News about GMP/cGMP

On 18 April, the EMA launched a new draft version of the Guideline on Good Agricultural and Collection Practice (GACP) for for starting materials of herbal origin.

This update brings the document up to date with current standards, incorporates the increased development of indoor growing technologies and also covers best practice and legal interpretations published over the last 10 years.

On 10 April, the EU Parliament approved a legislative package to reform the EU‘s pharmaceutical legislation, with the aim of boosting innovation and improving the accessibility and affordability of medicines. The package, which includes a new directive and a regulation, recieved strong support from Members of the European Parliament (MEPs).

The Japanese Pharmacopoeia (JP) and the European Pharmacopoeia (Ph. Eur.) are launching a joint project to harmonise pharmacopoeial standards for active substances and medicinal products. This initiative aims to reduce the burden on manufacturers by aligning pharmacopoeial standards across different regulatory regions.

On 27 March 2024, Japan's PMDA (Pharmaceuticals and Medical Devices Agency) published an English-language version of its updated recommendations on the quality, safety, and efficacy of biosimilars. The 14-page document, Questions and Answers on Guideline for Ensuring the Quality, Safety, and Efficacy of Biosimilars, has been updated to reflect the current state of scientific knowledge. The revised sections of the document are indicated and relate to Q&As 9, 10, and 11.

Appendix 3 of the EMA’s Nitrosamine Q&A has been updated. The Appendix deals with the enhanced Ames test conditions for N-nitrosamines.

On 22 March, the German Cannabis Law was passed by the Bundesrat. The law will therefore come into force on 1 April as planned.

The European Commission adopted two implementing decisions on the sterilisation of medical devices. These decisions were made in accordance with the regulations governing medical devices and in vitro diagnostics (IVDs) in the EU.

The European Court of Justice (ECJ) has ruled that harmonised technical standards are part of EU law and should therefore be freely accessible to EU citizens (Judgment of 05.03.2024, ref. C-588/21 P).

Are you involved in the production of medicinal Cannabis? Then the Cannabis GMP Wiki is of interest to you.

An update of the EMA's Appendix 1 to the questions and answers for marketing authorisation holders/applicants on nitrosamine impurities in human medicinal products has just been published (EMA/72902/2024 /Rev. 3).

On 23 February, the German Bundestag approved the government's bill on the "controlled use of cannabis". The law allows adults to possess up to 50 grams of cannabis in private and up to 25 grams in public.

The ICH Q12 Implementation Working Group (IWG) "Regulatory and Technical Considerations for Pharmaceutical Product Lifecycle Management" Module 8 Training Material is now accessible on the ICH website.

The ICH Q3C “Guideline for Residual Solvents” has undergone revision to become finalised as version R9 using the Minor Revision Procedure. This revised document was published on 24 January 2024 and reached Step 4 of the ICH Process, which is the adoption of a harmonised guideline.

The European Directorate for the Quality of Medicines and HealthCare (EDQM) has published the top 10 deficiencies identified in 2023 following the initial evaluation of new applications for Certificates of Suitability (CEP).

On 31 January 2024, the Medicines and Healthcare products Regulatory Agency (MHRA) announced the designation of two new UK Approved Bodies (UKAB) to increase the capacity to certify the performance and safety of medical devices.

The World Health Organization (WHO) has published the 10^th edition of the "Quality Assurance of Pharmaceuticals: a Compendium of Guidelines and Related Materials, Volume 2, Good manufacturing practices (GMP) and inspection".

The US Food and Drug Administration (FDA) has released its Quality Management System Regulation (QMSR) final rule after years of development. It is a rework of the Quality System Regulation (QSR) – 21 CFR Part 820.

Swissmedic has further specified risk assessment measures for Nitrosamine Drug Substance-Related Impurities (NDSRI). Initially identified in 2018, nitrosamine impurities, including those in antihypertensives, prompted ongoing evaluations and measures by Swissmedic to prevent such impurities.

The Indian Health Ministry has introduced revised rules under Schedule M of the Drugs and Cosmetics Rules, aimed at ensuring robust quality control for pharmaceutical and biopharmaceutical products. Schedule M outlines Good Manufacturing Practices (GMP) for pharmaceutical products.

The European Directorate for the Quality of Medicines & HealthCare (EDQM) has elaborated a document describing the principles for the declassification of documents pertaining to the CEP (Certificate of Suitability to the Monographs of the European Pharmacopoeia) procedure while ensuring when necessary, the confidentiality of information.

On 9 January 2024, the Swiss Medicines Agency Swissmedic informed about critical deficits in the system of medical device regulation. 

The EMA has published 3 new or updated questions and answers on Annex 1 of the EU GMP Guide. They deal with bioburden levels and sampling, and open versus closed isolators. The answers are summarised below:

The European Medicines Agency (EMA) has added 7 Q&As to their quality of medicines questions and answers. They refer to EMA‘s 1998 guidance on the shelf-life of sterile products for human use after opening or reconstitution (CPMP/QWP/159/96 corr).

The European Medicines Agency (EMA) has answered nine questions on the application of revised Brexit rules to centrally authorised medicinal products for human use in Northern Ireland (Regulation (EU) 2023/1182).

The EDQM informs that the standards cannabis flower for system suitability HRS (Herbal Reference Standard) and cannabidiol for cannabis CRS (Chemical Reference Substance) that are described in the newly adopted monograph on Cannabis flower (3028) are now available for users under catalogue code Y0002440 and Y0002422 respectively.

On 11 December, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) announced a validity extension of GMP and GDP certificates.

On 7 December 2023, the European Medicines Agency (EMA) published an important update on the validity of GMP certificates after COVID-19 on its Good Manufacturing Practice website:

The validity of GMP and GDP certificates, which were automatically extended to the end of 2023 under COVID-19, will be extended until 2024. Either the validity date until 2024 or the conclusion of the next on-site inspection applies, whichever comes first unless stated otherwise in the relevant document. The working group of GMP/GDP inspectors decided to continue the extension.

On 5 December 2023, the European Commission (EC) announced that it has adopted an implementing act to designate five EU reference laboratories (EURLs) for class D in vitro diagnostic medical devices (IVDs).

The EDQM pre-published the revised monograph on Propylene glycol (0430) adopted by the European Pharmacopoeia Commission (EPC) at its 177th session held on 21 and 22 November 2023. The revision took part as a response to the public health risk posed by the discovery of ethylene glycol (EG) and diethylene glycol (DEG) contamination in several medicinal products in Africa and Asia and confirmed cases of propylene glycol adulterated with EG with over 190 fatalities in Indonesia.

On 9 November 2023, the EMA published a 5-page document with three Q&As on the extended interpretation of Annex 12 of the EU GMP Guideline "Manufacture of medicinal products using ionising radiation" for X-ray sterilisation processes. The questions relate to the use of X-ray sterilisation for single-use systems (SUS) in pharmaceutical manufacturing. These processes are becoming increasingly established.

From 6 to 7 November 2023, the PIC/S Committee Meeting took place in Bangkok, Thailand, chaired by Paul Gustafson from Health Canada. The Ministry of Public Health of the Thai Food and Drug Administration (Thai FDA) hosted the meeting.

The meeting was attended by 37 of the 56 Participating Authorities (PAs) as well as various applicants, pre-applicants and partner organisations.

On 31 October 2023, Swissmedic published a Q&A with the title "Interpretation of GMP Annex 1 2022 (Rev. 1)". In the 25-page document, the Swiss Agency for Therapeutic Products provides key answers to questions related to Annex 1, which came into force in August 2023, and to repeatedly asked questions from the previous version.

The Assembly of the International Council for Harmonisation (ICH) has adopted the revised Q5A(R2) Guideline on the Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin. The guideline describes a general approach to testing and assessing the viral safety of those products and sets out the data that should be submitted in marketing authorisation applications and registration packages. These products include biotherapeutics and biological products derived from characterised cell cultures of human or animal origin (mammals, birds, insects). The term "virus" used therein does not include non-conventionally transmissible pathogens, such as mammalian prion-associated pathogens.

After only ten days, the European Medicines Agency (EMA) published yet another revised version of the Q&A on nitrosamine impurities for marketing authorisation holders on 12 October 2023. With revision 19, Annexes 2 and 3, among others, were removed from the document and are now available as separate Appendices.

On 7 November 2023, MedTech Europe published a position paper on the Medical Devices Regulation (MDR (EU) 2017/745) and the In Vitro Diagnostic Medical Devices Regulation (IVDR (EU) 2017/746). In the report, the association presents its vision for a regulated legal framework and outlines possible solutions to the ongoing challenges, which have not been overcome after the implementation phase of the MDR and IVDR.

On 30 October 2023, the World Health Organization (WHO) recognized regulatory authorities as "WHO-Listed Authorities" for the first time. WHO-Listed Authorities (WLA) are regulatory authorities that operate in accordance with international standards and fulfil the requirements based on an established benchmarking and performance evaluation process.

The Assembly of the International Council for Harmonisation (ICH) adopted the revised Q2(R2) Guideline on the Validation of Analytical Procedures and the new Q14 Guideline on Analytical Procedure Development. They jointly describe the development and validation activities that should be applied during the life cycle of an analytical procedure to assess the quality of medicinal substances and products.

Every year since 2008, the International Criminal Police Organisation (INTERPOL) has carried out large-scale operations to combat the illegal trade in medicines, known as Operation Pangea.

The UK Medicines and Healthcare products Regulatory Agency (MHRA) has announced that it is planning to establish a new AI-based "regulatory sandbox" to help artificial intelligence (AI) developers test and provide evidence for their technologies in a virtual space under regulatory monitoring. The so-called AI-Airlock is expected to go into operation in April 2024.

On 24 October 2023, the European Commission adopted steps to prevent drug shortages and increase the security of supply in the European Union.

Team-NB, the European association of Notified Bodies, strongly recommends that medical device manufacturers of Class D devices submit applications for In Vitro Diagnostic Regulation (IVDR) certification this year to ensure timely processing.

In October 2023, the International Council for Harmonisation (ICH) published training materials to complement the revised Q9(R1) guideline on quality risk management.

The new monograph on Cannabis flower (3028) will be published in Ph. Eur. Supplement 11.5 in January 2024. Given the exceptionally high interest from stakeholders in having access to the new text as soon as possible, the Ph. Eur. decided to make the monograph immediately available on the EDQM website for information.

A new part of the ISO 14644 cleanroom series has been published: ISO/TR 14644-21:2023 Cleanrooms and associated controlled environments — Part 21: Airborne particle sampling techniques.

The EMA Q&A on nitrosamine impurities has been updated on 2 October 2023 and is now available as Revision 18. The update concerns Q&A 3 regarding the “call of review” and how to report steps 1 and 2 to the competent authorities. The update highlights the responsibilities of MAH(s) to control, report, and mitigate the detection of Nitrosamine impurities throughout the product life cycle, using the established procedure.

On 25 September 2023, Swissmedic expanded a list of frequently asked questions for marketing authorisation holders submitting adverse drug reaction (ADR) reports under the authority's pharmacovigilance program. The Swiss surveillance authority is thereby preparing manufacturers in its area of application for the additional documentation requirements in individual case reports, which will be mandatory from 1 January 2024.

MedTech Europe, along with 34 national associations, published an open letter to EU Health Commissioner Stella Kyriakides on 14 September 2023.

The EMA has published 14 questions and answers for biological products on its website. The CHMP Biologics Working Party developed the page that provides their agreed positions on issues that typically arise from discussions or correspondence during assessment procedures of biological human medicinal products.

The WHO has recently published a draft document that will be of interest to all GMP practitioners in the field of pharmaceutical quality control laboratories: WHO good practices for pharmaceutical quality control laboratories. It provides recommendations for a Quality Management System (QMS) within which analyses of pharmaceutical products should be performed by quality control laboratories. The aim is to ensure accurate and reliable analytical results.

According to Swissmedic, the independent SwissGMDP database will be launched in the first quarter of 2024. The database will be maintained similar to the European EudraGMDP database of the EMA. The GMP or GDP certificates of every company in Switzerland that has a valid Swissmedic operating licence will be listed. Contrary to the EudraGMDP, the SwissGMDP certificates contain all approved activities, i.e. the GDP activities and Switzerland-specific GMP activities of the Swiss companies will also be listed in the certificates.