What do the regulatory authorities say?
If the manufacturer is the distributor for the product as well, can the QP for manufacturing be responsible for distribution as well?
Yes. The Qualified Person (QP) named in the manufacturing license can take responsibility for storage and distribution. In this case, there is no need for the manufacturer to have a separate responsible person for distribution.
Who can be a QP? What education background do they need?
A Pharmacist degree is desirable. However, anyone who has enough in-depth understanding and experience in medicinal products that demonstrate a good knowledge of GDP can be a QP. Some of the areas of expertise is mentioned below:
o Storage conditions/requirements for different types of pharmaceutical product;
o Basic understanding of degradation pathways and stability profiles of pharmaceutical products;
o GDP legislation and relevant guidance;
o Requirements for storage facilities, temperature control and monitoring programmes, including mapping and qualification;
o Quality Management Systems and how to manage these effectively;
o Handling of returns/complaints/recalls;
o Bona Fide checks;
o Risks associated with Falsified Medicines;
o Expectations of a robust Technical (Quality) Agreement with any sub-contractors;
o Controlled Drug legislation and requirements of the relevant Member State(s);
o Trained auditor.
o Experience of picking /packing procedures and FEFO (First Expiry, First Out) principles;
o Handling complaints and customer queries;
o Active involvement in GDP regulatory inspections;
o Audited internally to monitor the Quality Management System (QMS) and preferably also external audits covering the various stages in the distribution process;
o Supplier and Customer approval process;
o Creating/maintaining/auditing the documentation and records involved to ensure compliance with GDP.
What are the responsibilities for a QP?
· They should ensure that a QMS is implemented and maintained
· They should focus on the management of authorised activities and the accuracy and quality of records
· They should ensure that initial and continuous training programmes are implemented and maintained
· They should be responsible for coordinating and promptly performing any recall operations for medicinal products
· They should ensure that relevant customer complaints are dealt with effectively
· They should ensure that suppliers and customers are approved
· They should approve any subcontracted activities which may impact on GDP
· They should ensure that self-inspections are performed at appropriate, regular intervals following a prearranged programme and necessary corrective measures are put in place
· They should keep appropriate records of any delegated duties
· They should decide on the final disposition of returned, rejected, recalled, or falsified products
· They should approve any returns to stock
· They should ensure that any additional requirements imposed on certain products by national law(s) are adhered to
What training should all the personnel involved in the distribution undergo?
The management and the QP should organize continuous training of the personnel based on the updates in the regulations and the industry standard. The QP designs and implements the training program.
What written training program does the regulations require?
Training should have regular competency tests and records should be maintained in at least a simple spreadsheet. The trainings for individual personnel should involve the identification of the area they need training, development of SOPs, implementation of SOPs, evaluation of the outcomes.
Location/premises and equipment
What does physical segregation of different materials mean in a warehouse? Can one use a computerized system for this?
Segregation based on a computerised system is possible for:
· Products pending a decision as to their disposition
· Products that have been removed from saleable stock
· Product suspected of falsification
· Returned products
Physical segregation is mandatory for:
· Medicinal products received from a third country and not intended for EU market
· Falsified medicinal products
· Expired products
· Recalled products
· Rejected products
What are the requirements for computerized segregation system?
Personnel with access to the computer must have unique login and password to allow traceability of their actions. Access to the different modules in the system must be based on their role. Only the QP or a designated person can change the status of materials in the system. The IT policies should comply with EU GMP regulations and GDPR.
What are the requirements for physical segregation?
The rooms must be clearly marked, and the access should be restricted to authorized personnel only. Storage for controlled substances must be segregated and secured in accordance with local laws.
What should one consider before designing the receiving and dispatching bays?
Protection from weather conditions should be taken into account where a canopy, vehicle tunnels and appropriate doors should be present. The floors should have clear markings for reception and dispatching areas.
What cleaning procedures are required for the premises and storage facilities?
Cleaning SOPs should be performed regularly and should cover all areas (floors, racks, walls etc.). Frequency of cleaning should be based on risk assessment.
Specific cleaning procedures should be present in case of spillages.
Cleaning equipment should be clean and dry and should be replaced periodically. Disinfectants and cleaning agents should be specified in the SOPs and no other agents are allowed. Cleaning agents should not damage the products by chemical reaction or leave any odour. All cleaning activities should be logged. Effectiveness of cleaning should be assessed by a self-inspection program with periodic checks for fungal/mould growth (especially in cold storage areas).
What preventative pest control programme is recommended?
Procedure should include
· Site plan
· Location of different pest control measures (e.g., bait boxes, ultraviolet insect killers)
· Frequency of inspections
· Review of reports
It should be based on risk assessment of the facility. It can be outsourced to licensed pest control experts in which case, a clear contract should be in place to cover that work.
Can the personnel in the storage area take personal medications?
Usually, no. Leave medications in the changing lockers. Exceptions are made for asthmatics and diabetics. However, this should also be risk based.
Where to put the temperature monitoring systems?
Air flow simulations should be performed, and the temperature monitoring sensors should especially be put in the worst-case positions along with the most suitable locations.
What are the key equipment that needs regular maintenance?
All equipment that may impact the product quality needs regular maintenance (HVAC, alarms, thermometers, barcode sensors, printers etc.)
How to validate computerized systems?
It should be based on risk assessment. Key points to keep in mind are:
· URS (User Requirement Specification) to document what is expected from the system,
· DQ (Design Qualification),
· IQ (Installation Qualification),
· OQ (Operational Qualification),
· PQ (Performance Qualification
Access rights should be defined and controlled. Backups of IT systems should be regularly performed.
Who authors the documents and who approves them?
Instructions (SOPs) should be written by experts and then reviewed and approved by the management, QA and QP. The forms should be filled out by the facility personnel who are responsible for each step (in the computer of course to prevent unofficial records such as notebooks or pieces of paper). All the documents are reviewed by the QA and/or QP and then signed before release of the product.
How to handle personal data?
Refer to GDPR regulations.
Which language to use for documentation?
A language which is understood by everyone involved in the process.
How long should the documents be kept for?
At least 5 years according to EMA. However, some local regulatory authorities may require up to 7 years.
Are paper copies of documents allowed?
In the absence of electronic systems, yes. One may also print out SOPs and/or instructions to make sure errors are not made. It is also necessary to ensure that the staff keep the latest versions of the printed documents. Preferably, printed copies should have a date stamp and can be valid just for a specific period (e.g., one day or one week). All the older copied are to be destroyed so as to prevent confusion.
However, if anything is documented on the printed paper (e.g., deviations), they should immediately be recorded in the electronic systems.
What needs to be considered if importing medicinal products from outside the EU?
The importer should have a Manufacturing Importation Authorisation (MIA) obtained from the local authorities. This license does not follow GDP, but the importer should have a QP to make sure they comply with the appropriate GMP regulations.
How to check if a supplier has the proper legal authorization/license? Use EnduraGMDP database for suppliers in the EU. It keeps track of the audits and notes from the failed inspections. In addition to the database, the supplier should also provide a copy of their authorization. Records of the intermediate actors (brokers) are maintained by the national authorities and not all EU member states publish a list.
Why does a distributor need to qualify customers?
This is done by authorised companies and wholesalers to maintain a reliable chain of custody until it reaches the patient and reduce the risk of products being misdirected and/or misused.
What other environmental factors must be considered besides temperature?
Light: Usually, the packaging protects the pharma product from light. However, strong light exposure might bleach the labels.
Moisture: Products exposed to high humidity can be susceptible to hydrolytic degradation. High humidity may also lead to a build-up of mould.
Vibration: This could lead to segregation of powders in suspension or breaking of glass vials/bottles.
Others: Strong odours from spilled chemicals could lead to damage in the packaging rendering them unsuitable for use in patients.
What is FIFO and FEFO?
FIFO = “first in, first out”; it means that products stored first are to be retrieved first.
FEFO = “first expiry, first out”; this is to ensure that product with shortest expiry date is placed into the market first. It also helps to ensure that products reaching end users have sufficient remaining shelf life.
Can a product be stored directly on the floor?
No. They are more susceptible to damage, contamination by spillages, water, dirt and/or pests.
Why is documentation needed for the destruction of obsolete drugs?
To ensure that these products never enter the supply chain or become diverted.
Where would be a good way to start to learn about GDP for medicinal products?
There is a “European GDP association” that has a lot of documentation on guidelines from EU and WHO
Where could one get some detailed information about the above-mentioned points that works in most jurisdictions?
The WHO website has a document that is a much easier read than the EU guidelines and here is a link to it. One can start with this and then move on to the more nitty-gritty specifics in the EU guidelines or US FDA guidelines.