If medicinal products are to be of the quality consumers and regulators expect, then the active substances within them need to be manufactured in accordance with Good Manufacturing Practice and their quality and integrity maintained throughout the supply chain through the application of Good Distribution Practice (GDP).
In Europe, the Falsified Medicines Directive (2011/62/EU) amended Directive 2001/83/EC to introduce legal requirements relating to the manufacture, importation and distribution of active substances. Subsequently, in March 2015, the European Commission published its ‘Guidelines on principles of Good Distribution Practice of active substances for medicinal products for human use’ (2015/C 95/01).
Having collaborated to produce a well-received monograph on GDP for medicinal products (revised PQG monograph 4, 2018), the Pharmaceutical Quality Group of the Chartered Quality Institute (PQG) and the ECA Foundation GDP Association (ECA) received several requests for similar guidance on the interpretation and implementation of the regulatory expectations of GDP for active substances. This led to the formation of a small working group and we are delighted to share the news that this has now resulted in the publication of a new monograph (PQG monograph 13).
The new monograph is built around the format and text of the 2015/C 95/01 guideline (presented in blue text) with guidance (black text) provided by experts drawn from the membership of both PQG and ECA. Where appropriate, text from the medicinal product GDP monograph has been reused as many of the same good practices apply to both products and active substances. However, the monograph also reflects the fact the regulatory guidelines for active substances are less detailed and that a risk-based approach allows for some differences. Although based on the European guideline, the advice is relevant to all geographical regions given that today’s pharmaceutical supply chains are frequently global with many distribution steps through which quality needs to be maintained.
This new monograph, which is now available from the PQG Shop, provides a sound basis for the implementation and maintenance of a GDP quality system for active substances with clear responsibilities and processes and the application of risk management principles. It will be of benefit to all involved in active substance distribution activities for initial training, continuing professional development and as a reference source or audit tool.
Thanks to the following for providing their time and expertise to produce this new monograph:
Philip Butson, Prabjeet Dulai, Martin Egger, Afshin Hosseiny, Denise Hosseiny, Saddam Huq, Sue Mann, Stephen Mitchell, Steve Moss, Wolfgang Schmitt and Neil Wayman
A number of recalls have occurred in the last two years following the finding of nitrosamine impurities in medicinal products, firstly the ‘sartans’ and then other products, notably ranitidine. This has led to enhanced regulatory agency and pharmaceutical industry action to assess and manage the risks. In Europe, a key element of this was the issue in Sep-2019 of EMA’s ‘Information on nitrosamines for marketing authorisation holders’ which, in addition to providing useful information on the potential sources of nitrosamine impurities, contains a request from the CHMP for all marketing authorisation holders (MAH) of human medicines containing chemically synthesised active substances to review their medicines for the possible presence of nitrosamines and to test all products at risk. A three-step process was outlined: Risk Evaluation – Confirmatory Testing – Changes to Marketing Authorisation.
The original requirement was for the first step of Risk Evaluation to be completed by 26-Mar-2020. It has now been announced that, following reports of the challenges encountered in meeting the original deadline which have been compounded by the impact of the severe restrictions in place to combat the Covid-19 pandemic, this date has been extended to 01-Oct-2020.
MAH should still inform national competent authorities as soon as possible if tests confirm the presence of nitrosamine, irrespective of the amount detected. They should also assess the immediate risk to patients and take appropriate action to avoid or minimise the exposure of patients to nitrosamines.
The MHRA have created a collection on their website for information related to Covid-19. Of particular interest to members will be information about clinical trials and MHRA services. The collection may be found here.
Separately, MHRA have issued a news release about the impact of Covid-19 on GxP inspections. The headline message is that MHRA will only be conducting essential inspections, but expect organisations to maintain GxP compliance. They will support the industry and NHS to focus on service continuity by using alternative approaches for routine regulatory oversight, such as office-based assessment and the sharing of information within the international regulatory network. The news release about GxP inspections may be found here.
UPDATE 23-Mar: For more information about inspections during the Covid-19 outbreak, see the latest MHRA Inspectorate Blog here.
With the ongoing Covid-19 situation, the organisers of Making Pharmaceuticals have reluctantly decided not to go ahead with the rearranged dates of 26/27 October 2020, but will now not hold a physical event at the Ricoh Arena until July 2021. However, a series of webinars will now be arranged. Keep an eye on the Making Pharmaceuticals website for further details. PQG will plan to attend the new dates and are looking into options for presenting webinars.
The European Commission has published the long-awaited draft Annex 21 on Importation of medicinal products. This is now open for stakeholder consultation until 20-Jun-2020. If you would like to feed comments in via PQG, then please email webmaster@pqg.org by end April.
The document is only short (140 lines). It focusses on the action of physically bringing product from outside the EEA/EU into the customs territory of an EU/EEA state. Imported dosage forms and intermediates which undergo further manufacturing operations are included within scope. Medicinal products which enter EU/EEA for export only and which are not processed or released for the EU/EEA market are out of scope. It is not explicit about whether Investigational Medicinal Products are in scope or not, but there is reference in one place to the Clinical Trial Authorisation. Responsibilities of the Marketing Authorisation Holder, Manufacturing/Importation Authorisation Holder and the Qualified Person are highlighted.
Welcome to the new PQG website!
We are excited about this development which we hope is a step towards making the site an even more valuable resource for our members. The site is now adaptable to optimise usage whether you are on a PC, tablet or phone. The new Blog functionality and interfaces with social media accounts will mean that the content is far more dynamic than in the past. The key features from the old site are still there, so please check out the Shop and the Events page.
Many thanks to Lloyd and Tom at Futuresys for their work on this and special thanks to Sarah, the PQG administrator, who has been very busy testing the functionality and populating the pages.
… CANCELLED
Due to the developing coronavirus situation, we have made the decision to cancel the AGM and 23rd annual discussion meeting with MHRA, which were due to take place in London on 24-Mar-2020.
We will look to rearrange these as soon as possible.
The AGM papers have still been made available in the Members area on the website and we encourage you to look at these and email chairman@pqg.org if you have any questions.
We will work with MHRA to try to provide written answers to questions submitted as soon as possible.
Another fully booked and well received evening workshop was held on 25th February covering the various aspects of Effective Change Management. The event was held at the modern and well equipped ETC venues in London. After a hot meal and some networking, the event kicked off and was co-hosted by John Nesnas, Damian Larrington and Andrew Lovell. The attendees varied in background and experience, from those who are new to their Quality role to others who had decades of experience but were using the event as a continuous development and networking opportunity. It was great to see a number of familiar faces from previous evening workshops. The topics covered included the relevant regulatory requirements, aspects of effective change management, common mistakes and regulatory findings. Practice based questions were discussed throughout with case studies at the end that allowed the attendees to put their learning into practice and to share experiences with their colleagues. Watch out for details of the next event.
A revised version of this annex has been released for limited consultation and may be found here (PQG member log in required).
PQG is not one of the limited organisations able to provide feedback on this consultation, but have teamed up with PHSS to enable members to do so.
If you have any comments on this document, please use this form (PQG member log in required) and email it to webmaster@pqg.org as soon as possible and no later than 20-Mar-2020.
The initial set of written answers to the questions posed at the PQG annual meeting with MHRA in 2019 are now available in the members’ area. The remaining answers will be provided by MHRA as soon as possible.