Last week’s round-up; 22 – 26 June 2020

Mutual Recognition of European/US GMP Inspections

Earlier this month, the European Commission, EMA and the FDA held their 2020 bilateral regulatory dialogue meeting. Various topics were discussed including the mutual recognition of GMP inspections. In July 2019, the authorities fully implemented the MRA for certain human medicines, and in this month’s meeting the next milestones in this regard were tackled. These milestones include the expansion of the MRA to veterinary medicines and the inclusion of vaccines and plasma-derived products by July 2022 is under consideration.

EC: European Reference Networks (ERN) ecosystem to horizon 2030

In 2 virtual meetings organized on 17 and 18 June, the Coordinators and the Board of Member States shared information on initiatives put in place during the pandemic to support patients affected by rare diseases and to draw lessons for a potential second wave. They discussed the questions related to the on-going enlargement process of the ERNs through the recent inclusion of Affiliated partners and the forthcoming new members in 2021. They also spoke to the implications in terms of financing, use of the virtual consultation platform CPMS and integration of the ERNs within national systems. The discussions on the current system, then kick-started a brainstorming concerning a more long term vision of the whole ERN ecosystem by horizon 2030, that will continue for discussion in future meetings.

The entire press release can be found here:

EMA nominates Emer Cooke as new EMA Executive Director

At an extraordinary virtual session on 25 June, the Board of the EMA selected Emer Cooke from a shortlist of candidates created by the European Commission.Ms Cooke will now be invited to give a statement to the European Parliament’s Committee on Environment, Public Health and Food Safety (ENVI) on 13 July 2020. The appointment of the new Executive Director will be made after that meeting. Emer Cooke, an Irish national, is currently the Director of the Regulation and Prequalification Department at the World Health Organization (WHO) in Geneva.

Further details of the press release can be found here:

EMA Press Release:  Data requirements for phase 3 COVID-19 trials

Convergence on key aspects of phase 3 CT designs will help developers to generate robust evidence on potential COVID-19 vaccines and to consistently meet the needs of global regulators. This should expedite and streamline development and authorisation of vaccines against COVID-19. On 22 June in a workshop organised by EMA and FDA under the umbrella of ICMRA, global regulators focused on non-clinical and clinical data from early phase studies that are needed before proceeding with advanced (phase 3) trials, further details can be found here:

Nitrosamines and other unexpected impurities: lessons learnt

The European Commission, the EMA, national competent authorities in the EEA and the EDQM have issued recommendations that draw on lessons learnt from the presence of nitrosamines in sartan medicines, which are widely used to control blood pressure. With these recommendations, European regulators aim to clarify the roles and responsibilities of pharmaceutical companies and to amend the guidance on the control of impurities and GMP. The management of detected impurities, communication with patients and healthcare professionals, and international cooperation are also included in the recommendations. The European Network hopes that this guidance will help regulators and companies prevent and mitigate the risks of nitrosamines and other unexpected impurities in the future.

FDA, EC and EMA intensify collaboration

The EC, EMA and FDA have further intensified their collaboration through regular interactions, notably under the umbrella of the International Coalition of Medicines Regulatory Authorities (ICMRA). Topics discussed in the June meeting include; sharing experience and challenges on development of Covid19 vaccines, co-operation on therapies for ultrarare diseases, real world evidence, GMP mutual recognition agreements, orphan and pediatric medicines.

The full press release can be found here:

Free EMA SAWP protocol assistance for Academia

Free EMA SAWP protocol assistance for Academia Applicants from the academic sector can receive free protocol assistance for developing orphan medicines, as of 19 June 2020.   EMA offers this incentive to further encourage the development of medicines for rare diseases. The fee waiver for academia is available to: public or private highereducation establishments awarding academic degrees; public or private non-profit research organisation whose primary mission is to pursue research; international European interest organisations (as defined in Regulation (EU) No1290/2013).  Firstly, the applicant must be established in the EEA.  Secondly, the applicant must neither be financed nor managed by private for-profit organisations in the pharmaceutical sector, nor have concluded any agreement with any pharmaceutical companies about sponsorship or participation in the research project in question.

Full details of the scheme can be found here:

EMA SAWP meeting dates for 2021

EMA has issued dates for the 2021 SAWP meetings and deadlines for submission of scientific advice, protocol assistance, qualification of biomarkers and parallel consultation requests. Full details can be found under this link:

EC requests expression of interest in a consultation on voluntary sharing of market launch intentions

The EC has invited stakeholders to comment on a pilot project which will request prospective MAHs to declare their market launch intentions on a voluntary and confidential basis. The pilot aims to raise awareness of the limited roll-out of CP medicines in some EU Member States, and to improve regulators’ understanding of the reasons behind delayed market launch. The focus of the pilot will be on orphan medicines and medicines to treat cancer with the deadline for comments on 22 July 2020.

As link to the EC site can be found here:

Ph. Eur. Revised Raman Spectroscopy Chapter Public Consultation

The Ph. Eur. is seeking feedback on the revised draft chapter 2.2.48 on Raman Spectroscopy. Recent technological developments in Raman spectrometry have prompted several updates as well as the addition of new sections to the chapter: • Update of the section on response-intensity scale. • A new section on spectral resolution using calcium carbonate. • Procedures for the comparison of spectra have been included. The draft chapter is published in Pharmeuropa 32.3 and is open for public consultation between July and September 2020. Users who wish to submit comments but are unable to do so by the end of the consultation period due to COVID-19, are encouraged to contact their National Pharmacopoeia Authority in Ph. Eur. member states or the EDQM Helpdesk.

EC proposes relaxing GMO regulations for COVID-19 vaccines

The European Commission (EC) has proposed changes to the EU regulation of genetically modified organisms (GMOs), which would relax the requirements for the development of COVID-19 vaccines. The proposed changes would allow the clinical trials of GMO-containing candidate vaccines and COVID-19 treatments to start within the shortest possible timelines. The EC still plans to include an environmental risk assessment as part of the marketing authorization procedure for any products that fall under the proposed relaxed GMO regulations. These proposed regulations would also allow the distribution of medicinal products containing GMOs under a compassionate use exemption of Regulation (EC) No 726/2004. The EC has also indicated that this proposed regulation is temporary and is applicable only for the duration of the pandemic:

EMA: Updated procedural advice for orphan medicinal product designation

The EMA updated its procedural advice for orphan medicinal product designations on 15th June 2020. Applicants are now required to provide a description of the mechanism of action of their medicine in lay language in a maximum of 100 words. The text should describe as simply as possible the clinically relevant principle mechanism of action, in relation to the condition applied for. If orphan status is granted the text provided will be included in the public summary of the orphan designation published on the EMA website. The preferred format of the document is word format which should be submitted via IRIS with the other required documents listed in section 3.2 of the procedural advice.

Brexit:  Joint letter on the need for a Mutual Recognition Agreement (MRA) between the EU and UK

Six organisations from biopharma industry, including EFPIA and EUCOPE, have urged the EU to separate talks about post-Brexit regulatory cooperation from broader political negotiations. The plea is made amid fears the collapse of free trade talks will force a hard split between the UK and EU regulatory regimes. Particularly in current environment they stress it is crucial to ensure as much cooperation as possible with regard to regulatory processes and the import and export of medicines and medical supplies across UK/EU borders, in order to minimise delays in products reaching patients.

The letter in full can be found here: 

International Coalition of Medicines Regulatory Authorities (ICMRA) issues statements on vaccines to the public and HCPs

ICMRA has issued statements on vaccine confidence for the general public and on vaccine safety and effectiveness for HCPs. They explain the robust scientific and independent processes that medicines regulators worldwide follow, that ensure only vaccines that conform to the highest standards of safety and effectiveness can reach and remain on the market.

Full details of the statements in 7 languages can be found under this link:

Last week’s round-up; 15 – 19 June 2020

Ph.Eur. Supplement 10.3

The EDQM has published the contents of the Ph.Eur. Supplement 10.3. The list includes several new texts, such as the new monograph for testing bacterial endotoxins using recombinant factor C (2.6.32), as well as many revised general chapters and monographs. These new and revised texts will be implemented by 1st January 2021. Several corrected texts are also included in the list and these should be implemented by 31st August 2020. The list also includes texts that will be deleted from the Ph.Eur.

The entire list of contents of Supplement 10.3 may be viewed here: 

New EMA Bioequivalence Guidance for Levothyroxine Tablets and Abiraterone Tablets

The EMA has released the following draft product-specific guidelines: • A new bioequivalence guideline for Levothyroxine tablets 12.5 mcg, 25 mcg, 50 mcg, 75 mcg, 100 mcg (and additional strengths) and 200 mcg. • An updated bioequivalence guideline for Abiraterone tablets, which includes the addition of the 500 mg strength.

These draft guidelines are open for public consultation until 30th September 2020.

EMA, EC and Health Canada Confidentiality Arrangement

EMA, the European Commission and Health Canada signed a confidentiality arrangement in 2007. This was renewed in 2013 and 2020. The most recent changes introduced in 2020 include references to personal data legislation and to ensure the permanent validity of the arrangement.

The full document is available here:

FDA testing methods to detect nitrosamine impurities in Metformin

The FDA has published two analytical methods that regulators and pharmaceutical companies may use to detect nitrosamine impurities in metformin APIs and drug products: • LC-HRMS method: an LC-MS method for the detection of NDMA in metformin drug substance and drug products. • LC-ESI-HRMS method: an LC-HRMS method for the measurement of amounts of eight nitrosamine impurities in metformin drug substance and drug products. Users are required to validate these methods if the resulting data is used to support a quality assessment of the API or drug product or regulatory submissions: 

Global regulators work towards alignment

The International Coalition of Medicines Regulatory Authorities (ICMRA) convened its regular meeting on 12 June 2020 to discuss high-level policy and regulatory approaches in response to COVID-19. They agreed that a clear distinction between exploratory clinical trials and confirmatory studies with investigational or repurposed medicines for treatment of COVID-19 is critical for prioritisation. Regulators also shared concerns about the discontinuation of clinical trials globally and the growing number of underpowered studies that might not generate the robust data required for decision-making. Full details of the output from the meeting can be found here

EDQM companion list of training materials for vaccines

In order to support vaccine developers during the COVID-19 pandemic, the EDQM has made the Ph.Eur. quality standards for vaccines freely accessible through an online database on the EDQM website. Further to this, the EDQM has now also compiled a companion list of training materials related to vaccines. The document is intended for COVID-19 vaccine developers, including universities and small and medium-sized enterprises, with the intention to fast track their understanding of the Ph. Eur. and to help them to apply the relevant texts. The EDQM’s companion list includes hyperlinks to various presentations that were originally given at an EDQM Training Session on Biologicals held in February 2020 and any content of specific interest for vaccine developers is highlighted.

The list is not exhaustive and will be reviewed and updated as required.

EMA and HMA news:  Mandate of the European Innovation Network

EMA and HMA have issued an update to the document describing the mandate of the European Innovation Network (EU-IN), which seeks to coordinate and integrate views of national agency innovation offices and EMA’s Innovation Task Force for the early identification of promising developments, integration in the EU adaptive pathways, facilitate national designation of small and medium enterprises (SMEs) and to investigate the establishment of harmonised criteria for borderline products.

The full mandate can be found here:

Last week’s round-up; 08 – 12 June 2020


Disinfectant residues can pose various risks to a cleanroom environment, and there is renewed focus on best practice related to their prevention and removal. Current industry thinking is that any residual chemical is a potential contaminant to a process and possibly to product, and regulators are showing increased concern over residual disinfectants. This article gives an overview on why these residues matter, their main sources, and how to assess related risks. It also explains ways to tackle these residues, including through a routine residue removal program, instituting “low-residue” disinfectant formulations, and focusing on operator training to control application:


The EMA’s SME office has just issued their annual report for 2019. It makes for interesting reading. Some of the highlights include the highest ever number of registered SMEs with 12% created over the last 3 years. Product pipelines include 27% Orphan Medicines, 10% advanced therapies, 12% paediatric medicines and 25% generic medicines. Noteworthy too is the number of positive PRIME eligibility recommendations of 7 out of 16.

The report in full can be found here:


The EMA has just issued new guidance on remote GCP inspections during the COVID19 pandemic. The inspection team, in agreement with the CHMP requesting the inspection, should make a case-by case decision on whether a remote inspection is considered appropriate and feasible. It too is assumed that Sponsors, CROs and service providers (e.g. medical imaging, central laboratories) have at their disposal advanced technologies, electronic systems and virtual working environments which facilitate remote staff or company locations worldwide to communicate systematically. These technologies may allow the necessary access for inspectors to the relevant systems (e.g. electronic trial master file (eTMF)) remotely and enable appropriate communication settings during inspection. The guidance covers initiation, preparation (setting, team location, technical requirements, agenda), conduct and reporting process.

The full document is available here:


The EMA has published a new ‘Clinical pharmacology and pharmacokinetics Q&A’ regarding biowaivers (Q&A 6.4) in fixed combination oral solid dosage forms. The EMA Guideline on the investigation of bioequivalence (CPMP/EWP/QWP/1401/98 Rev.1) allows for a biowaiver in multiple strength applications of fixed combinations as long as the applicant can demonstrate quantitative proportionality between the strengths. However, deviations from the quantitatively proportional composition are still considered acceptable under certain conditions. This extremely useful new Q&A provides clarification on these conditions and it also includes various examples.

Further information is available here:


EMA has just issued a neat 1-page leaflet describing their preparedness to support the development and marketing authorisation of safe, effective and high-quality therapeutics and vaccines against COVID-19. The Agency has put in place rapid review procedures related to COVID-19 to deliver assessments of high-quality applications from sponsors in the shortest possible timeframes.

The leaflet can be found here:


This morning I was reading a very interesting commentary on the EMA Regulatory Science strategy to 2025 published on the Nature site.  The article spoke to the core recommendations that stakeholders deem the most significant to advance evidence generation for medicines, including fostering innovation in clinical trials, reinforcing patient relevance in evidence generation, use of high quality real-world data in decision making, developing the regulatory framework for emerging data sources and contributing to HTAs’ preparedness and downstream decision-making for innovative medicines.

The article in full can be found


As of June 1st 2020, two new Pharmaceutical Inspection Co-Operation Scheme (PIC/S) guidance documents have entered into force: Questions and Answers on Implementation of Risk-based Prevention of Cross-contamination in Production and ‘Guideline on Setting Health-Based Exposure Limits for Use in Risk Identification in the Manufacture of Different Medicinal Products in Shared Facilities’, and an aide-memoire on health-based exposure limit (HBEL) assessments. The Q&A guidance on cross-contamination fully mirrors the EMA’s guideline of the same name except for an additional references section that points to other PIC/S guidelines. Whereas the HBEL guidance document “describes an approach to assessing HBEL that can be conducted by inspectors without specialised toxicology knowledge”.

Further information about these new guidance document may be found here:

Last week’s round-up; 01 -05 June 2020


We are delighted to have Michael Edwards join the team at Real Regulatory as a Senior Regulatory Consultant. Michael has worked in regulatory affairs since 2000, having held positions in the UK medicines competent authority, a couple of CRO/consultancies, a couple of small/medium pharmaceutical companies, and as an independent consultant, as well as taking some time out during that time to do post-graduate research and complete a PhD investigating the vascular bioactivity in vitro of the phenolic phytochemicals anthocyanins, and their in vivo degradation products or metabolites, in the Department of Nutrition at Norwich Medical School. His first degree was BSc Pharmacology with Toxicology (First) at King’s College London, including a year-long industrial placement in a large pharmaceutical company research centre. His regulatory experience includes clinical phase through post-marketing authorisation, national and European procedures. Michael will be a valuable asset to our company and to our clients.


At a recent virtual meeting of the ICH Assembly, the ICH has announced that Turkey’s Medicines and Medical Devices Agency (TITCK) is now one of its regulatory members and that Lebanon’s Ministry of Public Health (MOPH) is now a new observer. During the meeting, the Council also announced that the following guidelines have reached Step 4 in the ICH process: M8 electronic Common Technical Document (eCTD) v4.0 guideline; S11 Nonclinical Safety Testing in Support of Development of Paediatric Pharmaceuticals guideline; and S5(R3) Guideline on Revision of S5 Guideline on Detection of Toxicity to Reproduction for Human Pharmaceuticals. The Council has also announced that the Q3C(R8) guideline on residual solvents, which is currently under revision to include the permitted daily exposures for three new impurities, has reached Step 2 of the ICH process, and that the 4Q(R1) Common Technical Document (CTD) guideline will be revised.

Further updates given by the ICH during the Assembly may be found at the following link:


Joint procedural information is available from EMA and the FDA for medicine developers planning to submit a PIP to EMA and an iPSP, to the FDA, respectively, for a COVID-19 vaccine or treatment, the document can be found under this link

The joint document aims to make it easier for developers to submit paediatric development plans simultaneously to the regulators, to help speed up the development and approval of COVID-19 treatments and vaccines. Both agencies are encouraging medicine developers to submit PIPs and iPSPs early.


The FDA has just released 26 new and 43 revised draft product-specific guidances on the development of generic drugs. The documents are intended to clarify the FDA’s recommendations on demonstrating bioequivalence of generics to the corresponding reference products. The new drafts include recommendations to support ANDAs for generic versions of the acute myeloid leukemia drug gilteritinib, the PARP inhibitor talazoparib, the HIV-1 treatment dolutegravir/lamivudine, fish oil triglycerides, subcutaneous buprenorphine and extended-release metformin. The updated guidance documents include altered recommendations for generic versions of type 2 diabetes drugs dapagliflozin, dapagliflozin and saxagliptin, the renal failure treatment ferric citrate and transdermal buprenorphine.


The European Commission’s updated ‘Annex to the European Commission guideline on Excipients in the labelling and package leaflet of medicinal products for human use’ is effective from 22 November 2019. The guidance describes the information that should be available in the package leaflet on excipients that are known to have a recognised action or effect. In order to ensure compliance with the new guidance, marketing authorisation holders are required to submit a type IB variation within three years from the publication of the revised Annex. HPRA has pointed out that applicants should also be aware that some of the updates included in the Annex were also published in the previous version of the document, therefore, applicants are requested to submit the relevant variations by 9/10/2020.


New measures for all UK arrivals have been announced, including a 14 days’ self-isolation for anyone entering the UK, apart from a “short” list of exemptions. At moment of writing, these measures are due to come into effect on 8 June, although this could change given the backlash from the UK travel industry. The “short list of exemptions” is not really all that short, and amongst the many listed are including the following of note to the pharmaceuticals and clinical trials sectors: qualified persons and responsible persons for human medicines, clinical trials and pharmacovigilance quality assurance inspectors for human medicines sponsors and essential persons needed for clinical trials or studies The new measures can be found at:

The list of exemptions can be found at:


Horseshoe crabs’ blood has long been used in the pharmaceutical industry to detect the presence of bacterial endotoxins, causing concern amongst animal rights groups who are pushing for the use of synthetic alternatives. The USP Microbiology Expert Committee had proposed the inclusion of synthetic recombinant factors in ‘Chapter 85 Bacterial Endotoxins’. Based on public comments received, this will not happen. Instead, a new general chapter will be drafted, to provide guidance on the qualification of alternative tests by demonstrating comparability: <1085.1> Use of Recombinant Reagents in the Bacterial Endotoxins Test – Photometric and Fluorometric Methods Using Recombinantly Derived Reagents The proposed new general chapter should be available for public consultation by November 2020. More information may be found at the following link:

This matches the approach taken by Ph. Eur. in 2016 when ‘Chapter 5.1.10 Guidelines for Using the Test for Bacterial Endotoxins’ was updated. Ph. Eur. is further ahead as it has already published a new section ‘2.6.32 Test for bacterial endotoxins using recombinant factor C’ in supplement 10.3, effective from 1 January 2021.


The European Medicines Agency (EMA), European Commission and Heads of Medicines Agencies have updated their ‘Questions and answers on regulatory expectations for medicinal products for human use during the covid-19 pandemic’. The guidance document now includes a new section on temporary flexibilities for good manufacturing practice (GMP) and good distribution practice (GDP) that pharmaceutical companies may employ during the pandemic to ensure an adequate supply of medicines used to treat COVID-19 patients. A new section on the suspension of on-site inspections of plasma collection centres has also been included. Temporary flexibilities related to the duties of the responsible person (RP), the use of new equipment or newly authorized storage and distribution sites, and deviations from normal practice are also discussed in the document. Further information is available at the following link:

Last week’s round-up; 25 – 29 May 2020


The US FDA has found the carcinogenic nitrosamine impurity NDMA in several batches of extended-release (ER) formulations of metformin, which is used to treat patients with type 2 diabetes. The impurity was found to be above the acceptable limit in these products.

The agency has, therefore, called upon the five pharmaceutical companies involved to voluntarily recall these ER metformin products. Other metformin manufacturers which supply a large portion of the US market have not been affected by the recall. However, the FDA is collaborating closely with manufacturers to ensure appropriate testing for NDMA levels in these products. The agency is also conducting assessments to determine whether any shortages in metformin may arise due to the recalls, and it intends to help prevent or reduce the impact of any such shortages.


The EMA has issued a Q&A document (June 2020) highlighting some key points for successful qualification of digital technology-based methodologies used in medicines development, for example as part of the conduct of a clinical trial. The Q&A reflects the EMA’s current experience, and notes that if a digital technology is used in the context of product development, evaluation or monitoring, and could impact the benefit-risk assessment, then relevant aspects will be discussed at product assessment (such as reliability versus established data capture methods), and so qualification should be considered during development. Examples are given of technologies falling within the scope of the qualification programme, and the process for requesting advice or an opinion is outlined. The Q&A ends with five overarching guiding principles for a qualification submission, and in particular the importance of early and focused interactions with the agency.

The document is available here:


MHRA “Guidance Good clinical practice for clinical trials” gives guidance on how to show MHRA you’re meeting GCP standards and what to expect from an inspection. MHRA requests pre-inspection documentation information in the form of a GCP inspection dossier & a clinical trials spreadsheet within 30 days of notification of an inspection. The GCP dossier clinical trials spreadsheet which is used to prepare the GCP dossier and is part of the requested pre-inspection documentation was updated on the 22nd May 2020.

The updated GCP inspection dossier clinical trial spreadsheet can be viewed via this link


What are the key pharmacokinetic considerations in the assessment of biosimilarity?

The EMA has updated question 7.1 of its Clinical Pharmacology and Pharmacokinetics Q&A, which tackles the above issue. The related response clarifies the differences between requirements for biosimilar products and small molecule generics. It provides further detail on the following issues that need to be considered in assessment of biosimilarity: linear clearance, nonlinear clearance, anti-drug antibodies, batch selection and protein content correction, study population, dose level, sampling times, and statistical comparison:


Mexico has been welcomed as an observer state by the European Pharmacopoeia Commission.

Mexican authorities can now participate in the scientific work of the European Pharmacopoeia Commission and other activities of the European Directorate for the Quality of Medicines (EDQM). This brings the European Pharmacopoeia’s total observer countries to 30, together with the 39 European countries and European Union as signatory parties:


The WHO has released a new digital version of its Model list of Essential Medicines (EML).

This WHO reference tool is currently used by over 150 countries to compile their national essential medicines lists to ensure that these essential medicines are always available in their health care system in the appropriate dosage forms and quality, and at affordable prices.

Users will now be able to freely access the EML online database on smartphones and computers. The system also allows users to create their own customized lists by exporting the list (or part thereof) into an Excel or Word version.

Last week’s round-up; 18 – 22 May 2020


The EMA has released several updates to its pre-authorisation and post-authorisation procedural advice for users of the centralised procedure. Some of the updates include:


The EMA now aims to respond to queries within 10 days instead of 5. Other changes as can be seen in the tracked documents linked here:


The International Council for Harmonisation (ICH) Management Committee and Assembly has indicated that it intends to collaborate more closely with the Pharmaceutical Inspection Co-Operation Scheme (PIC/S) and that new topics and reflection papers are currently under development.

ICH Management Committee has proposed that the PIC/S would be involved in ICH guideline work relevant to regulatory assessor [MG1] and inspector disciplines, during the public consultation following Step 2b. Additionally as an ICH Observer, the PIC/S may also request to be part of Plenary Working Parties which would allow its involvement prior to Step 1.

A revised draft reflection paper on model-informed drug development and an update on a draft reflection paper on patient-focused drug development are also in the pipeline. The Biotechnology Innovation Organization has also proposed to develop a reflection paper on gene therapy harmonization.


Pharmeuropa has released new supporting information on the new draft Ph. Eur. Chapter 2.4.35 ‘Extractable elements in plastic materials for pharmaceutical use’, which is open for consultation until the end of June 2020. The document proposes that the long‑established individual tests for specific elements are maintained in the Ph. Eur. general chapters on plastic materials, since the quality of plastic materials influences that of the containers manufactured from them.

In future, cross‑reference to this new general chapter will also be made in each existing Ph. Eur. text on plastic materials. The supporting information also indicates that all the existing Ph. Eur. general chapters on plastic materials should be revised to delete the heavy metals test and to perform the tests on target elements according to the new general chapter.


“Field Safety Notices (FSNs) are a key part of the medical device vigilance system. Manufacturers are required to inform users about corrective actions involving their device as soon as possible using a Field Safety Notice (FSN). Published on the 20th May by the MHRA to advise manufacturers on how to write clear FSNs to maximise response rates the guidance provides supplementary information to MEDDEV 2.12/1 rev 8 (how to write and distribute effective FSNs) and covers such topics as good traceability, content, effective targeting of FSNs and Field Safety Corrective Action (FSCA) strategy. Manufacturers are advised to read the document via the following link:


We’re proud to have our Real expert, Dorothée Fouchier, attending the virtual 2nd Joint DIA-EUCOPE Workshop on ATMPs, Innovative Gene and Cell Therapies, next week alongside our industry peers to discuss the challenges, opportunities and political implications of advanced therapies. If you’re also attending, get in touch! To arrange a meeting visit:


The European Medicines Agency (EMA) has reduced the fee for on-site GMP inspections by 100%. This fee reduction is only applicable in cases where the GMP compliance of a manufacturing site with restricted access due to the COVID-19 pandemic, could not be confirmed via a distant assessment and an on-site inspection is, therefore, required. Fees for Plasma Master Files inspections will also be similarly reduced.

The EMA has also advised that during this initiative, remuneration to national competent authorities (NCA) will not be reduced, if the NCA provides a comprehensive inspection report for the distant assessment and a subsequent independent report for the on-site inspection. Further information is available here:


The scope of EMAs ITF covers regulatory, technical and scientific issues arising from innovative medicines development, new technologies and borderline products. The objective of the interactions with the ITF is to facilitate informal exchange of information and guidance during the product development process. Interactions take the form of informal brainstorming discussions are led by experts from the Agency network, working parties and committees. These meetings are free of charge and 1.5 hours long. ITF has just issued a new briefing meeting request form in order to standardise company initial dialogue. The form can be found here:


The MHRA inspectorate posted ‘How to manage temporary GDP process changes and risks through the COVID-19 pandemic’ on their blog on the 13th May to advise companies on how to manage changes to GDP processes to address exceptional circumstances that have arisen due to Covid-19. Such changes should be documented either as deviations, change controls or similar and incorporate quality risk management principles. Changes may be documented either as single reports or an over-arching one specific to COVID-19. The post has a link to GDP flexibilities introduced by the MHRA to assist with distribution of medicines during COVID-19 pandemic documented in ‘Guidance Exceptional GDP flexibilities for medicines during COVID-19’. The GDP flexibilities introduced cover Supply Chain, Transportation, RP, Facilities & Equipment and Reporting.

Companies applying these flexibilities need to report to Covid19.GMDP@ as outlined in the guidance, however you only need to report once for each flexibility and reports don’t require approval to implement. The post can be accessed via this link:


The 505(b)(2) route to marketing authorisation in the United States has become very popular. Companies owning a product registered (or eligible to be registered) via this pathway might also wish to submit their product in Europe. Real Regulatory can help companies navigate the significant complexities involved in choosing an appropriate legal basis for submission, setting regulatory strategy and dealing with scientific advice and marketing authorisation procedures.

Read the linked article for an overview of the intricacies and the ways in which we can assist.


The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has released a new version of its ‘Application for new Manufacturer’s “Specials” Licence (MS) (Human Use).

To access the new version of the application form please see the following link:

Last week’s round-up; 11 – 15 May 2020


The GCP IWP has published its meeting dates and a list of its priorities for 2020. The priorities of the group will continue with an EU focus and maintaining international relationships. However, of particular interest is the upcoming work to create and finalise a series of Q&As on the following noteworthy topics Q&A on inspectors’ access to patients’ medical records/data when the access of EEA inspectors to medical information is not clearly stated in the Informed Consent Form (ICF). Q&A on sponsor oversight of activities subcontracted to third parties. Q&A on expectations for provision of written information to clinical trial subjects in relation to new information requiring re-consent. Q&A on confidentiality undertaking of EU/EEA inspectors.

The full entirety of the work plan can be found under this link:


The EMA’s Dasatinib product-specific bioequivalence guidance is currently under revision. A revised draft guideline has been released for public consultation and comments will be received until 31st August 2020. The current adopted guidance concerns bioequivalence testing requirements for Dasatinib 20, 50, 70, 80, 100 and 140 mg film-coated tablets. The draft revised document also includes requirements for Dasatinib 10 mg/ml suspension and the additional requirement for a fed study for both dosage forms.


CMDh has updated the following guidance: – RMS validation checklist for human medicinal products in DCP – Data requested for New Applications in the MRP/DCP which are not stated in the current EU legislation and/or in Volume 2B, Presentation and format of the dossier Common Technical Document (CTD) and/or in the EEA approved Guidelines/Recommendation papers – Data requested for Variations and/or Renewal Applications in the MRP/DCP which are not stated in the current EU legislation and/or in Volume 2B, Presentation and format of the dossier Common Technical Document (CTD) and/or in the EEA approved Guidelines/ Recommendation papers – CMDh Best Practice Guide on the use of the electronic Common Technical Document (eCTD) in the Mutual Recognition and Decentralised Procedures – CMDh Questions & Answers on implementation of outcome of Art. 31 referral on angiotensin-II-receptor antagonists (sartans) containing a tetrazole group – Practical guidance for procedures related to Brexit for medicinal products for human use approved via MRP/DCP.

The updated documents (most with tracked changes) may be viewed here:


The MHRA has recently adopted a flexible and pragmatic approach to regulatory requirements for medical device clinical investigations during the COVID-19 pandemic. This is documented in Guidance “Medical devices clinical investigations (CIs) during the coronavirus (COVID-19) outbreak”. The updated guidance, which now includes a new section relating to COVID 19, details regulatory flexibilities introduced for ongoing and new submissions for CIs.

There is an expedited process in place for CIs directly relating to COVID-19. However, it states that if MHRA is unable to reach a decision by the new internal deadline, the 60-day assessment period still applies, and the applicant cannot start the study until they have received a final decision from the MHRA or until 60-days after the notification. The update also states that the MHRA is working on a process for studies where there is both a medicine and a medical device to allow for a single application via the Clinical Trials Unit to ensure a smooth and fast assessment of both elements.

The guidance document which can be accessed via this link: 


The EMA’s Committee for Medicinal Products for Human Use (CHMP) has recommended the precautionary suspension of all ranitidine medicines in the EU due to the presence of low levels of the potentially carcinogenic impurity, N-nitrosodimethylamine (NDMA).

Many European national authorities had already recalled ranitidine medicines as a precautionary measure during the EMA’s review. There is some evidence which shows that NDMA may form from the degradation of ranitidine itself over the course of its shelf-life, however, it is still unclear whether the impurity can also be formed from ranitidine inside the human body.

The CHMP recommendation will be forwarded to the European Commission, which will issue a final legally binding decision applicable in all EU Member States.


The 166th European Pharmacopoeia (Ph.Eur.) Commission session was still held electronically despite the restrictions and lockdowns brought on by the COVID-19 pandemic. During the Ph.Eur. Commission session, 91 texts, including 11 new texts, were adopted and will be published in the Ph. Eur. Supplement 10.4 and effective from 1st April 2021.

The new texts include general chapter 5.28 on Multivariate Statistical Process Control and monographs for Regorafenib Tablets, Riociguat Tablets, Rivaroxaban Tablets and Sorafenib Tablets. A list of the adopted texts will soon be available on the EDQM website. Monographs for sartan drug substances have also been revised to add a requirement for risk assessment of the manufacturing process and to replace interim limits for NDMA and NDEA with a 0.03 ppm limit. The next Ph. Eur. Commission session is due to take place on 23rd June 2020.