MEGGLE support for registering CPE co-processed excipients

MEGGLE Excipients & Technology can offer support in registering co-processed excipients (CPEs) to address regulatory uncertainty and prevent or minimize delays during drug approval.

While CPEs have proven to offer the easiest ways to develop oral dosage forms such as tablets, their regulatory status has not been fully established, increasing the need for full and timely registration.

Evolving Regulatory Picture:

Co-processed excipients are defined by the International Pharmaceutical Excipients Council of America (IPEC America) as: “Any mixture of compendial or non-compendial excipients that has been designed to be physically co-processed in a way which results in functional performance attributes when used in a drug application and which are not seen if the excipients are combined using simple mixing.”

The regulatory environment on Co-processed Excipients is changing all the time. Recent developments include:

• 2015: The USP Excipients Expert Committee (Excipients EC) deemed it appropriate to include co-processed excipients in the NF.
• 2017: The European Directorate for the Quality of Medicines (EDQM) published the second draft on a general monograph related to CPEs, as CPEs were not previously clearly defined in the European Union.
• 2019: IPEC Europe released a position paper and a stimuli article ‘The case for an Excipient Master File in Europe’ to highlight how the absence of an Excipient Master File system in Europe could form barriers to the introduction of novel excipients (see Resources).

Drug approval process: Compendial vs. Novel Excipients

Throughout a drug approval process a team of drug regulatory experts needs to compile mandatory documentation, which comply with the common technical documentation (CTD) format.

The CTD format section 3.2.P.4 Control of Excipients covers the mandatory description of the excipients used. These include:

• Excipient specification and justification
• Excipient´s analytical procedures and corresponding validation
• Excipient´s origin (human or animal)

The workload for filling in this excipient section will depend on the excipient actually being used, whether it is compendial (traditional) or novel.

• Compendial Excipients: These comply with monographs published in compendia such as Ph. Eur., USP-NF, JP, CP, etc., and are well accepted by the regulatory bodies. Thus risk of delayed drug approval process is small or negligible for the prospective marketing authorization holder.
• Novel Excipients: These are defined by the International Council for Harmonisation (ICH) as: “excipient(s) used for the first time in a drug product or by a new route of administration”. Use of novel excipients (often including co-processed excipients) requires additional documentation. The 2017 IPEC ‘Co-processed Excipient Guide for Pharmaceutical Excipients” acknowledges co-processed excipients as novel excipients.

MEGGLE CPEs

Regardless of the current development, MEGGLE has been producing co-processed excipients for more than 30 years, which have found their way into approved drugs (oral route of administration) in various countries, whose health authorities are members or observers of the ICH.

This means that MEGGLE’s CPEs such as Cellactose^® 80, MicroceLac^® 100, StarLac^®, and RetaLac^® do not form ‘novel excipients’ according to the ICH definition.

However, as MEGGLE continues to play a vital role in pioneering and developing new co-processed excipients, these new products will fall into the category of novel excipients making it necessary to consider excipient´s pharmacological and toxicological profile. In this regard, the IPEC Europe Co-processed Excipient Guide for Pharmaceutical Excipients gives advice and explains procedures how to evaluate pharmacology and toxicology. These procedures are acknowledged and embraced by MEGGLE, guaranteeing maximum regulatory certainty to all parties involved.

MEGGLE multi-level regulatory support

Meggle provides regulatory support on five different levels:

1. Control of Excipients: As MEGGLE fully understands the regulatory framework (ref. ICH Topic M 4 Q 2.3.P.4) in which pharma companies are operating, MEGGLE has decided to use excipients of pharmacopeial quality for the production of its co-processed excipients. Therefore, MEGGLE does not compromise excipients´ quality.
2. Analytical procedures: MEGGLE has decided to rely on well-established pharmacopeial analytical procedures for analyzing its co-processed excipients as much as possible. Proprietarily developed procedures and analytical validation information are shared either with the customer or the corresponding drug approving authority.
3. Supportive documentation: In order to provide adequate information in a standardized format MEGGLE has developed an EIP (Excipient Information Package), which is based on the IPEC Excipient Information Package (EIP): Template and User Guide, 2013. The primary goal of this IPEC document is to provide standards for the exchange of data between suppliers and users to simplify the process of information exchange.

The MEGGLE EIP consists of the following documents with separate revision cycles:

• Part I: Product Regulatory Datasheet
• Part II: Manufacturing Site Quality Overview
• Part III: Site and Supply Chain Security Overview

Specific EIPs are available for the entire MEGGLE product portfolio.

1. Regulatory Support: MEGGLE´s regulatory service is based on a strong expertise in developing innovative, functional products for application in new and existing dosage forms. All current and relevant regulatory aspects will be considered at any time. Experienced, well-trained and highly qualified pharma experts around the world are there to serve different time zones, geographical locations and language requirements.
2. Shaping the regulatory outlook: As a proud and active member of the IPEC Europe – MEGGLE is actively shaping co-processed excipients regulations for the benefits of their customers.

Resources

Click on CTD Common Technical Documentation Format for detailed information.
Click on IPEC Co-processed Excipient Guide for Pharmaceutical Excipients for IPEC guidelines.
Click on IPEC Stimulus Article to read ‘Case for an Excipient Master File in Europe’.