real 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An industry trade group and several manufacturers are calling for revisions to the FDA’s draft guidance on microbiological quality considerations for non-sterile drugs (NSDs). The draft guidance was designed to help manufacturers control microbiological contamination of their NSDs and stems from the Agency’s concerns over a high number of adverse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 week’s round -up;
03-07 January 2022

All you ever wanted to know about Ph. Eur. procedure 4 but never dared to ask

The EDQM has released a new document, ‘Procedure 4 (P4) – Everything you always wanted to know’, intended to help stakeholders understand the advantages of applying for monograph elaboration via this route. Procedure 4 monograph elaboration applies to active substances (and corresponding medicinal products) or excipients present in medicinal products that are still under patent or single source, provided that the medicinal product has been approved in at least one member state of the pharmacopoeial convention. It also applies to monographs on biotherapeutics as elaborated by the P4bio Working Party Advantages of P4 elaboration are: 1. Direct contact with the EDQM. 2. Regular updates during the elaboration process / full transparency. 3. Specifications as approved by the licensing authorities are unchanged. 4. A CEP can be requested immediately after adoption of the new monograph.

More clarity on ICH continuous manufacturing guideline requested

Several industry trade associations have requested more clarity on the ICH Q13 guideline on continuous manufacturing (CM), which covers CM of drug substances and drug products, including chemical entities and therapeutic proteins. Stakeholders have asked for clarity on what constitutes a state of control for a CM process, the scope of the guideline, and the definition of a batch size. More clarity on whether the principles in the guideline also apply to ATMPs has been requested. A stakeholder has also suggested that an example of a CM process being in a “state of control” should be provided as this would help in demonstrating when a state of control has been achieved. It has also been suggested that the definition of a batch should be expanded to include additional examples. Another stakeholder has suggested that the section of the guideline on non-conforming material or waste in CM should be revised, as manufacturing waste has not been a significant issue in CM. It has also been suggested that the guideline should make a clearer distinction between CM of small molecule drugs and biologics, since regulatory review, inspection, and management of post-launch process changes can differ significantly.

New FDA Guidance on the Inspection of Injectable Products for Visible Particulates

The FDA has released a new draft guidance on the Inspection of Injectable Products for Visible Particulates – Guidance for Industry. The draft guidance focusses on the development and implementation of a holistic, risk-based approach to visible particulate control that incorporates product development, manufacturing controls, visual inspection techniques, particulate identification, investigation, and corrective actions designed to assess, correct, and prevent the risk of visible particulate contamination. The guidance also clarifies that compliance with an applicable USP compendial standard alone is not generally sufficient for meeting the current GMP requirements for the manufacture of injectable products. However, the guidance does not cover subvisible particulates or physical defects that products are typically inspected for along with inspection for visible particulates such as container integrity flaws, fill volume, appearance of lyophilized cake/suspension solids.

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 weeks’ round -up;
15-26 November 2021

Good Machine Learning Practice (GMLP) – Guiding Principles

As the artificial intelligence and machine learning medical device field evolves, so too must best practice in Good Machine Learning Practice (GMLP). Through regulatory collaboration between the U.S. FDA, Health Canada, and the MHRA, 10 guiding principles have been identified which should be addressed when medical devices use artificial intelligence and machine learning software. These 10 guiding principles, which address the unique nature of these products are intended to lay the foundation for developing GMLP, in addition to the promotion of safe, effective, and high-quality medical devices that use artificial intelligence and machine learning.

Updated mitigation strategies to reduce the risk of nitrosamine drug substance-related impurities in drug products

The FDA has received reports of certain types of nitrosamine impurities that formed in several drug products. These nitrosamines share structural similarities to the active ingredient and are therefore referred to as drug substance-related impurities (NDSRIs). NDSRIs may be generated during manufacturing or during the shelf-life storage period of the drug product. NDSRI formation has also been attributed to nitrite impurities present in commonly used excipients, including water, at parts-per-million amounts. Manufacturers are expected to use the three-step mitigation strategy described in the FDA’s guidance (Control of Nitrosamine Impurities in Human Drugs) to determine the presence of nitrosamines, including NDSRIs in their drug products. The Agency is encouraging applicants to develop control strategies and/or design approaches to reduce NDSRIs to acceptable levels if unacceptable levels are detected. One mitigation strategy described in the guidance includes a supplier qualification program for potential nitrite impurities across excipient suppliers and excipient lots to reduce the risk of nitrosamine formation in the drug product.Other possible mitigation strategies are also described in the FDA article linked below.

CMDh meeting: Ph. Eur. finished product monographs / EMA

The CMDh has published the minutes for the meeting held between the 12th and 14th October 2021. During the meeting the QWP responses to the CMDh questions on Ph. Eur. Medicinal Product Monographs (MPMs) were presented. The QWP has advised that, in principle, already authorised products for which a Ph. Eur. MPM is official should comply with the requirements described in the monograph, unless otherwise described in the General Notices of the Ph. Eur. If the MPM is official before a generic product is approved, the generic product has to comply with the requirements described in the monograph. However, if the generic product is approved before the MPM is developed, the MPM should have been developed to embrace the quality of all approved medicinal products. If this has not been the case and the generic product specification is wider than the range described in the MPM, this should be communicated to the National Pharmacopoeia Authority and EDQM to be considered for inclusion in a revised monograph. Several other scenarios are also described in Section 3.9 of the meeting minutes below.

Last weeks’ round -up;
01-12 November 2021

FDA releases 48 new and updated product-specific guidances

The FDA has released 48 new or updated product-specific guidances (PSG) as well as a newly developed infographic that provides a snapshot of the overall PSG program. The new draft PSGs include guidances to aid in the development of generics for the malaria treatment artesunate, the non-statin cholesterol lowering drug bempedoic acid, small cell lung cancer therapy lurbinectedin, the cholangiocarcinoma treatment pemigatinib, and migraine drug rimegepant sulfate, among other reference listed medicines. The FDA’s webpage on upcoming PSGs for complex generic drug product development has also been updated, with the agency’s progress in meeting its commitments under the reauthorization of the Generic Drug User Fee Amendments (GDUFA II).

PDG signs-off on milestone harmonised general chapter on chromatography

On the 28th September 2021, the Pharmacopoeial Discussion Group (PDG) signed off the harmonised general chapter on Chromatography, which brings together the Ph. Eur., JP and the USP texts. The chapter contains harmonised requirements which promote the development of individual monographs with a consistent approach and enhance understanding of basic requirements by users in all three regions. Particular attention was paid to:

· System suitability: this section provides requirements intended to guarantee that the performance of the chromatographic system is appropriate. They apply to multiple monographs and are to be read in conjunction with the requirements described therein.

MDCG issues new Q &A document regarding repackaging and relabelling of medical devices

MDCG 2021-26 Questions and Answers on repackaging & relabelling activities under Article 16 of Regulation (EU) 2017/745 and Regulation (EU) 2017/746

FDA: Nitrosamine detection tests should be ‘fit for purpose’

The US FDA has advised manufacturers that analytical tests used for the detection of nitrosamines should be “fit for purpose” in order to ensure that the right test is measuring the right impurity. The Agency has also advised that orthogonal (additional) methods should be used to double-check results. Nitrosamine contamination can be process-related, the impurities may be introduced via the supply chain or formed over the shelf-life of the drug product. The RAPS article below describes various case studies highlighting the importance of cross-checking and using analytical methods that are fit for purpose while conducting nitrosamine risk assessments.

Medical Device Coordination Group issues new guidance for legacy devices

MDCG 2021-25 Application of MDR requirements to “legacy devices” and to devices placed on the market prior to 26 May 2021 in accordance with Directives 90/385/EEC or 93/42/EEC

Revised ICH guideline on general considerations for clinical trials, ICH E8(R1)

The revised ICH guideline on general considerations for clinical trials [ICH E8(R1)] has been adopted by the Committee for Human Medicinal Products and will come into effect on 14th April 2022. This is the first time the guideline has been revised since its original adoption in 1997, and its update is being considered the “first step towards the Renovation of Good Clinical Practice initiated in 2017”. The revised guideline adopts quality-by-design principles and highlights fit-for-purpose data quality as one of the essential considerations for all clinical trials. Main updates identified from the previous version are a basic set of critical-to-quality factors that can be adapted to different trials, incorporation of a broader range of trial designs and data sources, and an updated cross-referencing of all other relevant ICH Guidelines that should be referred to when planning clinical studies.

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;
18-22 October 2021

Final EMA feedback on Titanium Dioxide

The EMA has issued its final feedback to the EU Commission request to evaluate the impact on medicinal products of the removal of titanium dioxide from the list of authorised food additives. The request from the Commission was triggered by the opinion of the European Food Safety Authority (EFSA), published in May 2021: “that on the basis of all currently available evidence along with all uncertainties, in particular the fact that genotoxicity could not be ruled out, titanium dioxide can no longer be considered as safe when used as a food additive”. The Commission requested the EMA’s analysis in order to define the technical purpose of titanium dioxide in medicinal products, the feasibility of alternatives to replace it without negatively impacting the quality, safety and efficacy of medicines, and if confirmed, considerations to be taken into account to define a transition period for phasing out this excipient. The EMA concluded that the feasibility of replacing titanium dioxide cannot be confirmed at this stage, and an acceptable transition period is currently difficult to envisage or estimate.

ICH guideline proposes daily limits for seven mutagenic impurities

The International Council for Harmonization (ICH) issued its M7(R2) guideline for public consultation. The guideline sets new permitted daily exposure (PDE) limits for seven DNA-reactive substances to limit their carcinogenic risk. The guideline contains 21 mutagenic impurities including the following 7 newly added impurities with their PDE levels: · Acetaldehyde: (oral) 2 mcg/day – 185 mcg/day for all other routes · 1,2 Dibromoethane: 2 mcg/day · Epichlorohydrin: 3 mcg/day · Ethyl bromide: 32 mcg/day · Formaldehyde: (inhalation) 8 mcg or 215 parts per billion/day; all other routes 10 mg/day · Styrene: 154 mcg/day · Vinyl acetate PDE: (oral) 2 mcg/day – 758 mcg/day for all other routes The guideline has now been split up into one main guideline and an addendum containing PDEs or acceptable intake (AI) levels for each impurity, along with their monographs. It provides rationales for including the new mutagenic impurities.

New partnership between HRA and ISRCTN for public registration of UK clinical trials

The UK Health Research Authority (HRA) has announced a partnership with the ISRCTN primary clinical trial registry for the automatic public registration of clinical trials. From 2022, the HRA will register clinical trials in the UK which receive a favourable ethics opinion with ISRCTN directly, using data from the HRA’s systems, so research sponsors and researchers will no longer need to apply for public registration separately. Further details are available on the HRA and ISRCTN registry websites.

Dasatinib product-specific bioequivalence guidance

The EMA has issued a revised product-specific bioequivalence guidance for Dasatinib film-coated tablets 20, 50, 70, 80, 100 & 140 mg and suspension 10 mg/ml. This revised product-specific guidance for dasatinib includes the additional requirement for a fed study and the requirements for a suspension.

New Oxygen (98%) Ph. Eur. monograph

A new draft Ph. Eur. monograph for Oxygen (98%) has been published for comment in Pharmeuropa 33.4. The draft monograph is the outcome of a thorough examination of feedback from regulators, hospital pharmacists, industry representatives (gas producers and producers of oxygen generating equipment) and academics. The draft monograph is available for comment until 31st December 2021.

Last week’s round -up;
11-15 October 2021

Pharmeuropa 33.4 Just Released

Pharmeuropa 33.4 has just been released and is available for public consultation until the 31st December 2021. It consists of 41 draft monographs including the following:

USP General Chapter <1220> Analytical Procedure Life Cycle

The USP has published General Chapter <1220> Analytical Procedure Life Cycle, ahead of the official publication posting to allow stakeholders additional time for reading and understanding the new chapter. This new chapter covers the validation activities throughout the life cycle of an analytical procedure and will be incorporated into USP–NF 2022, Issue 1 on Nov. 1, 2021 and will become official on the 1st May 2022.

Ph.Eur Supplement 10.7

Ph. Eur. Supplement 10.7 is now available and will be applicable in 39 European countries from the 1st April 2022. Supplement 10.7 is included in the 2022 subscription to the 10th Edition of the Ph. Eur.

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.’

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 week’s round -up; 03-07 January 2022

All you ever wanted to know about Ph. Eur. procedure 4 but never dared to ask

More clarity on ICH continuous manufacturing guideline requested

New FDA Guidance on the Inspection of Injectable Products for Visible Particulates

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 weeks’ round -up; 15-26 November 2021

Good Machine Learning Practice (GMLP) – Guiding Principles

Updated mitigation strategies to reduce the risk of nitrosamine drug substance-related impurities in drug products

CMDh meeting: Ph. Eur. finished product monographs / EMA

Last weeks’ round -up; 01-12 November 2021

FDA releases 48 new and updated product-specific guidances

PDG signs-off on milestone harmonised general chapter on chromatography

MDCG issues new Q &A document regarding repackaging and relabelling of medical devices

FDA: Nitrosamine detection tests should be ‘fit for purpose’

Medical Device Coordination Group issues new guidance for legacy devices

Revised ICH guideline on general considerations for clinical trials, ICH E8(R1)

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; 18-22 October 2021

Final EMA feedback on Titanium Dioxide

ICH guideline proposes daily limits for seven mutagenic impurities

New partnership between HRA and ISRCTN for public registration of UK clinical trials

Dasatinib product-specific bioequivalence guidance

New Oxygen (98%) Ph. Eur. monograph

Last week’s round -up; 11-15 October 2021

Pharmeuropa 33.4 Just Released

USP General Chapter <1220> Analytical Procedure Life Cycle

Ph.Eur Supplement 10.7

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

Search Real Regulatory

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

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

Last week’s round -up;
03-07 January 2022

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

Last weeks’ round -up;
15-26 November 2021

Last weeks’ round -up;
01-12 November 2021

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

Last week’s round -up;
18-22 October 2021

Last week’s round -up;
11-15 October 2021

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

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