News about GMP/cGMP

Swissmedic has announced that as of now, the foreign comparator product with a biosimilar for the main studies can also originate from the USA, while that for supplementary studies can now also originate from Canada.

The Economic Times of India has published an article saying that the Indian government has issued showcause notices to eight Chinese pharmaceutical companies. Those companies were inspected by a special Indian inspection team and were found to supply poor quality APIs to drug manufacturers in India.

On 20 December 2017 the European Commission has published the long awaited draft of Annex 1 “Manufacture of Sterile Medicinal Products”. The public consultation period is open from 20 December until 20 March 2018.

Three years after the publication of a concept paper Q12 “Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management”, the ICH has now published the Step 2 draft document including an Annex with illustrative examples. The document was endorsed on 16 November 2017.

The EMA (European Medicines Agency) and the European Commission have published an updated version of the Q&A document which is intended to help the pharmaceutical industry to organise the UK’s withdrawal from the EU for their company.

On 24 November 2017, the European Medicines Agency has published a practical guidance document on post-Brexit Changes. The Practical Guidance for procedures related to Brexit for medicinal products for human and veterinary use within the framework of the centralised procedure comes in the form of nine questions and answers and outlines the practical and simplified requirements that companies should follow when they apply for changes to their marketing authorisation.

According to the Swiss Federal Office of Public Health FOPH, Switzerland is revising its medical devices legislation, closely modelled on the various new EU requirements aiming at an improvement on the safety and quality of medical devices.

On 24 November 2017, the European Commission has published the final version of the Guidelines on GMP specific to Advanced Therapy Medicinal Products. The term “Advanced Therapy Medicinal Products” (ATMPs)  is used to designate gene therapies, somatic cell therapies and tissue engineered products.

The city to host the new headquarter of the European Medicines Agency EMA is chosen. Amsterdam emerged as the winner ahead of Milan and Copenhagen, the two other cities that reached the second and final round.

The German Federal Ministry of Health “Bundesministerium für Gesundheit, BMG” has published the official German translation of Annex 16: Certification by a Qualified Person and Batch Release, which is part of the EU GMP Eudralex Volume 4 GMP guidelines.

A draft of the monography to Purified Water was published in the European Pharmacopoeia, which includes a new section on Elemental Impurities.

As of 1 November 2017, the Mutual Recognition Agreement (MRA) between the European Union and the United States enters the operational phase. The MRA, which will allow to recognise inspections of manufacturing sites for human medicines conducted in each partners’ respective territories shall update the agreement dating back to 1998.

On 16 October 2017, the EMA (European Medicines Agency) has published its 17-page Business Preparedness Plan to ensure continuity of the Agency’s operations once the United Kingdom is no longer a member country of the European Union.

The plan identifies three main priorities:

• Not to jeopardise EMA’s positioning in the pharmaceutical arena in the post-Brexit era.
• In parallel, to demonstrate its preparedness for addressing any emerging consequences by taking decisive and timely action when needed.
• To provide a balanced communication and full transparency, both internally and externally.

According to Swissmedic, the new Article 64a of the revised Therapeutic Products Act (revTPA) will already enter into force on 1 January 2018. This Article governs cross-border inspections and includes inspections carried out in Switzerland by foreign authorities, as well as inspections by Swiss authorities abroad.

Between 12 and 19 September 2017, authorities around the world targeted the illicit online sale of medicines and medical devices. More than 123 countries took part in Operation PANGEA X which led to a record number of 25 million illicit and counterfeit medicines seized worldwide.

The European Medicines Agency EMA has clarified its process for lifting a GMP non-compliance statement. The new process is outlined in an update to the question and answer document on GMP of the EMA.

On September 11, 2017, Michael Kopcha, Ph.D., R.Ph. and FDA’s director of the Office of Pharmaceutical Quality, Center for Drug Evaluation and Research (CDER), announced the opening of a public docket to seek input from experts in areas of science, technology and best practices concerning “Continuous Manufacturing”. To establish common guiding principles to this new technology shall help to push this production method forward.

PIC/S: Three New Participating Authorities
Swissmedic: Combat Against Illegal Pharmaceuticals

The US Food and Drug Administration's (FDA) Center for Devices and Radiological Health (CDRH) published a whole new round of warning letters. They are addressed to three manufacturers from the US and five in Brazil, the Netherlands, Germany, China and Bulgaria.

According to the ICH (International Council for Harmonisation), the ICH Q11 Q&A reached Step 4 of the ICH process in August 2017. The document is now entering Step 5 – the implementation period.

The British Medicines and Healthcare products Regulatory Agency (MHRA) is dealing with the outcome of the EU referendum to move things into the right direction for the post-Brexit period.

The European Medicines Agency EMA, the European Commission and the US FDA have signed a new confidentiality commitment. It enables US and EU regulators to share non-public and commercially confidential information, including trade secret information relating to medicine inspections.

The European Medicines Agency (EMA) is responsible for the scientific evaluation, supervision and safety monitoring of medicines in the EU. The agency will need to be relocated in the context of the UK's withdrawal from the EU. There have been 19 offers to host the European Medicines Agency (EMA).

The government of India has published a draft document on the „Essential Principles for Safety and Performance of Medical Devices“, e.g. fundamental design and manufacturing requirements. It provides an overview on meeting these principles leaving flexibility to the manufacturers rather than dictating how a manufacturer should prove that the essentials laid down are being met.

According to the published 15-page document that summarises the negotiating results of the Economic Partnership Agreement between the EU and Japan, the MRA (Mutual Recognition Agreement) in the area of GMP will be expanded to new pharmaceutical products.

The WHO Expert Committee on Specifications for Pharmaceutical Preparations has recently published its 51st report (Technical Report Series No. 1003). The WHO Technical Report Series covers the findings of various international groups of experts that provide WHO with the latest scientific and technical advice on medical and public health subjects. TRS No. 1003 summarises the outcome of the Expert Committee Meeting of October 2016 in Geneva. In addition, the 252-page report contains all adopted guidances or draft guidances in the form of Appendices.

According to pharmabiz.com, India is planning to set up a joint pharmaceutical venture in the region of Chelyabinsk in Russia and is now seeking views and suggestions from its pharmaceutical industry. On July 17, a interactive meeting with government senior officials and industry leaders will take place.

As a result of the revised Swiss Therapeutic Products Act of March 2016, the relevant ordinances also need to be comprehensively adjusted. This affects ordinances issued both by the Federal Council and the Agency Council of Swissmedic and will last until October 2017.

The European Council has published a timetable for the relocation of the Euorpean Medicines Agency (EMA) that is currently based in London.

On June 28, 2017 the US FDA (Food and Drug Administration) published a revision of its draft guidance on medical gases entitled „Current Good Manufacturing Practice for Medical Gases Guidance for Industry“. This document is intended to supersede the guidance already issued in 2003.

The FDA has released a Q&A document on the 21 CFR Part 11 “Use of Electronic Records and Electronic Signatures in Clinical Investigations Under 21 CFR Part 11 – Questions and Answers”.

According to ICH, the China Food and Drug Administration (CFDA) has been approved as a new Regulatory Member.

According to a press release by the BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte, the German Federal Institute for Drugs and Medical Devices), a counterfeit pack of Gilead Sciences’ hepatitis C drug Harvoni® has entered the legal supply chain in Germany. The “falsified medicinal product” was identified by a patient who noticed a change in colour which was orange instead of white.

The China Food and Drug Administration (CFDA) released a detailed report on inspections conducted throughout the last year. A total of 431 inspections including pre-approval inspections, GMP certification inspections, GMP follow-up inspections, unannounced inspections, overseas inspections, GSP unannounced inspection and inspection observations are analysed therein.

Following a Notice to MAHs (Marketing Authorisation Holders) based in the UK the European Medicines Agency EMA and the European Commission have now released a Q&A document regarding the withdrawal of the UK from the European Union. It should help the pharmaceutical industry to prepare for the upcoming changes.

According to the Swiss Therapeutic Products Agency Swissmedic, the agency achieved its objectives last year. Regulatory approval was granted for more than 40 innovative medicinal products partially due to a fast-track procedure.

In collaboration with APEC (Asia Pacific Economic Cooperation), the US FDA has created a Supply Chain Security Toolkit for Medicinal Products. The intention behind this new tool is to maximize available global resources and to deliver quality trainings and best practices in order to secure the global supply chain. It covers the entire supply chain and lifecycle from raw materials to use by patients.

On May 11, 2017 the US FDA issued a warning letter to Jintan Qianyao Pharmaceutical Raw Material Factory in Changzhou, China, for significant deviations from cGMP for APIs. The findings can be summarized as a complete lack of written procedures, quality-related procedures or an overall quality system.

In January 2017, the FDA issued the long-awaited Biosimilar Interchangeability Guidance for public consultation. In this guidance, the Agency details its expectations for demonstrating biosimilar interchangeability.

The deadline for commenting the draft guidance ended on 19 May, with a number of 45 comments being received. Comments came from big pharmaceutical manufacturers like Pfizer, Boehringer Ingelheim, Sandoz, Johnson and Johnson or Genentech or from organisations, e.g the American Society of Clinical Oncology, the Academy of Managed Care Pharmacy, the Combination Products Coalitions or the Biosimilars Forum.

The GMDP Inspectorate of the British MHRA (Medicines & Healthcare products Regulatory Agency) has published its yearly report on inspection deficiency findings. This time the method of gathering the data has been improved, thus introducing new data trending.

The European Medicines Agency plans to clarify its role regarding drugs manufactured in the EU solely for the export market.

EMA officials met with delegates from European and African nations to discuss the issue in a recent workshop in Malta.

Following PIC/S strong criticism on the proposed stand-alone ATMP (Advanced Therapy Medicinal Product) GMP Guidelines of the European Commission (we reported), PIC/S has now published a second letter to the EC on its website.

Following the introduction of ICH Q8, Q9 and Q10, the European Medicines Agency (EMA) and the United States Food and Drug Administration (US FDA) launched a joint pilot program for the parallel assessment of applications containing Quality by Design (QbD) in 2011. To facilitate the exchange of information between the two agencies the program was laid down under US-EU Confidentiality Arrangements. Both agencies have now issued a report that addresses the outcome of the 5-year-program so far.

This month the FDA has updated its yearly list of the new and revised draft guidances CDER is planning to publish in 2017.

In July 2015, US FDA released a draft guidance on quality metrics. The intention behind the introduction of quality metrics was described as a measure to improve drug quality and to encourage the implementation of a modern, risk-based pharmaceutical quality assessment system. The document aroused a storm of criticism by the pharmaceutical industry and its organisations as soon as it appeared.

In 2017, the US FDA has already listed the impressing number of 73 Warning Letters on its website. One topic that emerges again and again is the violation of data integrity, with rising tendency. Remarkably often, those violations are found in China and India. This time, the following pharmaceutical manufacturers are involved:

Last week the EMA (European Medicines Agency) published a concept paper on the need for revision of note for guidance on quality of water for pharmaceutical use (H+V) which addresses the need to update and revise the guidance which originally went into effect on 1st June 2002.

During its February Meeting in Switzerland, which was attended by representatives of 37 of its regulatory authorities, the Pharmaceutical Inspection Co-operation Scheme (PIC/S) unveiled a new road map for the next two years.

Following a three-year-process, the United States (represented by the US FDA) and the European Union (represented by the European Commission) have now finally announced their agreement to mutually recognise each other's GMP inspections of pharmaceutical facilities.

This news summarizes the latest regulatory changes for medical devices in China and the newly issued five year-plan of the CFDA (China Food and Drug Administration).