Last week’s round-up;
10 -14 August 2020

Evaluation of the medicines for rare diseases and children legislation

On 11 August 2020, the EC published an evaluation of the EU orphan and pediatric regulations, adopted in 2000 and 2006, respectively. Following an evaluation comprising several steps, the regulations were analysed according to five criteria: effectiveness, efficiency, relevance, coherence; and EU added value. It was concluded that the regulations met their main objectives of increasing the number of products for patients with rare and paediatric diseases in the EU. Conversely, however, issues were recognised including: · Products may not be equally accessible across the EU or affordable to national health systems; · Circumstances may have changed since the regulations were introduced; · The regulations do not have instruments to counteract observed clustering of products leaving areas of unmet need, or to direct development to areas most relevant to children; · The concept of prevalence as a tool to receive orphan designation and the length of the 10-year market exclusivity period may need to be re-examined. Looking forward, it was noted that some of the issues identified are closely linked to and will be tackled by the Pharmaceutical Strategy for Europe.

https://lnkd.in/daqjhgh

EMA addresses risk evaluation, mitigation for nitrosamines

The EMA has updated its Q&A document on nitrosamine impurity testing for marketing authorisation holders. MAHs need to perform a risk evaluation to determine whether chemically synthesized active pharmaceutical ingredients are at risk of containing nitrosamines by 31 March 2021 (extended deadline). This same requirement has now been extended to biologicals, with a deadline of 1 July 2021. Biologicals considered particularly at risk include those containing chemically synthesized fragments, those where nitrosating reagents are added, and those packaged in nitrocellulose blister packs. The document includes further deadlines for confirmatory testing where applicable, as well as related variation submission requirements. It also delineates specific requirements for analytical methods to be used in testing, mitigation measures when nitrosamines are detected, and daily acceptable limits for various nitrosamines.

https://bit.ly/RealCMC-2XSGoCR

Tackling serious impurities

Discovery of N-nitrosamines in a variety of medicines over the last two years could have a much wider impact on pharmaceutical manufacturers and regulators than previously expected. The underlying issue in all N-nitrosamine contamination cases was inadequate control of impurities, and so European Union regulators want manufacturers and national regulators to take more effective action in tackling all potentially carcinogenic impurities in APIs and finished products. This decision arises from results published by a ‘lessons learnt’ group within the EU medicines licensing network. The group has proposed a variety of guidance reviews, including those relating to marketing authorization holders, finished product and API manufacturers, active substance master file and CEP holders. Updates to ICH M7 and the EU’s good manufacturing practice guidance have also been proposed.

https://bit.ly/RealCMC-2DNXhax

GMP inspectorate audits, Brexit stockpiling, and MHRA’s Covid-19 divergences

The EMA’s Mutual Recognition partners can now take part in audits of the GMP inspectorates of national authorities. MRA partners could previously participate in audits as observers and, from now on, will also be able to participate as co-auditors if they express an interest in doing so. However, MRA partners still won’t be able to serve as lead auditor, as this role is reserved for European groups. In other regulatory news, the UK government has asked industry to stockpile medicines ahead of the next Brexit deadline at the end of the year. The MHRA has also highlighted nine areas where its COVID-19 flexibilities diverge from EU policies. The list includes MHRA’s positions on qualified person declarations, the 30-day limit for type 1B variation replies, leaflet mock-ups and over-labelling.

https://bit.ly/RealCMC-2PL1LBi

Endotoxin levels in investigational cancer treatments

The US FDA has released new draft guidance on setting limits for endotoxins during the clinical trial process for parenteral oncology drugs intended for serious and life-threatening cancers. This new document provides risk-based guidance on endotoxin limits for investigational therapies that are used in early clinical trials in conjunction with other approved treatments or with other investigational medicines. Patients’ possible exposure to endotoxin levels exceeding USP recommendations may be considered an acceptable risk under appropriate circumstances.

https://bit.ly/RealCMC-3ipJZzX

(more…)

Last weeks round-up; 27 April 2020 – 1 May 2020

DO YOU WANT UP TO 90% FEE REDUCTIONS AT EMA?

Do you want to access up to 90% fee reductions at EMA?

No existing legal company entity within EU/EEA?

Do you meet the criteria for SME status?

If YES, then Real Regulatory has the solution. Check out the criteria here https://lnkd.in/dKidU2Z, your company can abridge on the existing Real Regulatory SME status to quickly become eligible for the SME incentives. Contact us to action your application now. https://lnkd.in/daQjxxj

AMENDING THE DETAILS OF AN EU ORPHAN DRUG DESIGNATION SPONSOR

EMA has issued updated instructions on how to amend the name and/or address details of a Sponsor of an Orphan Drug Designation. This does not require a new legal act, provided that the sponsor remains the same person or legal entity. Sponsors need to use EMA’s IRIS platform to submit post-designation activities. EMA will not be able to process any submissions outside of IRIS. A change in the name and/or address can be requested only after a designation has been granted by the European Commission. Full details of the guidance can be found https://lnkd.in/dDuFNXs

MCDG GUIDANCE ON MDR CLINICAL INVESTIGATIONS AND EVALUATIONS

Guidance is now available to assist stakeholders in implementing the MDR Clinical Investigation and Clinical Evaluation requirements. The Medical Device Coordination Working Group (MDCG) developed the following guidance documents which were published on the website of the European Commission (EC) on the 23rd April:

The documents provide much needed clarification on MDR requirements pertaining to clinical data and demonstration of equivalence. The documents can be accessed via the following link https://bit.ly/35hqlkA.

EC: MITIGATING CLINICAL TRIAL DISRUPTION IN EUROPE

The European Commission (EC) has issued guidance to ensure that clinical trials can continue during the COVID-19 pandemic. The aim is to mitigate the disruption of clinical research without compromising on quality and safety. With more than 200 coronavirus clinical trials now registered in the EudraCT database, the guidance offers recommendations for simple and flexible measures. Key recommendations of the guidance cover, distribution of medicines to patients, remote source data verification, and communications with authorities. For the latter, the guidance clarifies the classification and notification of these actions. The measures will be used exclusively during the coronavirus pandemic, and will be revoked once the current health crisis in the EU/EEA has been surpassed. https://lnkd.in/gRc5XkX

MDR POSTPONED BY ONE YEAR

In response to Covid-19 the European Commission (EC) adopted a proposal on the 3rd April to postpone by one year the application of the Medical Devices Regulation (MDR). The European Parliament adopted the proposal on the 17th April, followed quickly by adoption of the Council on 22 April. The EC has announced that the amending Regulation 2020/561 was published in the Official Journal on the 24th April and has entered into force on its date of publication. This means that the date of application of the MDR will become 26 May 2021 instead of 26 May 2020 and that the Medical Devices Directives will be repealed one year later on the new date of application of the MDR. EC announcement can be viewed via link here https://bit.ly/2xgRpUq.

Last weeks round-up; 2 – 6 March 2020

RECOMMENDATIONS ON THE ELIGIBILITY TO PRIME SCHEME ADOPTED AT THE CHMP MEETING OF 24-27 FEBRUARY 2020

The recommendations on eligibility to the PRIME scheme adopted at the CHMP meeting of 24-27 February 2020 has been posted on the EMA website, along with the cumulative overview of recommendations on PRIME eligibility requests adopted since the scheme began in 2016. In keeping with the usual proportion of grants and denials, of 5 applications for the month, 1 was granted whilst 4 were denied. The one granted is a gene therapy for “treatment of X-linked Retinitis Pigmentosa owing to defects in Retinitis Pigmentosa GTPase Regulator” supported by clinical exploratory data. The four that were denied are chemical substances, all of which also included clinical exploratory data, in the therapeutic areas of cardiovascular diseases, gynaecology, endocrinology, and neurology. For further details, please click: https://lnkd.in/ePz256f

FINAL VERSION OF ICH GUIDELINE Q12 HAS BEEN PUBLISHED

ICH Q12 covers technical and regulatory c onsiderations for pharmaceutical product lifecycle management. It has been in the works for quite a while and is intended to globally harmonise the management of post-approval changes to chemistry, manufacturing and controls (CMC). However, there are some conceptual differences between ICH Q12 and the current EU legal framework, meaning that there are limitations on how fully ICH Q12 can currently be implemented within the EU.

Incompatible sections are those on scientific risk-based approaches to defining established conditions and associated reporting categories (described in Chapter 3.2.3 of the new guideline) and on the product lifecycle management document (PLCM, described in Chapter 5). Within the EU, regardless of the current text within ICH Q12, the definition of established conditions and their reporting categories must follow the requirements laid down in the current EU Variations Regulation and associated EU guidelines. The PLCM cannot currently be recognized if submitted. https://lnkd.in/g2vefsg

EMA NEWS: QUALIFICATION OF NOVEL METHODOLOGIES FOR MEDICINE DEVELOPMENT

EMA has just published the adopted Qualification Opinion on the Multiple Sclerosis clinical outcome assessment (MSCOA) and an overview of comments received. The intent is for this COA instrument to serve as a primary, co-primary, or secondary endpoint to assess efficacy in clinical trials at various stages of drug development, including proof of concept, dose-ranging, confirmatory and registration trials. There are four specified performance outcome measures assessing important dimensions of multiple sclerosis (MS), which are considered as a battery of tests, some or all of which could be used as a dysconjugate composite endpoint by sponsors in a clinical trial. Full details are available here  https://lnkd.in/d_WeSAN

EMA: ANNUAL REPORT ON THE USE OF THE SPECIAL CONTRIBUTION FOR ORPHAN MEDICINAL PRODUCTS DURING 2019

An important incentive offered by the legislation is the possibility for sponsors of orphan medicinal products to receive reductions in the regulatory fees payable to the Agency. A special contribution is allocated annually to the Agency by the European Union (EU) for fee reductions for orphan medicinal products. Since the year 2000, over 2,233 orphan designations have been issued by the European Commission, of which so far 169 have resulted in authorised medicinal products. This link https://lnkd.in/ddDfHfV presents a nice table detailing the EMA policy on the level of fee reductions reflects the priority given to ‘protocol assistance’ and the support to small and medium-sized enterprises (SMEs) and other information on the scheme. EMA has issued this updated presentation on the statistics for Orphans https://lnkd.in/gt-xChE

EMA ISSUES A PRESS RELEASE ON RECENT ORGANISATIONAL CHANGES

The purpose of the re-organisation has been stated as to ensure that the Agency operates as efficiently as possible, taking into account the rapidly evolving landscape for pharmaceutical research and development, and driven by the need to recalibrate to a lower head count following the relocation of the Agency to Amsterdam in 2019. Several org charts have been issued. A new EMA org chart  https://lnkd.in/ejYBSyJ, where operations in the area of human medicines have been integrated into one Human Medicines Division, which will be led by Alexis Nolte. In addition, four mission-critical task forces have been established to support the human and veterinary medicines divisions. Here is a link to the new task forces org chart  https://lnkd.in/esvDkNe. Updates to the existing org charts for Stakeholders & Communication Division, Information Management and Advisory functions have also been issued and can be found on the site.

Search Real Regulatory