EDQM Archives - Real Regulatory

Supplement 10.8 of the Ph. Eur. is now available and CEP Holders are invited to update their applications according to the revised monographs that will be implemented on the 1st July 2022. 16 revised Ph. Eur. monographs are now available including texts for ‘Calcium gluconate for injection’ and ‘Cholecalciferol concentrate (powder form)’. The article linked below provides a full list of the revised monographs as well as instructions for CEP holders and a description of information that should be submitted to the EDQM depending on the classification of the updates made to the monograph.

Manufacturers object to provisions in FDA’s microbiological quality guidance

An industry trade group and several manufacturers are calling for revisions to the FDA’s draft guidance on microbiological quality considerations for non-sterile drugs (NSDs). The draft guidance was designed to help manufacturers control microbiological contamination of their NSDs and stems from the Agency’s concerns over a high number of adverse events and recalls associated with contaminated products, including Burkholderia cepacia complex (BCC) in non-sterile water-based drug products. According to one manufacturer, one of the main issues with the guidance is a recommendation for the periodical identification of microorganisms in manufacturing facilities, which would be a “significant new requirement” that is not necessary for NSDs and which would be unsustainable. Another stakeholder has said that the new provision calling for manufacturers to test potential objectionable organisms for each nonsterile product, is not practical. Another issue brought up by the industry is that the draft FDA guideline is not aligned with the ICH Q7 guideline on APIs as the former calls for microbiological testing of components such as APIs and excipients, while the Q7 guidance does not. Further comments from stakeholders may be found in the RAPS article below.

Revised ICH Q9 guideline to improve risk assessments

The ICH has issued a revised ICH Q9(R1) guideline that aims to address the shortcomings of the current guideline by providing “more scientific and robust applications of quality risk management principles” leading to “fewer quality defects and recalls” and reduced costs for the pharmaceutical industry.

The revised Q9 guideline is intended to address four shortcomings of the current version:

· Lack of clarity on risk-based decision making The revision includes new text which acknowledges that some degree of subjectivity in QRM is unavoidable while offering methods to reduce or control subjectivity.

The document also includes a new section on formality in quality risk management and contains new text on the role of QRM in addressing product availability risks. The revised guideline is open for public consultation until the 15th March 2022.

Phthalates

Phthalates are commonly used as softeners to make plastics more flexible and durable. They can also be found in adhesives, sealants, paints, rubber materials, wires and cables, flooring, packaging, food contact materials, medical devices and sports equipment. Several ortho-phthalates may have endocrine effects and may affect the sexual development of boys which can lead to infertility in adults. Some phthalates are also harmful to the environment. From the 7th July 2020 the use of phthalates has been restricted in the EU/EEA. These restrictions are estimated to save approximately 2000 boys per year from impaired fertility. The Candidate List of substances of very high concern (SVHC) contains several ortho-phthalates. Manufacturers and importers must notify the ECHA if their products contain a substance on the list within six months after inclusion of the substance in the list. 14 phthalates are also on the REACH Authorisation List. Use of substances on the list will be prohibited after a given date unless the EC authorises the company to continue its use. Prior to applying for authorization, companies also need to demonstrate that the use of the substance is controlled, that there are no suitable alternatives and that the benefits of continued use exceed the risks.

FDA: Risk of benzene contamination in certain drugs

The FDA has alerted drug manufacturers to the risk of benzene contamination in certain drugs and is currently evaluating the root cause of contamination. Benzene is a known human carcinogen that causes leukaemia and other blood disorders. In pharmaceuticals, inactive ingredients such as carbomers (thickening agents), isobutane (a spray propellant), or other drug components made from hydrocarbons may be potential sources of benzene. The Agency is advising manufacturers to conduct risk assessments to evaluate the possible presence of benzene in their drug products and components, with a special focus on ingredients that are hydrocarbons or are manufactured with benzene or other hydrocarbons. According to ICH Q3C, benzene is classified as a Class I solvent and should not be used in the manufacture of drug substances, excipients, or drug products because of its unacceptable toxicity. However, the guidance does allow for limited cases where the presence of benzene may be tolerated up to a level of 2 ppm, unless otherwise justified. The article linked below provides information on how manufacturers should contact the FDA if benzene is detected in their drug products (including products that are already in distribution). It also contains information that the Agency may request during follow up.

Last weeks’ round -up;
06-17 December 2021

Ph. Eur. Commission – 171st Session Outcome

During the 171st session of the Ph. Eur. Commission, which took place in November 2021, 75 texts were adopted for publication in the 11th Edition of the Ph. Eur. These consist of 66 revised texts and nine new texts, including the following:

• Revised and harmonised (through the Pharmacopoeial Discussion Group) chapter on Chromatographic Separation Techniques (2.2.46);

• Revised and now harmonised monographs Paraffin, white soft (1799) and Paraffin, yellow soft (1554);

• Two new general chapters, Assay of Bet v1 allergen (2.7.36) and Microbiological examination of human tissues (2.6.39).

Change in EDQM timelines for CEP applications

As of the 1st October 2021, the EDQM launched a new IT tool to manage CEP applications. This new tool requires that timelines for evaluation of all CEP applications and their revisions/renewal be specified in working days instead of calendar days. This provides more clarity on deadlines for applicants, particularly when the Directorate’s offices are closed. However, to avoid disruptions in the applicants’ internal procedures, the timelines for response to requests for additional information, clarification, etc., for ongoing procedures will continue to be counted in calendar days/months.

Pediatric Clinical Trials Updates

In their annual report, the European network of paediatric research at the EMA (EnprEMA) has highlighted timelines relating to planned updates of the Pediatric and Orphan Regulation. A proposal for revision of the legislation will be published by the end of 2022, with the aim that this will be adopted between 2023-2024. The Working Group on international collaboration has also stated that two manuscripts are being drafted regarding clinical trial application approval by National Competent Authorities and Ethics Committees covering six jurisdictions. The full report can be read in the link :

Medicines repurposing – EU pilot project

Through a newly announced pilot project, EMA and national competent authorities will be offering tailored scientific advice to not-for-profit organisations and academia on repurposing an authorised medicine for a new indication. It is expected that applicant organisations would then work in partnership with, or handover to, a Marketing Authorisation Holder to generate a variation, extension, or new market authorisation application. Candidate medicines should be authorised, contain a well-established active substance, and be out of data exclusivity and market protection periods and out of basic patent/supplementary protection certificate protection. They must also target a new indication in a condition distinct from the currently authorised indication/s, in an area where important public health benefits or Union interests are likely to be achieved.

Update to EMA’s post-authorisation procedural advice for users of the centralised procedure

The EMA has emphasised the importance of site and organisation registrations in the Organisation Management Service (OMS) prior to related pre- and post-authorisation submissions for centrally authorised medicinal products. This registration became mandatory from 1st November 2021, and will constitute a validation blocking issue if not done.

Updated EMA procedural advice on classification of advanced therapy medicinal products

The EMA has revised its Procedural Advice on the Provision of Scientific Recommendation on Classification of Advanced Therapy Medicinal Products in Accordance with Article 17 of Regulation (EC) no 1394/2007. The procedure exists to address questions on borderline classification with other areas, such as medical devices, as early as possible. The document gives guidance for the steps to be followed by the applicant and EMA for the ATMP classification, and can be accessed through the link below.

Update to the EMA’s Sponsor Handbook on the new Clinical Trials Information System (CTIS)

The EMA has included new and updated sections in its Sponsor Handbook on CTIS. Updated sections include those on the OMS registration process, user personas and organisation models, product management, transitioning from the Directive to the Regulation, and SUSARs reporting. Sections that have been newly added relate to data fields and documents specifications, and the Sandbox environment for user training and organisation preparedness. The document can be accessed through the link below.

Last week’s round -up;
25-29 October 2021

Antimicrobial Resistance – expected regulatory implications

Activities of the Transatlantic Taskforce on Antimicrobial Resistance (TATFAR) are expected to have regulatory implications. Mentioned within their current progress report are agreements on clinical trial recommendations that will be reflected in updated guidance documents for several different types of bacterial diseases. Also identified for continued collaboration up till 2026 are strategies to improve financial incentives, access, research, and development of antimicrobial drugs, diagnostics, and alternatives. Furthermore, the definitions for multidrug-resistant (MDR), extensively drug-resistant (XDR) and pan-drug-resistant (PDR) bacteria for human infections will be revised.

Japan’s PMDA posts English translation of guidelines for bioequivalence studies

Japan’s PMDA has released an English translation of guidelines and questions and answers on bioequivalence studies of generic products.The guidelines cover bioequivalence studies, dissolution tests and other assessments for various dosage forms, including oral immediate release and oral extended-release products. The guideline also features a shorter section on non-oral dosage forms and dosage forms for which bioequivalence studies are waived.

Guidance on good lay summary practice

Guidance on good lay summary practice (GLSP) has recently been published by the European Commission. The guidance provides recommendations on how to prepare, write, translate, and disseminate summaries of clinical trial results in lay language, and was adopted by the expert group on clinical trials in July 2021. Sponsors should note that lay summaries on each clinical trial are a mandatory requirement of the upcoming Clinical Trial Regulation. Relatedly, the guidance highlights mandatory requirements under the regulation, and those which are optional recommendations based on ethical obligations and related best practices.

Updates from the EDQM

• A revised osmolality chapter for public comment in Pharmeuropa. The revised chapter focuses on osmolality reference solutions using sodium chloride that are required for instrument verification. The deadline for comments is the 31st December 2021.

• The Pharmacopoeial Discussion Group is preparing a pilot for global expansion of membership to integrate additional world pharmacopoeias.

• CEP holders are invited to comment on draft monographs published in Pharmeuropa 33.4. The deadline for comments is 31st December 2021.

• CEP holders are invited to update their applications according to the revised monographs published in Ph. Eur. Supplement 10.7 that will be implemented on the 1st April 2022.

Public consultation on EU pharmaceutical legislation

The European Commission has launched a public consultation on the revision of the EU’s pharmaceutical legislation. The consultation will last until 21st December 2021 and will gather views from stakeholders and the general public. The last review of the EU’s pharmaceutical legislation took place almost 20 years ago and the overarching aims of this revision are: to ensure access to affordable medicines, foster innovation, improve security of supply, adapt to new scientific and technological developments, and reduce red tape. In the consultation, the EC also asks if there are other problems it needs to address.

The EMA’s tailored scientific advice offering for biosimilar development will be continued

In its report on the initial pilot offering of tailored scientific advice for new biosimilar development, the EMA has announced that this will be continued as part of regular scientific advice operations. When using the procedure, developers are advised on the studies they should conduct, based on a review of the quality, analytical and functional data they already have available. The service will be capped at a maximum of 2 procedures per month, and the duration is set to 70 days if managed without a discussion meeting or 100 days if such a meeting is needed.

Updated Q&A on GMP compliance for IMPs

The European Commission has released an updated Q&A no. 8.4 on the Clinical Trials Regulation 536/2014. The updated Q&A covers the documentation that is required to show compliance of an IMP and AxMP with GMP, which is also outlined in Chapter IX and Annex 1 section F of the CTR:

• No documentation is required for IMPs authorised in the EU (even if not manufactured in the EU).

• For IMPs that are not authorised in the EU and do not have an MA from a third country that is party to ICH, and are not manufactured in the EU, an authorisation referred to in article 61(1) and a QP declaration of GMP equivalence is required. In the latter case, if a Mutual Recognition Agreement (MRA) covering clinical trials is in place with the particular country, the latter declaration is not required if the MRA provides for GMP equivalence already.

• An authorisation according to article 61 of the Clinical trial Regulation is required for all other cases.

• Information regarding the GMP compliance of APIs is not required by the CTR (and can therefore not be required by the Member States concerned).

Last week’s round -up;
04 -08 October 2021

EU extension of GMP and GDP certificates through 2022

EU regulators have automatically extended GMP and GDP certificates and other time-limited authorisations (manufacturing, import and wholesale authorisations) through 2022 due to COVID-19 safety and travel restrictions. This has been done to ensure the availability of medicines throughout the EU during the pandemic. For sites within the EEA, the extensions should occur without any action on the part of the certificate holder, unless any restrictions on the validity period are stated in the clarifying remarks of the certificate or the issuing/supervisory authority takes action that affects the validity of the certificate. The automatic extension does not apply to changes in the scope of the certificate. Distant assessments by an EEA supervisory authority may be required for new sites in third countries when no applicable mutual recognition agreement (MRA) exists with local regulators.

Risk of the presence of mutagenic azido impurities in losartan API

Following a report about the possible presence of potentially mutagenic azido impurities in certain sartan active substances, the EDQM has taken a number of measures to ensure that any active substances containing these impurities above the acceptable level would not be released onto the market. Holders of impacted CEPs were also requested to take corrective action to ensure that such impurities do not exceed their acceptable limits in the future. The EDQM’s recent investigations identified another azido impurity that has so far only been detected in losartan potassium (losartan azido impurity). This impurity has tested positive in a bacterial mutagenicity (Ames) test. The Directorate has advised that this azido impurity should be controlled at or below the Threshold of Toxicological Concern (ICH M7) due to the lack of additional information from in vivo studies. CEP holders were advised of their obligation to provide appropriate information relating to azido impurities to MAHs, therefore, enabling them to fulfil their legal responsibilities.

FDA: Microbial contamination in non-sterile drugs

The FDA has issued draft guidance to help manufacturers control microbiological contamination of non-sterile drugs (NSDs) due to concerns over a high number of adverse events and recalls associated with contaminated products. The draft guidance covers product development considerations, risk assessments, and GMP requirements that are relevant to control microbiological contamination in the manufacturing of a non-sterile drug. Solid non-sterile dosage forms as well as semi-solid forms and liquid non-sterile dosage forms including topically applied creams, lotions and swabs; and oral solutions and suspensions are covered in the guidance. The draft guidance applies to prescription or non-prescription drugs and approved NDAs or ANDAs as well as over-the-counter monograph drugs. Adverse events and recalls of drug products due to Burkholderia cepacia complex (BCC) contamination are included in the guidance, and prevention and testing for BCC in aqueous dosage forms of NSDs are also described. Further information on the draft guidance may be found in the link below and the deadline for comments is the 30th December.

Updated EMA Nitrosamines Q&A

A new draft Ph. Eur. monograph on Particle Size and Shape Determination by Image Analysis has been published in Pharmeuropa 33.4 for public consultation until the 31st December 2021. Image analysis is a computer-based technique used to determine the size and shape of particles from digital images efficiently and reliably. The images may be obtained by several techniques including optical microscopy, chemical imaging or electron microscopy. The measuring principle is based on a discretisation of an image into ‘pixels’, which are calibrated with respect to size and a software algorithm assigns the pixels to individual particles, which are thus characterised by a defined number of pixels of known size. The new guidance covers both static and dynamic image analysis. The dynamic technique can measure more particles than in static image analysis and is more reliable for wide size distributions, however, the technique is prone to systematic errors with respect to size.

Last week’s round -up;
27 September – 01 October 2021

CEPs: Revised terms of reference and rules of procedure

A revised version of the terms of reference and rules of procedure for certification of suitability has been adopted by the Certification Steering Committee and is available on the EDQM website. This revision clarifies the title and certain working procedures and takes into account the organisational changes in the EDQM Certification of Substances Department.

New EDQM IT tool for the management of CEP activities

As of October 2021, the CEP Department (DCEP) of the EDQM will use a new IT application for the management of its activities. The implementation of this tool will entail certain changes in the way the Directorate communicates with applicants for CEPs and CEP holders: Communication with companies regarding CEP applications will occur via e-mails or automatic notifications which will be sent instead of letters in an increasing number of situations, such as reminders and acknowledgements of receipt of responses to deficiency letters and requests for revisions. Therefore, applicants are strongly advised to provide the DCEP with the name and valid e-mail address of a suitable contact person and to inform the department whenever any changes occur. Applicants will now receive documents via the “EDQM DCEP Sharing tool”, which allows documents to be shared securely. Documents will be available for download for 60 days and will be deleted from the tool afterwards. The EDQM CERTIFICATION Database will display in real time the reasons why any CEPs are no longer valid (e.g. in case of suspension, withdrawal or expiry).

Medical Device Reforms – TGA to strengthen the regulation of medical devices in Australia

‘Early 2019 and mid 2021, the TGA undertook public consultations on proposals to reclassify a number of categories of medical devices so that they align, wherever possible, with the changes being introduced in European Union (EU) medical devices framework.From 25 November 2021, medical devices which are intended to be used in direct contact with the heart, central circulatory system (CCS) or the central nervous system (CNS) will be required to meet regulatory requirements demonstrating the safety and performance for Class III medical devices. Transitional arrangements are in place for medical devices registered with ARTG prior to 25 November 2021, to allow for continued supply your device whilst undergoing the transition to Class III medical device.’

Last week’s round -up;
06 -10 September 2021

Comments concerning revised texts published in Supplement 10.7

Ph. Eur. Supplement 10.7 is now available and will become effective on 1 April 2022. Some of the revised texts include the following general chapters and general monographs:

• Liquid preparations for cutaneous application (0927) Several active pharmaceutical ingredient monographs have also been updated.

The technical modifications can also be consulted in the Knowledge database under ‘View history’.

Revised EDQM guidance for electronic submissions for CEP applications

The EDQM has issued an updated “Guidance for electronic submissions for Certificates of Suitability (CEP) applications” to reflect the current practices to facilitate eCTD submissions for CEPs. One important recommendation in the revised guidance is that when switching to the eCTD format from another format, it will be mandatory to include any information already assessed and approved previously in a ‘baseline (full dossier)’ to facilitate lifecycle management. This update will be implemented by January 2022, however, the Directorate recommends that applicants implement this recommendation as soon as possible. The revised guidance also includes some clarifications regarding specific topics such as the submission of grouped revisions and examples of format issues hindering the receipt of applications.

Warning to pharmaceutical industry on nitrosamine risk assessments

During an IPEC webinar, the pharmaceutical industry was advised to closely evaluate suppliers’ testing and question dubious results to ensure that accurate methods are being used to assess nitrosamine risks in drug products. The warning was issued following a recent case where a supplier outsourced the testing of an excipient to a contract laboratory, due to a lack of in-house testing capabilities. The test results exceeded acceptable thresholds for each of the six nitrosamines tested. After a “lot of dialogue” between the supplier and the contract lab, the contract lab reviewed their testing documents and findings and subsequently uncovered errors in the testing. The lab retested the samples and found the excipient was actually within acceptable limits.

New draft Ph. Eur. 2.9.48 on Particle Size and Shape Determination by Image Analysis

Last week’s round -up;
23-27 August 2021

New multi-analyte methods for evaluating migration from printing inks

The EDQM has released an inter-laboratory study, conducted in 2020, on multi-analyte methods for the determination of substances migrating from printing inks to food or food simulants. The study is part of the process in the development of guidelines related to the quality and safety of materials and articles which come into contact with food. The new analytical methods were validated by 11 control laboratories and are intended for competent authority laboratories and for private laboratories to assess the safety of food contact materials and articles. These analytical procedures detect contaminants which can pass into food from printed packaging including 6 photoinitiators, 3 related degradation products and 1 plasticiser.

EMA Reflection Paper on Statistical Methodology for Comparative Assessment of Quality Attributes

The EMA has adopted a Reflection Paper on Statistical Methodology for the Comparative Assessment of Quality Attributes in Drug Development. The reflection paper provides statistical methodology for the comparative assessment of quality attributes in the settings of pre- and post-manufacturing change, biosimilar development and generics development. The paper addresses questions related to comparison objectives, sampling strategies, sources of variability, acceptance ranges and statistical analysis approaches to conclude on the similarity of two drug products based on quality attribute data. The main objective of the guidance is to establish a framework and a common language to facilitate future discussion among stakeholders and to invite comments in relation to the issues raised. This guidance complements other available regulatory guidance on comparative data assessment of quality attributes, but it also contains more detail on how to carry out the comparison task based on empirical sample data.

FDA stands by nitrosamine risk assessment deadline

The US FDA has rejected the pharmaceutical industry’s request to extend the deadline for conducting nitrosamine risk assessments to 1st September from the original 31st March 2021 deadline. In September 2020, the FDA issued guidance on nitrosamine testing for pharmaceuticals, which required manufacturers to assess the nitrosamine impurity risks associated with all chemically synthesized APIs and all approved or marketed drug products that contain those APIs or other sources of nitrosamines by 1st March 2021. The FDA extended the deadline to 31st March due to complaints received from the industry. The industry then requested a further extension to 1st September due to the “time-consuming” and “resource-intensive” risk assessments required. The industry also expressed concern that the global supply chain may be affected due to the “magnitude of the risk assessments and subsequent confirmatory testing” resulting in drug shortages. Although the FDA has worked with manufacturers that have detected a high amount of nitrosamine contamination to mitigate drug shortages, the Administration has said that it has “not planned for additional extensions at the current time”.

SWP opinion on Diethanolamine and Coconut Oil Diethanolamine Condensate as excipients

The EMA has issued the opinion of the Safety Working Party (SWP) regarding diethanolamine and coconut oil diethanolamine condensate as excipients. There are carcinogenicity and genotoxicity concerns because diethanolamine has been shown to have carcinogenic potential in mice. The SWP’s conclusions regarding use of these excipients in medicinal products were: (1) MA holders should assess whether the use of the excipients in their products is still justified. PDEs of 53 micrograms/day and 705 micrograms/day were set for lifetime use and for use up to 12 months respectively. For the condensate, the level of contamination with diethanolamine should be identified and controlled at the PDE. (2) The possibility of formation of the nitrosamine impurity NDELA must be avoided. (3) For rinse-off medicinal products, retention factors of 0.01 and 0.1 are considered acceptable for diluted and undiluted products respectively.

Last week’s round -up;
19-23 July 2021

New Ph. Eur. Golimumab concentrated solution monograph

The EDQM has released a new draft monograph on a single-source anti-TNF-alpha monoclonal antibody, Golimumab concentrated solution. The Ph. Eur. Commision has used the single-source approach to elaborate this draft monograph and the text reflects the considerations outlined in the EDQM’s scientific publication on “Elaborating European Pharmacopoeia monographs for biotherapeutic proteins using substances from a single source”. The draft monograph is open for public consultation until the 30th September 2021.

Notification for CEP holders: Implementation of Ph. Eur. Supplement 10.6

Ph. Eur. Supplement 10.6 is now available and the EDQM has invited CEP holders to update their applications according to the revised monographs that will be implemented on the 1st January 2022. The Directorate has provided a list of substances covered by a CEP and for which a revised monograph will be implemented, and updates are classified into two categories, “Case A” and “Case B”. “Case A” concerns cases where the specification of the substance should be updated according to the revised monograph. “Case B” concerns amendments to the monograph which require the submission of data to the EDQM. In the article linked below, the EDQM has provided detailed instructions for CEP holders and manufacturers on how to proceed depending on which case the updates relate to.

FDA ICH Q12 EC Pilot Program

ICH Q12 facilitates the management of post-approval CMC changes for new and marketed drug products and drug substances. According to the guideline, regulators will allow manufacturers to identify and submit established conditions (ECs) for new drug applications and prior approval supplements. ECs are defined as “legally binding information considered necessary to assure product quality.” Manufacturers can propose reporting categories for post-approval changes after identification of ECs. In 2019, the US FDA started the EC Pilot Program where sponsors could propose explicit established conditions (ECs) as part of an original new drug application, abbreviated new drug application, biologics license application or as a prior approval supplement.

The following RAPS article outlines the outcome of the pilot program and discusses the different approaches taken by manufacturers when defining ECs:https://bit.ly/RealCMC-3zfE60L

Revised Ph. Eur. general chapter on chemometric methods applied to analytical data

The revised general chapter Chemometric Methods Applied to Analytical Data (5.21) has been published in Pharmeuropa 33.3 and is open for comments until the 30th September 2021. This general chapter is published for information and is an introduction to the use of chemometrics and data science techniques. Some of the updates in the revised Chapter include: · An update of section 1 ‘General aspects’ with a review of parts of ‘Pre-processing’ and ‘Assessment and validation of chemometric methods’. · Two new sub-sections on ‘Independent component analysis’ and ‘Decision trees and random forests’. · A general review of sub-sections on ‘Similarity measures’, ‘Clustering’, ‘Multiple linear regression’, ‘Principal component regression’, ‘Support vector machines for supervised classification’ and ‘Artificial neural networks’. · A new section, 3. ‘Related application fields’, including sub-sections on ‘Chemometrics in chemical imaging’ and ‘Data fusion’. · An update of the Glossary and the Abbreviations.

Last week’s round -up;
01-05 February 2021

Pharmeuropa updates

The following draft revised monographs (with tracked changes) have been published in Pharmeuropa. The draft monographs are available for public consultation until 31st March 2021.

EMA News: EMA announces detail approach on training for the new Clinical Trial Regulation CTIS portal.

In anticipation of CTIS go-live in Dec 2021 to support implementation of the CTR, online training modules are foreseen from 21st Jan to ensure equal access for all. Once launched, CTIS will be immediately available for authorities and clinical trial sponsors, with a 3 year phased transition period from the current Directive 2001/20/EC. EMA plans 3 training streams

3. Targeting different forms of end-users on role specifics (e.g. admin, preparer, submitter).

Real Regulatory has SME status and will initially train on the 2nd stream. Training and our current involvement in pilot schemes now available will mean we can continue to provide best support to our clients.

EMA News: EMA has issued a new draft guidance on the Module 3 quality support packages required for MAAs of PRIME Designated Medicines.

PRIME was launched to enhance EMA support to the development of medicines that target an unmet medical need. EMA has just published a draft guidance on scientific elements and regulatory tools to support quality data packages for applications to the scheme. This should serve as a toolbox for building Module 3 quality data packages in the preparation of marketing authorisation applications (MAAs) of designated PRIME medicinal products.

EMA News: EMA has published detailed accelerated assessment timetables for ATMP full MAAs

The EMA has published a new document which details timetables for full MAA procedures for Advanced therapy medicinal products (ATMPs). Timings extend through to end of 2024, and include assessment of the initial submission (120 day timetable) and timings for assessment of responses to list of questions (30 day timetable after clock-stop).

UK MHRA updates Pharmacovigilance System requirements

Following user feedback, the MHRA have edited some of their guidance on Qualified Person responsible for Pharmacovigilance (QPPV) and pharmacovigilance system master files (PSMF) to make it easier to understand and to provide clarification on certain points. The updated guidance can be found here: http://bit.ly/3cAuxkU

UK MHRA publishes the submission dates for the new UK national MAA 150-day procedures

Marketing Authorisation Application submission dates for the new 150-day national and European Commission decision reliance procedures and guidance on how submissions using the EC decision reliance procedure work have been published on the MHRA website, and can be found here: http://bit.ly/3j8GNua

Updates from the EDQM

The EDQM has recently released the ‘New European Pharmacopoeia Technical Guide for the elaboration of monographs on medicinal products containing chemically defined active substances’.

• European Paediatric Formulary: Phosphate Oral Solution open for public consultation in issue 3 of Pharmeuropa PaedForm (17-Dec-20)

• European Pharmacopoeia Commission adopts new general chapter Contaminant pyrrolizidine alkaloids (2.8.26) (05-Jan-21)

• Pharmeuropa 33.1 just released: don’t miss this opportunity to provide your comments (06-Jan-21)

• Brexit: End of mutual recognition of Official Control Authority Batch Release between the EU/EEA and the UK (08-Jan-21)

• Adoption of Fritillariae thunbergii bulbus describing alternative quality control test (15-Jan-21)

• Implementation of the European Pharmacopoeia Supplement 10.5 – Notification for CEP holders (18-Jan-21)

• CEP holders invited to comment on draft monographs published in Pharmeuropa 33.1 (20-Jan-21)

Last week’s round -up;
30 November – 04 December 2020

Revised Palbociclib and Abiraterone product-specific bioequivalence guidance

The EMA has issued the following product-specific bioequivalence guidance: • A draft bioequivalence guidance for Palbociclib 75 mg, 100 mg and 125 mg hard capsules and 75 mg, 100 mg and 125 mg film-coated tablets. This guidance is open for public consultation until the 28th February 2021. • A newly adopted bioequivalence guidance for Abiraterone tablets 250 mg and 500 mg.

Comments concerning revised texts published in Supplement 10.5

The EDQM has published the technical modifications that have been made to revised texts adopted by the European Pharmacopoeia Commission at the June 2020 session and published in Supplement 10.5. The details may also be consulted in the Knowledge database under ‘View history’.

UK medicines regulator gives approval for first UK COVID-19 vaccine

The first COVID-19 vaccine for the UK, developed by Pfizer/BioNTech, has today been given approval for use following a thorough review carried out by the Medicines and Healthcare products Regulatory Agency (MHRA). A copy of the press release is at the link: https://lnkd.in/dvDb4FR The BBC was reporting this morning that the UK is the first country worldwide to authorise a COVID-19 vaccine for a mass-vaccination programme.

Specific permits required to order Residual solvent solution class 1 CRS COVID-19 vaccine

As of the 1st January 2021, specific permits will be required to order R0250000 – Residual solvent solution class 1 CRS. This reference standard contains two controlled substances, carbon tetrachloride and 1,1,1–trichloroethane, which are ozone-depleting substances and, thus, prohibited in the EU except under certain conditions for laboratory and analytical uses. Users that require delivery within the EU, must provide a valid LabODS number to the EDQM when ordering the Ph. Eur. RS R0250000 reference standard, while any orders for delivery outside the EU are subject to licensing requirements.

Updated Brexit post transition guidance

The MHRA has updated its guidance on the location and other authorised personnel requirements for the post transition period. Guidance on centrally authorised MAs, mutual recognition and decentralised MAs, existing UK national MAs, GB MAs, named distributor, manufacturing sites, quality control and QPs was updated. The MHRA has also published a new section on the definition of products placed on to the GB market.

Real Regulatory is now part of tranScrip – your life science powerhouse.

In March 2022, Real Regulatory became a subsidiary of tranScrip, a leading contract drug development organisation supporting the entire life cycle of medicines.

As a result, this website is now closed. You can now keep up-to-date with us at www.transcrip-group.com

This is a really exciting journey for both companies and we look forward to working with you on your development programmes, from discovery through to post-licensing.

Thank you.

Last week’s round -up; 10-21 January 2022

Ph. Eur. Supplement 10.8 Implementation – Notification for CEP holders

Manufacturers object to provisions in FDA’s microbiological quality guidance

Revised ICH Q9 guideline to improve risk assessments

Phthalates

FDA: Risk of benzene contamination in certain drugs

Last weeks’ round -up; 06-17 December 2021

Ph. Eur. Commission – 171st Session Outcome

Change in EDQM timelines for CEP applications

Pediatric Clinical Trials Updates

Medicines repurposing – EU pilot project

Update to EMA’s post-authorisation procedural advice for users of the centralised procedure

Updated EMA procedural advice on classification of advanced therapy medicinal products

Update to the EMA’s Sponsor Handbook on the new Clinical Trials Information System (CTIS)

Last week’s round -up; 25-29 October 2021

Antimicrobial Resistance – expected regulatory implications

Japan’s PMDA posts English translation of guidelines for bioequivalence studies

Guidance on good lay summary practice

Updates from the EDQM

Public consultation on EU pharmaceutical legislation

The EMA’s tailored scientific advice offering for biosimilar development will be continued

Updated Q&A on GMP compliance for IMPs

Last week’s round -up; 04 -08 October 2021

EU extension of GMP and GDP certificates through 2022

Risk of the presence of mutagenic azido impurities in losartan API

FDA: Microbial contamination in non-sterile drugs

Updated EMA Nitrosamines Q&A

Last week’s round -up; 27 September – 01 October 2021

CEPs: Revised terms of reference and rules of procedure

New EDQM IT tool for the management of CEP activities

Medical Device Reforms – TGA to strengthen the regulation of medical devices in Australia

Last week’s round -up; 06 -10 September 2021

Comments concerning revised texts published in Supplement 10.7

Revised EDQM guidance for electronic submissions for CEP applications

Warning to pharmaceutical industry on nitrosamine risk assessments

New draft Ph. Eur. 2.9.48 on Particle Size and Shape Determination by Image Analysis

Last week’s round -up; 23-27 August 2021

New multi-analyte methods for evaluating migration from printing inks

EMA Reflection Paper on Statistical Methodology for Comparative Assessment of Quality Attributes

FDA stands by nitrosamine risk assessment deadline

SWP opinion on Diethanolamine and Coconut Oil Diethanolamine Condensate as excipients

Last week’s round -up; 19-23 July 2021

New Ph. Eur. Golimumab concentrated solution monograph

Notification for CEP holders: Implementation of Ph. Eur. Supplement 10.6

FDA ICH Q12 EC Pilot Program

Revised Ph. Eur. general chapter on chemometric methods applied to analytical data

Last week’s round -up; 01-05 February 2021

Pharmeuropa updates

EMA News: EMA announces detail approach on training for the new Clinical Trial Regulation CTIS portal.

EMA News: EMA has issued a new draft guidance on the Module 3 quality support packages required for MAAs of PRIME Designated Medicines.

EMA News: EMA has published detailed accelerated assessment timetables for ATMP full MAAs

UK MHRA updates Pharmacovigilance System requirements

UK MHRA publishes the submission dates for the new UK national MAA 150-day procedures

Updates from the EDQM

Last week’s round -up; 30 November – 04 December 2020

Revised Palbociclib and Abiraterone product-specific bioequivalence guidance

Comments concerning revised texts published in Supplement 10.5

UK medicines regulator gives approval for first UK COVID-19 vaccine

Specific permits required to order Residual solvent solution class 1 CRS COVID-19 vaccine

Updated Brexit post transition guidance

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06-17 December 2021

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25-29 October 2021

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