Editorial | Open Access | Published ?

EDITORIAL - The Obligation to Supply a Drug Product

The Marketing Authorisation holder (MAH) has a responsibility of maintaining the supply of a medicine for which they hold the MA[1]. The regulations make this quite clear:

“The holder of a marketing authorisation for a medicinal product and the distributors of the said medicinal product actually placed on the market in a Member State shall, within the limits of their responsibilities, ensure appropriate and continued supplies of that medicinal product to pharmacies and persons authorised to supply medicinal products so that the needs of patients in the Member State in question are covered.”

“If the product ceases to be placed on the market of a Member State, either temporarily or permanently, the marketing authorisation holder shall notify the competent authority of that Member State. Such notification shall, other than in exceptional circumstances, be made no less than two months before the interruption in the placing on the market of the product. The marketing authorisation holder shall inform the competent authority of the reasons for such action in accordance with Article 123. Upon request by the competent authority, particularly in the context of pharmacovigilance, the marketing authorisation holder shall provide the competent authority with all data relating to the volume of sales of the medicinal product, and any data in his possession relating to the volume of prescriptions”[2].

Reading Article 23a and 81 together, marketing authorisation holders should notify any interruption of supply of medicinal products in good time (at least two months in advance). This notification should include, in particular, data on sales volumes and the volume of prescriptions and, where possible, indicate possible alternative medicinal products. It should also include information on the estimated duration of the supply interruption as well as any corrective action taken to remedy the situation. The notification should also describe with sufficient detail the reasons for the interruption in order to allow the competent authority to evaluate the situation. [3].

Wholesale dealers are only considered responsible if they caused the problem. If the MAH failed to meet the supply demand for any reason, then the MAH is considered to be responsible for the shortage. The MAH is expected to have contingency in the supply chain, be especially vigilant if they are the sole supplier or if the medicines supplied are emergency, critical or lifesaving medicines.

The EMA introduced new guidance in the management of drug shortages in July 2019[4]. This guidance addressed:

• What is a shortage?

• What issues should be reported by MAHs?

• Who is responsible for monitoring supply and reporting shortages?

• When should a notification be made?

• Who should be notified?

• What information should be included in notifications?

The new guidance states that the MAH must have systems in place to be able to predict and monitor the expected supply demands of their product. The guidance gives a proforma which should be used when advising a competent authority of a predicted drug product shortage.

PDA Technical report No.68[5] has an excellent Risk Based approach for prevention and management of drug shortages. The technical report contains a proforma for the assessment of patient risk caused by shortages, based on therapeutic use, availability if alternatives and likelihood of shortages.

The MAH needs to ask permission to withdraw a MA. In the UK the expectation is to ask permission 18 months prior to the projected withdrawal. The permission can be refused.

In my one experience of this issue the competent authorities did all in their power to ensure continued supplies of critical medicines by using alternative suppliers or by permitting the hospital use of packs released in other national printed packaging.

The MAH can be fined for a shortage or can be obliged to provide a competitor product to fulfil orders. Because there are so may reasons for a shortage there is no standard Competent Authority response to a failure to supply. The authority will do all it can to keep the patient supplied with the product. What is clear that the MAH is obliged to supply – this is part and parcel of being the MAH.

The MA holder is accountable for supply volumes as well as Quality, Safety and Efficacy of the product during its shelf life. The MAH is expected to know and monitor the output needed to fulfil the market requirements.

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[1] Article 81 of Directive 2001/83/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 6 November 2001 on the Community code relating to medicinal products for human use.

[2] Article 23a of Directive 2001/83/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 6 November 2001 on the Community code relating to medicinal products for human use.

[3] Paper on the obligation of continuous supply to tackle the problem of shortages of medicines Agreed by the Ad-hoc technical meeting under the Pharmaceutical Committee on shortages of medicines on 25 May 2018 Response to the calls by the Council and the European Parliament to monitor the implementation of Article 81 [and 23a] of Directive 2001/83/EC3

[4] 01 July 2019 EMA/674304/2018. Guidance on detection and notification of shortages of medicinal products for Marketing Authorisation Holders (MAHs) in the Union (EEA)

[5] PDA Technical Report No 68Risk-Based Approach for Prevention and Management of Drug Shortages, ISBN: 978-0-939459-71-1, © 2014 Parenteral Drug Association, Inc.