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.
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.
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:
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.
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.
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".
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.
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).
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.
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.
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.
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.
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.
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.
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:
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 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.
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.
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.
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.
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.
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).
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.
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
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).
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.
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.
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)
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.
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.
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.
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.
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.
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.
From 16 to 18 April 2018 the PIC/S Committee and PIC/S Executive Bureau meetings took place in Geneva, Switzerland.
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.