Review of Developments in GMP and the Regulation of Medicines Jan 2021
EJPPS vol 26.1A
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INTRODUCTION
During the last 4 weeks there have been a number of developments in the regulation of the pharmaceutical industry. This month reported issues have come from the UK, EU, USA and Australian regulatory authorities.
It is a particularly momentous month where we note the approval of the first three COVID 19 vaccines ( a tremendous achievement in what is a record time) and also the publication of the UK – EU Trade Agreement which gives some clarity for our industry in terms of impact on the way trade in medicines between the two partners will operate although we will need to see further clarification of detail before we can understand the full impacts of the agreement.
The topics covered in this edition of the “Update” include:
UK Government
UK-EU trade and cooperation agreement summary / full agreement
MHRA
Qualifications of suppliers and customers online: reliable or fake news?
Pharmacovigilance requirements for UK authorised products from 1 Jan. 2021
Brexit-related guidance for companies
Updated Q&A to Stakeholders on the implementation of the Protocol on Ireland/Northern Ireland
Treatments and vaccines for COVID-19
Transparency: exceptional measures for COVID-19 medicines
Q&A on labelling flexibilities for COVID-19 vaccines
ATMP Certification procedures for micro-, small- and medium-sized enterprises (SMEs)
Guidance on GMP &GDP – Updated Q&A
Product-information templates - Human
Excipients labelling
Cyberattack on EMA - updates
Stability Testing of new veterinary drug substances and medicinal products in climatic zones III and IV
EMA Management Board: highlights of December 2020 meeting
Ranitidine-containing medicinal products
VICH GL59 Harmonisation of criteria to waive laboratory animal batch safety testing for vaccines for veterinary use
COVID-19: EDQM business continuity plan to safeguard core activities
Updated European Pharmacopoeia vaccines package for COVID-19 vaccine developers
Webinar “N-nitrosamine impurities: latest update on the Ph. Eur. approach”
BREXIT: impact on ordering and shipment of EDQM products
Controlled Correspondence Related to Generic Drug Development
Consumer Antiseptic Rub Final Rule Q&A
Test method: UPLCC01 – Cannabinoids
UK Regulatory approval of Pfizer/BioNTech vaccine for COVID-19
Oxford University/AstraZeneca COVID-19 vaccine approved for use in UK.
EMA recommends first COVID-19 vaccine for authorisation in the EU
Pfizer-BioNTech COVID-19 Vaccine (USA)
Moderna COVID-19 Vaccine (USA)
RECENT DEVELOPMENTS IN GMP AND REGULATORY REQUIREMENTS
UK
UK Government
UK-EU trade and cooperation agreement summary / full agreement
Annex on medicinal products.
This Annex aims to facilitate availability of medicines, promote public health and protect high levels of consumer and environmental protection in respect of medicinal products. It provides for mutual recognition of Good Manufacturing Practice (GMP) inspections and certificates, meaning that manufacturing facilities do not need to undergo separate UK and EU inspections, as well as ongoing co-operation.
See:- page 9 point 22 for this Annex
Also in Chapter 5–Regulatory framework Section 2 -Mutual recognition of professional qualifications
Point 50. The UK and the EU have agreed a framework for the recognition of qualifications between the Parties which is based on the EU’s recent FTA agreements It makes improvements on those agreements, which are designed to make the system more flexible and easier for regulatory authorities to use.
Point 51. This approach will allow the UK and its regulators to maintain standards of professional competence. From early 2021, the government will provide help and guidance to UK regulatory authorities and professional bodies to help them benefit from these provisions as well as other recognition paths.
Point 52. The Agreement clarifies that the provisions on professional qualifications are without prejudice to alternative arrangements that the UK may agree with the EU, allowing for improved mechanisms to be agreed in future. Agreements will be negotiated on a profession-by-profession basis.
The text of the full agreement has now been published and the medicines annex (TBT-2 MEDICINAL PRODUCTS) is on pages 492-503
MHRA
Qualifications of suppliers and customers online: reliable or fake news?
Qualification and re-qualification of suppliers and customers are fundamental pillars of good distribution practice (GDP)., as well as being one of GDP,s highest risk areas, The Human Medicines Regulations 2012 require licence holders and responsible persons to implement robust procedures for establishing the authority and legitimacy of a customer and supplier. MHRA expects organisations to have qualification and re-qualification procedures implemented as part of a quality management system.
Online resources provide a certain degree of confidence for conducting independent checks on licence details, such as company name, company number, site name, site address, authorised licensable activities, authorised categories of products to be handled on site and contact information. Inspectors however often see stakeholders relying on this information available in the public domain to establish the legitimacy of a business partner. MHRA expects you to adopt practices that incorporate independent checks as part of your procedures. When verifying your business partners, it is crucial that you consider your sources of information and who else may potentially have the same access. Publicly available information certainly provides a high degree of convenience and confidence, but if you have free access to it, it is worth considering who else does.
You should also be mindful when publishing your company information online and making it accessible to everyone. MHRA has seen evidence of companies uploading authorisations issued by regulatory bodies, including MHRA and the Home Office. While it may be convenient to provide easy access to your licences, this practice increases the risk of misuse and we strongly discourage it.
Any suspicions of fraudulent activity or attempts to impersonate a licence holder should be reported to the competent authority and your local police. Case Referrals, within MHRA’s Enforcement team, is the responsible team at the MHRA and they will be able to provide support if you need to raise a report.
This is an interesting and useful Blo,
There are[some interesting examples showing how easy it can be to be duped MBH]
Pharmacovigilance requirements for UK authorised products from 1 Jan. 2021
From 1 January 2021, the MHRA will be the UK’s standalone medicines and medical devices regulator.
This pharmacovigilance webinar (on 13 Jan 2021 13.00 – 16.00hrs) will be led by the MHRA GPvP Inspectorate and will provide insights into post-EU Transition pharmacovigilance requirements for UK authorised products. The event is relevant to anyone working in pharmacovigilance, including service providers.
Europe
EMA
Brexit-related guidance for companies
Companies should check this page regularly for guidance on the consequences of Brexit, as EMA and the European Commission are maintaining a series of guidance documents.
The current update of these pages relates to The protocol on Ireland / Northern Ireland forms an integral part of the withdrawal agreement concluded by the EU and the UK. It will become fully applicable at the end of the transition period.
Updated Q&A to Stakeholders on the implementation of the Protocol on Ireland/Northern Ireland
Additional practical guidance on the applicable rules in Northern Ireland after the transition period with respect to EMA activities and medicinal products for human and veterinary use within the framework of the centralised procedure
Treatments and vaccines for COVID-19
EMA has updated its web pages on this topic
Transparency: exceptional measures for COVID-19 medicines
During the COVID-19 pandemic, the EMA is implementing exceptional measures to maximise the transparency of its regulatory activities on treatments and vaccines for COVID-19 that are approved or are under evaluation.
EMA is achieving this by shortening its standard publishing timeframes and publishing information it does not normally publish for other medicines.
Q&A on labelling flexibilities for COVID-19 vaccines
Changes implemented in Rev.1 are:-Question 2 – The Netherlands deleted from the list of Member States requiring the printed package leaflet in their national language. Question 6 – Estonia deleted from the list of Member States requiring equal number of printed package leaflets, corresponding to the number of doses.
ATMP Certification procedures for micro-, small- and medium-sized enterprises (SMEs)
The EMA’s Committee for Advanced Therapies (CAT) provides a certification procedure for advanced therapy medicinal [products (ATMPs) under development by micro-, small- and medium-sized enterprises (SMEs). This is an opportunity for SMEs to get an assessment of the data they have generated and check that they are on the right track for successful development.
The certification procedure involves the scientific evaluation of quality data and, when available, non-clinical data that SMEs have generated at any stage of the ATMP development process. It aims to identify any potential issues early on, so that these can be addressed prior to the submission of a marketing-authorisation application.
Guidance on GMP & GDP: Q&A
The EMA has updated this Q&A as of Dec 2020. Updates relate to:-
EU GMP Guide Part 1 CH 5 Q2 Is it possible to use multiple batch numbers in packaging of medicinal products Q5 what are the requirements for batch numbers appearing on the packaging of medicinal products subject to parallel trade
Product-information templates - Human
Quality Review of Documents (QRD) template v10.2 is revised to specify Northern Ireland in the list of local representatives at the end of the package leaflet.
As of 1 January 2021, any new marketing authorisation application submitted via the centralised procedure must comply with the revised QRD template v10.2 as early as possible, and by Day 181 of the procedure at the latest.
Holders of existing marketing authorisation granted via the centralised procedure must update the product information annexes by 31 December 2021, in any regulatory procedure that affects these annexes, to comply with the revised QRD template.
Marketing authorisation holders for medicinal products with no regulatory procedures affecting the product information annexes before 31 December 2021 must submit a dedicated notification under Article 61(3) of Directive 2001/83/EC to comply with the revised QRD template.
Excipients labelling
EMA has updated this guidance.
MA holders and applicants need to identify the excipients included in any human medicine authorised in the EU in its product information. Guidance is available from the European Commission and European EMA on what needs including in the labelling and package leaflet.
Cyberattack on EMA - update 1
The full investigation launched by the EMA, in close cooperation with law enforcement and other relevant entities, demonstrated that data has been breached. An initial review revealed that a limited number of documents belonging to third parties were unlawfully accessed. The concerned companies are being informed.
The Agency remains fully functional and its timelines related to the evaluation and approval of COVID-19 vaccines and treatments are not affected.
The ongoing investigation of the cyberattack on EMA, carried out by the Agency in close collaboration with law enforcement and other relevant entities, has revealed that the data breach was limited to one IT application. The perpetrators primarily targeted data related to COVID-19 medicines and vaccines and unlawfully accessed documents belonging to third parties. The companies concerned at this stage have been contacted and duly informed.
Stability testing of new veterinary drug substances and medicinal products in climatic zones III and IV
The Committee for Medicinal Products for Veterinary Use (CVMP) published this document on 5 December.
It is an annex to the VICH parent stability guideline, Stability Testing of New Veterinary Drug Substances and Medicinal Products (VICH GL3(R)) and provides guidance regarding the stability data package for a new veterinary drug substance and medicinal product to be included in a registration application submitted within the regions in climatic zones III and IV. The guideline seeks to exemplify the core stability data package for new veterinary drug substances and medicinal products, but leaves sufficient flexibility to encompass the variety of different practical situations that may be encountered due to specific scientific considerations and characteristics of the materials being evaluated. Alternative approaches may be used when there are scientifically justifiable reasons.
EMA Management Board: highlights of December 2020 meeting
The December 2020 meeting of the Management Board was Emer Cooke’s first Board meeting as EMA's Executive director since she took up leadership of EMA in November.
Topics reported include@-
Update on COVID-19
EMA budget for 2021
Update on the EU IT systems required by the Clinical Trial Regulation
Update on DARWIN EU (Data Analysis and Real World Interrogation Network)
EC
Ranitidine-containing medicinal products
Following the European Commission decision the EMA confirms the recommendation to suspend all ranitidine medicines in the EU.
VICH GL59 Harmonisation of criteria to waive laboratory animal batch safety testing for vaccines for veterinary use
This document provides internationally harmonised recommendations for criteria on data requirements to waive laboratory animal batch safety testing of veterinary vaccines in regions where it is required.
EDQM
COVID-19: EDQM business continuity plan to safeguard core activities
The EDQM has established a business continuity plan to anticipate and mitigate any risks of disruption to its activities, so that the standards necessary for the production and release of medicines by pharmaceutical manufacturers and for market surveillance testing by Official Medicines Control Laboratories (OMCLs) remain available during the COVID-19 pandemic. Specific measures have also been taken to ensure the granting and revision of certificates of suitability (CEPs).
To protect the health of staff and the public, most EDQM staff not essential to conducting experimental or physical operations on-site are working remotely during the current lock-down in France, the EDQM’s host country. The tools and measures implemented during the spring lock-down proved to be effective and efficient and the EDQM therefore remains able to provide its services even under these difficult circumstances. The EDQM is closely monitoring the situation and will continue to adapt its working methods to comply with the host country’s lock-down measures and strict health and safety regulations.
All EDQM operations are running and business continuity measures are being continually monitored and adapted, as necessary.
Updated European Pharmacopoeia vaccines package for COVID-19 vaccine developers
(EDQM) has released an updated set of pharmacopoeial quality standards for vaccines.
Originally published in June 2020, the package now includes a further 17 texts on analytical methods which are referenced in the recently released but are not restricted to this technology and may also be relevant for COVID-19 vaccines based on other technologies.
This initiative was taken to support COVID-19 vaccine developers in designing appropriate analytical strategies for their candidate vaccines and to help ensure the quality and safety of final products. The application of the package’s quality requirements may ultimately help facilitate regulatory acceptance of subsequent marketing authorisation applications, thus contributing to protecting public health.
Readers should also note that the updated Ph. Eur. vaccines package now can be obtained as a free download.
Webinar “N-nitrosamine impurities: latest update on the Ph. Eur. approach”
21 January 2021, 13:00-14:30 CET
During its 168th Session, the European Pharmacopoeia Commission adopted a new general chapter on the analysis of N-nitrosamine impurities in active substances (2.5.42, previously listed as 2.4.36). The new general chapter proposes three procedures and focuses mainly on the analysis of N-nitrosamine impurities in angiotensin-II-receptor antagonists (sartans) containing a tetrazole group, for which there are five Ph. Eur. monographs (valsartan, losartan potassium, candesartan cilexetil, irbesartan and olmesartan medoxomil), but may also be helpful to establish a control strategy for other active substances or for medicinal products.
This webinar will provide users and stakeholders with an update on the different activities linked with N-nitrosamine impurities including a detailed overview of the new general chapter.
BREXIT: impact on ordering and shipment of EDQM products
As from 01 January 2021 following the formal withdrawal of the United Kingdom (UK) from the European Union (EU) and the end of the transition period, the EDQM’s Terms and Conditions currently applicable to the countries outside the European Union will apply for all shipments to the United Kingdom.
United States of America
The US Food and Drug Administration (USFDA)
Controlled Correspondence Related to Generic Drug Development
This final guidance provides information regarding the process by which generic drug manufacturers and related industry or their representatives can submit to FDA controlled correspondence requesting information related to generic drug development. This guidance also describes the Agency’s process for providing communications related to such correspondence. This guidance replaces the September 2015 guidance for industry @
‘Controlled Correspondence Related to Generic Drug Development’
Consumer Antiseptic Rub Final Rule Q&A
This guidance is intended to help small businesses understand and comply with the Consumer Antiseptic Rub Final Rule; Finding of Ineligibility for Inclusion in Final Monograph (Consumer Antiseptic Rub FR) (84 FR 14847, April 12, 2019), which applies to active ingredients used in over-the-counter (OTC) consumer antiseptic rub products that are sometimes referred to as rubs, leave-on products, or hand sanitizers. The Consumer Antiseptic Rub FR also applies to active ingredients used in OTC consumer antiseptic wipes. The Consumer Antiseptic Rub FR established that 28 active ingredients used in nonprescription consumer antiseptic rub products are not eligible for evaluation under FDA’s ongoing rulemaking to evaluate the safety and effectiveness of OTC drug products marketed in the United States on or before May 1972, which is known as the OTC Drug Review. Drug products containing these active ingredients will require approval under a new drug application (NDA) or an abbreviated new drug application (ANDA) before they can be marketed. The Consumer Antiseptic Rub FR also established that three active ingredients used in consumer antiseptic rub products—benzalkonium chloride, ethyl alcohol, and isopropyl alcohol—are eligible for evaluation under the OTC Drug Review. In response to several requests submitted to the 2016 Consumer Antiseptic Rub Proposed Rule (Consumer Antiseptic Rub PR)(81 FR 42912, June 30, 2016), FDA temporarily deferred further rulemaking on making a generally recognized as safe and effective (GRAS/GRAE) determination for these three eligible active ingredients. Rulemaking was temporarily deferred to allow time for interested parties to complete the studies necessary to fill the safety and effectiveness data gaps FDA has identified for these three ingredients.
[Much focus in the USA has been on the recent election and its aftermath. Also, as the Current administration appeared to have had a focus more upon decrease rather than increase in regulation, it has come as no surprise to me that we have not seen a hurried throughput of new regulation as the administration approaches handover. MBH]
International
Australia
Test method: UPLCC01 - Cannabinoids
This method describes the analysis of samples derived from Cannabis species, specifically the assay of the primary compounds of regulatory interest [Tetrahydrocannabinolic Acid (THCA), Tetrahydrocannabinol (THC), Cannabidiolic Acid (CBDA) and Cannabidiol (CBD)] by UPLC coupled with UV or PDA.
This method is adapted from the Cannabis Flos Monograph, produced by the Netherlands Cannabis Bureau.
Products
UK Regulatory approval of Pfizer/BioNTech vaccine for COVID-19
The first COVID-19 vaccine for the UK, developed by Pfizer/BioNTech, was given approval for use on 2 Dec 2020 following a thorough review carried out by the Medicines and Healthcare products Regulatory Agency (MHRA).
Oxford University/AstraZeneca COVID-19 vaccine approved for use in UK.
The COVID-19 vaccine developed by Oxford University/AstraZeneca was given regulatory approval on 30 Dec 2020 by the UK Medicines and Healthcare products Regulatory Agency (MHRA) after meeting required safety, quality and effectiveness standards.
EMA recommends first COVID-19 vaccine for authorisation in the EU
Comirnaty, developed by BioNTech and Pfizer, to prevent coronavirus disease 2019 (COVID-19) in people from 16 years of age, is now authorised across the EU. This follows the granting of a conditional marketing authorisation by the European Commission on 21 December 2020.
Pfizer-BioNTech COVID-19 Vaccine (USA)
On December 11, 2020, the U.S. Food and Drug Administration issued the first emergency use authorization (EUA) for a vaccine for the prevention of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 16 years of age and older. The emergency use authorization allows the Pfizer-BioNTech COVID-19 Vaccine to be distributed in the U.S.
Moderna COVID-19 Vaccine (USA)
On December 18, 2020, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for the second vaccine for the prevention of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The emergency use authorization allows the Moderna COVID-19 Vaccine to be distributed in the U.S for use in individuals 18 years of age and older.
And finally…
Further information on these and other topics can be found in recent versions of the “Regulatory Update” on the PHSS website (members area) by utilising the hyperlink within that particular Update.
We hope that our readers find our reviews to be both informative and helpful in keeping up to date with pharmaceutical legislation and regulatory guidance.