BfArM reports further Xarelto® counterfeits
Once again, two counterfeit batches of the drug Xarelto® 20 mg from the original manufacturer Bayer AG in Polish-Slovak packaging were discovered at a parallel distributor in Great Britain. Xarelto®, with the active ingredient Rivaroxaban, is used to prevent strokes and systemic embolisms as well as to treat pulmonary embolisms and venous thromboses.
EU/US MRA on inspections: Luxembourg and the Netherlands accepted
On 10 June 2019, the FDA has confirmed the capability, capacity and procedures in place of Luxembourg and the Netherlands to carry out GMP inspections at a level equivalent to the US. This concludes the FDA's assessment of a total of 26 EU member states, whose inspection results will be trusted in the future. This process is to be completed for all EU states by 15 July 2019.
EC: 20 Questions & Answers about Notified Bodies
On 6 June 2019, the European Commission published a Q&A document to clarify new obligations under the medical device and in vitro diagnostic regulations (MDR/IVDR) regarding notified bodies (NBs).
The 8-page document has been endorsed by the Medical Device Coordination Group (MDCG). The MDCG is composed of representatives of all Member States and it is chaired by a representative of the European Commission.
It answers four sets of questions on a range of MDR/IVDR requirements relating to NBs. The clarifications cover organizational and general requirements, as well as resources requirements and process requirements.
WHO: Technical Report Series 1019, 2019 published
The WHO Expert Committee on Specifications for Pharmaceutical Preparations meets annually and their reports (Technical Report Series) include all adopted guidelines in the form of Annexes.
With the publication of the 53nd Technical Report Series No. 1019 of the WHO, several new and revised Guidelines were adopted and recommended for use.
TÜV SÜD designated as second Notified Body for MDR
TÜV SÜD Product Service was designated by the German Central Authority of the Länder for Health Protection with regard to Medicinal Products and Medical Devices (ZLG) as the second Notified Body for the EU Medical Devices Regulation (MDR).
PIC/S Meeting: What’s new for GMP?
In April 2019, the PIC/S Committee and the PIC/S Executive Bureau met in Geneva, Switzerland. The meeting was attended by 45 out of 52 PIC/S Participating Authorities as well as by a number of Applicants, Pre-Applicants, Associated Partners and Guests. Here are the topics addressed in the area of GMP:
EC confirms: Korean APIs in line with EU standards
On 14 May 2019, the European Commission confirmed that the quality of APIs produced in the Republic of Korea is in line with EU standards. APIs manufactured in third countries like the Republic of Korea, and intended for the EU market, have to be produced in an EU equivalent regulatory system. This includes the rules for GMP.
EMA Publishes Sterile Manufacturing Guidance
Q&A on Safety Features for Medicinal Products in Version 14
EU/US MRA on Inspections: Bulgaria and Cyprus accepted
On 29 April 2019, the FDA has confirmed the capability, capacity and procedures in place of Bulgaria and Cyprus to carry out GMP inspections at a level equivalent to the US. This concludes the FDA's assessment of a total of 24 EU member states, whose inspection results will be trusted in the future. This process is to be completed for all EU states by 15 July 2019.
Switzerland: Legal uncertainty for medical device manufacturers
In terms of the InstA (Institutional Agreement) between Switzerland and the EU, there is legal uncertainty. This directly impacts the entire medical technology industry in Switzerland, as it does not ensure an update of the MRA (Mutual Recognition Agreement) Switzerland/EU. Will the third country requirements of the MDR perhaps soon apply to Switzerland? And what has to be done to be prepared?
EU GMP Annex 1: When will the final version be released?
It has been and continues to be speculated when the final version of Annex 1 on the sterile manufacture of medicinal products will finally be published. At the beginning of this month, the issue was also discussed at the ISPE Annual Conference in Dublin. Dr. Sabine Paris from the editorial office of the GMP-Verlag was on site and brought these news with her:
EMA: Brexit-Q&A to the prevention of medicine shortages
EMA has published a 3-page questions-and-answers document (Q&A) on the work that the EU authorities are doing to prevent medicine shortages due to the United Kingdom’s withdrawal from the EU.
ICH: New Inhalation-PDE for Cadmium in Q3D-Guideline
On 22 March 2019, ICH published the final revision of the Guideline for Elemental Impurities Q3D (R1). The reason for the revision is an adjustment of the PDE value for cadmium by inhalation.
FDA: New Acting Commissioner Named
One week after the surprising resignation of FDA Commissioner Scott Gottlieb, Norman E. Sharpless, Director of the National Cancer Institute (NCI), was appointed Deputy Commissioner of the FDA, according to media reports.
MHRA: Six more documents on No-Deal Brexit
Brexit - and no end in sight. In preparation for a "No-Deal-Scenario", the British Medicines and Health Products Regulatory Authority (MHRA) published six new guidelines on a "No-Deal-Brexit" - five on the import and export of medicines and active ingredients and one on paediatric studies.
FDA: CDER List for Planned Guidance Documents in 2019
The U.S. Food and Drug Administration (FDA) published the yearly list of new and revised draft guidances, CDER is planning to release in 2019. A total of 93 planned guidance documents have been set out which are categorised in 15 different themes.
Brexit: News to Exemption for Batch Testing
As already reported, Marketing Authorisation Holders (MAHs) who are unable to transfer their batch testing site from the UK to the EU27 by 29 March 2019 may be permitted, for a limited period of time, to rely on quality control testing performed in the UK under certain conditions.This exempting provision has now been officially included in the EMA practical guidance as the 31st question:
Can I request a delay for transfer of batch control testing to the EU/EEA?
Furthermore, the EMA provides a 3-page template to be used for submitting such requests to the EMA.
EMA publishes Q&A to MDR-/IVDR Compliance
On 27 February 2019, the EMA published a question and answer document for the practical implementation of Regulation (EU) 2017/745 for medical devices (MDR) and Regulation (EU) 2017/746 for in vitro diagnostic medical devices (IVDR).
Brexit and EU: Exemption for Batch Testing
With not even one month left until Brexit, the European Commission has sent a letter to the Director of the EMA (European Medicines Agency) and the EU27 Heads of Medicines Agencies to inform about an exemption to certain batch testing requirements for pharmaceutical manufacturers that perform their batch testing in the UK.
Swissmedic uses EU’s EudraGMDP database
As reported by the European Medicines Agency EMA, the Swiss Agency Swissmedic, has started in 2019 to enter information on GMP compliance as well as on manufacturing authorisations related to Swiss manufacturers into the European Union’s EudraGMDP database. This applies for all new or renewed manufacturing authorisations and the related GMP-certificates issued using new templates (similar to those of EMA). This will allow replacing the current practice of issuing paper documents, i.e. GMP and should lead to easier information-sharing and efficiency gains for all stakeholders.
MHRA: Guidances on No-Deal-Brexit
The British MHRA (Medicines and Healthcare Products Regulatory Agency) has launched a new website containing all guidances and documents released for a no-Brexit-deal.
EU/US MRA on Inspections: Poland and Slovenia accepted
On 7 February 2019, the FDA has confirmed the capability, capacity and procedures in place of Poland and Slovenia to carry out GMP inspections at a level equivalent to the US. This concludes the FDA's assessment of a total of 22 EU member states, whose inspection results will be trusted in the future. This process is to be completed for all EU states by 15 July 2019. According to the EMA the plans for the agreement to come into operation in all EU Member States by 15 July 2019 are well on track. As Germany is still not officially recognised, the US FDA will continue to carry out its inspections there.
EMA/EC: Brexit Guidance Documents Updated
The European Medicines Agency and the European Commission have updated the following three documents related to Brexit that are intended to complement each other:
US-EU Trade Agreement: News for the GMP sector
The Executive Working Group, EWG has published an interim report on the current status of its work. The focus is on the development of short- and medium-term practicable solutions in regulatory matters. In the area of pharmaceuticals and medical devices, the following approaches are being pursued or further pursued:
EMA: Brexit Preparedness Plan in Phase 4
The relocation of the European Medicines Agency EMA to the Spark building in Amsterdam is proceeding according to plan. The move from London to Amsterdam should be completed by 1 March 2019. From 4 March, the EMA will then officially operate under a new address and the EMA staff will move into the new domicile in the week from 11 to 15 March.
PIC/S Work Plan 2019
At the beginning of the year, PIC/S published its annual work plan for 2019. In addition to organisational matters, a new group of experts on veterinary medicines will be set up and the training of inspectors will be further expanded. In the area of harmonisation, PIC/S is actively involved in the revision of the EU GMP guidelines.
Q&A to Safety Features in new Version 13
ICH-Meeting in Charlotte, USA
The International Council for Harmonisation (ICH) met in Charlotte, USA, from 10 to 15 November 2018. The steadily increasing number of members (16) and observers (28) is an indication of the continuous development of the ICH into a global initiative. During the General Assembly, the Iranian authority NRA was welcomed as a new regulatory member.
ICH Q2/Q14: Final Concept Paper for Analytical Procedure Development
The International Council for Harmonisation (ICH) has published the final concept paper for ICH Q14 (Analytical Procedure Development) on its website. In the course of the preparation of this new guideline, ICH Q2 (Validation of Analytical Procedures) will also be revised. It will be adapted to the state of the art to include modern analytical methods in the future. Both guidelines are intended to supplement the existing documents ICH Q8 - ICH Q12.
ICH: Final Concept Paper to ICH Q13 „Continuous Manufacturing“
The Management Committee of the ICH has endorsed the final concept paper and business plan on the new quality guideline ICH Q13 on continuous manufacturing for drug substances and drug products. Both documents are published on the ICH website.
FDA Finalises Guidance on Data Integrity
On 13 December 2018, the US FDA has announced the availability of the final guidance for industry “Data Integrity and Compliance with Drug CGMP: Questions and Answers.” The guidance updates a draft version released in 2016. It has been revised to include additional information on the agency’s current thinking on best practices and covers the design, operation and monitoring of systems and controls to maintain data integrity.
European Council Adopts Animals Medicines Package
As stated in a European Council press release on 26 November, the Council of the EU adopted the "Veterinary Medicinal Products Package" with two new Regulations in the following areas:
- veterinary medicinal products
- the manufacture, placing on the market and use of medicated feed
and changes to the existing rules laying down procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency.
PIC/S: Revised Draft Guidance for Data Integrity
New Version of Q&A to Safety Features for Medicinal Products
MRA EU-US: Five Additional European Countries Named
On 16/28 November 2018, the US Food and Drug Administration (FDA) confirmed the capability of the following five additional EU Member States to carry out GMP inspections at a level equivalent to the United States:
EMA reports impurities in Valsartan from Mylan
On 19 November 2018, the EMA informed on their website that Valsartan from the Indian manufacturer Mylan Labortories is currently not allowed to be used for the production of medicinal products containing Valsartan for the EU. The CEP (Certificate of Suitability) of Mylan has been suspended by EDQM (European Directorate for the Quality of Medicines and Healthcare) because N-nitrodiethylamine (NDEA) has been found in some batches of valsartan.
EU and Health Canada plan to include GMP inspections on APIs in MRA
The Comprehensive Economic and Trade Agreement (CETA) between the EU and Canada also includes the CETA GMP Protocol. In continuation of the MRA of 2003 between the EC and Health Canada this protocol also confirmed the continued mutual recognition of GMP inspections and batch certification between EU and Canada for medicinal products for human use and veterinary medicines.
EMA: Draft Guideline on the Quality of Water for Pharmaceutical Use
On 15 November 2018, the EMA has published a draft of the “Guideline on the Quality of Water for Pharmaceutical Use” for public consultation until 15 May 2019.
This 10-page document, once final, will replace the current “Note for guidance on quality of water for pharmaceutical use” from 2002 and the “CPMP Position Statement on the Quality of Water used in the production of vaccines for parenteral use".
EMA: Brexit Preparedness Plan Phase 3
The parallel preparing of the UK’s exit from the EU, the physical move to Amsterdam and operating “business as usual” as long as possible is the declared aim of the EMA. As of October 2018, EMA has launched Phase 3 of the “Brexit Prepardness Plan”, which results in additional temporary suspensions and scaling back of activities.
Australia and Canada expand their MRA
As of November 1, 2018 the Therapeutic Goods Administration (TGA) of Australia and Health Canada expanded their mutual recognition agreement (MRA) to cover active pharmaceutical ingredients (APIs).
PIC/S-Meeting 2018 in Chicago
The PIC/S Committee met on 24-25 September 2018, in Chicago. The meeting was attended by 38 Participating Authorities as well as by a number of Applicants, Pre-Applicants and Associated Partner Organisations. The event was hosted by the US FDA which symbolised the effort to strengthen inspectional approaches and assessments worldwide and to further share and discuss respective regulatory decisions and information. The keyword “harmonisation” and the impact of PIC/S on this matter had been especially highlighted by the FDA.
PANGEA XI: 500 Tonnes of Illegal Online Pharmaceuticals Seized
This year’s Operation PANGEA – an international effort to disrupt the online sale of fake and unlicensed health products around the world – took place from October 9 to 16, 2018. Starting with just eight countries in 2008, the operation has grown to 116 countries that participated this year.
ICH Q3C(R7) Published with Correction of PDE for Ethylenglycol
As announced on the ICH website on October 25, the ICH Q3C(R7) Guideline along with Q3C Support Documents 1, 2, and 3 have now been published. The new R7-version of ICH Q3C is the result of an error correction of the Permitted Daily Exposure (PDE) for ethylenglycol as per the correct value calculated in Pharmeuropa, Vol. 9, No. 1, Supplement, April 1997 S36.
CDSCO: Draft of Indian Schedule M published
According to pharmabiz.com, the Indian regulatory authority CDSCO has published a draft version of the revised Schedule M. However, the document is currently only available in Indian language.
MHRA asks for comments on “No-deal” Brexit
On October 4, the British MHRA (Medicines and Healthcare products Regulatory Agency) has launched a public consultation seeking views on how the agency’s legislation and regulatory processes would have to be modified in the event of the UK not securing a deal with the EU after the UK’s exit, with no implementation period. This consultation covers no-deal proposals on medicines, clinical trials and medical devices.
FDA introduces cGMP Declarations
On September 17, the US FDA announced a new online application, cGMP declarations. FDA's CDER will send ‘cGMP declarations’ to regulatory authorities in other countries where US firms want to market drug products.
CDRH publishes proposed Medical Device Guidance Development 2019
On 3 October 2018, the US FDA’s Center for Devices and Radiological Health (CDRH) has published three lists of guidance documents that may be published in 2019:
CDRH works on blending ISO 13485 with 21 CFR 820
We have already reported about the intention of the US FDA/CDRH to changing its quality system requirements for medical device manufacturers and utilise the International Organisation for Standardization (ISO) updated quality management standard, 13485:2016. Obviously the intention has already been put into action.
EU/US MRA on Inspections: Portugal accepted and Q&A updated
On 14 September 2018 the FDA has confirmed the capability, capacity and procedures in place of Portugal to carry out GMP inspections at a level equivalent to the US. There are now a total of 15 European Member States whose inspection results the FDA relies on to replace their own inspections.