EMA Archives - Real Regulatory

Please find below a roundup of our weekly Regulatory Tips and Insights from our Regulatory experts on our Real Regulatory LinkedIn page. The tips we published in January 2022 are collected here, for convenience. Make sure you follow Real Regulatory Ltd and Real CMC for regulatory news, reports and hints.

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;
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;
13 -17 September 2021

New EMA Product-Specific Bioequivalence Guidance

The EMA has adopted the following new product-specific bioequivalence guidance, which come into effect on the 1st November 2021:

· Palbociclib hard capsule 75 mg, 100 mg and 125 mg and film-coated tablet 75 mg, 100 mg and 125 mg

FDA’s novel excipient pilot program opens for candidates

The FDA has launched a new pilot program to review novel excipients for use in meeting unmet needs in formulating new drug products. The Authority will accept four initial proposals in the pilot “but will consider accepting more proposals as resources allow.” The following criteria will be used to select candidates:

· The potential public health benefit of the novel excipients; for example, such applications as use in opioid abuse-deterrent formulations or to promote new therapies for serious and life-threatening disease.

· The likelihood of the novel excipient manufacturer’s ability to submit a complete package within the established timeframe.

· The potential of the novel excipient to “meaningfully improve pharmacokinetic characteristics” and lead to the development of novel drugs. Following acceptance of the initial proposals, the excipient manufacturers concerned will then be requested to submit a full toxicology package as well as chemistry, manufacturing, and controls data in a process parallel to that for an investigational new drug application. Proposals for novel excipients are being accepted until the 7th December 2021.

New Ph. Eur. general chapter on balances

The Ph. Eur. Commission has adopted a new general chapter Balances for analytical purposes (2.1.7), which has been published in Supplement 10.6 in July 2021. This new chapter fills a gap in section 2.1 Apparatus by setting out clear requirements for the use of analytical balances, as weighing is one of the most critical tasks carried out in the laboratory since even the smallest error will affect the accuracy of results. The chapter covers installation and use of analytical balances, including good practices for weighing vessels and provides detailed information on calibration and performance checks. These checks focus on two weighing parameters that most significantly affect balance performance, repeatability and sensitivity. The result of the repeatability test described in the text can also be used to calculate the minimum weight of the balance. The new chapter complements existing guidelines for the use and qualification of balances. It is supplemented by the instructions related to “Quantities” given in the recently revised General Notices chapter, which is due to be published in Supplement 10.7.

Last week’s round -up;
30 August – 03 September 2021

New and Revised FDA Product-Specific Guidance

The US FDA has issued 23 new and 16 revised draft product-specific guidances which are intended to facilitate generic drug development, especially for medicinal products for which there are no approved generics. The newly issued guidance documents involve some products used to treat HIV, chronic obstructive pulmonary disease (COPD) and Cushing’s disease. Some of the new guidances for complex products cover ipratropium bromide nasal spray, ipratropium bromide inhalation spray and olodaterol hydrochloride inhalation spray. The FDA has also issued product-specific guidance for Type 2 diabetes drug semaglutide, which offers two paths to establishing bioequivalence.

Herbal medicinal products containing toxic, unsaturated pyrrolizidine alkaloids

The EMA has released a revised public statement on the use of herbal medicinal products containing toxic, unsaturated pyrrolizidine alkaloids (PAs). The document also includes recommendations regarding contamination of herbal medicinal products with PAs. Several PAs are regarded as both hepatotoxic and carcinogenic and are natural constituents of a number of plants used for medicinal purposes. This guidance describes chemical, toxicological, pharmacological and pharmacokinetic properties of PAs and sets out recommendations for the oral and cutaneous use of herbal medicinal products and traditional herbal medicinal products containing PAs. The revised public statement is a result of a review of newly available data and improved evaluation methods.

MHRA Guidance on Transfer of Analytical Methods

The MHRA Inspectorate has released new guidance for manufacturers and contract testing laboratories related to the process of transferring a method for outsourcing of testing. The Inspectorate has highlighted that the new guidance complements the requirements of EU GMP Chapter 7. The new guidance covers the formal process for the introduction of new methods which allows the receiving laboratory to demonstrate that they can perform the analytical method effectively and reproducibly. It also highlights that regulatory compliance is a shared responsibility between the transferring and receiving laboratories and a collaborative approach is encouraged. The MHRA has also recommended the use of risk management principles for analytical method transfer and the generation of a transfer report following a successful or even unsuccessful method transfer. A list of common shortcomings related to analytical method transfer is also included in the guidance.

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;
16-20 August 2021

ATMPs containing genetically modified cells – draft EMA guidance on PI for consultation

The EMA has published for consultation a draft guideline detailing the information to be included in the Summary of Products Characteristics (SmPC), labelling and packaging leaflet for Advanced Therapy Medicinal Products (ATMPs) containing genetically modified cells. The purpose is to provide applicants and regulators with harmonised guidance on the requirements for the Product Information (PI); the consultation period ends on 31st October 2021.

The UK’s NICE has launched a consultation on Review of Methods and Processes for HTA Evaluation

NICE has just published a consultation on proposals for change as part of its methods and processes review. The consultation period is open for eight weeks. As newer more advanced technologies become available the outcome is intended to help simplify NICE’s approach and to allow more flexible decision-making. All while continuing to be robust and responsive.

Full details of the consultation and a short video outlining the proposed changes, can be found here: https://lnkd.in/ecXED6rE

New ICH Q13 continuous manufacturing guideline

The ICH has released a new draft ICH Q13 guideline on continuous manufacturing of drug substances and drug products, which is open for public consultation in Europe until the 20th December 2021. The new guideline covers continuous manufacturing (CM) of drug substances and drug products for both chemical entities and therapeutic proteins and may also apply to other biological/ biotechnological entities. It provides guidance on CM for new products, including generics and biosimilars, and also on the conversion of batch manufacturing to CM for products that are already on the market. The guidance focuses on the integrated aspects of a CM system in which two or more unit operations are directly connected, therefore, any changes made in a unit operation of CM may have a direct and often immediate impact on downstream and upstream unit operations. The main body of the guideline covers fundamental aspects of CM that are not specific to technology, dosage form, or molecule type. The annexes contain illustrative examples and considerations specific to certain modalities (e.g. chemical entities, therapeutic proteins), technologies, and production methods (e.g. integration of drug substance and drug product manufacturing).

Update on replacement for EMA electronic application forms (eAFs)

Further details have been released for the Digital Application Dataset Integration (DADI) project to replace the current pdf-based human and veterinary medicine eAFs, from 2022 onwards, with web-based forms on a portal. A summary presentation of the project, an updated questions and answers document, and a features list for the human variations form, are available on the eSubmission website.

Clarity sought from the US FDA on ICH Q12 implementation

Following a public consultation, the US FDA has received several comments on its draft guidance on how ICH Q12 is to be implemented in the US. The ICH Q12 guideline facilitates the management of postapproval CMC changes for new and marketed pharmaceuticals and drug substances. Some members of pharmaceutical industry have asked the FDA to align reporting categories with the ICH Q12 guideline on postapproval changes. Other members seek clarity on how manufacturers can use postapproval change management protocols (PACMPs) to support a lower reporting category. Clarity has also been requested on whether the new guidance replaces the Agency’s guidance on established conditions (ECs) that was published in 2015 or whether the two guidelines should be used in conjunction.

Last week’s round -up;
09-13 August 2021

Revised WHO guidance on GMP for investigational products and R&D facilities

The WHO released a revised draft guidance to industry addressing GMP for investigational drug products and new draft guidance on GMP principles for research and development (R&D) facilities in the context of the COVID-19 pandemic. The guidance on GMP for investigational drug products contains news recommendations on GMP issues related to quality management, quality risk management, personnel and documentation considerations. Issues related to manufacturing premises, equipment and utilities, materials and production are also addressed. Sections on the quality unit, qualifications and validation, complaints, recalls, returns, shipping and destruction are also covered. Some of the new recommendations include the requirement for a responsible person to be designated for the release of batches. The GMP guidance related to R&D facilities covers quality management and quality risk management in product research and development. It includes recommendations on sanitation and hygiene, qualification and validation, outsourced activities, self-inspection and quality audits, personnel training, premises, equipment and instruments and materials, documentation, processing and process design, quality control, stability and technology transfer.

Both draft guidelines are available for comment until 31st August 2021: https://bit.ly/RealCMC-2VU4jUD

New EMA Q&A on Clinical pharmacology and pharmacokinetics

The EMA has released a new Q&A 6.5 on Clinical pharmacology and pharmacokinetics. The new Q&A gives recommendations on how large the deviations from proportionality in composition can be in the case of fixed combinations with highly soluble active substances in an application with multiple strengths. For fixed combinations (FCs) consisting of multiple strengths, small differences in proportionality of compositions may preclude the waiver of the additional strength and result in the request of an additional in vivo bioequivalence study. However, in the case that all the active substances in the FC belong to BCS Class I or III drugs (highly soluble active substances), the risk of non-bioequivalent additional strength formulations is negligible, if the conditions specified in the Q&A are fulfilled. Therefore, a waiver for additional strengths is acceptable even though the additional strengths deviate from proportionality in composition, provided the conditions are met.

UK MHRA publishes the new Access Consortium Strategic Plan for 2021-2024

The Access Consortium is committed to maximizing collaboration by aligning regulatory and policy approaches, reducing duplication, and facilitating the member country populations’ access to high quality, safe and effective health products. This group originally consisted of the regulatory authorities in Australia, Canada, Singapore and Switzerland (previously referred to as ACSS). With the addition of the UK MHRA in October 2020, ACSS changed its name to Access Consortium, and now represents a collective population base of 150 million people across the 5 member countries. The Access Consortium has now published a three-year strategy covering 2021-2024, and further information and the document itself can be found through the following link: https://bit.ly/RRL-3g88UJV

Reflection paper on GMP and Marketing Authorisation Holders

The EMA has adopted the Reflection paper on Good Manufacturing Practice and Marketing Authorisation Holders. Although many MAH companies are not directly involved in the manufacture of medicinal products themselves, the current European Commission Guide to GMP refers, in several places, to MAHs and their responsibilities in relation to GMP. The new Reflection Paper provides clarity as to what the various responsibilities are and what they mean for MAHs at a practical level. This reflection paper also addresses the various legislative provisions (i.e. in European Directives, Regulations and in other guidelines) which relate to GMP and which concern MAHs.

UK MHRA issues updated guide to “defective medicinal products”

The MHRA Guide to Defective Medicinal Products regarding reporting, investigating and recalling suspected defective medicinal products to the Defective Medicines Report Centre (DMRC) has been updated, and can be found at the following link: https://bit.ly/RRL-2VHcTFT

CMDh Meeting Report – July 2021

The CMDh has released a report on the meeting that was held on 20th-21st July 2021. Various topics were tackled during the meeting including the following:

· An update to the CMDh Questions & Answers on implementation of outcome of Art. 31 referral on angiotensin-II-receptor antagonists (sartans) containing a tetrazole group – As outlined in Q7, under Condition B a response to the Article 5(3) referral is always needed for sartans containing a tetrazole group. Therefore, since it is considered that a risk of nitrosamines is always present for tetrazole sartans, due to their chemical structure, a Step 2 response is always expected and MAHs who previously submitted a Step 1 ‘no risk’ response, are expected to reconsider and submit a Step 2 response.

· Active Substance Master File (ASMF) worksharing – The CMDh strongly recommends the use of ASMF worksharing to save resources and promote a harmonised assessment when submitting an application for a medicinal product containing an ASMF.

Last week’s round -up;
02-06 August 2021

Follow-up Survey of QPs on Remote Certification

In March 2020, the European Qualified Persons Association (EQPA) carried out a survey amongst its members on the topic of “Remote QP Certification”, which was perceived as an area of non-harmonized national interpretations. The EQPA sought to better understand the differences across the EU/EEA and on how QPs positioned themselves in such a procedure. One year later, in March 2021, the EQPA carried out another follow-up survey on the topic as it is “in the interests of all QPs” to review how this difficult period is being managed today. The follow-up survey contained similar questions to the first survey and more than 300 QPs took part. The pattern of answers “reinforces what was seen in March 2020 but with greater use of remote certification and more developed procedures generally. That may not necessarily be true with respect to the personal experience of each individual QP”. The survey also showed that “while many QPs made obvious progress to stabilize their certification processes in light of the pandemic, some gaps remain and should be closed”.

A detailed discussion of the results of the follow-up survey may be found in the following article: https://bit.ly/RealCMC-2WSnsX0

EMA News: Six month count-down to CTIS system go live

As set out in the Clinical Trials Regulation, the entry into application of that Regulation is set by the publication of a notice in the Official Journal of the European Union, which confirms that the clinical trial EU Portal and Database, one of the main deliverables of the Regulation and the key component of CTIS, has reached full functionality. The application of the Regulation and the go-live of CTIS take place six months after the publication of this notice. The EC has confirmed that the entry into application of the Clinical Trials Regulation and hence the go-live date for the Clinical Trials Information System (CTIS) will be on 31 January 2022.

New PIC/S guidance on PQS risk-based change management and COVID-19 risk assessments

The Pharmaceutical Inspection Co-operation Scheme (PIC/S) has adopted two new guidance documents on the effectiveness of pharmaceutical quality systems (PQS) and COVID-19 risk assessment for on-site inspections. The updated guideline “How to Evaluate and Demonstrate the Effectiveness of the Pharmaceutical Quality System with regard to Risk-Based Change Management”, includes a “checklist of lifecycle factors where inspectors should expect change to occur, which includes the introduction of new products, upgrades, changes in materials, test method changes, improvements in manufacturing processes and capacity, quality issue corrections, regulatory changes, improvement initiatives, and addressing PQS signals”. The COVID-19 risk assessment guideline for on-site GxP inspections provides recommendations for the risk assessment which should be performed during the inspection planning phase together with the site prior to the actual inspection.

HMA CTFG Date for last receipt of submissions for the VHP prodedure

HMA’s CTFG has announced that the date for last submission of a VHP application is 15th Oct 2021, in order that all procedures will have resolved in Jan 2022. This is to ensure a smooth transition to the full implementation of the CTR 536/2014 which is planned for the 31 January 2022; full details can be found here: https://bit.ly/RRL-3C6Ubbb

Last week’s round -up;
12-16 July 2021

Pharmeuropa 33.3

Pharmeuropa 33.3 has just been released for public consultation and the deadline for comments is the 30th September 2021. 47 draft texts have been published in Pharmeuropa 33.3 including the following finished dosage form monographs:

Ph. Eur. Commission 170th Session Outcome

The Ph. Eur. Commission has published the outcome of its 170th session which was held in June 2021. The Commission has adopted 69 texts that will be published in Ph. Eur. Supplement 10.8 and will be effective as of 1st July 2022. During the session, the Commission has also taken several decisions related to animal welfare including the replacement of the rabbit pyrogen test with suitable in vitro alternatives, within about 5 years. The test for specific toxicity in guinea pigs was deleted from 17 monographs for vaccines for human use containing the diphtheria component and 3 monographs on clostridial vaccines for veterinary use were revised to replace or encourage manufacturers to replace several animal tests with in vitro methods and delete the residual toxicity test on the final product. Work on two major new general chapters was announced including a chapter on phage therapy active substances and medicinal products for human and veterinary use and a general chapter on high throughput sequencing. A third PaedForm monograph, Phosphate 60 mg/mL Oral Solution was approved and a new text, Midazolam nasal spray, was added to the work programme.

EDQM “RTEMIS” pilot project

Travel restrictions brought on by the COVID-19 pandemic have caused interruptions in the EDQM’s inspection programmes and the directorate has had to find new ways to continue GMP evaluations of manufacturing sites. In view of this, the EDQM has developed a pilot system of Real-Time Remote Inspections (RTEMIS) which combines a live video feed, linking inspectors and API manufacturing sites, and the review of documentary sources, with the objective of monitoring compliance with both GMP and applications for CEPs in manufacturing sites. The approach is not meant to replace on-site inspections in terms of value and effectiveness, however, it allows inspectors to assess GMP compliance in companies that have already been inspected by the EDQM.

EMA Guide to CTIS Training material

EMA has published a detailed Guide to CTIS Training Material Catalogue. It comprises 23 modules ranging from an overview of the system, user management, practicalities of using the system, methods of supervision on the system, data protection and considerations for different user groups. A link to the guide and to the individual modules cited therein can be found here:

PIC/S finalizes GMP data integrity guidance

The Pharmaceutical Inspection Co-operation Scheme’s (PIC/S) new guidance on good practices for data management and integrity for pharmaceutical manufacturers and distributors has come into effect. The document serves as a guide to inspectorates in the planning of risk-based inspections relating to good data management practices, without imposing an additional regulatory burden and helps regulators clarify how current GMP/GDP requirements relate to “current industry data management practices”. The guidance covers all activities related to the handling of data including data policy, documentation, quality and security. Both on-site and remote, or desktop, inspections are included within the scope of the guidance.

Further information on the topics covered in the final guidance document may be found at the following link: https://bit.ly/RealCMC-3i2jEJB

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.

January 2022 Real Regulatory Tips and Insights

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; 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; 13 -17 September 2021

New EMA Product-Specific Bioequivalence Guidance

FDA’s novel excipient pilot program opens for candidates

New Ph. Eur. general chapter on balances

Last week’s round -up; 30 August – 03 September 2021

New and Revised FDA Product-Specific Guidance

Herbal medicinal products containing toxic, unsaturated pyrrolizidine alkaloids

MHRA Guidance on Transfer of Analytical Methods

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; 16-20 August 2021

ATMPs containing genetically modified cells – draft EMA guidance on PI for consultation

The UK’s NICE has launched a consultation on Review of Methods and Processes for HTA Evaluation

New ICH Q13 continuous manufacturing guideline

Update on replacement for EMA electronic application forms (eAFs)

Clarity sought from the US FDA on ICH Q12 implementation

Last week’s round -up; 09-13 August 2021

Revised WHO guidance on GMP for investigational products and R&D facilities

New EMA Q&A on Clinical pharmacology and pharmacokinetics

UK MHRA publishes the new Access Consortium Strategic Plan for 2021-2024

Reflection paper on GMP and Marketing Authorisation Holders

UK MHRA issues updated guide to “defective medicinal products”

CMDh Meeting Report – July 2021

Last week’s round -up; 02-06 August 2021

Follow-up Survey of QPs on Remote Certification

EMA News: Six month count-down to CTIS system go live

New PIC/S guidance on PQS risk-based change management and COVID-19 risk assessments

HMA CTFG Date for last receipt of submissions for the VHP prodedure

Last week’s round -up; 12-16 July 2021

Pharmeuropa 33.3

Ph. Eur. Commission 170th Session Outcome

EDQM “RTEMIS” pilot project

EMA Guide to CTIS Training material

PIC/S finalizes GMP data integrity guidance

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

January 2022
Real Regulatory Tips and Insights

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

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

Last week’s round -up;
13 -17 September 2021

Last week’s round -up;
30 August – 03 September 2021

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

Last week’s round -up;
16-20 August 2021

Last week’s round -up;
09-13 August 2021

Last week’s round -up;
02-06 August 2021

Last week’s round -up;
12-16 July 2021