ECA/PQG GUIDELINE FOR THE INTERPRETATION OF GOOD DISTRIBUTION PRAC TICES (GDP)

In March 2013 the EU Commission published the revised EU Good Distribution Practice (GDP) Guideline. Among other things, some ambiguous translations made it necessary to issue corrections in December of the same year. Moreover, the translation - as e.g. into German - also caused some discussions.

The updated version corrected errors in wording that had been identified in the guideline's chapters 5.5 and 6.3. It also provides more explanations about the reasons for the revision and the date of entry into force. Nevertheless, the GDP Guidelines published in March 2013 has been completely replaced.

In chapter 5.5 it now states in the English version: "Medicinal products that are nearing their expiry date/shelf life should be withdrawn immediately from saleable stock either physically or through other equivalent electronic segregation." The previous text also included medicinal products that already passed the expiry date.

The changes in 6.3 were necessary because they might have led to misunderstandings. The revised text requires that "medicinal products returned from a customer (…) should only be returned to saleable stock if they are returned within an acceptable time limit, for example 10 days". The old text required that they "should always be returned to saleable stock if they are returned within an acceptable time limit...".
Still, despite these clarifications there are many unclear details in the new EU GDP Guideline. There are interpretations possible, and there is also potential for misunderstandings. Compared to the draft from 2011 the structure of the final GDP Guide is substantially different. The structuring now resembles that EU GMP Guideline - with the chapters:

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• Chapter 1 - Quality Management
• Chapter 2 - Personnel
• Chapter 3 - Premises and Equipment
• Chapter 4 - Documentation
• Chapter 5 - Operations
• Chapter 6 - Complaints, Returns, Suspected Falsified Medicinal Products and Medicinal Product Recalls
• Chapter 7 - Outsourced Activities
• Chapter 8 - Self-Inspections
• Chapter 9 - Transportation
• Chapter 10 - Specific Provisions for Brokers

For the interpretation of the EU GDP Guideline, two interest groups have joined forces. The GDP Working Group of the ECA Foundation and the UK-based Pharmaceutical Quality Group (PQC) will jointly develop a Guideline for the implementation of EU GDP guidelines into practice. The working group under the direction of ECA Board Member Dr Afshin Hosseiny (Qualified Person and formerly with GSK) develops an interpretation of the requirements for each of the 10 chapters.

Already in November 2013 the first results were published - at this point texts for Chapter 1 "Quality Management" and Chapter 9 "Transport". In May 2014 Chapter 7 "Outsourced Activities" followed. The document not only contains the interpretation of the requirements defined in the GDP Guide, but also a template for a Quality Agreement which can be used for contracts with external GDP service providers. On September 1, 2014, the interpretation of Chapter 2 "Personnel" has been published.

Following some of the contents from these chapters are summarised.

Chapter 1 "Quality Management"

1.3 Management of outsourced activities

The quality assurance system should also be extended to the control and review of any outsourced activities for the purpose of procuring, storing, supplying or exporting medicinal products. The respective procedures should include the quality risk management and include:

i. Assessment of the aptitude and competence of the contractor to carry out the work and, where appropriate revise its licensing status;

ii. Definition of responsibilities and communication processes for the activities related to the quality assurance of the involved parties;

iii. Monitoring and reviewing the performance of the contractor and periodic determination and implementation of any necessary improvements.

What is the rationale for the point in the guidance?

When an activity is outsourced it remains the responsibility of the contract giver to ensure it is carried out correctly, but it is outside of their direct operational control. Management of outsourced activities is therefore necessary to provide assurance that these activities will be conducted as required and should therefore be part of the quality system. It is essential that the contract acceptor is both technically competent and legally able to undertake the required activities. To avoid any misunderstanding or uncertainty regarding requirements and responsibilities, there needs to be a written agreement between the parties and on-going communication processes. The contract giver needs to exercise appropriate oversight to ensure the ongoing suitability of the contractor's performance and act to address matters if this is not the case.

What are the risks and benefits associated with that piece of the guidance?

The risks to the contract giver are that the contract acceptor is not technically or legally able to undertake the activities required of them and that these are therefore not carried out appropriately. This could ultimately create a risk for patients at the end of the supply chain. The contract acceptor is also at risk if arrangements between the two parties are not clear. Through an initial and ongoing process of contractor assessment, coupled with clear written contracts and on-going communication, these risks can be substantially mitigated for both parties. The identification of any issues and the timely implementation of improvements is of benefit to both parties.

How might this be implemented/ what does it mean?

The company QMS should include a procedure describing the selection, assessment and appointment of potential service providers. The procedure should define the details of contract, ensuring that the quality and technical aspects of the contracted task (outsourced task) is clearly defined. The roles and responsibilities of each party should also be defined in the contract. The contract should be reviewed periodically to ensure it remains up to date. The contract should also include details of communication processes, including 'out of hours' contacts, and notification of quality issues. An agreed set of metrics (Key Performance Indicators) for monitoring performance can be beneficial to both parties, ensuring compliance and aiding improvement. There should also be regular communication between the parties, with frequency dependent on the volume and criticality of operations. The aim being to develop a partnership between the parties which is beneficial to both.

Chapter 2 "Personnel"

There are a lot of discussions around the role of the Responsible Person. In particular, their qualifications and their skills are not only those defined in the GDP Guideline. Here, too, the interpretation of the PQC and ECA GDP Group helps.

2.2 Responsible Person

The wholesaler must designate a Responsible Person. This Responsible Person should fulfil all the qualifications and requirements legally specified by the concerned member states (1). A college degree in pharmacy is desirable. The Responsible Person should also have adequate expertise and experience, and knowledge and training in good distribution practices.

What is the rationale for this point in the guidance?

The wholesaling, storage and distribution of medicinal products is subject to strict legislation which covers all aspects of wholesaling activities. Therefore, a person who is conversant in the legislation and able to implement and oversee the requirements within their organisation is essential, to ensure compliance is maintained. Any particular requirements regarding training and qualifications stipulated by a Member State must be known and met. Although a degree in pharmacy is generally desired, and in some Member States required, other qualifications may be accepted and, whatever qualifications an individual holds, it is vital that they have appropriate training and experience.

How might this be implemented/ what does it mean?

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. In a small organisation with a minimal number of product lines, it is acceptable for the license holder to be the RP (as long as they meet the requirements in the Member State concerned), whereas in a large multi-site wholesale distributor, a dedicated RP independent from the daily operations would be required, as well as having defined delegated duties.

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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:

Knowledge

• 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
• 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

Competent Authorities will assess the experience of individuals proposed as RPs. An RP is unlikely to be accepted unless they have a minimum of one year's experience of distribution activities. A longer period of experience, ideally in a management role, would be preferred.

Contract RPs

Contract RPs should have the same level of knowledge and training in company products and procedures as a permanent RP. This provides a practical limit on the number of licenses that an RP can effectively support.

License holders should ask potential contract RPs about other license commitments and be satisfied that they will be able to devote sufficient time to the support of their operations before appointment. it should be noted that Competent Authorities have refused RPs being named on what they consider to be too many licenses. the contract RP should also consider carefully if they are able to fulfil these professional responsibilities for another company.

The complete interpretation texts are available in English and can be downloaded from www.good-distributionpractice-group.org.

Author:
Oliver Schmidt
CONCEPT HEIDELBERG