Management (page 3)
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Personnel (page 14)
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Premises and Equipment (page 19)
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Documentation (page 28)
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Operations
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Complaints, Returns, suspected falsified Medicinal Products and Medicinal Product Recalls
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Contract Operations
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Self Inspection
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Transportation
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Brokers
Introduction
Distribution is an important activity in the integrated
supply-chain management of pharmaceutical
product. Numerous people and entities are
responsible for the handling, storage and
distribution of such products. In some cases, a
specific person or entity is responsible only for
specific elements of the distribution process.
The objective of this presentation is to assist in
ensuring the quality and identity of Pharmaceutical
product in the storage and distribution process is
maintained.
Scope
This training applies to the procuring, storage,
sale and distribution of pharmaceutical and
veterinary medicines and medical devices.
The training covers controls to be applied in
ensuring the product Quality, Safety and Efficacy
is not compromised during the supply chain
handling of product.
Note: Distribution of starting materials is not covered in this training.
Quality Management (1)
Quality System
Organisation
Structure
Policy
Procedure
Process
Resource
Quality Management (2)
Quality System
Quality Management (3)
Quality System
Quality Management (4)
Quality System
Quality Management (4)
Quality System
Quality Management (5)
Management of Outsourced Activities
Quality Management (6)
Management Review and Monitoring
Quality Management (7)
Management Review and Monitoring
Quality Management (8)
Quality Risk Management (QRM)
Personnel
The Responsible Person (RP) for GDP (1)
Personnel
The Responsible Person (RP) for GDP (2)
Personnel
Other Personnel for GDP
Personnel
Training
Hygiene
Premises and Equipment
Premises (1)
Premises and Equipment
Premises (2)
Premises and Equipment
Premises (3)
Premises and Equipment
Temperature and Environment Control
Premises and Equipment
Equipment (1)
Premises and Equipment
Equipment (2)
Premises and Equipment
Computerised Systems (1)
Premises and Equipment
Computerised Systems (2)
Premises and Equipment
Qualification and Validation
Documentation (1)
Documentation (2)
Documentation (3)
Documentation (4)
Operations
• Ensure the product identity is not lost and the product
is handled in accordance with the marketing
authorisation
• The supplier of all products sourced should be known
to minimise the risk of Falsified products entering the
legal supply chain
• If distributor intends to import a product, for which
they do not hold the MA (marketing authorisation),
they must first notify the MA holder and the
competent authority in the member state of their
intention to import into that market. This process of
notification should be defined in a procedure.
Operations Qualification of Suppliers (1)
• They must hold a Wholesale Distribution Authorisation
or a Manufacturing Authorisation
• They must comply with this training
• They must have written procedures for critical
distribution activities. eg. complaints, recalls, returns,
verification and other areas covered by this training
• They must be audited using questionnaires and site
visits prior to the service commencing
• An audit report must be completed and will form part
of the risk based approach of supply selection.
Operations Qualification of Suppliers (2)
• If product is obtained through a broker, check
that the are appropriately authorised to
supply product and comply with the
requirements of this training.
Operations Qualification of Customer (1)
• They must have authorisation to supply product to
the public in the member state concerned. The
checks performed should be documented
• These checks and periodic re-checks may include
and are not limited to:
– Requesting copies of customer’s authorisation
– Verifying status on an authority website
– Requesting evidence of qualification or entitlement
according to national legislation
• Monitor transactions and investigate any
irregularities in sale patterns to avoid diversion of
product and risks of misuse.
Operations Marketing Authorisation (MA)
• If a wholesale distributor is supplying, or intending to
supply product to a member state other than the
member state in which the MA was granted, they should
make available copy(ies) of the MA to the national
competent authority of the market in which they intend
to supply
• Where applicable the competent authority will inform the
wholesale distributor of the obligations imposed for
operating on their territory.
Operations Receipt of Goods
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If product is received into warehouse in Europe from a third country, for the purpose
of placing product in the EU market, they must possess a Manufacturer’s Importation
Authorisation (MIA)
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Procedures in place to detail checks performed on Goods Receipt.
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Checks performed to ensure Quality of Product received:
– Received from approved supplier
– Correct product and quantity
– If temperature controlled product, temperature logger data downloaded to
observe any temperature excursions during transit
– Free from damage
– If product suspected to be counterfeit, to be immediately segregated and
reported to local competent authority and marketing authorisation holder.
Operations Storage
• Conditions for storage of medicinal products
– Protected from the harmful effects of light, temperature and moisture
– Outer packaging and pallets cleaned before storage in warehouse
– Various categories of product appropriately sealed to prevent crosscontamination
– Clear segregation of products in quarantine, released, rejected,
returned or recalled products and those suspected to be counterfeit
products
– Stock rotation based on expiry date of product
– Handled with care to prevent spillage, breakage or cross contamination.
Minimise risk by not storing product directly on floor.
– Through regular checks any products not suitable for sale to be
immediately segregated from saleable stock (physically and
electronically)
– Stock inventories to be performed at defined periods using a risk based
approach. Any discrepancies to be investigated and documented.
Operations – Segregation of Goods
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There should be a system in place with written procedures to allow for
the segregation from harmful products (rejects, returns, toxic.
counterfeits).
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These products should be clearly labeled with access to only authorised
personnel
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If segregation only performed electronically then system to be risk
assessed to ensure it will provide security and it is appropriately
validated before electronic segregation is implemented.
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Segregated areas to be clearly defined and referenced in the applicable
procedures.
Operations Destruction of Obsolete Goods
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Products for destruction to be handled separately and stored separate for
saleable stock
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Written procedure should detail how these products should be handled
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Destruction should be in accordance with national and international
requirements for disposal
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Records of all disposed products should be maintained and destruction
witnessed for any controlled drug substances
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A technical agreement should be in place between the distribution
warehouse and the destruction company.
Operations Picking and Packing
• When picking:
 Procedure should be in place to ensure the correct product
is picked
 Ensure minimum shelf life of product as agreed with
customers and detailed in a procedure
 Should follow the FEFO rotation of stock
• When packing:
 Ensure packaging materials used will protect product from
any likely damage and maintain it’s storage conditions
(e.g. temperature) during transit
 Seal the container in which the product is packed to avoid
contamination
Operations - Delivery
• When Delivering:
 Ensure the customer receiving the product is appropriately
authorised/licensed to receive medicinal product
 Following information to be provided on delivery note to
customer:
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Delivery date
Product name
Form
Batch number
Quantity
Any safety handling instructions
Transport and storage conditions
Name and address of supplier and consignee
Temperature data or temperature loggers for temperature sensitive
products - to observe any adverse temperature conditions during
transit
Operations - Export
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An exporter of medicinal products must hold a wholesale dealer licence or a
manufacturing authorisation
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The export of medicines for wholesale distribution should follow these
training guidelines with the following exceptions:
– The product does not need to have a Marketing Authorisation (MA) in Europe or
in the member states
– The customer does not need to hold a distribution authorisation
– Any products imported from a third country for export, where the imported
product does not have a MA in the country of origin, the supplier does not need
to hold a wholesale distribution authorisation, however they may be required to
hold a specials licence subject to local regulatory requirements
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If the product is exported to a person in a third country where they are
entitled (licensed) to supply products to public then the requirements of this
training would apply.
Complaints, Returns, Suspected Falsified Medicinal
Products and Medicinal Product Recalls
• All complaints potentially concerning medicinal product defects must
be reviewed carefully in appropriate timescales to minimise any risk
to patient safety
• An assessment must be performed on all returns before deciding on
product disposition
• A good relationship must exist between partners within the supply
chain to prevent entry of falsified medicines
• A system must be in place for an effective recall of product and this
system must be challenged periodically
• Procedures must be in place to detail how complaints, returns,
falsified medicines and recalls will be managed.
Complaints
• There should be:
– A written procedure on how to handle complaints on
product Quality defects and those relating to
distribution. The MA holder should be notified of any
Quality/Safety related complaints promptly
– A person/ department responsible for handling
complaints
– A system of documenting and investigating all
complaints. The national competent authority should
be notified promptly of any justified complaints
– Where applicable, follow up action should be taken
after investigation and evaluation of complaint.
Returned Medicinal Products (1)
• There should be:
 A written procedure on handling and acceptance of returned
medicinal products
 A segregated area for returns. Returns should be kept in this
area until a decision is taken regarding the disposition of product
• Stock should only be returned to saleable stock if
all of the below requirements are met:
 The MA holder does not accept returns
 Secondary packaging is un-opened and not damaged, and in
good condition
 The customer returning product must return within five days of
original dispatch if they do not hold a wholesale distribution
authorisation
Returned Medicinal Products (2)
 Sufficient documentation/data exists to show the product has
been transported, stored and handled under specified conditions
 The documentation/data has been reviewed and assessed by an
appropriately trained, competent, authorised person. This person
should certify that the conditions, in which the product was
stored and handled, were in compliance with GDP
 Distributor has supporting documentation, including original
delivery note, to confirm the customer to whom the product was
supplied, batch and expiry details, and to satisfy themselves that
the product returned has not been falsified
 For cold chain products, there must be supporting temperature
data to show product stability has not been compromised when
outside the control of the distributor.
Returned Medicinal Products (3)
 The MA holder has assessed the packaging
components to ensure they are the regulatory
approved artwork
 The return to saleable stock or for disposal should be
approved by the Responsible Person and this should
be documented
 Any stock returned to saleable stock should be placed
back into the FEFO system
Suspected Falsified Medicinal
Products
There should be:
 Procedures in place on how to handle suspect or
confirmed falsified medicinal products, and on
informing the MA holder and the competent authority
 Initial and ongoing GDP training for staff to raise the
awareness of the risk of falsified medicinal products
entering the supply chain
 Physical and secure segregation of falsified medicines
from legitimate stock and a stock inventory
maintained.
Medicinal Product Recalls
• Procedure required for Management of recalls; this should be
periodically challenged and effectiveness reviewed
• A system for actioning recall from market promptly
• Distributor should follow instructions from MA holder and should
ensure where applicable, that the competent authority has given
approval for recall to commence
• Records available for recall activities performed and should be made
available to the competent authorities
• All records relating to the distribution of product should be made
available to the person(s) responsible for initiating the recall. This
should also include details of all customers who were supplied the
recalled product. Details of batch, expiry and Quantity
• A segregated and secure location for recalled products while
awaiting a decision on disposition
• The progress of the recall should be documented and a final report
issued. This should include a reconciliation between the delivered
and recovered quantities of the recalled product.
Contract Operations
• When outsourcing GDP related activities, a Technical
Agreement/ Quality Agreement should exist between
the Contract Giver and Contract Acceptor.
• The agreement should cover all wholesale distribution
activities and clearly detail both party duties and
responsibilities.
• Both parties must hold a distribution authorisation or
appropriately certified by a competent regulatory
authority.
Contract Operations –
Contract Giver
• Responsible for the activities contracted out.
• Assesses the contract acceptor through audits and
other means to ensure that principles and guidelines
of GDP are followed.
• Audits of contract acceptor should be performed
before service commences and thereafter on a
periodic basis.
• Should provide the contract acceptor with the
information necessary to carry out the contracted
service in accordance with the specific product and
regulatory requirements.
Contract Operations –
Contract Acceptor
• Should have adequate premises, equipment, knowledge,
experience and competent personnel to perform the
contracted service
• Where wholesale distribution activities are performed, the
contract acceptor is subject to all obligations detailed in
their wholesale distribution licence.
• Should not contract out any services to a third party
without an initial assessment eg. Audit, and prior approval
from the Contract Giver. A written agreement should exist
between the Contract Acceptor and third party in relation
to GDP activities.
• Informs Contract Giver of incidences or complaints,
relating to the Contract Giver’s Product, within agreed
reporting times defined in agreement.
Contract Operations –
Quality Agreement/Technical Agreement - Contents
Typical agreement contents for wholesale storage and distribution
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Country licensing requirements
Customer/client verification
Receipt of Product
Storage of Product
Transportation
Incidents
Returns
Complaints and falsified medicines (relating to product quality and safety)
Recalls
Audits and inspections
Sub-contracting
Contact details
Date of review
Signatures
(This list is not exhaustive and can vary depending on the type of GDP service provided)
Self Inspections
• A self-inspection programme should be implemented to cover
all aspects of GDP on site to ensure compliance with
regulations, guidelines and SOPs
• Should be performed by competent person(s) from the
company. Audits can also be performed by an independent
consultant, however they must be accompanied by a
competent person from the company
• Subcontractors should be part of the self inspection audit
programme. These audits should be tracked on a schedule
and performed on a periodic basis
• Should be documented in an audit report with observations
detailing deficiencies in breach of GDP guidelines. This report
is to be shared with company senior management.
• Corrections of deficiencies should be managed through a
CAPA process.
Transportation(1)
• It is the responsibility of the wholesale distributor to ensure
the transport conditions, through adequate precautionary
measures are maintained so as to protect the product from
any damage, contamination, theft or exposure to adverse
temperature.
• Products should be transported in accordance with the
storage conditions detailed on the secondary packaging
• A risk assessment should be performed when selecting a
method of transportation. This is to ensure the quality of the
product is not adversely affected whilst on transit
• Transportation conditions should be appropriately validated
Transportation(2)
Requirements for transportation:
 Transport within pre-defined limits and in accordance with product storage
conditions
 Deviations should be immediately communicated to the distributor to decide
on the fate of the transported product. Where necessary, the manufacturer
of the product should also be contacted to assess quality of affected product
 Delivery drivers, including contractors should be trained in GDP applicable to
their duties
 SOPs should be in place for the operation and maintenance of vehicles and
equipment used in the distribution process including their cleaning and
safety. Cleaning detergents should be carefully selected to prevent
contamination of medicinal product
 Temperature monitoring systems, in vehicles and/or containers should be
appropriately validated, maintained and calibrated at regular intervals
 Dedicated vehicles and equipment should be used where possible when
handling medicinal products. Where dedicated vehicles or equipment are not
used, SOPs should be in place to detail effective controls to be used.
Transportation(3)
Requirements for transportation:
 Medicinal products should only be delivered to the address on the
delivery note and must be handed into the care of the consignee
 In case of emergency deliveries outside of normal hours, an SOP must
be in place to detail how these deliveries will be made
 If transportation is provided by a third party, then a technical
agreement must be in place to detail GDP activities applicable to
transportation (see slides 51 to 54)
 If transportation hubs are utilised, medicinal products should be stored
for no longer than 24 hours at hub whilst awaiting onward
transportation. If products are stored for greater than 24 hours then
hub would require a wholesale dealer licence. If cold chain products are
stored at hub for any length of time, then storage hub will require a
wholesale dealer licence.
 Intermediate storage facilities where product is unloaded and loaded,
eg. terminals and hubs, need to be audited. In particular, temperature
monitoring, pest control, cleanliness, stock segregation and security.
Containers, Packaging and
Labelling
Ensure the following are used:
 Containers that are free from contamination
 Containers that protect from external contamination
 Containers and packaging should be of the right
dimensions to securely hold product and to provide
some protection from extreme external temperatures.
Packaging and shipment containers to be validated
for extended transit times and temperature extremes
 Container labels should have information on the
contents, supplier and storage and handling
precautions for product.
Transportation of Products
Requiring Special Conditions
• For deliveries or narcotics or psychotropic substances, the
distributor must maintain a safe and secure supply chain
and must adhere to the requirements laid down by the
concerned member state
• Additional controls must be in place for delivery of these
products with procedures on security and handling of
product theft
• Highly active and radioactive products should be
transported in secure containers by dedicated vehicles to
ensure product and handling personnel are safe from harm
• Any safety measures applied must be in accordance with
national and international legislations.
Temperature Control During
Transport
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Temperature-sensitive products must be transported in vehicles that are temperature controlled.
The refrigeration system in the vehicle should be validated and temperature mapped for seasonal
variations to ensure the temperature is maintained within pre-defined limits for full or partial load
throughout the year. A printout of the temperature in the vehicle during transit should be provided
to the recipient of the product.
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Where vehicles are not temperature controlled, products should be packaged in thermal
packaging/temperature controlled containers which should be validated. When validating, extreme
conditions should be taken into consideration to ensure product quality is not affected where there
is a deviation from the ideal delivery conditions
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Temperature loggers should be packaged with product during transportation. The loggers should be
reviewed by product recipient to ensure that the product was transported within the specified
temperature range
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In the event of a temperature excursion (eg.vehicle breakdown) this needs to be documented in a
Deviation Report and investigated to identify root cause and prevention measures. The process of
handling such deviations should be detailed in an SOP
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All temperature monitoring devices must be frequently serviced, callibrated, and challenged
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When packing product with cool packs in container, ensure product does not come in contact with
cool pack as this can damage the product. Staff must be trained against an SOP on how to pack
products with cool-packs, assembly of boxes (seasonal configurations) and on how cool packs can
be re-used.
Specific Provisions for Brokers
(1)
• Brokers:
• Are people who negotiate independently and on behalf of their
customer for the sale or purchase of medicinal product
• Are subject to a competent authority registration and must have
a permanent address and contact details in the union under
which they are registered
• Must notify the competent authority immediately of any changes
in relation to sale or purchase of medicinal product
• Do not procure, supply or hold medicines therefore principles or
directive 2001/83 EC on premises, installations and equipments
do not apply. However principles that apply to wholesale
distribution do apply. In particular maintenance of a QMS that
ensures records are kept; emergency plans for supporting
recalls are in place; and competent authorities are immediately
informed of any suspect falsified medicines offered in the supply
chain.
Specific Provisions for Brokers
(2)
• Quality System:
• Should consist of a number of written procedures which should be reviewed
and kept up to date. The procedure should cover responsibilities, processes
and risk management
• Personnel:
• Anyone involved in Brokering must be trained in the applicable EU and
national legislations, GDP guidelines applicable to brokerage and on the
issues concerning falsified medicinal products.
• Documentation:
• General provisions on documentation would apply (slide 28 to 32)
• Following procedures required as a minimum
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Complaints handling
Informing competent authority and MA holder of suspected falsified medicinal products
Supporting recalls
Ensuring products brokered have a Marketing Authorisation
Verification of suppliers to ensure they hold the appropriate licence and this is checked
periodically
• Records of any transactions of medicinal products brokered should contain
the minimum information
– Date; name of medicinal product; quantity brokered; name and address of the supplier and the
customer; batch number and expiry of the medicinal product.
Thank You
Any Questions?