On Tuesday 22 September 2020 PQG organised a Data Integrity Webinar with Dale Carter, Head of Quality – Evonik Corporation.
In this presentation, Dale reviewed the recently released position paper on Data Integrity for Pharmaceutical Grade Excipients published by the International Pharmaceutical Excipients Council Federation (IPEC).
The paper was developed to supplement published Regulatory guidance defining Data Integrity requirements for drug substances and medicinal products, some of which are not easily adaptable to the manufacture of excipients.
The presentation (supporting slides available here) covered Data Integrity principles, Regulatory guidance documents and recommendations on how to apply Data Integrity to excipient manufacturing and distribution.
Just in case you missed some of this week’s news, here are the highlights:
From 1 January 2021, the Medicines and Healthcare products Regulatory Agency (MHRA) will be the UK’s standalone medicines and medical devices regulator.
Transition from the EU allows the UK to offer fully independent regulatory decisions for both devices and pharmaceuticals, both nationally and in joint work with other international regulators.
Stakeholders need to get ready for new rules from 1 January 2021.
This guidance covers the following topics:
The draft strategy details how the European medicines agencies’ network can continue to enable the supply of safe and effective medicines that meet patients’ needs in the face of challenges posed by ever-accelerating developments in science, medicine, digital technologies, globalisation as well as emerging health threats, such as the COVID-19 pandemic.
It outlines six priority areas for the network:
From 1 January 2021, a wholesale dealer in Great Britain may only import Qualified Person (QP) certified medicines from the European Economic Area (EEA) if certain checks are made by the ‘Responsible Person (import) (RPi)’.
The guidance published on 1 September 2020 describes how you can apply to be a RPi, and how to verify that QP certification of a medicine has been done in the EEA.
The registration scheme for RPi candidates will be applicable from 1 January 2021 and RPi applications may be submitted through the MHRA Portal after this date.
The Responsible Person (import) (RPi) is described in regulations 45AA and 45AB of the Human Medicines Regulations 2012 (as amended) and is responsible for implementing a system to confirm that the required QP certification has taken place for products that have been imported into Great Britain (England, Wales and Scotland) from countries on an approved country for import list (initially, this will be countries in the EEA).
Out of scope
There will products which will not require RPi oversight such as medicinal products sourced from Northern Ireland. For wholesale purposes they are out of scope of this guidance and this is permitted under the supervision of a Responsible Person (RP).
Products with a UK or Great Britain marketing authorisation that are imported into Great Britain from outside the UK without QP certification from a country on the list will require QP certification under a UK manufacturing and import authorisation before being placed on the market.
Products without a marketing authorisation in the UK, Northern Ireland, Great Britain or a listed country are outside the scope of this guidance. Importation of such products is permitted under the supervision of a Responsible Person (RP), with notification to the MHRA of each importation that is for supply to the Great Britain market.
IPEC have issued a position paper outlining the content and purpose of three documents* addressing GMP requirements for excipients and the role that each can play in the implementation of appropriate GMP in the QMS of an excipient manufacturer. This will be helpful to those involved in both the manufacture of pharmaceutical excipients and the assurance of excipient quality within pharmaceutical manufacturers. The paper may be found here
*1. The International Pharmaceutical Excipients Council & The Pharmaceutical Quality Group: The Joint Good Manufacturing Practices Guide for Pharmaceutical Excipients;
2. EXCiPACT™ Certification Standards for Pharmaceutical Excipient Suppliers, GMP Annex;
3. NSF/IPEC/ANSI 363, Good Manufacturing Practices (GMP) for Pharmaceutical Excipients, American National Standard (ANSI 363).
PQG has received the 2Q 2020 Board Report from EXCiPACT and this may be read here
Our very first virtual event was held on 30th June, dedicated to our QPs, Trainee QP and Sponsors. The event was held using the “WebEx Training” platform and limited to 30 attendees. The attendees varied in background and experience, from those who are training to become a QP to others who had decades of experience as QP and were using the event as a continuous development opportunity. The event kicked off with a comprehensive Pharmaceutical Regulatory and Legislative update by Pete Gough (Vice President, NSF). The use of “WebEx Training” then enabled us to split the attendees in 6 small virtual breakout groups to practice Viva type questions providing attendees with the opportunity to discuss several scenarios, share their experience and verbalise their answers. David Moulding (Registration Standards Specialist, RSC) then gave an overview of the application process for QP Eligibility, covering also some aspects related to the current Covid-19 pandemic situation.
Many thanks to all the speakers, facilitators and attendees. The extremely positive feedback received will help us to shape future virtual events – watch out for a new “trainee QP Day” later in the year!
A link to where Pete Gough’s presentation can be downloaded and a copy of David Moulding’s presentation are now available on the PQG meetings page in the members only area.
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.