The Regulatory Times

October 2018

Your monthly round-up of international Life Sciences regulatory news from the past month


Quality Attribute Considerations for Chewable Tablets

This guidance suggests manufacturers of chewable tablets for human use with CDER’s current thinking on the critical quality attributes that should be assessed during the development of these drug products. This guidance also provides recommendations for sponsors/applicants regarding the submission of developmental, manufacturing, and labelling information for chewable tablets in applications.

The recommendations in this guidance applies to new drug applications (NDAs), abbreviated new drug applications (ANDAs), and certain chemistry, manufacturing, and controls (CMC) supplements to these applications. Some of the recommendations about the submission of developmental information may also apply to investigational new drug applications (INDs). The recommendations about assessing critical quality attributes apply to all immediate release (IR) chewable tablets for human use, including non-application products.

The United States Pharmacopeia (USP) recognizes and differentiates between two types of chewable tablets: (1) those that may be chewed for ease of administration, and (2) those that must be chewed or crushed before swallowing to avoid choking and/or to ensure the release of the active ingredient. The concepts in this guidance are applicable to both types of chewable tablets.

This guidance describes the critical quality attributes that should be considered when developing chewable tablets and recommends selection of acceptance criteria that are appropriate and meaningful indicators of product performance throughout the shelf life of the product.

For details please refer to the link provided below:

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Post-approval Changes to Drug Substances

This guidance provides insight to holders of approved new drug applications (NDAs), abbreviated new drug applications (ANDAs), new animal drug applications (NADAs), and abbreviated new animal drug applications (ANADAs) and holders of drug master files (DMFs) and veterinary master files (VMFs) who want to make a change to the drug substance manufacturing process during the drug product application’s postapproval period. It does not address holders of biologics license applications (BLAs) or holders of any master files cross-referenced in BLAs. The guidance applies to synthetic drug substances and the synthetic steps involved in preparing semisynthetic drug substances. The guidance covers the following changes:

  • Facility, scale, and equipment changes associated with all steps of drug substance manufacturing.

  • Specification changes to starting materials, raw materials, intermediates, and the unfinished and final drug substance.

  • Synthetic manufacturing process changes.

  • Changes in the source of the drug substance.

  • Changes to the container closure system for the drug substance.

This guidance does not address postapproval changes to peptides, oligonucleotides, radiopharmaceuticals; or drug substances isolated from natural sources or produced by procedures involving biotechnology; or nonsynthetic steps (such as fermentation) for semisynthetic drug substances. This guidance also does not address complex active ingredients.

Follow the link for full details:

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Improving understanding of biosimilars in the EU

As part of on-going alliance program to improve understanding of biosimilars across the European Union (EU), the European Medicines Agency (EMA) and the European Commission have published additional information material on biosimilar medicines.

A biosimilar is a biological medicine that is highly similar in all essential aspects to a ‘reference’ biological medicine already authorised.

This initiative includes an animated video for patients that explains key facts on biosimilar medicines and how EMA works to ensure that they are as safe and effective as their reference biological medicines.

Follow the link for full details:

EMA Website

NEW – QRD form for submission and assessment of user testing bridging proposals

A new QRD form has been developed by CMDh to provide guidance and facilitate the submission of user testing bridging proposals by applicants as well as to facilitate the assessment by the RMS.

All sections of this form should be completed by applicants and submitted for assessment when applying for bridging.

The existing CMDh guidance “Consultation with Target Patient Groups: meeting the requirements of Article 59(3) without the need for a full test – Recommendations for bridging” will be revised in the near future to reflect the use of the form.

Follow the link for full details:

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Portugal to also benefit from EU-US mutual recognition agreement for inspections

European Union (EU) and the United States (US) have progressed further in adding Portugal on mutually recognising inspections of manufacturing sites for human medicines conducted in their respective territories. The USFDA confirmed on 14 September 2018 the capability of one additional EU Member State (Portugal) making it a total of 15 member states to carry out good manufacturing practice (GMP) inspections at  a level equivalent to the US.

Follow the link for full details:

EMA Website

MHRA Guidance: Notify MHRA about a clinical investigation for a medical device

In the process to obtain the CE marking for medical device, the applicant may need to carry out a clinical investigation and must inform MHRA at least 60 days before starting the investigation.

The updated guidance provides the following information:

  • How to notify MHRA of your clinical investigation.

  • In Vitro Diagnostic Medical Devices (IVDs).

  • Special circumstances for healthcare establishments.

  • Health Research Authority (HRA) approval.

Follow the link for full details:

GOV UK Website

CMDh agreement on improvements for renewals

To improve the renewal process further, CMDh has decided that renewals for all medicinal products approved according to Article 10(1) can be handled according to the shortened renewal procedure, i.e. with a 30-day timetable, submitted with a cover letter and an application form (without annexes) and a declaration that full documentation will be available for submission upon request.

The decision is also applicable for renewal applications already submitted for such products, even if they are submitted with full documentation according to Annex 3 of the Best Practice Guide on the processing of renewals in MRP/DCP. It is up to the RMS to decide if already submitted applications will be run according to the shortened timetable.

Follow the link for full details:

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Emerging Markets


The Poisons Standard and medical devices – Version 1.1 September 2018

The purpose of this guidance is to help manufacturers and sponsors understand how the TGA interprets requirements, and thus indicate how manufacturers and sponsors comply.

Change which has been updates with this version is:

Minor amendments to align with changes to the Therapeutic Goods (Medical Devices) Regulations 2002 regarding conditions applying automatically.

Follow the link for full details:

TGA Website

Colourings used in medicines for topical and oral use – Version 2.2 August 2018

This guidance relates to colourings in medicines for topical and oral use that do not require evaluation of data by the TGA and the information required to evaluate a colouring that is not in:

  • Colourings for use as excipients in medicines for topical use only.

  • Colourings for use in medicines for oral and topical use.

Updation done with this version is relevant to Updated ‘Colourings that do not require evaluation’ to allow general excipients to be used as colours.

Follow the link for full details:

TGA Website

Certificates of free sale and export certificates for medical devices – Version 1.0 September 2018

This guidance assists the sponsors attempting to have certificates of free sale and export certificates notarised and endorsed. TGA have reviewed and streamlined the process. As a result, sponsors will now be able to submit their applications, and receive their certificates, electronically. To apply for a certificate of free sale you will need to have a current ARTG inclusion for your product(s) that allows them to be supplied and sold within Australia.

To apply for an export certificate, you will need to have a current Export Only ARTG inclusion for your product(s).

Follow the link for full details:

TGA Website

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