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Good Distribution Practices (GDP) - FAQs
1. General Questions & Answers on Good Distribution Practices (GDP)
2. Questions & Answers about the Scope of the GDP Guideline
3. Questions & Answers on Chapter 1 QUALITY MANAGEMENT of the EU Good Distribution Practice Guideline
4. Questions & Answers on Chapter 2 of the EU Good Distribution Practice Guide
5. New: Questions & Answers on Chapter 3 of the EU Good Distribution Practice Guide (Premises and Equipment)
Is it necessary for a manufacturer of medicinal products to comply with the Good Distribution Practices (GDP) or is this the task of the wholesalers and distribution companies?
>> GDP requirements are very similar to the requirements stated in the GMP for manufacturers in relation to storage of medicinal products. Manufacturers must comply with the product storage requirements as stated in the GMP.
Iin addition, if they are responsible for the distribution of their products, they
also need to follow the GDP requirements; these include storage and transportation of their products in line with the product label, ensuring its safety and security throughout the supply chain.
According to Chapter 2, paragraph 2.2. each wholesaler needs to designate a person as Responsible Person for GDP. Are there any circumstances in which the manufacturer of the medicinal product needs to designate a Responsible Person?
>> The EU Manufacturing authorization includes the wholesaler’s license, therefore a manufacturer can legally distribute its products, the QP named in the Manufacturing License
can take the responsibility for storage and distribution of the product.
As a consequence, there is no need for the manufacturer to name an RP. However, depending on the organization structure and
the complexity of the operation, the company may appoint a person responsible for product distribution.
Each Wholesaler needs an authorization issued by the competent authority of the Member State where the wholesaler is located. Are there any authorizations needed for a warehouse/storage facility?
>> Yes, if a product is stored in a storage facility this facility should be included in either the manufacturers' (Manufacturing License) or
the wholesaler’s license. In the EU, you cannot store products in an unlicensed facility (except at the distribution hub for short durations, e.g. 24 hrs)
Each manufacturer of a medicinal product needs to control and supervise the supply chain (wholesaler, transport and distribution companies etc) of the finished products. Is this
in the responsibility of the Qualified Person of the manufacturer of the medicinal product?
>> The Owner of the product in the supply chain is responsible for its management in the supply chain, if the manufacturer owns the product in the supply chain, then their QP is normally responsible for the product in the supply chain. Of course this responsibility can be delegated to another QP or an RP, but the ultimate responsibility will remain
in the hands of the product QP.
I've heard about a requirement that medicinal products should not be stored for more than 24 hours because in that case the facility would need to have a licence. What is the reference for this requirement?
>> Chapter 9 of EU GDP (Last Paragraph) states ‘ Provision should be made to minimize the duration of temporary storage while awaiting the next stage of the transportation route’ this duration should be specified in companies SOPs based on risk assessment. The current industry practice is 24-72 hours storage at temporary facilities. Longer storage periods are classed as long term storage of product and the facility must have a licence to operate.
As a manufacturer of finished medicinal products, do I need to audit all transport organisations, all warehouses and all wholesalers who will handle my products? What about transportation hubs e.g. at airports. There might be hundreds of such facilities.
>> The Current EU GDP requires manufacturers to have audited and approved all their outsourced activities and have a technical/quality agreement with their service providers. The approach to selection and approval of these facilities should be supported by risk assessment, companies can use shared audits or ‘paper audit’ depending on the complexity of operations and sensitivity of the products involved.
1) Does the EU GDP Guide cover both Human Medicinal Products and Veterinary Medicinal Products?
The full text of the EU GDP Guide provides the answer: Guidelines of 5 November 2013 on Good Distribution Practice of medicinal products for human use (2013/C 343/01). This means Veterinary Products are not covered but it might be useful to adopt GDP principles based on a risk assessment on a voluntary basis.
2) Does the EU GDP Guide cover Investigational Medicinal Products (IMPs) and Radiopharmaceuticals?
The GDP Guidelines focus on wholesale distribution of medicinal products. And IMPs are normally not distributed via wholesalers. However IMPs are not particularly excluded. The Guideline may therefore give some guidance on how to supply clinical trail material. More detailed guidance might be given by the Questions and Answers section of the European Medicines Agency. In the part on supplementary requirements, Annex 13 a few Q&As are dealing with storage and transportation of IMPs.
Radiopharmaceuticals are Medicinal Products and therefore within the scope of the EU GDP Guideline. The GDP Guideline contains a reference to them: “Medicinal products comprising highly active and radioactive materials should be transported in safe, dedicated and secure containers and vehicles.”
3) Are there any GDP requirements for APIs and Excipients in place?
Good Distribution Practice of Active Pharmaceutical Ingredients (APIs) is covered in a separate Guideline. The requirements can be found in: Guidelines of 19 March 2015 on principles of Good Distribution Practice of active substances for medicinal products for human use. These requirements are legally binding in Europe. For Excipients there is no such regulation in Europe. However, an industry standard exists and should be applied on a risk based approach: IPEC Good Distribution Practices Guide for Pharmaceutical Excipients.
4) Is Transportation covered by the EU GDP Guide and can Transport companies receive a GDP Certificate?
This question has been addressed by the EU Commission in a Q&A paper: “Transport companies do not need to hold a wholesale distribution authorisation to transport medicinal products. However, they should follow the parts of the GDP guideline relevant to their activities, amongst others Chapter 9.” Therefore Transport companies need to follow GDP but will not receive a GDP certificate. GDP should be assessed by the customers who ship medicinal products with certain transport companies.
5) Who does issue a GDP Certificate?
The so called competent authorities in Europe have to issue the GDP certificate. Please find here a list of the competent authorities. The details (including the exact procedure and documentation) of the GDP Inspection and Certification is defined in the EMA/EU Commission: Compilation of Community Procedures on Inspections and Exchange of Information.
According to the document: “The contents of the initial inspection report should be sent to the company for its comments to enable the report to be finalised within the relevant timeframe of the inspection request and to enable, if applicable, the issue of a GDP certificate within the statutory 90-day timeframe…… The GDP certificate or the non-compliance statement shall be entered in the Union database referred to in Article 111(6) of Directive 2001/83/EC……The intervals between inspections should be set at a level that provides confidence that the wholesale distributor maintains continued compliance with GDP and its principles. The maximum period between inspections per site should not exceed 5 years as lack of continuity may give rise to lower awareness of current GDP or allow significant deficiencies to develop”.
6) Are Transport Hubs covered by EU GDP?
Hubs are sometimes needed to store goods for a short time period, e.g. in order to collect goods for further shipment. Hubs can be found at airports and usually store products between 24 and 72 hours. They are not intended to store products for a longer time. Chapter 9 of EU GDP (Last Paragraph) states: Provision should be made to minimize the duration of temporary storage while awaiting the next stage of the transportation route.
This duration should be specified in companies' SOPs based on risk assessment. The current industry practice is 24-72 hours storage at temporary facilities. Longer storage periods are classed as long term storage of product and the facility must have a licence to operate. This means that Hubs will not have a GDP certificate but will need to comply with EU GDP based on a risk assessment.
1) Chapter 1 requires a Quality System. Is a Quality System according to ISO 9001 and the certification appropriate to comply with the requirements?
ISO 9001, is a generic quality management system providing a good framework for any organisation. However, the EU GDP expectations are not clearly detailed in this standard. It is therefore recommended that companies using the ISO framework incorporate the specific GDP requirements to ensure a compliant and workable QMS is available for the company. It is worth noting that the EU GMP and GDP both have been designed around the structure of the ISO9001. In simple terms ISO 9001, certification is not sufficient to meet the GDP licencing requirements. It is important that a Quality System is designed to identify and supervise all distribution activities of the medicinal product. The Quality System should be designed to assure the quality of the medicinal products at all levels of the supply chain.
2) What are the key requirements for a Quality System which is demanded by the EU GDP Guide?
Some key aspects are mentioned in section 1.2:
(i) medicinal products are procured, held, supplied or exported in a way that is compliant with the requirements of GDP;
(ii) management responsibilities are clearly specified;
(iii) products are delivered to the right recipients within a satisfactory time period;
(iv) records are made contemporaneously;
(v) deviations from established procedures are documented and investigated;
(vi) appropriate corrective and preventive actions (commonly known as ‘CAPA’) are taken to correct deviations and prevent them in line with the principles of quality risk management.
Also the control of outsourced activities, and Quality Risk Management should be an essential part of the Quality System. In general, the Quality System should have written procedures e.g. in the Quality Manual and in SOPs about how each requirement in the 10 Chapters of the EU GDP Guide will be implemented in the company.
3) In the Supply Chain many logistic activities are outsourced to service providers e.g. transport and storage. Is it possible to agree a contract with the service providers so that they will be solely responsible also for the quality system and the quality of the medicinal product?
No, the responsibility for the compliance with the GDP requirements as well as for the quality of the medicinal product will always remain with company who wants to outsource certain services to a service provider (i.e. the WDA holder). Moreover, the company and its Responsible Person is also responsible for all services which might be outsourced by the service provider. This will help ensure that subcontracting will not cause additional risks to the products. It is recommended in these situations to have a quality agreement in place that defines duties and responsibilities between outsourced service providers and WDA holders. Both must have implemented a quality system that complies with GDP requirements. In principle the same requirements will apply for outsourced activities as for internal processes. This is why outsourced services should be covered in an internal audit programme as described in Chapter 8 (Self-Inspection). Chapter 7 deals only with outsourced activities and what is needed in detail to comply with the GDP Guide. A key component of the Quality System is detailed contracts with every company who takes over the defined activities. These contracts and the compliance with the contracts should be monitored as part of the Quality System of the Contract Giver.
4) According to Chapter 1.5 a Quality Risk Management should be in place. What is required also with regard to the necessary documentation?
Quality Risk Management is a fundamental part basis of a GDP-compliant Quality System. Application of risk management techniques will identify potential high risk areas in the business allowing the management to take appropriate preventive action to protect the business as well as the customers of the company. It also helps reduce wasting resources on low risk areas. Chapter 5 contains a reference to ICH Q9, a Guideline dealing with Quality Risk Management for Medicinal Products. It is recommended using this Guideline when developing and implementing a Quality System. The EU GDP provides several examples where a risk management tools can be applied: For example:
- 3.2.2. Temperature and environment control: The mapping exercise should be repeated according to the results of a risk assessment exercise or whenever significant modifications are made to the facility or the temperature controlling equipment.
- 3.3. Equipment: Equipment used to control or to monitor the environment where the medicinal products are stored should be calibrated at defined intervals based on a risk and reliability assessment
- 3.3.2. Qualification and validation: The scope and extent of such qualification and/or validation activities (such as storage, pick and pack processes) should be determined using a documented risk assessment approach.
- 5.1. Operation – Principles: The wholesale distributor should use all means available to minimise the risk of falsified medicinal products entering the legal supply chain.
- 6.3. Returned medicinal products: Returned products must be handled according to a written, risk- based process taking into account the product concerned, any specific storage requirements and the time elapsed since the medicinal product was originally dispatched.
- 9.2. Transportation: Risk assessment of delivery routes should be used to determine where temperature controls are required.
The answers are made by using the PQG/ECA Interpretation Guide on GDP
1) According to Chapter 2, paragraph 2.2. each wholesaler needs to designate a person as Responsible Person for GDP. Are there any circumstances in which the manufacturer of the medicinal product needs to designate a Responsible Person?
The EU Manufacturing authorization includes the wholesaler’s license, therefore a manufacturer can legally distribute its products, the QP named in the Manufacturing License can take the responsibility for storage and distribution of the product. As a consequence, there is no need for the manufacturer to name an RP. However, depending on the organization structure and the complexity of the operation, the company may appoint a person responsible for product distribution.
2) Chapter 2, paragraph 2.2 requires that the responsible person should have appropriate competence and experience as well as knowledge of and training in GDP. A degree in pharmacy is desirable. If a RP is not a pharmacist what qualification may be accepted by authorities?
The appointment of a RP must be carefully considered to ensure to the correct person is put in place. This appointment is dependent on the size of the organisation, the complexity of the services to be provided and the product classes to be supplied. The nominated responsible person should be able to show an in-depth understanding of medicinal products and must be able to demonstrate knowledge of GDP, and how it is imbedded within the systems and processes implemented within the wholesale distributor. Some key areas of knowledge and experience are listed below:
- Storage conditions/requirements for different types of pharmaceutical product;
- Basic understanding of degradation pathways and stability profiles of pharmaceutical products;
- GDP legislation and relevant guidance;
- Requirements for storage facilities, temperature control and monitoring programmes, including mapping and qualification;
- Quality Management Systems and how to manage these effectively;
- Handling of returns/complaints/recalls;
- Bona Fide checks;
- Risks associated with Falsified Medicines;
- Expectations of a robust Technical (Quality) Agreement with any sub-contractors;
- Controlled Drug legislation and requirements of the relevant Member State(s);
- Trained auditor.
- Experience of picking /packing procedures and FEFO (First Expiry, First Out) principles;
- Handling complaints and customer queries;
- Active involvement in GDP regulatory inspections;
- Audited internally to monitor the Quality Management System (QMS) and preferably also external audits covering the various stages in the distribution process;
- Supplier and Customer approval process;
- Creating/maintaining/auditing the documentation and records involved to ensure compliance with GDP.
3) What are the key elements which should be covered a job description for Responsible Person?
The following objectives and responsibilities should be covered in the job description:
An example of a job description can be found in the Code of Practice for RPs which has been published by the GDP Association. You can download the document in the Members Area (if you are not a member yet you can apply for free membership here.
- The RP should ensure that a QMS is implemented and maintained;
- He/she should focus on the management of authorised activities and the accuracy and quality of records;
- The RP should ensure that initial and continuous training programmes are implemented and maintained;
- He/she should be responsible for coordinating and promptly performing any recall operations for medicinal products;
- The RP should ensure that relevant customer complaints are dealt with effectively;
- The RP should ensure that suppliers and customers are approved;
- The RP should approve any subcontracted activities which may impact on GDP;
- The RP should ensure that self-inspections are performed at appropriate, regular intervals following a prearranged programme and necessary corrective measures are put in place;
- He/she should keep appropriate records of any delegated duties;
- The RP should decide on the final disposition of returned, rejected, recalled or falsified products;
- He/she should approve any returns to stock;
- The RP should ensure that any additional requirements imposed on certain products by national law are adhered to.
4) Chapter 2, paragraph 2.4 requires that all personnel involved in wholesale distribution activities should be trained on the requirements of GDP. They should have the appropriate competence and experience prior to commencing their tasks. How can this be achieved in practice?
It is the responsibility of senior management in conjunction with the RP to ensure that the initial and continuous training of personnel is implemented. The RP should have direct input into the design and implementation of a GDP induction programme for all personnel. This should be based on the job description and the level of detail should reflect the position of responsibility within the QMS and organisation as a whole.
The induction training should be captured in a procedure and clearly outline the minimum requirements and tasks which may consequently be performed. It should also include details of the approval process.
Subsequent training in GDP should be planned and cover greater detail. This must be captured in the overall training programme for the organisation. Mechanisms must be in place to ensure that persons not yet trained in GDP are not allowed or asked to complete any relevant tasks. This relies on good management oversight of the training programme and matrix for their direct reports. It also relies on personal integrity of individuals to resist the temptation to complete tasks for which they have not been inducted or trained and the training programme should emphasise this.
5) Chapter 2 requires a written training programme. What does this mean in practice?
The overall training programme is often captured in a training matrix. This method is effective and can be tailored to roles and departments. Training frequency and results of competency tests can also be captured along with prompts for retraining. A simple Excel spreadsheet can be effective providing it is regularly maintained and reviewed. Training should be clearly split into stages tied with activities that may or may not be consequently performed by the individual.
Training processes can be split into 4 stages:
1. Training needs identification
2. Training guides developed (SOPs)
3. Training implementation
4. Training outcomes evaluation
More details about the 4 stages can be found in the PQG/ECA Interpretation Guide on GDP. You can download the document in the Members Area (if you are not a member yet you can apply for free membership here.
1a) Segregation of different materials: Which products can be stored in the warehouse with segregation based on a computerised system? And which products do need physical segregation?
Segregation based on a computerised system is possible for:
Physical segregation is mandatory for:
- Products pending a decision as to their disposition
- Products that have been removed from saleable stock
- Product suspected of falsification
- Returned products
Some regulatory authorities in the EU Member States might have differing perspectives on this point, so it is important to understand specific national requirements.
- Medicinal products received from a third country and not intended for EU market
- Falsified medicinal products
- Expired products
- Recalled products
- Rejected products
1b) What are the pre-requisites for segregation based on a computerised system?
Computerised (electronic) segregation is accepted where validated to provide appropriate security. Personnel with access to electronic systems must have unique user identifications and passwords to allow clear traceability of actions taken. Staff access within electronic systems should be tied to the functionality that they require to perform their job. The ability to change material status should be limited to the Responsible Person or a designate. An IT policy should be in place for the management of system access and passwords in line with EU GMP Annex 11, Section 12.
1c) What are the pre-requisites for the area for physical segregation?
A dedicated and clearly identified area is needed. Access to these areas must be managed with restriction to authorised personnel only. An appropriate degree of security should be applied in these areas to ensure that products remain separate from saleable stock.
Storage areas for controlled substances must be segregated and physically secure in accordance with national legislation.
2) How can receiving and dispatch bays be designed to protect products from prevailing weather conditions?
Protection from adverse environmental conditions can be achieved via a combination of an external canopy, vehicle tunnels, appropriate doors and procedures during receipt and dispatch.
The facility should be designed and operated with logical product flow reflected by clear signage and floor markings in place to identify separate inbound/outbound areas. It should be ensured that adequate space and lighting is available for all activities.
3) For premises and storage facilities, adequate cleaning programmes should be in place. How can this be realised?
The cleaning regime should be systematic, covering all areas, including racking, on an appropriate frequency to maintain cleanliness. The respective process should be defined in writing based on a risk assessment evaluating all relevant factors and conditions. Checklists may be useful.
Cleaning procedures should also cover the handling of spillages.
Cleaning equipment should be kept clean and dry and periodically replaced. Cleaning agents need careful selection to ensure that products are not damaged by chemical reaction or tainted by odour.
Disinfectants and cleaning agents should be specified in procedures and no other agents allowed to be used.
All cleaning activities should be recorded (log file).
The effectiveness of cleaning should be assessed as part of the self-inspection programme. Periodic checks for fungal/mould growth should be made, especially in cold stores.
4) What is an adequate preventive pest control programme?
The pest control procedure should include:
Pest control agents should be selected to avoid the risk of contaminating products.
Many companies use licensed pest-control experts or a pest control service. A contract should be in place to cover such work.
- Site plan
- Location of different pest control measures (e.g. bait boxes, ultraviolet insect killers)
- Frequency of inspections
- Review of reports
5) Can I take personal medication into the storage area?
Requirements for personal medication should be risk based. Generally, medication should be kept in lockers and not taken into storage and distribution areas. However exceptions may be appropriate, e.g. allowing asthmatics to carry reliever inhalers with them.
6) Where should we put temperature monitoring equipment?
Warehouse temperature monitoring should be based on a mapping exercise which has identified the worst case positions.
Ideally, the first mapping exercise should be carried out before a storage area is used (this may not always be possible, e.g. in the case of an existing warehouse already in use). Once the initial mapping has been completed, the data should be assessed and used to determine where the most suitable locations for monitoring devises are. These are typically locations seen to have experienced the largest temperature fluctuations. A second exercise should be carried out once the facility has been approved and product is in place. Repeat exercises should then be carried out based upon the results of a risk assessment considering also seasonal whether variations.
7) What is “key equipment” which needs planned maintenance and qualification activities?
This is basically all equipment that may have an impact on product quality. Examples of this equipment are: HVAC systems, alarms, measuring equipment etc. For those facilities performing labelling operations these are also: printers, bar code scanners, etc.
8) What is needed for a sound validation of computerised systems?
All computerised systems with a potential to impact product quality within the facility should be identified by risk assessment.
Steps in the validation process include:
Controls and access rights should be defined and implemented. All changes should be subject to a formal change control process.
- URS (User Requirement Specification) to document what is expected from the system,
- DQ (Design Qualification),
- IQ (Installation Qualification),
- OQ (Operational Qualification),
- PQ (Performance Qualification).
A Business Continuity Management Plan should exist to cover the event of IT system failure. Regular backups of IT systems should be performed.