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:

· 2.2.35. Osmolality

· 2.9.48. Particle size and shape determination by image analysis

· Fluorocholine (18F) injection

· Monoclonal antibodies for human use

· Oxygen (98 per cent)

· Somatropin concentrated solution

· Somatropin powder for injection

· Technetium (99mTc) sestamibi injection

· Winter ulcer vaccine (inactivated, oil-adjuvanted, injectable) for salmonids

https://bit.ly/RealCMC-3aGEI5q

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.

https://bit.ly/RealCMC-3iZNG2i

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.

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

 

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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.

http://bit.ly/RealCMC-3gLOXIf

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.

http://bit.ly/RealCMC-3wxVM6Y

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.

Further information on the recommendations may be viewed at the following link: https://bit.ly/RealCMC-3vg0y7F

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Last week’s round-up;
14 – 18 September 2020

Investigations in the GMDP environment

The MHRA Inspectorate has released a blog post on the most common issues related to investigations in the GMP and GDP environment that are encountered during inspections. The aim of the article is to help pharmaceutical manufacturers and wholesalers improve the outcome of their investigations, and it is applicable to deviations, customer complaints and other Pharmaceutical Quality System (PQS) activities. Several issues that may be encountered during investigations are covered, as well as the relevant implications on CAPA systems, risk assessments, patient safety and root cause analysis.

http://bit.ly/RealCMC-3hHkTfo

EMA:  Clinical Data Publication temporarily suspended – except for COVID-19 related products

EMA suspended all new activities related to the publication of clinical data on 1st Aug 2018. This was done as a result of the implementation of the third phase of EMA’s business continuity plan during the relocation of its offices from London to Amsterdam. However, the agency has just clarified that the suspension of clinical data publication does not apply to COVID-19 related products, in line with EMA’s exceptional transparency measures for treatments and vaccines for COVID-19. Pharmaceutical companies should contact EMA as soon as possible concerning publication of clinical data if they plan to submit an application for a COVID-19 related product.

Further details can be found under this link: https://lnkd.in/dKsuUA3

EC:  Proposed European agency for biomedical advanced research and development

The EC President Ursula von der Leyen yesterday (16th Sept 2020) gave her state of the union address, in which she called for lessons to be learned from the current pandemic. She asserted that Europe must build a stronger European health union, with a future-proof and properly funded EU4Health programme, a reinforced European Medicines Agency (EMA) and a strengthened European Centre for Disease Prevention and Control (ECDC). The President also pledged to build a European agency for biomedical advanced research and development to enhance Europe’s capacity to respond to cross-border threats and called for a debate on new competences for the EU in the field of health, as part of the forthcoming Conference on the Future of Europe.

Full details of the address can be found under this link https://lnkd.in/gfEZ8sE

USP General Chapter <1469> Nitrosamines – Public consultation

A new USP general chapter <1469> Nitrosamines has been proposed. The aim of this standard is to ensure the appropriate control of potentially carcinogenic nitrosamine impurities, eliminating or reducing their presence in drug products and drug substances. This USP chapter also covers potential sources of nitrosamines, risk assessments, nitrosamine limits, testing and analytical procedures, test method performance characteristics of nitrosamine methods and USP reference standards. The chapter has been published in draft form in Pharmacopoeial Forum 46(5) and is open for public consultation until the 30th November 2020.

https://bit.ly/RealCMC-33NQirF

Biotherapeutics Ph. Eur. Monographs Updates

The EDQM has updated its Ph. Eur. monograph portfolio on Biotherapeutics. Several monographs are under revision and the EDQM intends to emphasise “greater flexibility as a means of better addressing the structural complexity and naturally occurring heterogeneity of these substances, and the potential diversity of the preparation resulting from different manufacturing processes”. Several individual Ph. Eur. monographs are also under revision including Erythropoietin concentrated solution, Follitropin, Follitropin concentrated solution, Human coagulation factor VIII rDNA, Somatropin concentrated solution, Somatropin, Somatropin for injection and Somatropin solution for injection. The Ph. Eur. Biotherapeutics portfolio also includes a list of new monographs that are currently in preparation. Since the portfolio was published, the revised version of Erythropoietin concentrated solution (1316) monograph has been adopted. The updates include several changes which bring about a significant improvement in the analytical performance of the monograph, while also providing the sought-after flexibility. The updates to the monograph are discussed in the following link: https://bit.ly/32xVMHD
http://bit.ly/RealCMC-32tnzJa

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Last week’s round-up;
29 June – 03 July 2020

New Ph.Eur. Test for bacterial endotoxins using recombinant factor C

The new general chapter 2.6.32. Test for bacterial endotoxins using recombinant factor C (rFC) is now available in the Ph. Eur. Supplement 10.3. A revised chapter 5.1.10. Guidelines for using the test for bacterial endotoxins, which has been updated to reflect the new status of rFC-based methods and give prerequisites for their deployment by users of the Ph. Eur., has also been published. The new chapter describes an analytical method for bacterial endotoxins that can be used as an alternative to the classic limulus amoebocyte lysate-based methods for the quantification of endotoxins from gram-negative bacteria. The currently used classic method relies on two endangered species of horseshoe crab as a source of lysate, while the new method involves the use of a recombinant factor C based on the gene sequence of the horseshoe crab and fluorimetric detection. The new method has been developed to help reduce the need for the endangered horseshoe crab. Both chapters will become effective on the 1st January 2021. https://bit.ly/RealCMC-2NUh0

EMA: Procedural advice for orphan medicinal product designation

The EMA updated its procedural advice for orphan medicinal product designations on 25th June 2020. Clarification has been provided on the proof of establishment requirements for sponsors that are an individual. If the sponsor is a natural person of a country of the EEA, in order to respect data protection rights and freedoms, they should not include proof of establishment in the portal folder of the submission. Once EMA receives the application, the Orphan Office will e-mail the individual sponsor outside the submission portal to verify their citizenship of a country of the EEA e.g. copy of passport. At the end of the validation process all personal data are deleted from EMA’s systems. The requirements when the sponsor is an organisation remain the same. https://lnkd.in/gSb22Qe

Stakeholder comments on PBPK modelling and simulation EMA guidance

An overview of comments received from 12 stakeholders on the ‘Guideline on the qualification and reporting of physiologically based pharmacokinetic (PBPK) modelling and simulation’ has been published by the EMA: https://bit.ly/RealCMC-2NPTV8Q

EMA Clinical Trial Information System (CTIS)

At its meeting held in June 2020 the EMA MB endorsed the methodology and next steps to further develop the CTIS ‘Go-Live’ plan. It is proposed to fix the Go-Live date of CTIS to December 2021, which means the Clinical Trial Regulation would also enter in application at that time (i.e. that is the end of the six months after the European Commission publishes its notice in the Official Journal). Further details can be found in the press release from this meeting ( https://lnkd.in/dhmqqjN ). And a CTIS newsletter on the topic will be issued twice yearly.

USP novel excipients survey

The US Pharmacopoeia (USP) has conducted an online survey in order to understand how drug formulators view the current state of innovation in excipients, as well as the problems experienced in relation to new or novel excipients. Most pharmaceutical formulators reported that drug development had been limited, at least some of the time, to excipients currently used in FDA-approved drugs. The most cited challenges related to novel excipients include regulatory issues followed by safety concerns. Based on the results of the survey, the USP supports the FDA’s proposal for a pilot review program for the toxicological and quality evaluation of novel excipients intended for use in human medicines. The following article highlights the results of USP’s survey in key areas concerning limitations created by currently used excipients as well as why these limitations have affected innovation and have resulted in reformulations, discontinuations, and delays of pharmaceuticals for the US market: https://bit.ly/RealCMC-3ijTTE9

EMA:New points to consider on implications of COVID-19 on ongoing clinical trials

It is foreseeable that the COVID-19 pandemic will interfere with the conduct of many ongoing trials, not limited to the collection, analysis and interpretation of clinical trial data.The recommendations include pre-planning the capture of systemic deviations. If feasible, data collection should not stop and continue as far as possible. Risk assessment should be performed on the effect of COVID-19 directly on subjects and the ability to conduct the CT. If not already in place an independent DMC should be set up for all affected. Follow up considerations are also outlined.

The document can be found here https://lnkd.in/ex875f3

Extended consultation re elemental impurities in plastic materials

The consultation period for the new Ph.Eur. general chapter on Elemental Impurities in Plastic Materials for Pharmaceutical Use has been extended to the 30th September 2020 due to high public interest and the importance of the monograph. The new draft chapter covers elemental impurities that may be present in plastic materials used in the manufacture of containers for pharmaceutical preparations. An additional document with supporting information, including a more detailed explanation of the text, has also been published alongside the chapter. This supporting document shows that the impact of elemental impurities in plastic materials, on the quality of the containers produced from these materials, needs to be taken into account even though these are not within the scope of existing texts.

Two other new general chapters on specific plastic materials, Cyclo-olefin polymers (3.1.16) and Cyclo-olefin copolymers (3.1.17), which refer to the general chapter on Extractable elements in plastic materials for pharmaceutical use have also been republished, unchanged, in order to extend the deadline for comments until the 30th September 2020: https://bit.ly/RealCMC-2NEd5yp

ICH: Harmonsation of drug development requirements

Reading an excellent article this morning written by Pär Tellner of EFPIA. He describes the achievements of ICH, which reaches its 30th anniversary in 2020. The article mentions that ‘ICH has encouraged greater collaboration among scientific, technical and medical experts from regulators and companies. It has helped mitigate confusion regarding regulatory processes. ICH has reduced redundancy in requirements at every step of medicine development: in non-clinical studies, clinical trials, submissions, and manufacturing processes.’ He considers that the electronic Common Technical Document (e-CTD) a good concrete example of the level of harmonisation achieved. A very considerable body of guidances (over 80) from about 30 active working groups leads the author to conclude that ICH’s mission has never been more important to ensure the availability of life-changing medicines to patients worldwide. Particularly, bearing in mind, the innovations that are envisaged over the coming years.The article in full can be found here https://lnkd.in/dSExcfT

Last week’s round-up; 01 -05 June 2020

WELCOME TO THE TEAM!

We are delighted to have Michael Edwards join the team at Real Regulatory as a Senior Regulatory Consultant. Michael has worked in regulatory affairs since 2000, having held positions in the UK medicines competent authority, a couple of CRO/consultancies, a couple of small/medium pharmaceutical companies, and as an independent consultant, as well as taking some time out during that time to do post-graduate research and complete a PhD investigating the vascular bioactivity in vitro of the phenolic phytochemicals anthocyanins, and their in vivo degradation products or metabolites, in the Department of Nutrition at Norwich Medical School. His first degree was BSc Pharmacology with Toxicology (First) at King’s College London, including a year-long industrial placement in a large pharmaceutical company research centre. His regulatory experience includes clinical phase through post-marketing authorisation, national and European procedures. Michael will be a valuable asset to our company and to our clients. https://bit.ly/2Ulm2jS

ICH UPDATES ON UPCOMING GUIDLINES, ADDS NEW PARTICIPANTS

At a recent virtual meeting of the ICH Assembly, the ICH has announced that Turkey’s Medicines and Medical Devices Agency (TITCK) is now one of its regulatory members and that Lebanon’s Ministry of Public Health (MOPH) is now a new observer. During the meeting, the Council also announced that the following guidelines have reached Step 4 in the ICH process: M8 electronic Common Technical Document (eCTD) v4.0 guideline; S11 Nonclinical Safety Testing in Support of Development of Paediatric Pharmaceuticals guideline; and S5(R3) Guideline on Revision of S5 Guideline on Detection of Toxicity to Reproduction for Human Pharmaceuticals. The Council has also announced that the Q3C(R8) guideline on residual solvents, which is currently under revision to include the permitted daily exposures for three new impurities, has reached Step 2 of the ICH process, and that the 4Q(R1) Common Technical Document (CTD) guideline will be revised.

Further updates given by the ICH during the Assembly may be found at the following link: https://bit.ly/RealCMC-2Y63Xai

EMA AND FDA ISSUE JOINT DOCUMENT ON PIPS AND iPSP FOR COVID19 TREATMENTS AND VACCINES

Joint procedural information is available from EMA and the FDA for medicine developers planning to submit a PIP to EMA and an iPSP, to the FDA, respectively, for a COVID-19 vaccine or treatment, the document can be found under this link https://lnkd.in/d4mespk.

The joint document aims to make it easier for developers to submit paediatric development plans simultaneously to the regulators, to help speed up the development and approval of COVID-19 treatments and vaccines. Both agencies are encouraging medicine developers to submit PIPs and iPSPs early.

NEW FDA PRODUCT-SPECIFIC GUIDANCE

The FDA has just released 26 new and 43 revised draft product-specific guidances on the development of generic drugs. The documents are intended to clarify the FDA’s recommendations on demonstrating bioequivalence of generics to the corresponding reference products. The new drafts include recommendations to support ANDAs for generic versions of the acute myeloid leukemia drug gilteritinib, the PARP inhibitor talazoparib, the HIV-1 treatment dolutegravir/lamivudine, fish oil triglycerides, subcutaneous buprenorphine and extended-release metformin. The updated guidance documents include altered recommendations for generic versions of type 2 diabetes drugs dapagliflozin, dapagliflozin and saxagliptin, the renal failure treatment ferric citrate and transdermal buprenorphine.

https://bit.ly/RealCMC-36WJtoL

EXCIPIENTS IN THE PRODUCT INFORMATION OF MEDICAL PRODUCTS

The European Commission’s updated ‘Annex to the European Commission guideline on Excipients in the labelling and package leaflet of medicinal products for human use’ is effective from 22 November 2019. The guidance describes the information that should be available in the package leaflet on excipients that are known to have a recognised action or effect. In order to ensure compliance with the new guidance, marketing authorisation holders are required to submit a type IB variation within three years from the publication of the revised Annex. HPRA has pointed out that applicants should also be aware that some of the updates included in the Annex were also published in the previous version of the document, therefore, applicants are requested to submit the relevant variations by 9/10/2020.

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

UK ARRIVALS 14-DAY SELF-ISOLATION EXEMPTIONS RELATED TO PHARMACEUTICALS AND CLINICAL TRIALS SECTORS

New measures for all UK arrivals have been announced, including a 14 days’ self-isolation for anyone entering the UK, apart from a “short” list of exemptions. At moment of writing, these measures are due to come into effect on 8 June, although this could change given the backlash from the UK travel industry. The “short list of exemptions” is not really all that short, and amongst the many listed are including the following of note to the pharmaceuticals and clinical trials sectors: qualified persons and responsible persons for human medicines, clinical trials and pharmacovigilance quality assurance inspectors for human medicines sponsors and essential persons needed for clinical trials or studies The new measures can be found at: https://lnkd.in/ddFU_XE

The list of exemptions can be found at: https://lnkd.in/dVUpska

USP GUIDANCE ON THE USE OF RECOMBINANT REAGENTS FOR BACTERIAL ENDOTOXIN TESTING

Horseshoe crabs’ blood has long been used in the pharmaceutical industry to detect the presence of bacterial endotoxins, causing concern amongst animal rights groups who are pushing for the use of synthetic alternatives. The USP Microbiology Expert Committee had proposed the inclusion of synthetic recombinant factors in ‘Chapter 85 Bacterial Endotoxins’. Based on public comments received, this will not happen. Instead, a new general chapter will be drafted, to provide guidance on the qualification of alternative tests by demonstrating comparability: <1085.1> Use of Recombinant Reagents in the Bacterial Endotoxins Test – Photometric and Fluorometric Methods Using Recombinantly Derived Reagents The proposed new general chapter should be available for public consultation by November 2020. More information may be found at the following link: https://bit.ly/RealCMC-3eFwASp

This matches the approach taken by Ph. Eur. in 2016 when ‘Chapter 5.1.10 Guidelines for Using the Test for Bacterial Endotoxins’ was updated. Ph. Eur. is further ahead as it has already published a new section ‘2.6.32 Test for bacterial endotoxins using recombinant factor C’ in supplement 10.3, effective from 1 January 2021.

Q & A ON GXP FLEXIBILITIES DURING THE COVID-19 PANDEMIC

The European Medicines Agency (EMA), European Commission and Heads of Medicines Agencies have updated their ‘Questions and answers on regulatory expectations for medicinal products for human use during the covid-19 pandemic’. The guidance document now includes a new section on temporary flexibilities for good manufacturing practice (GMP) and good distribution practice (GDP) that pharmaceutical companies may employ during the pandemic to ensure an adequate supply of medicines used to treat COVID-19 patients. A new section on the suspension of on-site inspections of plasma collection centres has also been included. Temporary flexibilities related to the duties of the responsible person (RP), the use of new equipment or newly authorized storage and distribution sites, and deviations from normal practice are also discussed in the document. Further information is available at the following link: https://bit.ly/RealCMC-2VYSVnu

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