Editorial and PHSS News

By Kay O'Hagan Editor-in-Chief

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.

[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.

PHSS News - Our New Chair

Hello, my name is Jenni Tranter and I am very pleased to take up the position of Chair for the PHSS. I have been the Vice chair since July 2015 and have been an active member of the Management Committee since joining in November 2013.

So, a bit more about me. I have been working in Healthcare and Medical Industries since August 1998, after graduating from UWIC in 1998 with BA(Hons) in Business Management. I worked for Healthcare manufacturers prior to joining STERIS AST in May 2003, as a Regional Sales Manager, then in 2009 became Marketing Communications Manager, transitioning to Business Development Manager in 2013 before moving into my current role of Senior Marketing Manager in 2016. In my role with STERIS I am involved in a wide variety of areas, from strategic planning, supporting acquisitions and integrations to running global projects looking after our Customers Experience. On a daily basis I am responsible for all Marketing activity conducted within the EMEAA region. This involves engaging with colleagues and Customers, managing projects ranging from Market segmentation/development, Competitor surveillance, Event & CRM Management to Brand values and Employee engagement initiatives.

I am excited to continue the excellent work conducted by the PHSS, I believe we attract some of the best thought leadership and opinion influencers in our industry. The PHSS’ focus is entirely on its members, delivering, practical guidance to support its membership. The membership fee is of incredibly good value given the resources, information, events and networking opportunities that is provided each year. PHSS is the go-to Society for assistance with the challenges associated with regulatory change and manufacturing.

We will be continuing with the excellent foundations and strategic direction set by James Drinkwater our outgoing Chair. I look forward to working with all our members and supporters to deliver great education events, bringing exceptional value to our membership and the industry.

As you can read, I bring something different to the society, however I am keen to follow in the footsteps of a very credible individual who has directed the society well over the last 10 years. I am confident that my 21 years of industry experience, has a solid base, to give full appreciation for industry requirements and serve our membership well.

PHSS Activities and initiatives EJPPS report September 2019

By James Drinkwater - Head of PHSS Aseptic processing and Containment Special interest group

The PHSS Annual conference on 10 September 2019 had a focus around the challenges of manufacture and certification/ release of advanced therapeutic medicinal products (ATMPs) and Biological products. There was a real insight provided to what Gene and Cell therapies are and the challenges in manufacture and cross contamination control.

The challenging role of the QP was discussed where products or therapies use biological delivery systems being autologous or allogenic (single patient or targeted patient groups) where the significance of cross contamination control adds to the classical requirements of contamination control in sterile product manufacture.

The role of the QP and challenges in product certification for release will be further discussed at the annual PHSS QP Forum in Wales November 2019 – details on the PHSS Website.

The Annual conference in London also included an update on the PHSS initiative in preparation of Clarity on GMP Guidance notes of which there are sixteen in preparation. The key points to be included in each guidance note were presented with the slide deck available from the PHSS office. Focus groups are now appointed to prepare the guidance notes so drafts will soon become available. The full PHSS Aseptic processing special interest group will review the drafts before finalization and issue to the MHRA for regulatory review before publication on the PHSS Website.

Planning is now in progress for 2020 Aseptic processing workshop syndicates and Annual Challenges in Sterile product manufacturing conference in Manchester UK April and June respectively. These are typically sold out events so those interested should contact the PHSS as soon as information is released.

The PHSS has increased the management team skill set/subject matter experience to extend to non-sterile product manufacturing where bioburden control is required. Information on the initiative to extend support in non-sterile product manufacturing over sterile product manufacturing GMP, that the PHSS is well known for, will be shared in the next issue of the EJPPS.

Annex 1 revision status. It is now understood from various sources that there is a draft version of the Annex 1 revision that is the outcome of the consultation process (revised from the published draft to reflect industry comments) and after review may be published early 2020. This statement is not official but just an insight to current information as the industry awaits this important publication. There is also talk of a ‘targeted’ consultation process on key points of Annex 1 that may form part of the review process before publication. There still remains rumors and myths around Annex 1 publication so still uncertainly remains on the final content and publication date but hopefully we are now closer to the end of this long process of revision and all involved in sterile product manufacturing can finally complete a gap analysis to identify shortfalls and address new regulatory guidance and expectations under the increasing requirements of Quality Risk Management (QRM).