GMP Archives - Real Regulatory

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 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;
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;
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;
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

Last week’s round -up;
14-18 June 2021

Draft PIC/S EU Annex 16 on batch release by QPs

The Pharmaceutical Inspection Cooperation Scheme (PIC/S) intends to incorporate the EU GMP Annex 16 on batch release by a qualified person (QP) into a PIC/S guideline. The aim of PIC/S is for non-EU/EEA members to incorporate Annex 16 into their regulatory systems. The decision to incorporate Annex 16 is a result of the memorandum of understanding signed between the EMA and PIC/S following the revision of Annex 16 in 2016. The draft PIC/S Annex 16 is currently under consultation which is focussed on the non-EU/EEA members of PIC/S, however, the consultation is also open to the public until 15th September 2021.

New EMA Deferasirox product-specific bioequivalence guidance

The EMA has released a new product-specific bioequivalence guidance for Deferasirox, dispersible tablets (125 mg, 250 mg and 500 mg), film-coated tablets (90 mg, 180 mg, and 360 mg) and granules (90 mg, 180 mg and 360 mg). The guidance comes into effect on the 1st January 2022. An overview of the comments received during the public consultation stage of this new guidance has also been released.

New USP harmonized chapter on visual inspections proposed

Pharmaceutical industry officials have proposed that the USP, together with input from the Ph. Eur. and Japanese Pharmacopoeia, develop a new harmonized chapter on visual inspections of parenteral drugs that would address current testing gaps. The proposed chapter would allow for more robust detection of visible particles in parenteral drugs, which is a common reason for recalls and warning letters in the US. The harmonised compendial chapter would include the use of ‘universally available standards’ to train inspectors, qualify the methods and validate results.

Last weeks’ round -up;
31 May – 11 June 2021

Draft revised Ph. Eur. General Chapter 2.8.2 on Foreign Matter

A draft revised general chapter on Foreign Matter (with tracked changes) has been published in Pharmeuropa 33.3 and is available for comment until the 30th September 2021. Requirements for other foreign elements like moulds, insects and other animal contamination have been further specified in the revised chapter which may be viewed at the following link: http://bit.ly/RealCMC-357VGXl

Comments concerning revised texts published in Supplement 10.6

The EDQM has released information regarding the technical modifications that have been made to revised Ph. Eur. texts adopted by the European Pharmacopoeia Commission at the November session and published in Supplement 10.6. Modified texts are indicated by horizontal or vertical lines in the margin of 10.6. The details given in the article linked below complete this information but are not necessarily exhaustive. The details concerned may also be consulted in the Knowledge Database under View History.

UK-Canada mutual recognition of GMP certificates and batch testing continues

The MHRA has confirmed that Canada and the UK will continue to recognise Certificates of Good Manufacturing Practice (GMP) Compliance issued by each country’s regulatory agencies and to accept batch testing certificates held by a manufacturer without re-control of that batch at import, following entry into force on 1 April 2021 of the comprehensive UK-Canada Trade Continuity Agreement (TCA) entered into force on 1 April 2021. For further details and a link to the TCA itself, please see the MHRA page at the following link: https://lnkd.in/eWZcrhS

New Ph. Eur. general chapter on cell-based assay for potency determination of TNF-alpha antagonists

A new draft general chapter on cell-based assay for potency determination of TNF-alpha antagonists (2.7.26) has been published in Pharmeuropa 33.2 and is open for public consultation until 30th June 2021. This new general chapter is the first in a series of three planned new “horizontal standards” for therapeutic monoclonal antibodies (mAbs). It covers the execution of four specific cell-based assay procedures and provides considerations on data analysis, system suitability, assay acceptance criteria and results evaluation, as well as best practices for the adjustment of assay conditions, addressing certain critical aspects. http://bit.ly/RealCMC-3yWvInr

Revised Ph. Eur. General Chapter on Particulate Contamination: Sub-visible Particles

A revised general chapter 2.9.19. Particulate Contamination: Sub-visible Particles has been published in Pharmeuropa 33.2. This revised chapter is the result of discussions held between the Japanese Pharmacopoeia and the United States Pharmacopoeia within the Pharmacopoeial Discussion Group (PDG). The revised chapter includes a harmonised procedure for each of the analytical procedures described and includes the following changes: the light obscuration particle count test allows the use of sample volumes less than 5 mL depending on the instrument capability, the microscopic particle count test no longer requires at least 10 units to be combined for small volume preparations, and a combination of fewer units for this test is permitted depending on instrument capability and sample properties. The chapter is open for public consultation until 30th June 2021.

Last week’s round -up;
22-26 March 2021

WHO/IAEA investigational radiopharmaceutical GMP draft guidance

The World Health Organization (WHO) and the International Atomic Energy Agency (IAEA) have released a draft guideline on GMP for investigational radiopharmaceuticals, due to the rapidly expanding use of radiopharmaceuticals to diagnose and treat cancers and other diseases. The draft guidance sets out the minimum GMP standards for Phase 1-3 clinical investigations of novel radiopharmaceuticals that are not yet authorized or approved. The draft guidance is open for public consultation until the end of April 2021, and a revised document is expected to be worked up for public consultation by July 2021.

EC-DG SANTE/HMA-CTFG/EMA joint training on the Clinical Trials Regulation (EU) 536/2014

The EC-DG Sante has published a raft of presentations from their recent training on 9th to 10th March 2021. The aim of the training was to provide an outline of the key changes which will apply under CTR.

Nitrosamine Impurities in Sartans – Updates

The following updates concerning nitrosamine impurities in sartans are available: • Euro Roundup: EDQM clarifies implications of new sartan monographs for the holders of a currently valid Certification of Suitability (CEP). • CMDh Questions & Answers on implementation of outcome of Art. 31 referral on angiotensin-II-receptor antagonists (sartans) containing a tetrazole group (with tracked changes) • Rapid implementation of the revised sartan Ph. Eur. monographs (Valsartan, Losartan potassium, Irbesartan, Candesartan cilexetil and Olmesartan medoxomil) on 1 April 2021. • General chapter 2.5.42. N-Nitrosamines in active substances and revised sartan monographs.

Last week’s round -up;
15-19 March 2021

EU-UK cooperation

The EMA is collaborating with the UK as per the EU-UK Trade and Cooperation Agreement (Annex TBT2 – Medicinal Products). Under the agreement, the EU and UK recognise the outcomes of GMP inspections carried out by the other party in their territories and may also recognise the outcomes of inspections carried out in other third countries. The products covered by the agreement include marketed medicinal products for human or veterinary use, including marketed biological and immunological products for human and veterinary use, advanced therapy medicinal products, active pharmaceutical ingredients for human or veterinary use and investigational medicinal products.

CEP holders – Avoiding the rejection of notifications

The EDQM Guideline on requirements for revision/renewal of Certificates of Suitability to the European Pharmacopoeia Monographs (PA/PH/CEP (04) 2, 7R corr) lists different notifications and associated conditions for CEP revisions and renewals. Any change that is not classified as a notification or a major change should be classified as a minor change by default (except for editorial changes which are covered by specific guidance in the policy document) to avoid rejection. For revised discussions on impurities in section 3.2.S.3.2, and the submission of nitrosamine risk assessments, minor revisions should be submitted. Changes to the synthesis or to the control strategy that are introduced to reduce or eliminate the risk for the formation of nitrosamine impurities or other mutagenic impurities, should be classified according to the EDQM guideline (i.e. minor, major revision or sister file application).

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 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 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; 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; 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; 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

Last week’s round -up; 14-18 June 2021

Draft PIC/S EU Annex 16 on batch release by QPs

New EMA Deferasirox product-specific bioequivalence guidance

New USP harmonized chapter on visual inspections proposed

Last weeks’ round -up; 31 May – 11 June 2021

Draft revised Ph. Eur. General Chapter 2.8.2 on Foreign Matter

Comments concerning revised texts published in Supplement 10.6

UK-Canada mutual recognition of GMP certificates and batch testing continues

New Ph. Eur. general chapter on cell-based assay for potency determination of TNF-alpha antagonists

Revised Ph. Eur. General Chapter on Particulate Contamination: Sub-visible Particles

Last week’s round -up; 22-26 March 2021

WHO/IAEA investigational radiopharmaceutical GMP draft guidance

EC-DG SANTE/HMA-CTFG/EMA joint training on the Clinical Trials Regulation (EU) 536/2014

Nitrosamine Impurities in Sartans – Updates

Last week’s round -up; 15-19 March 2021

EU-UK cooperation

CEP holders – Avoiding the rejection of notifications

Search Real Regulatory

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

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

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

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

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

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

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

Last week’s round -up;
14-18 June 2021

Last weeks’ round -up;
31 May – 11 June 2021

Last week’s round -up;
22-26 March 2021

Last week’s round -up;
15-19 March 2021