Standards Organizations Update

Worldwide standards organizations implemented changes to pharmacopeial standards, published new guidelines, and continued to work toward harmonization as 2014 drew to a close. The following are a few of the latest developments.

Elemental Impurities
The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Steering Committee has moved Q3D Guideline on Elemental Impurities (Q3D) to Step 4 of the ICH process, recommending it for adoption by regulatory agencies. The guideline now enters the implementation period (Step 5), which is carried out according to national or regional procedures that apply to other regional regulatory guidelines and requirements in the European Union, Japan, United States, Canada, Switzerland, and other areas.

Q3D, which is available for download on the ICH website, applies to new finished drug products (as defined in ICH Q6A and Q6B) and new drug products containing existing drug substances, provides a global policy for limiting metal impurities qualitatively and quantitatively in drug products and ingredients. According to the Q3D document, it “presents a process to assess and control elemental impurities in the drug product using the principles of risk management as described in ICH Q9. This process provides a platform for developing a risk-based control strategy to limit elemental impurities in the drug product.”

Impurities are classified in an existing ICH Q3A guideline as “organic, inorganic, and residual solvents,” and Q3A and Q3B discuss requirements for organic impurities. ICH Q3C provides clarification of the requirements for residual solvents. The new Q3D guideline would provide similar clarification of the requirements for metals, which are included in the ICH inorganic impurities classification.

United States Pharmacopeial Convention
In November 2014, the United States Pharmacopeial Convention (USP) published the USP Compounding Compendium to provide access to quality-related standards for compounded medicines. The compendium gives compounding practitioners access to all compounding-related general chapters from the United States Pharmacopeia-National Formulary (USP-NF) and features more than 40 supporting general chapters and more than 170 compounding preparation monographs. It also includes the USP-NF General Notices and Requirements, “which provide definitions and important information necessary to correctly interpret and apply compounding standards.”

The USP Compounding Compendium will be updated with the release of each new USP-NF edition and supplement. Subscribers can access and download all updates during their 12-month subscription period. USP has partnered with the International Academy of Compounding Pharmacists (IACP) and the National Community Pharmacy Association (NCPA) to enable their members to purchase the USP Compounding Compendium directly through the IACP and NCPA websites.

In their continuous efforts to harmonize standards, USP and the Chinese Pharmacopoeia Commission (ChP) jointly hosted the ChP & USP Science Symposium and 2014 ChP Science Annual Meeting on Nov. 13-14 in Chengdu, China. The theme of the meeting was “Strengthening cooperation, Harmonizing standards, Promoting mutual recognition” and focused on international coordination and mutual recognition of pharmaceutical standards in chemical medicine, biologics, traditional Chinese medicine, pharmaceutical excipients, packaging materials, and other related fields.  

The two-day forum featured leaders and experts from pharmacopoeias and regulatory authorities in the United States, China, Europe, the United Kingdom, Japan, Brazil, and other countries. The symposium also included more than 400 representatives from China Food and Drug Administration (CFDA) and China’s National Food and Drug Inspection System, along with scientific research institutes and drug manufacturers.

An industry roundtable session included representatives from industry associations and multinational pharmaceutical companies. As part of the open discussion, according to a press release, “ChP and USP encouraged participants to engage with pharmacopoeias to explore ways of promoting international cooperation and harmonization, and mutual and multilateral recognition. USP and ChP also engaged in bilateral discussion about future opportunities to work together.”

European Pharmacopoeia Commission
The European Pharmacopoeia Commission held its 150th session in Strasbourg in November 2014, in which it adopted 13 new texts for inclusion in the European Pharmacopoeia (Ph. Eur.). Six revised general chapters and 28 revised monographs were also adopted during the session.

Revised monographs included the suppression of reference to calomel electrodes, because of EU regulation 847/2012, which restricts the use of mercury in measuring devices. Revised general chapters included “Water: micro-determination (2.5.32)” and “Potentiometric titration (2.2.20).”

At the session, the Commission endorsed the inclusion of tests for pro-coagulant activity in monographs on immunoglobulins (intravenous and subcutaneous), which will require collaboration with worldwide regulators.

The European Directorate for the Quality of Medicines & Healthcare (EDQM) published the list of revised monographs and adopted texts on the EDQM website. The revised texts will become effective on Jan. 1, 2016 in the 37 member states and will be published in supplement 8.6 of the Ph. Eur.