Anne-Sophie SOHIER

Securing the distribution of medicines represents an unprecedented challenge for public health. Although France has always benefited from a particularly secure drug distribution system and a strict legislative framework from the health authorities, the risk of falsified drugs is increasing on a global and European scale.

Faced with this major challenge, Directive 2011/62/EU of the European Parliament and of the Council of June 8, 2011 introduced the serialization system, which details were subsequently specified by Commission Delegated Regulation (EU) 2016/161 of October 2, 2015, in order to strengthen the safety of the distribution chain of medicinal products and to fight against their falsification. The obligations relating to the serialization of medicinal products and anti-counterfeiting devices are applicable since February 9, 2019.

Now 4 years after the entry into force of the European regulation, let’s look back at the implementation of the serialization system.

As a reminder, the serialization device is composed as follows:

• A tamper-evident device for all drugs, affixed by the manufacturer and verified by the pharmacist to check the integrity of the product before dispensing (e.g. transparent adhesive tape);
• A unique identifier (UI) on each box of mandatory prescription medication, affixed by the manufacturer and scanned by the pharmacist before dispensing to the patient (datamatrix).

The serialisation system contributes to the implementation of a European system to fight against the introduction of falsified medicines by providing additional security to guarantee the authenticity, safety and quality of medicines on the territory of the European Union. It completes the existing batch traceability by authenticating each box at the time of dispensing.

The implementation of this system required the collective commitment of all the stakeholders in the drug supply chain (manufacturers (CMOs) and Exploitants/Marketing Authorization Holders, wholesalers and distributors, pharmacies and hospitals, software publishers, etc.), as well as the Ministry of Solidarity and Health, the French National Agency for the Safety of Medicines and Health Products (ANSM) and the regional health agencies (ARS).

Indeed, this new system has required organizational changes at all levels, from drug production to delivery to the patient: adapting production lines to implement the unique identifier and the anti-tampering device, adapting the IT systems of all drug professionals, setting up governance bodies at national (NMVO) and European (EMVO) level, adapting procedures, etc.

The question of ultimate responsibility for implementing serialization has been the subject of numerous debates, which have now been settled, with the central issue of downloading unique identifiers at the time of manufacture and the possible outsourcing of this activity. The introduction of the OBP portal registration requirement and fees to finance the infrastructure of national (NMVS) and European (EMVS) repositories systems has also had an impact on the drug chain stakeholders.

WHAT ABOUT THE IMPLEMENTATION OF SERIALIZATION IN PHARMACIES IN FRANCE?

Serialisation is a regulatory obligation for all pharmacies. Indeed, such a system can only operate with the participation of all pharmacies in the Member States in order to ensure that no falsified box is delivered to a patient in the European Union.

This obligation, which came into force on February 9, 2019, was reminded in the Order of February 26, 2021 on good dispensing practices for medicinal products in order to make the obligations incumbent on all pharmacists under European regulations more visible in a text of national scope.

However, to date, despite the health crisis and the strong mobilization of pharmacists, the connection of pharmacies to the system has been delayed and remains insufficient in France. As of February 6, 2023, only 17,901 pharmacies (86.2%) were complying with their obligations to serialize their medicines, with a target of 100% by December 31, 2022.

Given France’s considerable delay in implementing effective verification of the serialization system in pharmacies, a bill was adopted by the Senate on December 14, 2022, defining the financial penalties that may be imposed on pharmacy holders in the event of non-compliance with the obligation to deactivate the unique identifier.

On the page dedicated to serialisation in pharmacies on its website, the Ministry of Health stresses the importance of reaching this 100% objective as soon as possible to guarantee better safety and traceability of medicines for all French people.

Article written by Amélie NICOLAS-VERLEY, Regulatory and Pharmaceutical Affairs Advisor

What is an APQR?

Both US and EU Good Manufacturing Practices (GMP) require manufacturers of all authorized medicinal products to perform Annual Product Quality Reviews (APQR in the US, PQR in EU). These reviews are conducted with the objective of verifying the consistency of the existing process, the appropriateness of current specifications for both starting materials and finished product, to highlight any trends and to identify product and process improvements. Such reviews are conducted and documented annually, (taking into account previous reviews), and include a number of review areas.

The Qualified Person is responsible for ensuring that each single batch is manufactured and controlled in compliance with the applicable regulation, in accordance with MA specifications and GMP, and is responsible for the APQR.

What’s special in France?

As it is the case everywhere, APQR duties involve the manufacturer and the MA Holder. But in France, there is another party involved, the Exploitant (see related article “The mysterious thing that an Exploitant is”). The Exploitant can sometimes be the MAH.

Moreover, French GMP specify that when the manufacturer, the MAH and the Exploitant are distinct, all of them are individually responsible for assessing the results of the APQR and evaluating the need to implement corrective and/or preventive actions or to perform any revalidation.

When the MAH is not the manufacturer and/or the Exploitant, contracts/Quality Agreements must be in place to define each party’s responsibilities in performing APQRs.

So, although mainly the manufacturer and the MAH are involved in performing the APQR, all parties including the Exploitant share responsibilities in reviewing the APQR. This means, for every single product exploited, that the APQR has to be received and checked by the Exploitant. This review has to be a critical review, and has to be documented in order to show that the Exploitant is continuously aware of the quality of the product, and is able to challenge the processes in case of any trend is identified.

APQR review is particularly critical as it is highly challenged by ANSM during routine inspections (both in the content and timelines of the review).It is therefore crucial for an Exploitant to have an effective APQR review process in place.

ATESSIA has a dedicated team performing APQR reviews that meet ANSM’s expectations and can help you in getting it right!

Article written by Raphaël DAUVERGNE, Regulatory and Pharmaceutical Affairs Advisors

In concrete terms, what does it mean to be a consultant in regulatory and pharmaceutical affairs at ATESSIA, Life science advisors?

At ATESSIA, we firmly believe that consulting is not a job that you do, but a talent that you keep developing. Our consultants have a strong technical background to meet the needs of our customers and a strong experience that allows them to solve complex problems. But it is also their behavioral and interpersonal skills that are necessary for them to succeed in this challenging profession. While the past has been almost exclusively focused on deliverables in the consulting world, at ATESSIA we believe that the present and future are entirely driven by the experience offered to our clients before, during and after the service is provided.

What qualities do we look for in our consultants?

Listening

“He who knows how to listen will become the one who is listened to” – Vizier Ptahhotep

A consultant must have the quality of active listening. Active listening to the needs of the customers enables us to set up innovative solutions in a culture of continuous improvement.

Listening to what the customer says about his needs and problems is the most useful way to be able to propose adequate solutions. In addition to being a good listener, it is also important to ask relevant and open-ended questions and not to impose a method or a solution without having really heard the client’s needs.

At ATESSIA our approach is thoughtful and detail oriented.

Empathy

“The first rule before taking action is to take the place of the other. No real research for the common good will be out of there. “- Abbé Pierre

ATESSIA has chosen to position itself on the axis of human relations. We place the human being at the heart of our strategy, and we behave with empathy towards all our stakeholders. Empathy is an essential quality in the world of consulting, because if we do not put ourselves in the client’s shoes, we will not be able to understand his problem and thus respond to his request. In a world that has become more and more digitalized, we want to cultivate our human qualities that make all the difference.

Empathy is what reflects our signature: placing the human being at the heart of our customer relations.

Sense of urgency

“It doesn’t make sense to hire smart people and then tell them what to do. We hire smart people so they can tell us what to do.” – Steve Jobs

Agility and proactivity infuse everything we do, as well as the wisdom to consider options thoroughly. A sense of urgency allows the consultant to quickly identify potential problems, which then gives him the time to carefully craft solutions. In this unpredictable and ever-changing environment, our consultants respond with agility while remaining calm to get things done in an effective and efficient manner.

Trust

“Trust is a major element: without it, no project will succeed. – Eric Tabarly

ATESSIA’s consultants are committed to establishing a relationship of trust with their clients by understanding their environment and values and by being available and close to them when necessary. Firm believers in a customized approach, our consultants take into account the specificity of our clients’ businesses and the particularity of their operating methods. Our team overcomes obstacles, finds solutions, and delivers outstanding results. To achieve this, we remain transparent about our role and objectives. We pay particular attention to credibility, which depends on clearly communicating all the details of the mission while respecting the deadlines.

Critical thinking

“There is no fair wind for him who does not know where he is going” – Seneca

ATESSIA’s clients appreciate our ability to apply and communicate cutting-edge approaches in a clear and compelling manner. ATESSIA’s consultants base their thinking on the rational data of the cases. Our consultants are critical and independent thinkers who can effectively analyze data and draw conclusions based on the evidence at hand. This critical thinking involves breaking down information based on the available data and drawing logical conclusions based on the facts.

If you are interested in ATESSIA’s consulting world, contact us at hello@atessia.fr

Article written by Hiba MASSOUDY, Human Resources Manager