In this article we want to discuss the responsibilities and authority of the Responsible Person and the designated person as defined in the European Guidance Documents for Good Distribution Practices. We want to bring forward first that there actually are two EU GDP guidelines, one for finished Medicinal Product and one for Active Pharmaceutical Ingredients (API’s). The guidance for Good Distribution Practices for Medicinal Products for human use (2013/C 343/01) was issued in 2013 and the guidance document for Good Distribution Practices for Active Substances for Medicinal Products for human use (2015/C 95/01) was issued two years later in 2015. There is some overlap between both guidelines, but there are also marked differences. In this article we will first discuss the role and responsibilities of the Responsible Person as defined in the GDP guide for Medicinal Product and then indicate the differences compared to the role and responsibilities of the Designated Person as defined in the GDP guide for Active Pharmaceutical Substances.

Responsible Person- GDP for Medicinal Products
As per EU-guidelines on Good Distribution Practices (GDP) of Medicinal Products for Human Use the company responsible for distribution of a medicinal product shall either have a Manufacturing and Importation Authorisation license (MIA), or a Wholesale and Distribution Authorisation license (WDA). Companies in possession of a MIA are not only authorized to manufacture and/ or import medicinal products, but they are also entitled to distribute the manufactured or imported products throughout the European Union. Companies in possession of a WDA license are authorized to purchase and distribute medicinal products in the EU, but they are not authorized to manufacture and/ or import medicinal products into the EU. Any alteration to the original product (e.g. re-labelling) could be considered a manufacturing action and hence companies involved in making such alterations might be required to have a manufacturing (MIA) license.

All manufacturing activities of medicinal product in the European Union shall be performed under full application of GMP, whereas wholesale and distribution of medicinal products in the EU shall be performed under full application of GDP guidance. GDP can be applied by either type of licensed company; it does not matter whether they are in possession of a MIA or a WDA. 

As stated; manufacturing and Importation require a quality system based on GMP guidance and with that the presence of a Qualified Person (QP). The GMP guidance includes storage and warehouse functions and therefore has overlap with some parts of the GDP guidance, but it does not fully overlap. Distribution is not covered under GMP. GDP does not only include all storage and warehouse functions, but also distribution functionality and requires a GDP based quality system and the presence of a Responsible Person (RP). A Qualified Person of a MIA holder can function as RP for the warehouse function and distribution as far as this is arranged in appropriate job descriptions by the MIA holder to which the QP is employed. Often there are separate QPs and RPs present within a company and the quality system is split in a GMP and a GDP part.

WDA license holders do not have QPs. They operate a GDP quality system under responsibility of a Responsible Person (RP). The GDP quality system shall focus on the activities authorized under the WDA license and it shall express a clear focus on accuracy and quality of records of operation. The RP shall have a defined reporting line with the registered WDA license holder. The roles and responsibilities, as well as the authority of the RP shall be covered in a suitable job description, and in organisation charts.

RP responsibilities
The RP is personally responsible for the implementation and maintenance of a GDP Quality System suitable for the company. The RP is responsible for the quality system and with that also additional responsibilities are defined in the EU GDP guidance, amongst others:

• The RP shall ensure there is a training program implemented for all personnel working under the GDP system.
• The RP shall ensure both suppliers and customers (to whom medicinal products are supplied) are regularly evaluated and approved by a suitable qualification program.
• The RP is authorized to decide on the final disposition of returned, recalled, reject or falsified products.
• The RP is authorized to decide that returned products can be included in saleable stock again, after a suitable documented evaluation.
• The RP shall perform recall operations and shall ensure the recall process is functioning well in case its use is needed.
• The RP shall ensure that complaints reported at the WDA holder are handled appropriately and reported to the involved MIA holder as soon as possible. The RP shall function as first point of contact for the complainant.

It needs to be recognized that not all responsibilities that can be assigned to the RP are fully listed in the EU-GDP guidance. In addition to the above listed responsibilities the RP should also be held responsible to:

• Ensure that all provisions of the WDA license are observed.
• Ensure that full and prompt cooperation with product license holders (MIA) is established.
• Ensure that the correct procedures were followed before a batch of medicinal product is distributed to pharmacies and other legal entities authorized to supply medicinal product to the public. This implies that the RP is deemed responsible to decide on the disposition of each to be distributed (sub-) batch of product.

For such action a recorded release statement may function as a traceable and formal confirmation of such decision. Note that the GDP guidance does not mandate the need for release statements, but we would like to encourage the use of such statements strongly.

• Understand the requirements of the products under license and ensure that the operations covered under the WDA will never compromise the quality of the medicinal products.

To fulfill all responsibilities and authorities the RP shall have a suitable level of education and in addition to that shall undergo a specific training program for becoming eligible to be registered as RP.

The RP shall have access to all areas, sites, stores and records which relate to the licensed activities and at regular intervals perform monitoring and evaluation on these items. The RP for medicinal product wholesale and distribution shall be appointed by senior management and shall be registered by the competent authorities. The competent authority shall, as part of the registration process, perform an evaluation of the education, competence, experience and knowledge of GDP. Once registered the RP shall ensure that the GDP knowledge shall be maintained by follow-up courses and training.

The GDP guidance is applicable as of release of medicinal product from the warehouse of the MIA holder up to the point where the product is handed over to a registered pharmacy or other legal entity authorised to supply medicinal product to the public. Note that the last part of the distribution chain -from pharmacy to patient- is not covered in the GDP guidance, these are activities covered in guidance and normative documents for the pharmacy sector. Of course the storage and distribution in the last section of the distribution chain shall meet requirements as defined by product specifications and where possible shall include the principles of GDP.

GDP for drug substances
Next to the EU GDP guidance for medicinal product there is a separate EU GDP guidance for Active Pharmaceutical Ingredients (EU 2015/C 95/01). Where the GDP guidance for Medicinal Products excludes the importation of medicinal products into the EU/EEA the GDP for APl’s explicitly includes importation of active ingredients. For medicinal Products this is an activity that is covered under MIA license and hence has to follow GMP, for Active Substances the importation can take place under the WDA license. The GDP guidance for API’s does not define the role and responsibilities of the RP as it is done in the GDP guidance for medicinal products. Instead the GDP for APIs defines that at each location of the WDA holder there shall be an appointed Designated Person responsible for the management and maintenance of the quality system, but this person is not registered as RP. The role, responsibilities and authority of the designated person shall be well documented and included in the Quality System. The designated person shall be responsible for the quality system and for oversight on correct execution of processes and instructions. It is therefore logical to assign a Quality Assurance function to this person. The responsibilities of the designated person at an Active Pharmaceutical Ingredient wholesale dealer should be highly equal to those listed for the responsible person for Medicinal Products, especially regarding all matters related to the Quality System. 

It needs to be noted though that for the quality representative under the GDP for APIs no authority or responsibility has been defined for taking decisions on batches of Active Pharmaceutical Product. In the GDP for API’s it is only defined that well trained and authorised personnel should release Active Substances for return to stock. Despite this it would be recommendable to have the authorisation to release batches to saleable stock limited to the responsibilities of the Designated Person and have this covered in the function description and the training of the involved individual.

Progress
As discussed in the article above there are still some areas in the different EU-GDP guidance documents that may require interpretation of the involved company and where necessary close cooperation with the involved regulatory authorities. It also requires the involved company to design and implement a strong quality management system to withstand any inspection or audit of such system. Progress can help you in all aspects of GDP for both Active Pharmaceutical Ingredients and for Medicinal Products. Progress consultants have been trained and registered as Responsible Person and Qualified Person for several companies and have acted as designated person. We can help you to set up a suitable Quality Management System including a risk-based material and supplier qualification program and also perform any assessments and audits as part of this program.