The Access Consortium is a collaborative initiative of like-minded, medium-sized regulators from Australia, Canada, Singapore, Switzerland, and the United Kingdom.
On 16 November 2022, the European Medicines Agency EMA published a concept paper on the planned revision of Annex 11 "Computerised Systems". The reason: The existing document of the EU GMP Guideline dates back to 2011 and no longer corresponds to the state of the art in various areas or does not consider increasingly important new technologies for the GMP field, according to the EMA.
On 8 November 2022, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) published a blog post announcing the resumption of international on-site inspections.
Important to know: Notwithstanding, the ‘expiry’ of GMP certificates issued by the MHRA will again be extended until the end of 2023.
On 25 October 2022, the UK Regulatory Agency MHRA, announced that the introduction of the future UK Medical Device Regulation will be delayed by twelve months. The intended date for introduction of the new and standalone regulation is now set for July 2024.
On 10 October 2022, the EMA published a 24-pages document on data quality (DQ) framework, which is open for consultation until 18 November 2022. As the topic of data quality and data overall becomes more and more critical to regulating medicinal products, a Data Quality Framework for EU medicines regulation is a logical consequence to provide a unitary approach. Thus, the amount of data that digitalisation brings along not only opens up new possibilities, but also increasingly complex data landscapes.
On 30 September 2022 the MHRA informed that the use of the European Commission Decision Reliance Procedure (ECDRP) for Great Britain has been extended for another 12 months until 31 December 2023. The procedure allows a company to submit a product that has received approval from the EMA directly to the MHRA. The MHRA can then grant a license with a shorter review than normally conducted, relying on the EMA’s decision.
DEKRA Certification UK Ltd has become the first organisation after Brexit to complete the new designation process that any potential organisation must go through to become approved to certify medical devices in the UK. With this step taken it is now designated as a UK approved body to undertake assessments for general medical devices (known as Part II designation) and has joined the three current UK Approved Bodies BSI Assurance UK Ltd, SGS United Kingdom Ltd, and UL International (UK) Ltd. These three bodies had been approved before Brexit.
The United States Pharmacopeia (USP) has opened a 90-day review period for their proposed Cannabis Species Inflorescence Monograph in the Herbal Medicines Compendium (HMC), a laboratory quality standards testing reference used internationally.
The European Medicines Agency (EMA) plans to establish clear quality guidelines for drug companies manufacturing synthetic peptides and oligonucleotides. This week, EMA published new concept papers, explaining current requirements on impurities testing, specifications and the control of DNA-reactive chemicals either partly or fully exclude synthetic peptides and oligonucleotides.
The revised Annex 1 to the PIC/S GMP Guide on the manufacture of sterile products has been published and will enter into force on 25 August 2023, except for point 8.123 which is postponed until 25 August 2024. The date of entry into operation is aligned with that of the revised EU Annex 1, which is identical to PIC/S Annex 1 (with some very minor editorial differences).
The European Borderline and Classification Working Group (BCWG), a sub-group of the Medical Device Coordination Group, has created a manual for determining whether a product is classed as a medical device under the new regulations MDR and IVDR. BCWG developed the document as part of an attempt to prevent member states from having different interpretations of the legislation.
Are you prepared for the possible changes? The comparison shows you where there is a need for action.
The long-awaited final version of the new EU Annex 1 "Manufacture of Sterile Medicinal Products" was published on 25 August 2022. The deadline for entry into force is 25 August 2023. Regarding section 8.123 on freeze-drying and product transfer, the deadline for entry into force is two years from now and will thus become mandatory on 25 August 2024:
One thing is certain: The FDA’s utilizing remote regulatory assessment is here to stay and remain a regular tool to support onsite inspections. This was addressed by FDA Commissioner Robert Califf and his associate Commissioner for Regulatory Affairs, Judith McMeekin, in a statement released end of July.
The Committee for Medicinal Products for Human Use (CHMP) and the CMDh (Coordination Group on Mutual Recognition Procedures and Decentralised Procedures) of the EMA extended the deadline for submission of variation applications under Step 3: "Variation of marketing authorisation for chemical medicinal products" from 26 September 2022 to 1 October 2023.
From 23 to 30 June 2022, Interpol conducted its 15th globally coordinated operation PANGEA against the illegal online trade of medicines. From fake COVID-19 tests to doping substances or narcotics, the range of illegal shipments was broad.
The EDQM informs that the 11th Edition of the European Pharmacopoeia (Ph. Eur.) is now available. Holders of Certificates of suitability to the monographs of the Ph. Eur. (CEPs) are invited to update their applications according to the revised monographs that will be implemented on 1 January 2023, and to follow the instructions that the EDQM provides.
For the third time in a row, the European Commission has updated its Q&A on nitrosamine impurities (we reported). Version 10 was published on 23 June 2022. Questions 5, 10 and 14 have been revised. What is new?
In June 2022, the European Commission published the Question & Answers document on safety features for medicinal products for human use in version 20, coming along with one new Q&A on UI verification of authenticity.
The newly added question 5.14 “Is it allowed to verify the authenticity of the UI when the product is not in physical possession?” is answered with “Yes, but only as an additional check to Article 20 of Commission Delegated Regulation (EU) 2016/161.”
On 4 July 2022 the European Commission published the Implementing Regulation (EU) 2022/1107 to establish common specifications for certain class D in vitro diagnostic medical devices considered to be high-risk. These relevant harmonised standards had already been partially introduced in the repealed Directive 98/97/EC. Now the specifications have been updated and adapted to the state of the art.
The International Coalition of Medicines Regulatory Authorities (ICMRA) is announcing the initiation of two regulatory collaboration pilots addressing facility inspections and Chemistry and Manufacturing Controls (CMC) and Post-Approval Change (PAC) submission assessments and related regulatory actions.
The FDA issued a draft guidance outlining a framework of methods, designs and controls for preventing cross-contamination of non-penicillin beta-lactam antibacterial drugs and compounds, which serves as an update for a 2013 guidance with the same title. (Non-Penicillin Beta-Lactam Drugs: A CGMP Framework for Preventing Cross-Contamination; Draft Guidance for Industry; Availability).
The Pharmaceutical Inspection Cooperation Scheme (PIC/S) has published its 2022 work plan with the organization’s planned actions for this year. Not only does PIC/S plan to resume its assessments for membership application but also to revise or draft new GMP guidelines.
Concurrent with the application of the IVDR in the EU, the new Swiss regulation on in vitro diagnostic medical devices, IvDO, came into force on 26 May 2022. This is the first time since 2001 that the "third country rules" apply to IVDs in Switzerland, as they already do for all other medical devices for a year now (we reported). As of the same date, clinical trials with in vitro diagnostic medical devices are regulated in the Ordinance on Clinical Trials with Medical Devices (CTO-MedD) and no longer in the Ordinance on Clinical Trials (ClinO).
After a one-year postponement period, the European In Vitro Diagnostic Medical Devices Regulation (IVDR) finally came into force on 26 May 2022 and follows the Medical Device Regulation (MDR), which has been in force for one year.
The US FDA has revised its 16-year-old guidance on how to investigate out-of-specification (OOS) test results in laboratories. The document includes all necessary steps to be taken when investigating OOS test results. It also considers the responsibilities of the analyst and the laboratory supervisor in case of OOS results being identified, along with additional testing steps and a final evaluation of all results.
ICH Q3D (R2) has reached Step 4 of the ICH-Process and will now be distributed to the Member States for implementation. The revision (R2) focused on
- the establishment of limits for elemental impurities by the dermal route of exposure, summarized in a new Appendix 5 Limits for Elemental Impurities by the Cutaneous and Transcutaneous Route
- and error corrections of the PDEs for Silver (oral), Gold (oral, parenteral and inhalation) and Nickel (inhalation).
The EMA has published a four-page consultation document in the form of Q&As concerning the physical attendance and the place of a personal residence of a Qualified Person on 11 May 2022. The guidance states that the work of a QP must be adapted to current standards to enable remote certifications without a QP being present at the site. A public consultation is possible until 13 June 2022.
On 26 May 2022, the European IVD Regulation (EU) 2017/746 (In vitro Device Regulation) will enter into force. This will be accompanied by various transitional periods and requirements, which have been summarised and explained by the MDCG (Medical Device Coordination Group) in a new guidance document. The 17-page Guidance on significant changes regarding the transitional provision under Article 110(3) of the IVDR is aimed at manufacturers who have so far complied with the requirements of Directive 98/79/EC and may continue to market their in vitro diagnostic devices in accordance with this Directive during the transitional periods.
The European Medicines Agency (EMA) has updated the annexes for the conduct of GCP inspections. First published in 2007, the annexes compile a number of seven documents.
Japan's PMDA (Pharmaceuticals and Medical Devices Agency) published changes to its principles for global clinical trials late last year. This revised document was published in English at the end of April 2022.
Centrally authorised medicinal products placed on the market in one European Member State may be marketed under the same name in any other Member State by a distributor independent of the marketing authorisation holder. This process of parallel distribution is supervised by the EMA.
The EMA has released the comments of the ICH guideline Q9 (R1) draft from december 2021 in late april. The document contributes principles and examples of tools for quality risk management. The document consists of 56 pages of comments from organizations such as the PDA, EFPIA and many others. In the following some excerpts:
On 19 April 2022, the EMA published the annual report of the GMP/GDP Inspectors Working Group for the year 2021. Both, Brexit and the COVID pandemic had resulted in no reports being issued for the last three years. Instead the EMA had published a Business Continuity Plan (BCP), which was primarily based on a prioritisation of tasks.
The US Food and Drug Administration (FDA) presented a "scaled-down" plan for collecting quality metrics from drug manufacturers end of March. The docket is an attempt to reactivate previously paused efforts to collect manufacturing quality metrics data. The primary aim of the program is to mitigate potential drug shortages and promote improved quality management in the pharmaceutical industry.
The Australian regulatory authority for therapeutic goods TGA has updated its 19-pages quality requirements for medical cannabis products. These are now in line with TGO 93 and refer to
- any medicinal cannabis product imported into or supplied in Australia
- cannabis plant used in the manufacture of medicinal cannabis products e.g., as an ingredient or as a starting material for an extract used as an ingredient
- any other ingredients used in the manufacture of medicinal cannabis products, such as excipients
- steps and procedures carried out in the manufacture of medicinal cannabis product.
The Medical Device Coordination Group MDCG, a group of Member States experts, endorsed a joint implementation plan on the implementation of the IVDR, more precisely Regulation (EU) 2017/746 on invitro diagnostic medical devices. The plan should serve to set priority actions and monitor their implementation. The IVDR will enter into force on 26 May 2022 with an extended transitional period of five years.
On 14/15 March 2022, the ISPE Aseptic Conference took place in North Bethesda, USA. The hybrid conference opened with a keynote presentations on regulatory news.
Paul A. Gustafson, who is chairing the PIC/S this year, gave an overview on the PIC/S activities and in this context referred to the future Annex 1 of the EU GMP Guide: The document is in its final adoption process. A publication is to be expected between the beginning of July and the end of September this year. The European Commission is currently awaiting the review of the PIC/S and the WHO. Both organisations had contributed to the two draft documents of Annex 1. The European Commission has not revealed a release date, yet.
The HPMC (Committee on Herbal Medicinal Products, HPMC) of the EMA has published a concept paper on Good agricultural and collection practice for starting materials of herbal origin on 1 March 2022. Of interest to GMP professionales is, that the revision of the original guideline dating back to 2006, will address open questions about the applicability of GACP versus GMP, or a requirement of a combination of both. With a growing market for herbal medicinal product, e.g., Cannabis products, enhanced guidelines on the subject intent to clarify open issues.