News about GMP/cGMP

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).

The ICH (International Council for Harmonisation) has developed a training presentation on the ICH Q11 Q&A document Selection & Justification of Starting Materials. Therein the Expert Working Group gives answers to the following questions:

The European Medicines Agency (EMA) has just released a “Concept paper on developing a guideline on quality requirements of medicinal products containing a device component for delivery or use of the medicinal product”.

The ICH has now published the Meeting Minutes of the ICH Assembly meeting which was held in Osaka, Japan in November 2016. Following you will find the key points on guidance progress in the area of GMP and on new members and observers in brief:

The US Food and Drug Administration (FDA) already issued 7 Warning Letters in 2017, one of which went to Porton Biopharma Limited in Salisbury, United Kingdom. The UK-government owned manufacturer of biopharmaceutical products was inspected from March 7 to 18, 2016 and previously on January 12 to 23, 2015. Both inspections resulted in similar violations and a Form 483.

The following chapters of the PIC/S GMP Guide have been revised based on the equivalent chapters of the EU GMP Guide:

The US Food and Drug Administration released a 59-page final guidance on the CGMP requirements for combination products. The guidance describes and explains specific provisions from 21 CFR Part 4 (final rule on CGMP for combination products) that was released in 2013. A draft version of this document was issued in January 2015.

The U.S. Food and Drug Administration (FDA) published the yearly list of new and revised draft guidances, CDER is planning to publish in 2017. A total of 102 planned guidance documents have been set out.

The EMA has released a Q&A draft document with its focus on setting health-based exposure limits for risk identification and the risk-based prevention of cross-contamination. The draft covers 14 questions and answers relating to the “Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities”, which was published in November 2014 and has been in force since June 2015.

The US FDA (Food and Drug Administration) released a warning letter sent to Interquim S.A., Barcelona, Spain. The drug manufacturing facility was inspected in May 2016. It summarizes significant deviations from current GMP for active pharmaceutical ingredients (APIs).

The ICH Q11 Questions and Answers (Q&As) on the Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/Biological Entities) regarding the selection and justification of starting materials, reached Step 2b of the ICH process and enters the consultation period.

The ICH Q3C(R6) Guideline “Impurities: Guideline for Residual Solvents” reached Step 4 of the ICH Process in November 2016 and now enters into the implementation period (Step 5).

On 23 November 2016, the US Food and Drug Administration (FDA) released a Revision 1 of the draft guidance to Quality Metrics which was initially published in July 2015. The revision with the new title “Submission of Quality Metrics Data” came on short notice and is open for comments and suggestions until 24 January 2017.