Deficiencies and deviations: when the dialogue with AIFA is getting tricky


In the second part of the XV national QP day settled by AFI in the case of the 2021 Simposium, different speakers have underlined how an open dialogue with AIFA could create effective synergies. However, it is harder than it appears to maintain a quiet cooperation. It is not always easy for an agency to deal with its own deficiencies. This is why Domenico Di Giorgio, who has more than one charge in AIFA, including that of Unavailabilities Technical Table manager, is going to explain AIFA point of view, about the drug deficiencies. The inspectors, Luisa Stoppa and Raffaella Sardelli, on the other hand,  will deepen the topic of the recurrent deviations during GMPMED inspections.

What is deficient

Drug deficiency is a persistent problem that Domenico Di Giorgio has spent a lot of time and energy into, in orden to solve it. The core of this issue resides into the matter of falsification. AIFA and NAS, by focusing on some products which appeared to be deficient, figured out illegal activities of drug roundup, to be sold abroad.

This kind of activities create a lack of medications, called anavailability, which is not a matter of production, but because of a distributive distorsions. According to Di Giorgio these distorsions are one of the main phenomena, together with productive deficiency and lack of hospital supply, that is express itself as a drug deficiency. Those are phenomena profoundly different one another in terms of dynamics, normativity and management.

It is sure that patients do not care about the reason why the medications they need are missing. This is why AIFA tried to face the problem.

Facing the deficiency

Di Giorgio resumes the most common causes, in seven circumstances: trouble with raw materials supplies or with packaging material, quality defects, production problems, commercial policy, suspension of regulatory proceedings, sudden increase in consumption, health emergencies. Whatever the cause is, the QP role in the manufacturer agency is not secondary at all.

However, it is up to AIFA to run for the resolution of the deficiency problem.First of all, AIFA manage the monitoring of the issue, by publishing a list of deficient drugs, which is updated periodically. The information it contains are so important that they are working for a system integration with pharmacies and general practitioners, in order to improve the deficiencies management. Moreover, the coordination of agencies and associations is a fundamental step to get the procedure more effective, by a proper disclosure of information.

In addition, AIFA can authorize imports of drugs anologues abroad or their production from the Military Pharmaceutical Chemical Establishment. The authorization for imports can be released by both AIC holders and health facilities. For the latter, AIFA is considering a new directive to involve local widespread network, to allow a less fragmented management. Even comunication is a very important acpect. Often, misunderstandings or media cases can cause unsubstantiated fear of deficiencies which results in bad hordings. For this reason AIFA is publishing explanatory notes, to spread only reliable information.

The Unavailabilities Technical Table role

AIFA cannot, of course, force agencies to produce any drug. However, the Unavailabilities Technical Table conceived an effective tool to face an insidious issue. It is a plan recognized at European level, which got Italy deserving the leadership of the crusade against the deficiencies, set up by the European Commission.

Facing their own deficiencies

Talking about agencies deficiencies and shortcomings, we cannot miss to think of deviations. AIFA inspectors Stoppa and Sardelli deepen this issue by presenting the recurrent deviations they found during inspection from 2018 to 2021. Indeed, some problems tend to emerge in different agencies, so that they suggested AIFA to collect them all in a paper that will be useful as a guideline.

Top 6 deviations

At the first place of the recurrent deviations Stoppa spots those about qualifications and validations, whom deficiencies are related to sterilization cycles and sterility tests. About cleaning validation, deficiencies depends on CHT, DHT and SHT, besides production cleaning procedures. Even risk assessment processes can cause deviations due to some risk factors or beacause of forgotten updates.

It cannot be missing the data integrityrole. The integrity and the data completeness, the different  access security levels and the role separation are the main topics the agencies are not very prepared about. Also during the media fill test, into which the timing of some critical stages are not always challenged. Lastly, the Quality Technical Agreement sometimes rivealed holes, especially those stipulated with the packaging material providers.

Finally, Stoppa’s special mentions goes to asepsis procedures. The partial API use and its storage for a reuse and the transfert of sterile material management are just examples of it. Moreover, Stoppa speaks about the management of the thermic storage areas and the calibration of scales too.

Medicinal gases, radiotherapy and biologics

Deviations in pharmaceutical production of medicinal gases, radiotherapy and biologics are presented by inspector Sardelli.

Starting with biologics, we can consider, besides some shared deficiencies with other productions, some paculiarities. For example, sometimes it lacks the precision needed to manage raw and starting material both in imports and safety. In fact, especially when dealing with this kind of productions, there is a high contamination risk that is sometimes underestimated, even in some production phases. Also technical aspects, such as validity criteria of essays, are often criticized together with equipment cleaning and management, particularly complex because of their intrinsic discontinuity. Moreover, donor-recipient traceability is not always managed with due precision. In addition, the preparation of the staff dealing with the risk assessment, should be adequate to the specific production.

Sardelli continues then with medicinal gases. Validations are sometimes misaligned with the real production, and this is very criticized. Even in products, valves and cylinders lots traceability there are some trouble.

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