JAPANESE

[Stability Testing related News – vol.59]

◆  EDQM implements “Real-Time Remote Inspections” (05-Apr-22 ECA)

Due to the Corona pandemic and the resulting changes in working conditions, a new type of inspection was needed in addition to the classic inspections carried out on site at the active pharmaceutical ingredient producers’ manufacturing facilities and paper-based GMP assessments.

For this purpose, the pilot project for so-called “Real-Time Remote Inspections (RTEMIS)” was created. The pilot phase started in November 2020 and ended successfully at the end of 2021. Numerous European authorities of the EEA (European Economic Area), such as the EDQM (European Directorate for the Quality of Medicines & HealthCare), participated in the pilot phase of the project, and issued GMP certificates during this period after a successfully completed remote inspection. These certificates clearly indicate that the associated inspection was carried out as a “distant assessment” and thus clearly distinguish themselves from previously issued certificates.

According to the EDQM, the components of a successful remote inspection include the following four points:

  • The flexibility of the parties involved (manufacturer and authority representatives)
  • A sufficient IT infrastructure within the company to be inspected
  • Preparatory meetings including connection tests
  • Stable IT systems for videoconferencing and secure virtual document exchange system

As the pilot phase has been successfully completed, the EDQM has now included real-time remote inspections as an integral part of the inspection system for monitoring active substance manufacturers and indicates that from January 2022 CEP applicants can be contacted regarding a remote inspection. This will require sufficient IT infrastructure and associated hardware, with all further technical details to be announced in each case during the preparatory phase.

Further information on EDQM’s inspection programme and the pilot phase of real-time remote inspections can be found on the EDQM website.

◆  M7(R2) ADDENDUM: APPLICATION OF THE PRINCIPLES OF THE ICH M7 GUIDELINE TO CALCULATION OF COMPOUND-SPECIFIC ACCEPTABLE INTAKES (Apr-22 FDA)

Docket Number: FDA-2022-D-0055
Issued by: Center for Drug Evaluation and Research

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) has the mission of achieving greater regulatory harmonization worldwide to ensure that safe, effective, and high-quality medicines are developed, registered, and maintained in the most resource-efficient manner. By harmonizing the regulatory expectations in regions around the world, ICH guidelines have substantially reduced duplicative clinical studies, prevented unnecessary animal studies, standardized safety reporting and marketing application submissions, and contributed to many other improvements in the quality of global drug development and manufacturing and the products available to patients.

◆ Microbiological Quality of Herbal Substances (01-Jun-22 ECA)

The United States Pharmacopeia (USP) Botanical Dietary Supplements and Herbal Medicines (BDSHM) Expert Committee is working on a new USP General Chapter <1114> Ensuring Microbiological Quality of Articles of Botanical Origin.

Pharmacopoeial Standards Needed
Herbal substances generally have a higher bioburden compared to synthetic or purified materials. According to the USP BDSHM Expert Committee, this presents “particular challenges as undesirable microorganisms may be carried over to botanical dietary supplement products”. In addition, spores and mycotoxins (e.g. Aflatoxins, Ochratoxin, Vomitoxin) may also be present and these are more difficult to eliminate, once they are present in the herbal material. Pharrmacopoeial provisions and Good Manufacturing Practices (GMPs) require the control and prevention of microbiological contamination of raw materials and finished products. Decontamination technologies (e.g. by using ozone, irradiation, etc.) applied to control the bioburden can have an impact on the quality of the herbal drug / substances (e.g. degradation of active ingredients). The proposed USP chapter will therefore provide information on “practices to prevent” as well as “methods to treat” microbial contamination of articles of botanical origin (ABOs) as well as considerations for maintaining quality.

The European Pharmacopoeia (Ph. Eur.), for example, contains a “special provision for herbal substances for oral use” (Ph. Eur. 5.1.4) and provides different categories (Ph. Eur. 5.1.8 A, B, C) for microbiological requirements for herbal medicinal products and extracts for oral use (for example category B for herbal drugs, in case a pre-treatment for reducing microbiological contamination is possible).

Proposed Outline of USP <1114>
The following sections are proposed to be included in the General Chapter

  • Introduction
  • Pharmacopeial microbiological quality and regulatory compliance
  • Practices for preventing microbial contamination
  • Methods for reduction of microbial contamination
  • Validation of microbial control measures
  • References

USP is requesting early input from stakeholders (e.g. suppliers of botanical ingredients, dietary supplement manufacturers, testing laboratories) on this newly proposed informational General Chapter until 29 May 2022. The chapter is then planned to be published for comment in Pharmacopeial Forum PF 48(6) [Nov.- Dec. 2022].

More information is available at USP´s Compendial Notices website in New General Chapter Prospectus: <1114> Ensuring Microbiological Quality of Articles of Botanical Origin General Chapter Prospectus.

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