Regulatory Intelligence Bulletin
January 2, 2016
Highlights of this issue
EMA: External guidance on the implementation of the European Medicines Agency policy on the publication of clinical data for medicinal products for human use
FDA: Draft Guidance for Industry: Providing Regulatory Submissions in Electronic Format-Submission of Manufacturing Establishment Information
TGA: Update on compliance verification GMP clearance applications
HPRA: Application for Registration of Schedules 3, 4, 5 Controlled Drugs
WHO: WHO Expert Committee on Biological Standardization, Sixty sixth report, TRS 999
NPRA (formerly BPFK): ASEAN Joint Assessments Procedure for Pharmaceutical Products Information
ICH guideline Q3C (R6) on impurities: guideline for residual solvents: Step 5, EMA/CHMP/ICH/82260/2006 (December 6, 2016) (Date for coming into effect: 14 June 2017)
The objective of this guideline is to recommend acceptable amounts for residual solvents in
pharmaceuticals for the safety of the patient. The guideline recommends use of less toxic solvents and
describes levels considered to be toxicologically acceptable for some residual solvents.
Approaches, EMA/CHMP/CVMP/JEG-3Rs/450091/2012 (December 15, 2016)
This guideline aims to encourage stakeholders and authorities to initiate, support and accept
development and use of 3Rs testing approaches.
The European Medicines Agency (EMA) will launch a pilot project in February 2017 to test the added value and feasibility of tailored scientific advice for the development path of biosimilar medicines. Through this new initiative, EMA aims to provide developers of biosimilars with advice on the studies/tests they should be conducting, on the basis of the quality, analytical and functional data they have already available for the medicine.
Draft guideline on the clinical investigation of human normal immunoglobulin for intravenous administration (IVIg), EMA/CHMP/BPWP/94033/2007 Rev. 3 (December 22, 2016) (Consultation end date: 3/13/2017)
This Guideline describes the information to be documented when an application is made for a marketing authorisation for a human normal immunoglobulin for intravenous use (IVIg). The guidance covers biological data, clinical trials and patient follow-up. Quality aspects are outside the scope of this guideline.
Clinical pharmacology and pharmacokinetics: questions and answers: 4.8 CHMP request to PKWP for clarification on demonstrating bioequivalence of low dose acetylsalicylic acid gastro-resistant formulations in fixed dose combinations with substitution indication – NEW December 2016
(EudraVigilance Access Policy), EMA/759287/2009 Revision 3 (December 16, 2016)
The revised framework describes the objectives and consolidates the methodology of the Agency’s
interaction with healthcare professionals in relation to medicines for human use. Its ultimate goal is to
promote participatory design in EMA’s work and ensure a sustainable model of interaction with
Screening for adverse reactions in EudraVigilance, EMA/849944/2016 (December 19, 2016)
The purpose of this guidance is to provide a scientific discussion on the methods recommended and implemented in EudraVigilance for screening for adverse reactions. It does not provide regulatory requirements, which are laid down in good pharmacovigilance practices (GVP) Module IX on signal management.
Post-Authorisation Measures (PAMs) assessed by PRAC, EMA/403287/2015 Rev.2 (December 16, 2016)
When shall I submit my type-IA or -IAIN variation? Rev. December 2016
How shall I present and submit my type-IA or -IAIN variation? Rev. December 2016
What changes are considered type-II variations? Rev. December 2016
Is the co-rapporteur involved in type-II variations? Rev. December 2016
Is the PRAC Rapporteur involved in type II variations? NEW December 2016
How shall I present my Type II Variation application? Rev. December 2016
How shall I present my application for a new or modified therapeutic indication? NEW December 2016
When shall I submit my type II variation application? Rev. December 2016
How shall my Type II application be handled (timetable)? Rev. December 2016
How should parallel type II variations that affect the product information be handled? NEW December 2016
When do I have to submit revised product information? In all languages? Rev. December 2016
Will there be any publication on the outcome of my type II Variation? Rev. December 2016
Do I need to confirm the maintenance of my orphan designation when applying for a type II variation? Rev. December 2016
What groups of variations would be considered acceptable? Rev. December 2016
How shall I present a grouped variations application? Rev. December 2016
What procedure number will be given to grouped variation applications? Rev. December 2016
(Non-) Clinical changes Rev. December 2016
How should I present a variation application under worksharing? Rev. December 2016
What procedure number will be given to variation applications under worksharing? Rev. December 2016
CONCLUSIONS ON THE GRANTING OF THE CONDITIONAL MARKETING AUTHORISATION AND <SIMILARITY AND DEROGATION> <AND> < THE REQUEST FOR ONE-YEAR <MARKETING PROTECTION> <DATA EXCLUSIVITY>> PRESENTED BY THE EUROPEAN MEDICINES AGENCY
Template 1- orphan designation transfer form
Organisations, EMA/89918/2016 (December 16, 2016)
The current framework describes the objectives and methods used by the Agency in its interaction with
healthcare professionals with the aim to raise awareness about the Agency’s activities, enhance
targeted communication, and encourage and facilitate their participation in the Agency’s work in
relation to medicines for human use.
There is a need for further guidance in order to ensure that Policy 0070 meets its objectives. For this
purpose EMA has prepared the following documents:
- External guidance on the procedural aspects related to the submission of clinical reports for the
purpose of publication in accordance with EMA Policy 0070 (see Chapter 2).
- External guidance on the anonymisation of clinical reports for the purpose of publication in
accordance with EMA Policy 0070 (see Chapter 3).
- External guidance on the identification and redaction of commercially confidential information in
clinical reports submitted to EMA for the purpose of publication in accordance with EMA Policy 0070
(see Chapter 4).
The aim of the MNAT concept is to allow a broader involvement of national competent authorities (NCAs) in the work of the EMA scientific committees, as well as optimising the use of national resources, whilst maintaining the high quality scientific work of the committees. At this stage the MNAT concept is available to all Member States, and it applies to:
- Rapporteurs and Co-Rapporteurs for initial marketing authorisation applications for human and
- Rapporteurs for MRL applications.
- Coordinators for scientific advice procedures for both human and veterinary medicines.
The European Medicines Agency (EMA) has published today clinical data for two additional medicines on its clinical data website, which now totals six products. This further publication follows the launch of the website on 20 October 2016 and is in line with the Agency’s policy on the publication of clinical data (Policy 0070).
Parallel import licences granted in November 2016 (December 21, 2016)
Marketing authorisations granted in November 2016 (December 21, 2016)
Advertising investigations: November 2016 (December 22, 2016)
Decisions made by MHRA following investigations into complaints about advertising for licensed medicines.
Public list of companies in the UK who have had their licence to manufacture or wholesale medicines revoked or suspended.
Regulator investigating the diversion of prescription only medicines (December 16, 2016)
The Medicines and Healthcare Products Regulatory Agency (MHRA) is conducting a large scale investigation into the diversion of prescription only medicines to the criminal market
MHRA statement on products containing Cannabidiol (CBD) (December 30, 2016)
The Medicines and Healthcare Products Regulatory Agency has issued an opinion on the regulatory status of products containing CBD
The Food and Drug Administration (FDA) and the Office for Human Research Protections (OHRP), Department of Health and Human Services (HHS), are announcing the availability of a guidance entitled “Use of Electronic Informed Consent—Questions and Answers.” The guidance is intended for institutional review boards (IRBs), investigators, and sponsors engaged in or responsible for oversight of human subject research under HHS and/or FDA regulations. The guidance provides recommendations on the use of electronic systems and processes that may employ multiple electronic media to obtain informed consent for both HHS-regulated human subject research and FDA-regulated clinical investigations of medical products, including human drug and biological products, medical devices, and combinations thereof. This guidance finalizes the draft guidance entitled “Use of Electronic Informed Consent in Clinical Investigations—Questions and Answers” issued in March 2015.
This guidance discusses the requirements for a valid electronic submission of manufacturing establishment information (MEI) under the Federal Food, Drug, and Cosmetic Act (the FD&C Act). This action will streamline the review of all manufacturing establishments involved in the preparation of a drug or biological product by consolidating information in one location and eliminating the inclusion of erroneous and/or outdated information from other Agency files.
This guidance is to assist the pharmaceutical industry and other investigators engaged in biosimilar product development in determining the clinical pharmacology data necessary for evaluation of a proposed biosimilar product. This guidance finalizes the draft guidance with the same name issued in May 2014. This guidance is one in a series of guidances that FDA is developing to implement the Biologics Price Competition and Innovation Act of 2009 (BPCI Act).
Update on compliance verification GMP clearance applications (January 5, 2017)
Where recent evidence is available from a recognised overseas regulatory agency, using the equivalent GMP code for the same scope, we may issue a GMP clearance without conducting an on-site inspection via the following pathways: Mutual Recognition Agreements (MRA): assessment of a GMP Certificate issued by a country with which Australia has an MRA in relation to the relevant overseas manufacturing site; or
Compliance Verification (CV): assessment of a recent GMP inspection report of the relevant overseas manufacturing site prepared by a competent overseas regulatory agency acceptable to the TGA, together with supporting manufacturing documentation supplied by the sponsor or manufacturer.
Scheduling delegate’s final decision: codeine, December 2016 (December 20, 2016)
The medicines scheduling delegate (the delegate) referred the following scheduling proposal for consideration by the Advisory Committee on Medicines Scheduling (ACMS) at the August 2015 meeting:
Final decision on re-scheduling of codeine: frequently asked questions (December 20, 2016)
Sponsors and manufacturers of codeine products
I’m a sponsor of a low-dose codeine containing medicines. Will this decision affect my products?
What will happen to my current stock of OTC codeine-containing medicines?
How do I amend the Australian Register of Therapeutic Goods (ARTG) records in relation to our existing OTC low-dose codeine products to reflect the new scheduling status?
Update of codeine safety and efficacy review January 2015-November 2016 (December 20, 2016)
The aim of this review is to ascertain whether any further evidence has accrued in relation to the safety and efficacy of low-dose codeine containing products for analgesia since the completion of the TGA commissioned review Investigating the efficacy and safety of over-the-counter codeine containing combination analgesics for pain and codeine-based antitussives.
Consultation: Proposed Amendments to the Poisons Standard – ACCS, ACMS and Joint ACCS/ACMS meetings, March 2017: Scheduling medicines and poisons (December 22, 2016) (Consultation closes February 10, 2017)
The TGA is seeking comments from interested parties on the following proposed amendments to the Poisons Standard referred by the delegate for scheduling advice to the Advisory Committee on Chemicals Scheduling (ACCS), the Advisory Committee on Medicines Scheduling (ACMS) and the Joint ACCS-ACMS.
After significant consideration and consultation on the effects of medicines containing codeine on people’s health and wellbeing, Australia’s medicine’s regulator, the Therapeutic Goods Administration (TGA), has decided that products containing codeine will not be able to be sold over the counter in pharmacies, making such products available on prescription only. This change does not come into place until 1 February 2018 so there will be no change to the availability of products occurring now or in 2017.
Codeine re-scheduling Regulation Impact Statement (RIS) (December 20, 2016)
The codeine Regulation Impact Statement (RIS) and the associated economic modelling report prepared by KPMG are now publicly available, in addition to the delegate’s final decision on the rescheduling of codeine.
The RIS reviews the significant public health concerns regarding the use of codeine, the scheduling options available (Table 1) and the regulatory impacts associated with these scheduling options.
ASEAN Joint Assessments Procedure for Pharmaceutical Products Information (December 9, 2016)
National competent authorities in countries forming part of the Association of Southeast Asian Nations (ASEAN) have agreed to jointly assess drug marketing authorization applications (MAAs) under a two-year pilot to be launched in January 2017.
The World Health Organization is offering support and technical advice for the pilot, which appears to be based on the EU’s decentralized procedure for evaluating MAAs under which a company can simultaneously submit identical marketing applications in several EU member states. The assessment is led by the EU national authority acting as the “reference member state” and all the participating national authorities recognize the first assessment undertaken by the lead state.
In the ASEAN pilot, pharmaceutical companies would also be able to simultaneously submit the same marketing application (i.e., having the same technical content) to all participating national authorities once a decision is made on which regulatory agency will lead the assessment process.
*ASEAN Joint Assessments Procedure for Pharmaceutical Products Information for Applicant available for download at link