Second Impurity Found in Valsartan
Health Canada has identified a second impurity, N‑nitrosodiethylamine (NDEA) in valsartan manufactured by Zhejiang Huahai Pharmaceuticals in China. All drugs containing valsartan manufactured from that source have already been recalled in Canada after the first impurity, N-nitrosodimethylamine (NDMA), was identified earlier this summer. Both, NDEA and NDMA are classified as probable human carcinogens, which means that long-term exposure could cause cancer.
EMA: Tracking Tool for Relocation to Amsterdam
The EMA has published a tracking tool on its website, showing how things stand for the relocation to Amsterdam. It covers all aspects on EMA's temporary premises, its permanent premises, staff relocation, financial and legal aspects, removal and logistics and external communication.
FDA Publishes Internal Policy on Inspection Priorisation
On 5 September 2018, the US FDA has published a 7-page Manual of Policies and Procedures, MAPP, on how manufacturing facilities are prioritized and scheduled for surveillance inspections. This step should add greater transparency around the “Site Selection Model (SSM)”, used by CDER staff.
Six Asian Drug Manufacturers refuse FDA Inspection
The US Food and Drug Administration, FDA, has added six Asian drug manufacturers to its import alert list this month, that refused a planned inspection of the FDA.
EU Task Force of EMA/HMA with New Programme on Medicine Shortages
The European Medicines Agency (EMA) and the Heads of Medicines Agencies (HMA) have set up a task force with representatives from the European Commission, interested national competent authorities and other regulatory working groups. Their aim is to develop and coordinate actions for better prevention, identification, management of and communication on issues that can affect the availability of medicines.
UK Government Prepares for "No-deal Scenario" with EU
Even though it is unlikely to happen, the UK government has got its plan B if, in any case, a no deal scenario for leaving the EU might materialise. Guidance thereto was published by the Department for Exiting the European Union on August 23, 2018.
Update on Medicines Containing Valsartan from Zhejiang Tianyu
Following the suspension of the CEP – a certificate verifying that the quality of its valsartan meets European requirements – for Zhejiang Huahai in July 2018, a second Chinese company Zhejiang Tianyu has now lost its authorisation to manufacture the valsartan active substance for EU medicines.
Intended Revision of mandatory USP chapter <797> “Sterile Compounding”
The Compounding Expert Committee intends a revision of the General Chapter USP <797> Pharmaceutical Compounding – Sterile Compounding. The draft version has been published for public commentation until November 30, 2018.
EMA scale back and suspend activities
EMA reported, that it will lauch the next phase of its business continuity plan on 1 October 2018 at the latest. This will allow the Agency to safeguard core activities related to the evaluation and supervision of medicines, while it has to intensify its preparations for the physical move to Amsterdam in March 2019 and cope with significant staff loss.
New MDR: Are deadlines in danger?
The MedTech Europe industry group calls on the European institutions to offer solutions to meet the deadlines for the new MDR and IVDR. Both regulations will apply from May 2020 and May 2022 respectively.
Biosimilars: WHO publishes Q&A draft
The World Health Organization (WHO) has prepared a new questions and answers document to clarify earlier biosimilar guidelines. It will provide answers to questions asked by regulators over the last eight years.
UK votes to participate in EMA after Brexit
On 17 July 2018, the Members of the British Parliament voted 305-301 to continue a close collaboration with the EMA after Brexit. This amendment to the Brexit Trade Bill on ‘UK participation in the European medicines regulatory network’ means that British Government is now 'in charge' to negotiate an active and full participation in the EMA following the United Kingdom’s exit from the EU.
EU and Japan: Reinforcement of Collaboration
The European Union and Japan have extended their Mutual Recognition Agreement (MRA) on 18 July 2018. The MRA now also includes sterile products, APIs and biologicals including vaccines.
EMA identifies gaps in Brexit preparedness of Industry
The European Medicines Agency EMA expresses “serious concerns” over the preparedness of some marketing authorisation holders for centrally authorised products with an important step in their regulatory processes in the United Kingdom (UK) regarding the necessary actions to smoothly transition once the UK will exit the EU in March 2019. This conclusion was drawn after evaluating the results of an industry survey which was initiated by the Agency in January 2018 (we reported).
ICH Prepares for Future Topics
The ICH (International Council for Harmonisation) met in Kobe, Japan, from June 2 – 7, 2018. The corresponding press release provides insight on the topics discussed.
FDA: Two Voluntary Programs on Quality Metrics
The US FDA initiated two new programs on a voluntary basis to gather industry feedback regarding the use of quality metrics. Namely these are a
- Quality Metrics Feedback Program and a
- Quality Metrics Site Visit Program
Ist Highly Purified Water = WFI?
Highly Purified Water (HPW) wird aus dem europäischen Arzneibuch gestrichen, so berichtet die Europäische Arzneibuch-Kommission nach ihrer 160. Sitzung, die vom 20.-21. März 2018 in Straßburg stattfand. Die Monographie 1927 wird aufgrund der Redundanz von HPW und Wasser für Injektionszwecke (WFI) im April 2019 entfallen. Die revidierte Monographie für WFI (Wasser für Injektionszwecke, 0169) ist seit April 2017 in Kraft (wir berichteten).
EU GMP Guidelines in Progress
On 26 and 27 June 2018, the PDA Europe Annual Meeting took place in Berlin. Thomas Peither, Excecutive Editor and President of Maas & Peiter AG, participated in the conference and brought back interesting insights.
EC: Final Annex 2 for Manufacturing Biological Products
EC: Final Version of Annex 17 RTRT and Parametric Release
Almost two years after publishing a draft document of Annex 17: Real Time Release Testing the European Commission has now published the final version newly entitled Annex 17: Real Time Release Testing and Parametric Release. The eight-page document will come into operation on 26 December 2018 and will finally replace the preceding version of the year 2002.
New PIC/S Guidance Documents published
The following new PIC/S Guidance documents have now been published on the PIC/S website:
- PIC/S Aide-Memoire on “Cross-Contamination in Shared Facilities” (PI 043-1).
- PIC/S Guidelines on the formalised risk assessment for ascertaining the appropriate good manufacturing practice for excipients of medicinal products for human use (PI 045-1);
- PIC/S Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities (PI 046-1);
- PIC/S Guidelines on the principles of Good Distribution Practice for active substances for medicinal products for human use (PI 047-1)
EMA Updates Two Brexit Guidance Documents
On 19 June 2018 the European Medicines Agency (EMA) published
- Revision 2 of its practical guidances for procedures related to Brexit for medicinal products for marketing authorisation holders (MAH) and
- Revision 3 of the related Q&A document.
Both documents shall assist pharmaceutical manufacurers in preparing for Brexit.
More than 16,000 Packages of Fertility Drugs Stolen in Italy
The US FDA is currently alerting patients, health care professionals and those involved in the drug supply chain of more than 16,000 packages of the injectable fertility medications Gonal-f RFF Redi-ject and Gonal-f Multi-Dosethat have been stolen in Italy.
WHO: Technical Report Series No.1010 published
EU/US: MRA on Inspections – Lithuania and Ireland Added and Q&A Published
The US Food and Drug Administration (FDA) confirmed the capability of Lithuania and Ireland to carry out GMP inspections at a level equivalent to the US.
ICH Q3D: Public Consultation on Cadmium Inhalation PDE Level
EMA: Draft Guideline on Handling and Shipping of IMPs according to GMP
On 23 May 2018, the European Medicines Agency (EMA) released a guideline laying out the principles for managing investigational medicinal products for use in a clinical trial and in accordance with Good Clinical Practices (GCPs) and Good Manufacturing Practice (GMPs) for public consultation.
FDA Warning Letters go to Manufacturers in China, Ireland, Australia and India
In May the US FDA has issued five Warning Letters that address cGMP-violations on a large scale. The drug facilities involved are:
- Jilin Shulan Synthetic Pharmaceutical und Nox Bellcow Cosmetics Co, China
- Jalco Cosmetics, Australia
- Europharma Concepts, Ireland
- Reine Lifescience, India.
Post-Brexit Agreement for UK's Pharmaceutical Industry Needed
The UK government must secure a post-Brexit deal for the pharmaceutical industry that ensures the closest possible regulatory alignment with the EU and the minimum border friction possible or risk harming patients and seeing the pharma sector losing its status as a world leader, say the Business, Energy and Industrial Strategy Committee of the UK parliament.
PIC/S Meeting in April 2018
From 16 to 18 April 2018 the PIC/S Committee and PIC/S Executive Bureau meetings took place in Geneva, Switzerland.
Danish-Japanese collaboration – FDA Confidentiality Commitment
The Danish Medicines Agency recently met with representatives from the Japanese Ministry of Health, Labour and Welfare (MHLW), and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) in Copenhagen.
Finally: EMA’s Q&A on Health-Based Exposure Limits was published
MHRA five-year Corporate Plan 2018-2023
On Tuesday, 27/4/2018, MHRA (Medicines and Healthcare products Regulatory Agency) published is five-year Corporate Plan for 2018 - 2023.
EMA and the Netherlands agree on Seat Agreement
The European Medicines Agency (EMA) and the Netherlands have finalised the text of a Seat Agreement which describes how the Agency, its bodies and its employees will be treated by the Dutch once they start operating in the Netherlands.
PMDA: Continuous Manufacturing
In July 2016, the Pharmaceuticals and Medical Devices Agency (PMDA) established the Innovative Manufacturing Technology Working Group (IMT-WG) as part of the “Projects Across Multi-Offices” in PMDA. The IMT-WG launched activities to examine desirable regulations that streamline the introduction of new manufacturing technologies, and selected continuous manufacturing as their primary target.
ICH Q3C(R7) Guideline for Residual Solvent in Step 1
Almost one year ago, the ICH published its Guideline for Residual Solvents in the version ICH Q3C (R6) introducing new PDE-Levels for Triethylamine and Methylisobutylketone.
FDA Finalises ICH Q7 "Q&A on GMPs for APIs"
The FDA (US Food and Drug Administration) finalised the ICH Q7 Q&A Guidance on GMPs for APIs on Thursday April 19, 2018.
EMA: Report on International API Inspection Programme
With an increasing globalisation of medicine manufacturing and supply chains, regulatory authorities across the world consider themselves responsible to cooperate in the overall interest of public health. Pharmaceutical companies that are outsourcing their production of APIs to contract manufacturers located in other countries have led to an increased need for inspections, to ensure adequate oversight of these facilities
WHO: Three Draft Documents for Comments
The WHO has released three interesting documents on its website for public comments:
EMA: Public Consultation on GMP Non-compliance Statement
US experts call for early preparation for European MDR, IVDR and what about 21 CFR 820?
At the International Conference on Medical Device Standards and Regulations in Arlington VA, hosted by the AAMI (Association for Advancement of Medical Instrumentation), experts discussed the upcoming regulatory changes occurring with the new European regulations on medical devices (MDs) and in vitro diagnostics (IVDs). They urged the companies to prepare for these changes because it is likely that the medical device industry needs to invest a lot of time and resources to prepare for and comply with the upcoming requirements when it comes to trading goods with the European industry or manufacturing in the EU.
Counterfeit Drugs on German Market
The German BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte) published a statement about counterfeit CellCept® 500 mg film-coated tablets on March 14, 2018. The medicinal product which is manufactured by Roche Reg. Ltd., is used to avoid rejection reactions after transplantations.
EMA Management Board: Highlights of the March 2018 Meeting
The European Medicines Agency (EMA) discussed the following points at its 15 March meeting in London:
MHRA: „GxP Data Integrity Guidance and Definitions“ now final
Two years after the release of a draft data integrity document, the British MHRA published the final version of its GxP data integrity guide on March 9, 2018. Data integrity (DI) is important throughout the pharmaceutical lifecycle.
FDA Warns OTC Drugmakers in China and Hong Kong, Drug Manufacturer in the US, Sends 483s to Aurobindo and Sun
The US Food and Drug Administration (FDA) released two warning letters sent to over-the-counter (OTC) drugmakers in China and Hong Kong and a third one to a drug manufacturer in the USA. In addition, two Form 483s for India-based Sun Pharmaceutical Industries and Aurobindo Pharma were released.
Will the UK Be Part of EMA After Brexit? –EC and UK Follow Different Approaches
While Theresa May promoted the benefits of the UK becoming an associate member of the EMA, the EU took quite an opposite position. In a draft guideline published on 7 March 2018 the EU sets out how the EU council sees its future with the UK. A comment by the British newspaper “The Guardian” states that while the British government does Brexit by speeches the EU prefers releasing documents.
EU/US: MRA on Inspections – Four More Member States Added
On 1 March 2018, the FDA listed four additional recognised authorities under Article 7 of the Sectoral Annex for Pharmaceutical Good Manufacturing Practices (GMPs). This confirms the capability of the following four European Member States to carry out GMP inspections at a level equivalent to the US:
MHRA: Out of Specification Guidance
The MHRA has updated its interesting guidance on how to handle OOS results. The issue faced when dealing with “Out of Specification” results is always a challenge. Many customer requests we receive address this issue.
EMA Publishes Work Plan for the GMP/GDP Inspectors Working Group
The European Medicines Agency EMA has published the adopted 2018 Work Plan for the GMP/GDP Inspectors Working Group. The 8-page document lists, inter alia, new guidance documents and also guidance documents to be revised within the EU GMP Guide. According to the EMA, the plan has been agreed in view of preparing for the relocation of the agency to Amsterdam and is, therefore, subject to further review and reprioritisation.
New Q&A on safety features concerning falsified medicines
Following the Commission Report on Member State penalties for falsification (we reported) the European Commission has released a Questions and Answers document alongside this topic (Version 9) on 13 February 2018. The document addresses an overall of 90 frequently asked questions regarding the implementation of the rules on the safety features for medicinal products for human use. These rules are enshrined in Articles 47a, 54(o) and 54a of Directive 2001/83/EC, and in the Commission Delegated Regulation (EU) No 2016/161. They will become mandatory in February 2019.