Already in March last year, an adaption of the Delegated Regulation (EU) 2016/161 on safety features allowed a temporary derogation of the obligation for wholesalers to deactivate the individual identifier (IE) of medicinal products exported to the UK - as a third country (we reported). This exemption was granted for the year 2021.
The European Commission published Version 19 of the Q&A on safety features for medicinal products in late December 2021.
- Question 1.29: Do the unique identifiers of reference and retention samples taken from stock in compliance with Annex 19 of the EU GMP Guidelines5 and uploaded to the EMVS have to be decommissioned? If yes, to what status?
Answer: Yes, if a sample of a batch is taken as reference or retention sample after uploading in EMVS, it should be decommissioned as "sample". If a sample is taken voluntarily by a wholesaler that fall outside the scope of Annex 19, they should be decommissioned as "destroyed".
On 16 December 2021, EMA published the ICH Q9 draft document on Quality Risk Management (QRM) in step 2b. The draft provides important additional guidance on four specific areas:
- the levels of subjectivity in risk assessments and in QRM outputs,
- the product availability risks,
- the lack of understanding as to what constitutes formality in QRM work, and
- the lack of clarity on risk-based decision-making.
The International Coalition of Medicines Regulatory Authorities, ICMRA, has published a comprehensive reflection paper on experiences with different inspection models to maintain GCP and GMP inspections during the covid pandemic. The working group responsible for the paper was composed of representatives from various regulatory agencies around the world. To anticipate the group's conclusion: Remote inspections enable minimal regulatory oversight during the pandemic but will not be able to replace on-site inspections in the future.
The Australian authority TGA has published a revision of the guideline on licenses and certification "Guidance on Australian manufacturing licenses and overseas good manufacturing practice (GMP) certification" on 1 December 2021. The revision relates to an expansion of possible inspection types as well as the scheduling of the inspection for licensing procedures.
To ensure market surveillance of medical devices, manufacturers, authorized representatives and importers based in Switzerland must register with Swissmedic within three months of first placing a product on the market. This was revealed in a Swissmedic announcement in late November.
After the applicants have undergone the process, they will be assigned an individual Swiss identification number, the Swiss Single Registration Number (CHRN).
As of 2 December 2021, the new general chapter <1469> on nitrosamine impurities has been added to the United States Pharmacopeia (USP). With this, it is intended to support both pharmaceutical manufacturers and authorities in assessing the presence of nitrosamines and implementing appropriate control strategies and analytical procedures. The chapter is aligned with the current FDA guidances.
The European Medicines Agency (EMA) has published a 13-page Q&A including 87 questions and answers from a webinar held on the topic of integrating EudraGMDP and OMS (Organisation Management Services) into the new regulatory framework for veterinary medicines.
Finally, the long-awaited nomination for the next FDA commissioner is here. President Biden has nominated Dr. Robert Califf, a clinical trial expert and founding director of the Duke Clinical Research Institute.
The European Medicines Agency has published two new concept papers for Annex 4 and Annex 5 for veterinary medicinal products on 11 November 2021:
- Concept paper on the revision of annex 4 of the guidelines on good manufacturing practice – manufacture of veterinary medicinal products other than immunologicals
- Concept paper on the revision of annex 5 of the guidelines on good manufacturing practice for medicinal products – manufacture of immunological veterinary medicinal products
The European Commission has tasked its ad-hoc working group (WG) on pharmaceuticals in the environment with drafting a concept paper on the regulatory framework. The WG formed in 2020, is joined by the following Member States: Austria, The Czech Republic, Finland, France, Germany, Ireland, The Netherlands, Slovenia, Spain, Sweden, Poland, Romania, Italy and the European Medicines Agency (EMA).
The Australian Therapeutic Goods Administration, TGA, updated its GMP approach to overseas manufacturers of medicines and biologicals on 1 November 2021. With the COVID-pandemic still being an issue, TGA named remote inspections the only currently available option for certification applications.
The FDA’s Center for Devices and Radiological Health (CDRH) has published its lists with guidance documents intended to be published next year. At this stage CDRH is interested in receiving external feedback on whether the listed documents should be revised or withdrawn.
The US FDA, Health Canada, and the British regulatory agency MHRA have jointly released 10 guiding principles to support the development of Good Machine Learning Practice (GMLP). As a basic framework it should help to promote safe, effective, and high-quality medical devices, while using AI (artificial intelligence) and ML (machine learning).
The FDA’s Office of Regulatory Affairs (ORA), responsible for inspections and other field activities, has released its summary on inspectional observations listed on FDA Forms 483 from October 2020 to September 2021.
The United States Pharmacopeia has released a new Chapter 1220 on “Analytical Procedure Life Cycle” prior to its official publication and entering into force on 1 May 2022. The chapter considers the validation activities that take place across the entire life cycle of an analytical procedure and provides a framework for the implementation of the life cycle approach.
On 14 October 2021, the European Commission has proposed a “progressive roll-out” of the upcoming In Vitro Diagnostic Medical Devices Regulation, IVDR. The reason given for that is to prevent disruption in the supply of those essential healthcare products that fall under it, as well as a serious shortage of notified body capacity. The IVDR was planned to apply as of 26 May 2022.
The European Medicines Agency EMA has further updated its Q&A on nitrosamine impurities. The document is intended to support marketing authorization holders of human medicinal products and considers the latest regulatory requirements (we reported).
The Chinese NMPA applied for PIC/S pre-accession on 24 September 2021. Although this stage is a voluntary assessment process, gaps are identified between PIC/S membership requirements and the system used by the regulatory agency that is interested.
The European Directorate for the Quality of Medicines, EDQM, has identified another azido impurity which was tested positive in a mutagenic evaluation. So far, it has only been found in "Losartan potassium".
The European medicines regulatory network has announced the automatically applied extension of the validity of GMP and GDP certificates for sites in the EEA (European Economic Area) until the end of 2022, unless there are restrictions on the validity period stated in the clarifying remarks of the certificate. This extension also applies to time-limited manufacturing and import and wholesale authorisations.
As communicated by the EMA, the EUDRAGMDP database will be „merged“ with EMA’s Organisation Management Service (OMS). This is an important change to be aware of for all manufacturers, importers and distributors of human and veterinary medicines whose information is recorded in EUDRAGMDP.
On 21 September 2021, an amendment to Delegated Regulation (EU) 2016/161 was published in the Official Journal of the European Union. Article 47 "Evaluation of notifications" was adapted and in Annex I, containing the list of medicinal products exempted from the obligation to bear the safety features, a new entry has been added.
On September 15, the U.S. Pharmacopeia USP published the final draft of the chapter <1083> Supplier Qualification.
As of July 2021, the European Pharmacopoeia (Ph. Eur.) now contains chapter 2.1.7 "Balances for analytical purposes". It was included as an addition to section 2.1 Apparatus and defines the requirements placed on the "balance" tool in an analytical procedure.
This month, the Medical Devices Coordinating Group of the European Commission, MDCG, published a 7-page guideline for notified bodies, distributors, and importers of medical devices. It should provide a basis for the certification of quality management systems (QMS) related to repackaging and relabeling processes of medical devices according to MDR and IVDR.
The WHO has published three GMP-relevant draft documents in recent weeks:
- WHO good manufacturing practices for investigational products
- WHO good manufacturing practices for medicinal gases, Rev.1
- WHO good practices for research and development facilities of pharmaceutical products
The European Medicines Agency (EMA) has issued a 31-page draft guideline describing the information to be included in the Summary of Product Characteristics (SmPC), labelling and package leaflet for Advanced Therapy Medicinal Products (ATMPs) that contain genetically modified cells.
On 27 July 2021, ICH published the anticipated draft of its Q13 Guideline on Continuous Manufacturing of Drug Substances & Drug Products. In Stage 2 of the ICH process the 44-page document has thus been released for public commentation.
The guideline is intended to provide "scientific and legal considerations for the design, implementation, operation and lifecycle management of continuous manufacturing (CM)".
As part of the annual budget planning acting FDA Commissioner Janet Woodcock has addressed the problem of weaknesses in the medical devices supply chain and its overall dependence on foreign medical devices.
The European Commission announced on 14 July 2021, that the Italian company Kiwa Cermet Italia S.P.A. has been appointed as the 21st Notified Body under the EU Medical Devices Regulation (MDR) 2017/745. It has been assigned the number 0476 in the EC's Nando database.
EMA has updated its Q&A document on drug-device combination products by end of June 2021. It includes the current requirements under the Medical Devices Regulation (MDR), which entered into force on 26 May 2021. Marketing authorisation holders of combination products are provided with detailed information on all current adjustments.
On 2 July 2021 the European Medicines Agency has released a revised version of the 17-pages Q&A to aid marketing authorisation holders to assess their risk for nitrosamine impurities. The revision affects questions 3 and 10:
For the ‘call for review’ for chemically synthesised and biological medicinal products, when and how should MAHs report steps 1 and 2 to competent authorities? (Q&A 3)
Which limits apply for nitrosamines in medicinal products? (Q&A 10).
The aborted negotiations between Switzerland and the EU on the institutional framework agreement (we reported) are casting their shadow: new regulations are needed to ensure the safe supply of medical devices within Switzerland. However, not only Swiss manufacturers are affected. Medical device manufacturers who are not domiciled in Switzerland but who place products on the market there must also mandate an authorized representative in Switzerland.
The Netherlands’ DEKRA Certification B.V. was named the fifth notified body under the Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR) in June 2021. Dekra Certification B.V. is also a designated notified body under the MDR.
PIC/S has started the consultation process for the adoption of Annex 16 of the EU GMP Guide. It is a very important step towards international harmonisation of GMP requirements.
As every year, the EMA now publishes its report for 2020, in which it outlines achievements, decisions and objectives of the year.
In early June, the FDA unveiled the Generic Drug Cluster, the first forum for leading regulatory authorities to address the global development of generic drugs.