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.
Once a year, operation PANGEA takes place, a globally organized action by Interpol against the online distribution of illegally imported medicines. Within this week of action, participating countries check (and close) suspicious websites and seize counterfeit medicines. In addition, this action aims to create public awareness of the issue.
The European Medicines Agency, EMA, has updated its regulatory and procedural guidance documents on parallel distribution as of 9 June 2021.
The two facilities of the Italian company Steril Milano S.r.L. in Monza and Reggiolo have closed their doors since March 2021. The company, which offers a sterilization service for medical devices, is facing serious allegations of manipulation. In the meantime, Steril Milano S.r.L's certificate has been withdrawn by the responsible accreditation body.
The FDA has finalized two guidance documents to help ensure that prescription drugs are identified and traced properly while moving through the supply chain. The documents address how to comply with the DSCSA (Drug Supply Chain Security Act) requirements.
Finally the date has come: as of 26 May 2021 the EU rules on medical devices (EU MDR) entered into force. Following a one year postponement due to COVID-19, this regulation is considered a big step forward to improve the safety and quality of medical devices. There are, however, still plenty of uncertainties for their manufacturers, but there is also a saying that every journey begins with single steps.
The new European medical device regulation came into force on 26 May 2021. Parallel, a complete revision of the Medical Devices Regulation MepV was carried out in Switzerland, under the responsibility of the Swiss BAG (Federal Office of Public Health). In context of the alignment of the MepV and the KlinV-Mep with the new EU regulations MDR and IVDR on medical devices, it was also necessary to update the existing MRA (Mutual Recognition Agreement) between Switzerland and the EU. This agreement ensures barrier-free market access and joint implementation. The MRA is, in turn, part of an "overall package" of an institutional framework agreement (Insta), which has not yet been conclusively agreed on. On the contrary: Switzerland has meanwhile broken off negotiations with the EU and described them as "having failed".
On 18 May 2021, Swissmedic and the Federal Office of Consumer Protection and Food Safety (BVL) signed a first Memorandum of Understanding on cooperation in the area of veterinary medicinal products.
On 17 May 2021 the USFDA has released a revised version of its Q&A guidance on remote inspections. The 14-page document was originally published in August 2020 (we reported). As the pandemic still restricts most onsite inspections the FDA further clarifies general questions that came up since then.
The British MHRA has set up a standalone MHRA-GMDP database as a new service (alpha release). This step obviously separates the UK from the EudraGMDP where the competent EU authorities publish manufacturing and wholesale approvals, GMP certificates and non-compliance reports.
ICH published the revised version (Step 4) of the ICH Q3C(R8) Guideline on Impurities: Guideline for Residual Solvents on 22 April 2021.
As announced by PIC/S on 23 April, 2021, the PIC/S GMP Guide has been revised. The changes will take effect on 1 May 2021.
On 16 April 2021, Swissmedic announced that it is seeking harmonization with EU regulations regarding the handling of nitrosamine impurities.
On 12 April 2021, Dr Janet Woodcock, acting head of the US FDA, announced Dr Patrizia Cavazzoni's new role as director of CDER.
The European Union has published the Delegated Regulation (EU) 2021/457 in its Official Journal on 17 March 2021. It amends the Delegated Regulation (VO) 2016/161 on safety features necessary for the packaging of medicinal products for human use. The amendment is to exempt the obligation for wholesalers to deactivate the unique identifier of medicinal products exported to the United Kingdom, being considered a third country now.
EMA published Revision 3 of the Q&A on the Protocol on Ireland and Northern Ireland on 5 March 2021. The 11-page document contains 28 pairs of questions and answers. It is updated regularly and will be of interest to all GMP professionals who have business relationships with companies in Northern Ireland.
The CMDh (EMA's Coordination Group for Mutual Recognition and Decentralized Procedures) has approached one of the EMA's Safety Working Parties (SWPs) with the following two questions regarding chlorobutanol:
- Can the Safety Working Party confirm that the levels of chlorobutanol commonly used in medicinal products are safe from a toxicological point of view?
- Is it possible to determine acceptable intake levels of chlorobutanol?
The EMA published the 15-page SWP response document to these questions on March 17, 2021.
The MHRA announces its return to on-site risk based GxP inspections starting from 29 March 2021. However, it is planned to use a combined approach of both, remote and on-site inspections.
The Medical Device Coordination Group (MDCG) published an eight-page Q&A document titled Questions and Answers on Custom-Made Devices & considerations on Adaptable medical devices and Patient-matched medical devices (MDCG 2021-3) on 15 March 2021.
The European Commission published a Notice this January dealing with the legal framework for medicinal products marketed in Northern Ireland. On 9 March 2021, the UK MHRA, for its part, followed up and also addressed the issue.
On 4 March 2021, Swissmedic announced the numbers on medicinal products illegally imported into Switzerland. In 2020, 6733 illegal imports were recorded. Compared to the previous year, the number has decreased only slightly. Among the countries of origin, Singapore has replaced India, which has long been in the lead. It was followed by Western European countries such as the UK and Germany in particular.
Singapore is increasingly being used as a hub by suppliers of illegal medicinal products.
WHO published a 31-page draft guideline, "GMP for investigational radiopharmaceutical products", in March 2021. It offers recommendations for minimum standards in the manufacture of new radiopharmaceuticals for Phase I-III clinical trials that do not have a marketing authorization (MAA).
As reported earlier, the European Pharmacopoeia Commission implemented five new sartan monographs in a rapid procedure at the end of February. They are scheduled to become effective already on 1 April 2021. For holders of a Certification of Suitability (CEP), this may, but does not necessarily, mean adjusting their control strategies for nitrosamine impurities. EDQM has now published supplemental information on this topic:
On 23 February 2021, the European Directorate for the Quality of Medicines & HealthCare (EDQM) announced that five monographs on sartans have been revised. They will be effective immediately as of 1 April 2021.
On 15 February 2021, the European Commission published a 13-page document on the management of legacy devices. It clarifies questions on how these will be identified in EUDAMED or how the different Unique Device Identifiers (UDI) will be generated or assigned.
On 24 February 2021, the U.S. Food and Drug Administration announced a revision to its September 3, 2020, Guidance for Industry, Control of Nitrosamine Impurities in Human Drugs. The revision extends the recommended timeframe for manufacturers to assess the risk of nitrosamines in active pharmaceutical ingredients (APIs) and drug products from 6 to 7 months.
On 17 February 2021, Swissmedic announced that it will now permanently support the "Orbis" project. Orbis enables manufacturers to submit their marketing authorization applications submitted to the US FDA simultaneously to other international regulatory authorities, provided they participate in the project.
The WHO published a 29-page draft guideline on Good Manufacturing Practices for Medical Gases in February 2021. The reason given for this step is a sharp increase in the demand for medical gases, particularly oxygen used to provide respiratory care to covid patients.
As announced by the European Commission on 18 February 2021, the Italian Istituto Superiore di Sanità (ISS) has been designated as the 19. Notified Body under the EU Medical Devices Regulation (MDR) 2017/745.
EMA published the document "GMP requirements applicable to the early manufacturing steps for comminuted plants and herbal extracts used as active substances" in February 2021.
Following the detection of 1-nitroso-4-methyl-piperazine (MeNP) impurities in some batches of rifampicin in February 2021, the EMA is requesting manufacturers to test the drug for the presence of MeNP.
The European Medicines Agency (EMA) has launched an initiative to collaborate with non-EU authorities and WHO to drive the evaluation processes for COVID-19 vaccines and therapeutics.
As announced on 26 January 2021, the Jordan Food & Drug Administration (JFDA) has submitted a complete application for membership to the PIC/S.
In January 2021, the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) published the English translation of the document on remote inspections, Procedure for Remote Inspection as a Part of Compliance Inspection on Drugs and Regenerative Medical Products.
This year's Center for Drug Evaluation and Research (CDER) list of guidance documents scheduled for publication includes 18 categories with a total of 105 documents.
PIC/S has updated the following four Aide-Mémoires, which became effective on 1 January, 2021:
Dr. Janet Woodcock has been appointed as acting commissioner of the FDA. The previous commissioner, Dr. Stephen M. Hahn, stepped down from his role at the start of President Biden's term of office.
Questions about the EU-UK Trade and Cooperation Agreement, which will apply from January 1, 2021, were clarified by the European Commission in a 39-page Q&A on the EU-UK Trade and Cooperation Agreement on December 24, 2020. In total, it consists of 133 pairs of questions and answers.
The competent authorities of the Russian Federation submitted a complete membership application to PIC/S in Geneva on 13 January 2021. The rapporteur(s) will be appointed in written procedure or at the next meeting of the PIC/S Committee.
In the second week of January, the European Commission (EC) published a list of members appointed to the MDR and IVDR expert panels. On 10 September 2019, the 12 expert panels were designated by the Commission Implementing Decision (EU) 2019/1396.
On 5 January 2021, the UK MHRA published a joint statement by the UK and Canada, which applies on an interim basis and is intended to avoid trade disruptions as a result of the Brexit.
The transition period until Brexit came into effect ended on 31 December 2020. The UK Medicines and Healthcare products Regulatory Agency (MHRA) has published another batch of documents for the processes that are now starting. They cover all aspects of the regulation of medicinal products and medical devices in the UK.
On 11 January 2021, the European Commission (EC) announced what needs to be considered when Notified Bodies conduct remote audits of medical device and in vitro diagnostic manufacturers due to the COVID-19 situation.
Shortly before the end of the year, WHO published a 38-page draft with twelve chapters and two appedices on technology transfer in pharmaceutical manufacturing.
In December 2020, the Medical Device Coordination Group (MDCG) of the European Commission published a six-page Q&A document on Notified Body audits of medical device manufacturers during the COVID 19 pandemic.
As announced by the UN Commission on 2 December 2020, cannabis was removed from Schedule IV of the 1961 Single Convention on Narcotic Drugs following WHO's recommendation.
What should a crisis-proof drug supply in Europe resemble? In this regard, the European Commission presented a 25-page pharmaceutical strategy on November 25, 2020. It was awaited with great interest. One thing is for certain: the implementation of the strategy will not leave the EU pharmaceutical legislation unaffected.