Latest Pharma GMP News and Regulatory updates
We publish the latest GMP news every week. This weekly GMP news consists of newly published FDA Guidelines, EMA Guidelines, MHRA Guidelines, and guidelines from other regulatory authorities.
The weekly GMP news post aims to share consolidated updates with the pharmaceutical professionals and keep tech-publish.com readers updated with current regulatory requirements. In addition, the GMP news consists of source and reference links so that readers can reach respective organizations’ or authoritys’ websites.
Keywords: GMP news, GMP news today, newly published GMP guideline, FDA guidelines, Pharmaguidelines, GMP guidelines, EMA guidelines, MGRA guidelines
Latest Pharma GMP News and Regulatory updates
Pharma GMP News of the Week: 8-May-2022
Period: May 1, 2022 to May 7, 2022
EC proposed European Health Data Space to enable research opportunities
Date of news: May 3, 2022
The European Commission launched the EHDS (European Health Data Space). It will help the European Union to support the way healthcare is provided to people across Europe. This launch will enable people to control and use their data in other Member States or in their home country.
New on by ICH: “The Model-Informed Drug Development (MIDD) Discussion Group, which was established in January 2021, has provided as an output of its discussions, considerations with respect to future MIDD related guidelines in the form of a “roadmap”.”
Date of news: May 3, 2022
MHRA updated its guidance “Exporting active substances manufactured in Great Britain for use in EEA and Northern Ireland”
Date of update: May 04, 2022
The guidance is updated for “Register of Written Confirmations for UK active substance manufacturers”.
International Medical Device Regulators Forum (IMDRF) proposed document, “Principles and Practices for the Cybersecurity of Legacy Medical Devices” for public comment
Date of news: May 04, 2022
EDQM published new on “New policy for the development of monographs on medicinal products containing chemically defined active substance hydrates or solvates”
Date of news: May 5, 2022
As per the news Ph. Eur. commission approved a new policy for the development of monographs on medicinal products containing chemically defined active substances in hydrate or solvate form on its 172nd session in March 2022.
In this policy the difference between hydrates and solvates is explained. Hydrates are which have H2O as the solvent molecule.
The solvates are those that have an organic solvent.
US FDA published draft guideline on “Fostering Medical Device Improvement: FDA Activities and Engagement with the Voluntary Improvement Program”
Date of issue: May 06, 2022
FDA has announced a 3rd party quality maturity appraisal and continuous improvement program.
The intent of this program is to improve medical device quality and production. This is a voluntary program and does not mandate anyone to abide by the requirement. In this program participating manufacturer’s capability and performance will get reviewed with respect to key business processes. For more details, refer to the guidance.
Pharma GMP News of the Week: 1-May-2022
Period: April 24, 2022 to April 30, 2022
FDA Center for Biologics Evaluation and Research and Center for Drug Evaluation and Research issued guidance on “Providing Submissions in Electronic Format — Postmarketing Safety Reports”
Date of issue: April 27, 2022
The objective of the guideline is to assist industry for regulatory submissions in electronic format to CDER and CBER. The document provides information regarding the electronic submission of postmarketing reports as per the following provisions of regulations:
21 CFR 314.98 and 314.80 – approved NDAs and ANDAs, including combination products or drug constituent parts with approved NDAs or ANDAs.
21 CFR 600.80 – approved BLAs, including combination products or biological product constituent parts with approved BLAs.
21 CFR 310.305 – prescription drug products marketed for human use those are not approved NDAs or ANDAs
21 CFR part 4, subpart B – additional reports for combination products with approved BLAs, ANDAs or NDAs
FDA Center for Drug Evaluation and Research issued guidance on “Electronic Submission of IND Safety Reports Technical Conformance Guide”
Date of issue: April 29, 2022
The objective of the guideline is to provide specifications, general considerations, and recommendations on how to submit electronic IND application safety reports to the CDER or CBER. This is the supplement guide to the draft guidance “Providing Regulatory Submissions in Electronic Format: IND Safety Reports dated October 2019”, as per requirements of section 745A(a) of the FD&C Act.
FDA Center for Drug Evaluation and Research issued guidance on “FDA Regional Implementation Guide for E2B(R3) Electronic Transmission of Individual Case Safety Reports for Drug and Biological Products”
Date of issue: April 29, 2022
The objective of the guideline is to assist in electronic submission of individual case safety reports (ICSRs) and attachments to the CDER and CBER in the FDA . This guideline describes technical approach from FDA for submitting ICSRs, for adding its regionally controlled terminology, and for adding FDA FAERS regional data elements that are not given in the ICH E2B (R3) Implementation Guideline (IG) for the following products:
- NDAs and ANDAs for human use
- Prescription drug products for human use with no an approved applications
- OTC for human use
- BLAs for human use.
FDA Center for Drug Evaluation and Research issued guidance on “E2B(R3) The Electronic Transmission of Individual Case Safety Reports Implementation Guide —Appendix to the Implementation Guide — Backwards and Forwards Compatibility”
Date of issue: April 29, 2022
FDA Center for Drug Evaluation and Research issued guidance on “E2B(R3) Electronic Transmission of Individual Case Safety Reports Implementation Guide — Data Elements and Message Specification; and Appendix to the Implementation Guide — Backwards and Forwards Compatibility”
Date of issue: April 29, 2022
MHRA published Guidance on “Innovative Licensing and Access Pathway” that supports innovative approaches to the timely, safe, and efficient medicine development to improve patient access.
Date of last update: April 29, 2022
The ILAP aims to speed up the time to market and provide patient access to medicines. It covers biological medicines, new chemical entities, repurposed medicines, and new indications.
The Innovative Licensing and Access Pathway is open to non-commercial and commercial developers of medicines within the UK or global.
Note: ILAP – Innovative Licensing and Access Pathway
MHRA published Guidance on “Compliance Monitor (CM) Overview and Application Process”
Date of publication: April 29, 2022
As per the MHRA website, they are going to run a pilot scheme to monitor organizations that fail to comply with GMP and GDP and are referred to the IAG post inspection and compliance escalation process being initiated for them. (Note: IAG – Inspection Action Group)
The process will support the agency in focusing resources on completion of the routine risk-based inspection for ensuring patient safety.
During this process IAG will monitor and support the implementation of an agreed Compliance Protocol. As per the details provided on the website, “A company offered the CM oversight route may choose not to accept this and can continue with the routine IAG process”.
This process from the CM will help the company to focus on remediation of the CAPA and augment the oversight of the MHRA.
PMDA, Japan published translation of “Amendment to Basic Principles on Global Clinical Trials”
Month of publication: April 2022
US Food and Drug Administration (FDA) officials asserted at a 26 April Generic Drug Forum (GDF) that firms with weak quality cultures are more susceptible to submit abbreviated new drug applications (ANDA) with data integrity problems than companies with stronger culture. Yet officials continue to see data integrity problems across the board, affecting all elements of ANDA submissions.
Information on “Generic Drugs Forum 2022: The Current State of Generic Drugs” by FDA that conducted on April 26 – 27, 2022
As per the FDA representatives, organizations with weak quality cultures are more susceptible to have data integrity concerns in the submitted ANDA applications compared to the companies with stronger culture.
During this forum, FDA officials discussed the common deficiencies found in submitted ANDAs and lessons learned from remote interactive evaluations.
Watch entire Day 1 and Day 2 as using following videos:
Generic Drugs Forum 2022: The Current State of Generic Drugs – Day 1
Generic Drugs Forum 2022: The Current State of Generic Drugs – Day 2
European Commission’s Medical Device Coordination Group issued guideline to help define ‘borderline’ products
Month of issue: April 2022
The guideline is issued to clarify how developers identify the correct regulatory framework for these so-called “borderline”. This document provides a flowchart to determine whether the product is meeting the definition of a medical device under the MDR.
The purpose of the flow chart is to decide “whether a product fulfills the definition of a medical device per the MDR in order to ensure a consistent approach in the decisions concerning the borderline between medical devices and medicinal products.”
ICH published “The ICH E8(R1) Introductory Training Presentation” on the ICH website
Date of publication: April 28, 2022
The ICH E8(R1) Guideline is related to General Considerations for Clinical Studies. The guideline is reached Step 4 of the ICH Process on 6 October 2021.
This Step 4 Presentation (Introductory Training) is developed by the Experts.
Pharma GMP News of the Week: 24-April-2022
Period: April 17, 2022 to April 23, 2022
The HAD (Healthcare Distribution Alliance) issued guideline to support pharma industry for placement of bar code labels on their products to meet the Drug Supply Chain Security Act (DSCSA)
Date of issue: April 18, 2022
FDA published final guidance on “Drug Products, Including Biological Products, that Contain Nanomaterials – Guidance for Industry”
Date of issue: April 21, 2022
The objective of this guideline is provides guidance on the product development such as biological products having a nanomaterial in the finished dosage form.
The objective on nanomaterials in drug product may be different depending on the functionality. It could be active ingredients, carriers loaded with an active ingredient or inactive ingredients.
Pharma GMP News of the Week: 17-April-2022
Period: April 10, 2022 to April 16, 2022
FDA published Guidance on “Providing Regulatory Submissions in Electronic and Non-Electronic Format – Promotional Labeling and Advertising Materials for Human Prescription Drugs”
Date of release: April 11, 2022
The objective of the guidance is to provide requirements of submission of promotional materials for human prescription drugs to the FDA, produced by made by Applicant, Manufacturers, Distributors, Packers, or Entity acting on behalf of the applicant. The guideline also explains aspects e-Submission of promotional materials in eCTD.
The guideline covers:
Advertising and promotional labeling materials, regardless of the manner, format, or medium of presentation. Examples of promotional materials are television ads, booklets, brochures, internet websites, detailing pieces, exhibits, print ads, radio ads, or sound recordings.
Press release from MHRA: “The MHRA are seeking views to strengthen conflicts of interest policy for independent advisors”
Dare of news: April 12, 2022
MHRA has invited UK public and stakeholders to have their view on how the MHRA manages the conflicts of interest for experts those are independent and how involvement of patients in expert committee meetings to ensure transparency and consistency.
MHRA is open for consultation on a new Code of Practice for the Expert Advisory Committees
Date of news: April 12, 2022
MHRA is consulting on a proposals sets to strengthen and improve the Code of Practice for experts.
Where these expert are involved in giving advice that can be used for decisions about the regulation of medical devices and medicines. The objective of this guidance is to ensure that experts giving the advice and opinion as an independent entity and impartial, and process is robust and clear enough to to manage conflicts of interest.
This consultation closes at 11:45pm on May 24, 2022.
EMA and the EUnetHTA 21 joint work plan published “The European Medicines Agency and the European Network for Health Technology Assessment have published a joint work plan until 2023“
Date of news: April 12, 2022
There will be a close collaboration between EMA and Health Technology Assessment (HTA) bodies to bring synergy with the aims to facilitate patients’ access to medicines in the European Union.
U.S. FDA published Manual of Policies and procedures “Classifying Approved New Drug Products and Drug-device Combination Products as Complex Products for Generic Drug Development Purposes”
Date of release: April 13, 2022
The document provides details regarding examples and definitions of drug-device combination products, complex drugs The document also outlined responsibilities and process for the Office of Generic Drugs’ Complex Drug Working Group.
FDA published draft guideline on “Diversity Plans to Improve Enrollment of Participants From Underrepresented Racial and Ethnic Populations in Clinical Trials; Draft Guidance for Industry; Availability”
Date of issue: April 13, 2022
The objective of this guideline is to recommend to sponsors who are in the process of developing medicinal formulations with the approach for evolving a Race and Ethnicity Diversity Plan to select representative Nos. of members from different populations in the US.
This approach helps to ensure that the data gathered during the development work reflect the racial and ethnic diversity and helps to identify effects on efficacy or safety outcomes associated with, or occur commonly within these populations.
FDA published draft Guidance on “Considerations for Waiver Requests for pH Adjusters in Generic Drug Products Intended for Parenteral, Ophthalmic, or Otic Use”
Date of release: April 14, 2022
The objective of this guidance is to identify the information that US FDA commonly asks while evaluating pH adjusters waiver request for generic drug products intended for ophthalmic, parenteral, or otic use. The guidance is applicable for the applicants of ANDA.
News from MHRA: “Sunset clause: request for public health exemption”
On April 14, 2022, the information was updated to provide additional details regarding notification date for changes
Bioavailability Studies Submitted in NDAs or INDs – General Considerations
Date of release: April 15, 2022
The objective of this guideline is to recommend applicants and sponsors for submitting (BA) bioavailability information for INDs, NDAs, and NDA supplements.
The requirement specified in this guidance is for dosage forms applicable for oral route of administration. It includes capsules, tablets, suspensions, solutions, IR, MR, ER, DR drug products.
The guidance also covers details regarding non-orally administered formulations that are appropriate to rely on systemic introduction to determine the BA (e.g., transdermal delivery systems, nasal drug products etc.).
The guideline is not applicable for ANDAs and ANDA supplements.
Pharma GMP News of the Week: 10-April-2022
Period: April 03, 2022 to April 09, 2022
MHRA update: “Medicines: reclassify your product – Pharmacy, prescription-only (POM), and general sale list (GSL) medicines: apply to move your medicine to a different classification”
Date of Update: April 4, 2022
Update: Updated Approved reclassifications to Mar 31, 2022
The FDA Office of Pharmaceutical Quality published a white paper “Quality Management Maturity: Essential for Stable U.S. Supply Chains of Quality Pharmaceuticals”
Date of white paper: April 05, 2022
The white paper is published with the aim of having a maximally efficient, agile, flexible manufacturing sector that reliably produces high-quality drug products without extensive regulatory oversight.
Manufacturers reach to the quality management maturity (QMM) state when they have reliable, consistent, and robust processes to run business that achieves quality objectives and also it promotes continual improvement.
News from ICH “The ICH E11A draft Guideline reaches Step 2 of the ICH process”
Date of news: April 5, 2022
ICH E11A draft Guideline is open for public consultation as per the ICH news.
This guideline provide information related to
- The Paediatric extrapolation
- approaches that can be used and systematic approach for paediatric extrapolation
- Study designs and statistical analysis methods that can be usedfor a paediatric drug development plan.
FDA published draft guidance “M7(R2) Addendum: Application of the principles of the ICH M7 guideline to calculation of compound-specific acceptable intakes”
Date of issue: April 06, 2022
News from EDQM: EDQM Call for experts to join the Ph. Eur. network!
Date of news: April 06, 2022
The European Pharmacopoeia (Ph. Eur.) is looking for scientific experts independent to collaborate with EDQM experts and working parties.
Who can apply: It includes professionals from official medicines control laboratories, pharmacopoeial authorities, inspectorates, licensing authorities, private sector such as chemical or pharmaceutical industries, research organisations, academia, and other experts.
FDA published final guidance “E8(R1) General Considerations for Clinical Studies”
Date of issue: April 08, 2022
The objective of this guideline is to help to design clinical studies, and to improve the quality of the studies to be submitted to regulatory agencies.
(1) Protecting participants and getting reliable and significant results
(2) Address broad design
(3) Provide reference of other ICH guidance to conduct clinical research
FDA published draft guidance “Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions”
Date of issue: April 08, 2022
The scope of this guidance is applicable to medical devices having software/ firmware/ programmable logic and software as a medical device.
The scope is not limited to medical devices with network or other mode of connecting capabilities.
The guidance provides information regarding the cybersecurity that should be submitted while premarket submission of following types:
De Novo requests, Premarket Notification (510(k)) submissions, Premarket Approval Applications (PMAs) and PMA supplements, Investigational Device Exemption (IDE) submissions, Product Development Protocols (PDPs) and Humanitarian Device Exemption (HDE) submissions.
News from MDCG (Medical Device Coordination Group) – “Joint implementation and preparedness plan for Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR)”
Month of News: April 2022
News from CDSCO, India: BSE certificates is not required if materials come from negligible risk countries
Month of News: April 2022
It has been proposed by India for its Medical Device Rules, 2017 that certain transmissible disease certificates are not required when sourcing animal products from negligible-risk countries.
Pharma GMP News of the Week: 27-March-2022
Period: March 20, 2022 to March 26, 2022
News from EDQM, “Metals and alloys used in food contact materials and articles: updated technical guide released for consultation”
Date of news: March 21, 2022
EDQM open the text for 2nd edition, for consultation by all concerned parties viz. business operators, national authorities, control laboratories and manufacturers from March 21, 2022 – April 29, 2022.
This edition includes:
- Alignment of text with Council of Europe Resolution;
- Updating of (SRLs) specific release limits, and (TDIs) tolerable daily intakes;
- use recommendations and quality requirements;
- Section about zirconium (New);
- Enhancement related to release testing;
- improvements in terms of uncertainty measurements.
FDA released final guidance on “Certain Ophthalmic Products: Policy Regarding Compliance With 21 CFR Part 4 Guidance for Industry”
Date of news: March 22, 2022
The objective of this FDA guidance is to provide guidance to manufacturers with respect to compliance requirements as per 21 CFR part 4 applicable for ophthalmic drugs packaged with eye droppers, eye cups, or other dispensers.
This guidance applies to approved products, pending applications, and products marketed under the section 505G of the FDA without an approved application under section 505 as per OTC monograph drugs).
FDA did not seek public comments prior to implementing this guidance because the FDA has determined that it is feasible or appropriate.
IPEC (The International Pharmaceutical Excipients Council) releases guideline on “How to document to the ECHA’s Proposal for an EU-wide Restriction on Intentionally Added Microplastics Implications for pharmaceutical excipients, medicinal products and food additives”
Month of news: March 2022
IPEC has published how to guideline to help the pharmaceuticals to comply with latest labeling and reporting rules for microplastics which are intentionally included in pharmaceuticals.
DoP organization (India) is seeking comments on Uniform Code for Medical Devices Marketing Practices (UCMDMP).
This draft has been made in response to a request from the medical device industry. As per current requiring, the guidance is must to comply however, industry seeking own voluntary regulatory requirements.
Feedback will be accepted by DoP is until April 15, 2022.
Date of notice: March 16, 2022
Source: Indian Department of Pharmaceuticals (DoP) https://pharmaceuticals.gov.in/sites/default/files/DoP_Public%20Notice_Dated%2016032022.pdf
MHRA has granted a list of herbal medicines currently holding a traditional herbal registration.
Date of news: March 25, 2022
MHRA updated “Medicines: get scientific advice from MHRA”
Date of news: March 25, 2022
Pharma GMP News of the Week: 20-March-2022
Period: March 13, 2022 to March 19, 2022
European Pharmacopoeia (Ph. Eur.) invites experts to join the Ph. Eur. network.
Date of news: March 14, 2022
Ph. Eur. is inviting independent experts to join Ph. Eur. groups and working parties. This includes experts from authorities such as official medicines control laboratories, pharmacopoeial authorities, inspectorates, and licensing authorities, and from private sector of chemical and pharmaceutical industries, research organisations, academia, etc.
Details of application are provided here.
The long awaited EU’s revision of Annex 1 applicable for sterile drug products may be published in 2022, mid-year.
Date of news: March 14, 2022
The news is based on the announcement by Chairperson of the Pharmaceutical Inspection Co-operation Scheme (PIC/S), Paul Gustafson during ISPE Aseptic Conference on March 2014.
This regulation was drafted by EU, with the help of PIC/S and the WHO.
News from MHRA: Metformin in pregnancy shows no safety concerns
Date of news: March 15, 2022
As per the studies, it has been understood that there are no safety concerns relating to the use of metformin during pregnancy.
Now, the metformin can be considered for use during pregnancy as well is during periconceptional phase. This can be an addition or an alternative to insulin (when clinically needed).
FDA released two draft guidelines –
(i) Human Gene Therapy Products Incorporating Human Genome Editing, and (ii) Human Gene Therapy Products Incorporating Human Genome Editing
Date of news: March 15, 2022
European Pharmacopoeia to launch survey to have manufacturers’ opinion on use of total organic carbon (TOC) test in replacement of oxidisable substances test for WFI (Water for injections)
Date of news: March 17, 2022
Proposal for replacement of the test, (replacement of oxidisable substances test with TOC) was discussed with other Pharmacopoeias (Japanese Pharmacopoeia and United States Pharmacopeia,)
The purpose of this survey is to have official consultation from manufacturers on method and acceptance criteria for its appropriateness.
PICS published following seven guidance documents in Feb 2022 and March 2022 (up to Mar 19, 2022)
(i) Assessment and joint reassessment programme audit report (template) – PS/W 12/2002 (Rev.3, Draft 4)
Date of guideline: February 16, 2022
(ii) Joint reassessment programme procedure – PS/W 10/2005 (Rev 1, Draft 4)
Date of guideline: February 16, 2022
(iii) Travel guidance for on-site assessment visits – PS/W 9/2014 (Rev. 1, Draft 2)
Date of guideline: March 1, 2022
(vi) Assessment & joint reassessment programme cv for auditors (template) – PS/W 9/2002 (Rev. 2, Draft 1)
Date of guideline: March 1, 2022
(v) Assessment and joint reassessment programme criteria for observing inspections (template) – PS/W 11/2002 (Rev. 3, Draft 2)
Date of guideline: March 1, 2022
Assessment and joint reassessment programme procedure for observing inspections – PS/W 10/2002 (Rev. 3, Draft 2)
Date of guideline: March 1, 2022
(vi) Guidelines for accession to the pharmaceutical inspection co-operation scheme – PS/W 14/2011 (Rev. 3, Draft 3)
Date of guideline: March 1, 2022
(vii) Guidelines for the pre-accession procedure1 – PS/W 12/2019 (Rev. 1, Draft 1)
Date of guideline: March 1, 2022
Pharma GMP News of the Week: 13-March-2022
Period: March 6, 2022 to March 12, 2022
EDQM published batch release guideline on Pandemic COVID-19 vaccine (Recombinant Spike Protein)
Date of news: March 8, 2022
FDA released draft guidance on “Verification Systems Under the Drug Supply Chain Security Act for Certain Prescription Drugs”
Date of news: March 09, 2022
The objective of this revised draft FDA guidance is to addresses and comply the requirement as amended by the Drug Supply Chain Security Act (DSCSA) of Federal Food, Drug, and Cosmetic Act (FD&C Act).
These compliance requirements are for
• Drug product manufacturers
• Wholesale distributors
The verification system required to be used to determine to be suspect and the quarantine and disposition of a product determined to be illegitimate.
The guidance also covers notification requirement when it is determined that the product is not an illegitimate product and cleared by manufacturer, wholesale distributor, repackager, or dispenser.
The guidance also covers the process for responding to requests for verification and processing returns.
FDA released final guidance on “Current Good Manufacturing Practice and Preventive Controls, Foreign Supplier Verification Programs, Intentional Adulteration, and Produce Safety Regulations: Enforcement Policy Regarding Certain Provisions”
Date of news: March 11, 2022
MHRA has published blog “Compliance Monitor process (Part 1) – An introduction” on its website.
This is the 1st part of blog series on the Compliance Monitor process. This process will be piloted by the MHRA from April 2022.
Potential benefits of the program are:
The company will benefit from being able to concentrate on the delivery of the required improvements without having to divert their resources to manage MHRA supervision inspections to assess compliance remediation activities.
Under this pilot program, the GMP and GDP remediation will be supervised by eligible consultants that will act as Compliance Monitors. The potential benefits are:
• Agency resources can concentrate on routine risk-based inspection programme.
• Minimize potential shortages medicines supply using risk-based supervision and monitoring.
Date of news: March 11, 2022
Pharma GMP News of the Week: 6-March-2022
Period: February 27, 2022 to March 5, 2022
WHO published working document “1.14.1 CHROMATOGRAPHY 3 Draft proposal” for inclusion of it in the International Pharmacopoeia, Working document QAS/21.905
Month of news: February 2022
The draft proposal by WHO covers text regarding TLC, HPLC and GC. The initial draft document was prepared by referring and internationally harmonized (by the Pharmacopoeial Discussion Group).
The document covers following topics:
• Definitions of Distribution constant, Peak-to-valley ratio, Dwell volume, Plate number, Plate height, Relative retardation, Separation factor, Resolution, Symmetry factor, Signal-to-noise ratio and, System repeatability
• System suitability
• Detector response
• Interfering peaks
• Measurement of peaks
• Reporting threshold
FDA released final guidance on “Pre-Launch Activities Importation Requests (PLAIR)”
Date of news: March 01, 2022
The objective of this guidance is to describe the FDA’s policy about importation requests of unapproved drug products by applicants of NDA, and ANDA who is preparing for product launch in U.S. market based on anticipated approval.
The guideline is also applicable for biologics licensing applications (BLAs) for which NDA, BLA, or ANDA approval is anticipated.
FDA released final guidance on “Pre-Launch Activities Importation Requests (PLAIR)”
Date of news: March 01, 2022
As per the guidance, this master protocol is designed with multiple sub-studies. This guidance recommendation is applicable for drugs or biologics for the treatment of cancer.
The guidance recommends designing a master protocol to conduct clinical trials intended to simultaneously evaluate more than one investigational drug and/or more than one cancer type within the same overall trial structure for adult and pediatric cancers.
As per EMA website, “Regulation on EMA’s extended mandate becomes applicable” from March 01, 2022
This is a structures and processes was established by EMA during the COVID pandemic on a more permanent footing. The agency is now responsible for medicine shortage monitoring, that may cause a crisis situation, and also reporting shortages of critical medicines during a crisis.
FDA released final guidance on “Initiation of Voluntary Recalls Under 21 CFR Part 7, Subpart C”
Date of news: March 03, 2022
The objective of this FDA guidance is to provide clarity on FDA’s expectation from industry and FDA staff regarding prompt initiation of voluntary recalls to recover unsafe goods from the market.
The document discusses about required preparations by firms with respect to distribution chain of distributors, and manufacturers’ procedure to initiate recalls; identification and prompt action; and to promptly communicate recall regarding information, press releases or any other public notices.
Pharma GMP News of the Week: 27-February -2022
Period: February 20, 2022 to February 26, 2022
As per EMA website “European medicines regulatory network adopts EU common standard for electronic product information”
Date of news: February 22, 2022
On adoption of this process, it will provide key benefits of providing up-to-date and unbiased information to the patients regarding all the medicines approved in EU through the electronic means.
This will also include the product information of a medicine and will be helpful for healthcare professionals for all the medicines approved and authorized within the region of European Union.
EDQM towards making remote inspection as a permanent element of EDQM’s inspection scheme!
Date of news: February 23, 2022
In view of pandemic in 2020, there was an interruption in the inspection programme of the European Directorate for the Quality of Medicines & HealthCare (EDQM). This situation lead EDQM to think on alternative approach of inspection and EDQM came up with Real-Time Remote Inspections (RTEMIS) to evaluate the company’s GMP compliance using live video streaming of facility and interaction with the manufacturing sites. They have started pilot phase in the month of November 2020 and carried out several remote inspection.
Based on plot phase, EDQM has arrived at conclusion that the approach is suitable to become an integral part of its inspection system. Now, in 2022, CEP applications may get notification for Real-Time-Remote Inspections as part of approval process.
MHRA announced “MHRA Good Practice Symposia Week (7 to 11 March 2022)” on its Blog site
Date of news: February 24, 2022
As per the website, MHRA will be hosting series of Symposia on Good Practice. It will be live stream and online event. This can be accessed by registered delegates as recordings after the symposium. The purpose of recording is to prevent difficult situation because of different time zone of attendees and people may not be able to watch completely in real time.
You can find more about this at https://mhra-good-practice-symposia.co.uk/home.
FDA released new guidance on “Patient-Focused Drug Development: Methods to Identify What Is Important to Patients”
Date of news: February 25, 2022
The objective of this guidance is to describe how stakeholders such as researchers, patients, medical product developers, and others should collect and submit the data that is related to the patient experience and other associated information from patients and caregivers. This is the second guideline in a series of four guidelines to provide methodological Patient Focused Drug Development.
Pharma GMP News of the Week: 20-February -2022
Period: February 13, 2022 to February 19, 2022
EMA published list of “Principal Documents taken into account for the preparation of procedures for GCP inspections requested by the CHMP”
Date of document: February 14, 2022
The given list in the published document is not an exhaustive list. Section, “Good clinical practice”, on the EMA website also should consult for additional guidance documents.
European Commission published Updated guideline “Guideline on the requirements for quality documentation concerning biological investigational medicinal products in clinical trials”
Date of publication: February 14, 2022
European Commission published Updated guideline “Guideline on the requirements to the chemical and pharmaceutical quality documentation concerning investigational medicinal products in clinical trials”
Date of publication: February 14, 2022
As per EDQM news, Ph. Eur. adopts harmonised chapter on Chromatographic separation techniques (Chapter 2.2.46.)
Date of news: February 15, 2022
The text of chapter revised as per pharmacopoeial harmonisation text (agreed by Pharmacopoeial Discussion Group (PDG – the United States Pharmacopeia (USP), the Japanese Pharmacopoeia, and the Ph. Eur.). The agreement was done on September 28, 2021.
The revised text will be available in the 11th Ph. Eur. edition in the month of July 2022 and that will be implemented from 1 January 1, 2023.
Key changes are as follows:
EMA published PFD on “Human medicines highlights of 2021”
Date of news: February 15, 2022
As per the EMA, it recommended 90+ medicines for MA. 53 out of them are new API first time authorized in the EU, which is 30% more than 2020. For more details, download the PDF provided in the following link.
FDA released its latest quarterly batch of product specific guidances (PSGs) to support generic drug development
Date of news: February 18, 2022
As per FDA notice the guidance “provide product-specific recommendations on, among other things, the design of bioequivalence (BE) studies to support abbreviated new drug applications (ANDAs)”.
EMA updated the Union Product Database – FAQs for industry users
Date of publication: February 18, 2022
As per the EMA, the document is a compiled FQA asked by marketing authorisation holders (MAHs) on the usage of the Union Product Database (UPD) and its answers.
Pharma GMP News of the Week: 13-February -2022
Period: February 6, 2022 to February 12, 2022
EMA updated “Questions and answers for marketing authorization holders/applicants on the CHMP Opinion for the Article 5(3) of Regulation (EC) No 726/2004 referral on nitrosamine impurities in human medicinal products”
Date of news: February 04, 2022
The EMA has updated question and answer guidance to provide guidance on how (MA) marketing authorization holders supposed to identify the risk and control it with respect to nitrosamines identified in formulation and active ingredients (APIs).
The guidance includes “Decision tree with control options for products containing multiple N-nitrosamines”
As per the guidance, there are following two acceptable options for determining nitrosamine limits when there are more than nitrosamines available. The approach helps to ensure not to exceed the acceptable risk level of 1:100,000 as outlined in ICH M7(R1) guideline:
- The sum of daily expose/ intake of all identified N-nitrosamines should not to be exceed the Acceptable Intake of the identified most potent N-nitrosamine
- The sum of all calculated N-nitrosamines risk level should not be exceeded is 1 in 100,000
FDA published draft guidance “Clinical Pharmacology Considerations for Antibody-Drug Conjugates Guidance for Industry”
Date of news: February 07, 2022
The purpose of the graft guidance is:
- To provide recommendations and assist industries and parties involved in the development of antibody-drug conjugates (ADCs) with a cytotoxic small molecule drug or payload.
- The guidance reflects the FDAs current thinking on
- Clinical pharmacology considerations
- Recommendations for development that includes bioanalytical methods, dosing strategies, dose- and exposure-response analysis, intrinsic factors, QTc assessments, immunogenicity, and drug-drug interactions (DDIs).
- Specific emphasize on clinical pharmacology considerations of ADC development programs with appropriate reference.
FDA published “COVID-19 Public Health Emergency Policy on COVID-19-Related Sanitation Tunnels”
Date of news: February 08, 2022
Purpose of this policy document is FDA’s concerns regarding safety of human. The guidance discourages development, approval, and usage authorization for sanitation tunnels (also called as disinfection/ sanitizing tunnels)
Examples are chambers, walkways, or similar arrangements that is made using sensor operated spray with a mist of sanitizing solution that gets sprayed when they passes through these tunnels.
EDQM have announced a Ph. Eur. tentative policy on assay RSDs
Date of news: February 09, 2022
As per EDQM, this tentative policy is applicable for monographs on medicinal products with chemically defined active substances – End of trial period postponed.
MHRA has published article on MHRA blog on “New year, new standards for investigational medicines”
Date of news: February 10, 2022
Recently, Clinical Trial regulation came into effect in the EU, “the Commission guidelines on good manufacturing practice for investigational medicinal products for human use” (It is revised Annex 13 of EU GMP).
Even though the EU is EU CTR will not be applicable for UK, the UK requirements will not get changed until completion of consultation on legislation for new proposals with respect to UK clinical trial. As per the blog, UK will be aligned with the globally harmonised standards of PIC/S and the EU, including requirements for the Qualified Person.
Pharma GMP News of the Week: 6-February -2022
Period: January 30, 2022 to February 5, 2022
MHRA published guidance for “Risk-Adapted Approach to clinical trials and Risk Assessments
Through this guideline, the agency is directing to the sponsors to carryout and record a formal risk assessment as early as possible to understand that the clinical studies falls under the Clinical Trials legislation, categorization of trial and possibility of barriers in execution of the studies. The topics covered under guidance are:
• When and how to undertake the risk assessment
• Retention and distribution of the Risk Assessment
• Revision of the Risk Assessment
• Investigator site staff experience and training in clinical trials/GCP etc.
• Submission of risk assessment to the MHRA and the REC
• Benefits of the risk assessment process
• GCP Inspections
• Examples of risk assessments
News from EDQM on new IT tool used to for sharing of EDQM documents secure between DCEP and CEP holders or applicants during the CEP lifecycle
Date of news: January 31, 2022
FDA has published draft guidance on “Formal Meetings Between FDA and Sponsors or Requestors of Over-the-Counter Monograph Drugs”
Date of issue: February 01, 2022
The guidance describes the process and mechanism for formal meetings between FDA and sponsors for an OTC drug.
This guidance describes the method how sponsors can receive suggestion on studies to support their applications.
The guidance also specifies types of meeting, formats of meeting, process of sponsors request, timelines of agency response on the meeting requests, package of meeting, and process of cancellation and rescheduling the meetings.
As per the guidance, there are three types of formats – Type X, Type Y and Type Z those are “otherwise stalled”, “milestone” and “meeting not fall under either of X or Y”.
PIC/S revised Guide to Good Manufacturing Practice (GMP) for Medicinal Products to include revised Annex 13 and new Annex 16.
Date of news: February 1, 2022
The revision of PIC/S Annex 13 is based on Clinical Trials on EC Regulation No. 536/2014. This guidance replaces EU Annex 13.
The Annex 16 is a new annex for the PIC/S. When the Annex 16 was adopted by EU, it was historically not adopted by PIC/S. Previously, this annex was considered by PIC/S as EU specific. After consultation of PIC/S Participating Authorities in 2017, it was considered to have beneficial to better convey expectations associated with product release
From next week, US FDA will resume routine domestic surveillance inspections
Date of news: February 02, 2022
On February 02, 2022, FDA announced that conducting domestic surveillance inspections will be begin from on February 07, 2022.
FDA has published guidance on “Population Pharmacokinetics”
Date of issue: February 03, 2022
The purpose of this guideline is to support new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), and investigational new drugs (IND) applicants and sponsors with respect to population for pharmacokinetic (PK) analysis.
EDQM published a guide to reminds CEP holders about their responsibilities towards their customers
Date of news: February 03, 2022
EDQM experienced recently issues that have demonstrated the lack of knowledge of some CEP holders about their responsibilities and obligation towards their customers/ marketing authorization holders. EDQM has published a guidance document describing summarized CEP holders’ responsibilities.
Pharma GMP News of the Week: 30-January-2022
Period: January 23, 2022 to January 29, 2022
FDA has published revised draft guidance on “Revising ANDA Labeling Following Revision of the RLD Labeling Guidance for Industry”
Date of issue: January 25, 2022
The purpose of the guideline is
(1) To help industry and ANDA holders in updating their labeling based on revisions of a reference listed drug (RLD) labeling.
(2) Helps to identify updates on revision of RLD labeling and submission requirements for ANDA holders.
FDA has published guidance on “Patient Engagement in the Design and Conduct of Medical Device Clinical Studies”
Date of issue: January 26, 2022
As per the FDA, this purpose of this guidance is
(1) Engagement of patient volunteer to improve the design of medical device
(2) Advantages of above approach of using patient volunteer
(3) Criteria for selection of patient volunteer
(4) Q&A about misconceptions regarding collecting and submitting patient engagement information to the FDA
FDA has published guidance on “Principles for Selecting, Developing, Modifying, and Adapting Patient-Reported Outcome Instruments for Use in Medical Device Evaluation”
Date of issue: January 26, 2022
The intent of this guidance is:
1. To provide principles that can be used while Patient-reported outcome (PRO) uses instruments for the evaluation of medical devices;
2. Provide guidance about the significance of assuring the PRO instruments are fit for the intended use.
3. Provides brief about best practices to develop, modify, or adapt reliable, relevant, and sufficiently robust PRO instruments and using the minimum difficult approach.
FDA has published guidance on “Principles of Premarket Pathways for Combination Products”
Date of issue: January 26, 2022
This guidance provides outline about:
(1) General and high-level information about combination products
(2) How to coordinate and interact with FDA regarding combination product regulation
(3) Approach of FDA while reviewing the combination products before they are marketed.
(4) How to determine the type of premarket submissions that is appropriate for combination products.
FDA has published guidance on “Information Requests and Discipline Review Letters Under GDUFA”
Date of issue: January 26, 2022
The purpose of this guideline is to:
(1) Provide explanation about issuance and use IR (information request) and a DRL (discipline review letter) during the assessment of ANDA.
(2) Amendment to a supplement, supplement and amendment made in response to a CRL (complete response letter) does not covered under scope of this guidance.
(3) Commitment of FDA on performance goals for acting on received ANDAs
(4) Committed of FDA to provide preliminary thoughts on possible deficiencies when discipline finishes its initial assessment.
FDA has published guidance on “Good ANDA Submission Practices”
Date of issue: January 26, 2022
The intent of this guideline is to:
(1) Assist applicants in preparing to submit ANDAs.
(2) Provides an idea about common and recurring deficiencies to prevent delay in the approval of an ANDA.
(3) Provides recommendations that how to prevent such deficiencies that helps early approval.
Major change in Clinical Trials Regulation in the EU: Harmonistion of the assessment and supervision processes throughout the European Union as per Clinical Trials Information System (CTIS)
In EU region, clinical trials undergo a major change as soon as Clinical Trials Regulation (Regulation (EU) No 536/2014) comes into effect on January 31, 2022. There will be a hamonisation in assessment and supervision processes through Clinical Trials Information System (CTIS) in entire EU. There will be a centralized portal and database for this purpose in EU.
The ICH published Training Material on E9(R1) its website
On 28 January 28, 2022 ICH announced the availability of training material on ICH E9(R1) “Addendum on estimands and sensitivity analysis in Clinical trials to the guideline on statistical principles for clinical trials”
Date of news: January 28, 2022
Pharma GMP News of the Week: 23-January-2022
Period: January 09, 2022 to January 22, 2022
MHRA’s new proposals for the future clinical trial legislation
Published on: January 17, 2022
The Medicines and Healthcare products Regulatory Agency (MHRA) has invited to contribute their views on far-reaching proposed revisions to the clinical trial legislation in the UK. As per MHRA, rhe objective of this proposal is to “improve and strengthen the UK clinical trials legislation to make the UK the best place to research and develop safe and innovative medicines”.
Consultation period is eight-week.
FDA announced regarding extending On-Site Surveillance Inspections for another 2 Weeks Because Of Omicron
Date of news: January 21, 2022
FDA has announced that the US Food and Drug Administration is not going to conduct on-site surveillance inspections for another two weeks at a minimum.
The agency said on January 21, 2022 that “The FDA is extending the pause on domestic surveillance inspections through Feb. 4 with the goal of restarting these activities as soon as safely possible”.
As per FDA, “The agency continues to conduct both foreign and domestic mission-critical inspections … leveraging a variety of tools, including remote assessments and import operations surveillance”.
EU introduces clinical trials transformation initiative
Month of news: January 2022
EU release a note for version 5.0 of the Harmonised Technical Guidance for eCTD Submissions in the EU
Date for coming into effect (version 5.0): February 1, 2022
Harmonised Technical Guidance for eCTD Submissions new version has been drafted by the HHG and reviewed by the eSubmission Expert Group and the CMDh before it’s acceptance.
Industry is asking more time for reporting manufacturing volume data that is required as per “Reporting Amount of Listed Drugs and Biological Products Under Section 510(j)(3) of the Federal FD & C Act; Draft Guidance for Industry (October 2021)”; under the “Coronavirus Aid, Relief, and Economic Security Act (CARES Act)”.
US FDA has recently publish the guidance “Reporting Amount of Listed Drugs and Biological Products Under Section 510(j)(3) of the Federal FD & C Act; Draft Guidance for Industry (October 2021)”; under the CARES Act. As per this guidance, each Drugmakers and active pharmaceutical ingredient (API) needs to provide the manufacturing volume they produced during the calendar year 2020 and calendar year 2021. These reports for calendar year 2020 need to be submitted February 15, 2022 and reports for calendar year 2021 need to be submitted by May 16, 2022.
The Association for Accessible Medicines (AAM) requested to FDA for delay the reporting date for 2020 data in September 2022.
Furthermore, PhRMA requested that FDA for exemptions for certain types of biologics to cover made-to-stock cell and gene therapy products. FDA proposed to exempt two categories of products from the reporting requirement and those are “blood and blood components for transfusion” and “cell and gene therapy products”.
Example format for reporting:
Pack wise and Month wise volume distributed
|ANDA No.||Product Name||Strength||Pack type||NDC||Jan 2020||Feb 2020||Mar 2020||Apr 2020||May 2020||Jun 2020||Jul 2020||Aug 2020||Sep 2020||Oct 2020||Nov 2020||Dec 2020|
Draft guideline: https://www.fda.gov/media/153665/download
Pharma GMP News of the Week: 9-January-2022
Period: January 02, 2022 to January 08, 2022
New European Pharmacopoeia texts and that have undergone technical revisions are published for comments.
Date of news: January 05, 2022
Total 48 drafts monographs published for comments on Pharmeuropa 34.1 and deadline for the comments is 31 March 2022.
ICH published brief overview ICH’s mission, structure and current work
Date of publication: January 05, 2022
ICH released a Leaflet on ICH’s mission, structure and current work.
MHRA updated guidance for regulating medical devices in the UK
Date of publication: January 01, 2022
The purpose of the guidance updated was to reflect changes to medical device regulatory requirements that will take effect from January 1, 2022. It covers what one should do to deploy a medical device in the Great Britain, European Union (EU) markets, and Northern Ireland.
MHRA published official Statistics regarding expected time taken to process and grant a marketing authorisation or a variation to a marketing authorisation.
Date of publication: January 04, 2022
MHRA updated various documents and guidance from January 1, 2022 to January 7, 2022
Date of updates: January 1, 2022 to January 7, 2022
- Great Britain Marketing Authorisations (MAs) for Centrally Authorised Products (CAPs)
- Clinical trials for medicines: apply for authorisation in the UK
- Apply for the early access to medicines scheme (EAMS)
- Innovative Licensing and Access Pathway
- Coronavirus (COVID-19) vaccines adverse reactions
- Suspended and revoked licences and registrations for manufacturers and wholesalers of medicines and ingredients
- Importing medicines into Northern Ireland
- Regulatory approval of Vaxzevria (previously COVID-19 Vaccine AstraZeneca)
- Notify the MHRA about a clinical investigation for a medical device
- Medicines: licensing time-based performance measures
- Human and veterinary medicines: register of licensed wholesale distribution sites
- Medicines: new manufacturing and wholesale dealer licences
- Register of brokers authorised to deal in human medicines
- Medicines: terminated and cancelled manufacturing and wholesale dealer licences
- Regulating medical devices in the UK
- Register medical devices to place on the market
The eur-lex.europa.eu on January 04, 2021 officially acknowledged harmonized standards for medical devices that device manufacturers can use in order to comply requirements under the Medical Devices Regulation (MDR).
Date of publication: January 04, 2021
Biological evaluation of medical devices
Use of symbols in product information
Quality management systems
According to the European Commission, “devices that are in conformity with the relevant harmonised standards, or the relevant parts of those standards, the references of which have been published in the Official Journal of the European Union, are to be presumed to be in conformity with the requirements of that Regulation covered by those standards or parts thereof.”
Commission Implementing Decision (EU) 2021/1182 dated 16 July 2021
|Sr. No.||EN ISO Standard||Description of standard|
|1.||EN ISO 25424:2019||Sterilization of health care products – Low temperature steam and formaldehyde – Requirements for development, validation and routine control of a sterilization process for medical devices (ISO 25424:2018)|
|2.||EN ISO 11137-1:2015||Sterilization of health care products – Radiation – Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices (ISO 11137-1:2006, including Amd 1:2013)|
|3.||EN ISO 11135:2014||Sterilization of health care products – Ethylene oxide – Requirements for the development, validation and routine control of a sterilization process for medical devices (ISO 11135:2014)|
|4.||EN ISO 11737-2:2020||Sterilization of health care products – Microbiological methods – Part 2: Tests of sterility performed in the definition, validation and maintenance of a sterilization process (ISO 11737-2:2019)|
|5.||EN ISO 10993-23:2021||Biological evaluation of medical devices – Part 23: Tests for irritation (ISO 10993-23:2021)|
Commission Implementing Decision (EU) 2022/6 dated 4 January 2022
|Sr. No.||EN ISO Standard||Description of standard|
|6.||EN ISO 10993-12:2021||Biological evaluation of medical devices – Part 12: Sample preparation and reference materials (ISO 10993-12:2021)|
|7.||EN ISO 10993-9:2021||Biological evaluation of medical devices – Part 9: Framework for identification and quantification of potential degradation products (ISO 10993-9:2019)|
|8.||EN ISO 13408-6:2021||Aseptic processing of health care products – Part 6: Isolator systems (ISO 13408-6:2021)|
|9.||EN ISO 11737-1:2018||Sterilization of health care products – Microbiological methods – Part 1: Determination of a population of microorganisms on products (ISO 11737-1:2018)|
|10.||EN ISO 14160:2021||Sterilization of health care products – Liquid chemical sterilizing agents for single-use medical devices utilizing animal tissues and their derivatives – Requirements for characterization, development, validation and routine control of a sterilization process for medical devices (ISO 14160:2020)|
|11.||EN ISO 13485:2016||Medical devices – Quality management systems – Requirements for regulatory purposes (ISO 13485:2016)|
|12.||EN ISO 17664-1:2021||Processing of health care products – Information to be provided by the medical device manufacturer for the processing of medical devices – Part 1: Critical and semi-critical medical devices (ISO 17664-1:2021)|
|13.||EN ISO 15223-1:2021||Medical devices – Symbols to be used with information to be supplied by the manufacturer – Part 1: General requirements (ISO 15223-1:2021)|
|14.||EN IEC 60601-2-83:2020||Medical electrical equipment – Part 2-83: Particular requirements for the basic safety and essential performance of home light therapy equipment|
FDA mission-critical work certain – inspectional activities has temporarily postponed
Date of press-announcements: January 4, 2022
According to press-announcements, “On Dec. 29, the FDA implemented temporary changes to its inspectional activities to ensure the safety of its employees and those of the firms it regulates as the agency further adapts to the evolving COVID-19 pandemic and the spread of the omicron variant. Through Jan.19, the agency intends to continue mission-critical work but has temporarily postponed certain inspectional activities with the hopes of restarting these activities as soon as possible”.
Delay in Indian rules for use of unique device identifiers
Pharma GMP News of the Week: 2-January-2022
Period: December 26, 2021 to January 1, 2022
FDA published “Questions and Answers on Questions and Answers: Integration of FDA Facility Evaluation and Inspection Program for Human Drugs: A Concept of Operations”
Date of release: December 29, 2021
On December 29, FDA published important Q&A regarding Integration of FDA Facility Evaluation and Inspection Program for Human Drugs: A Concept of Operations. Key questions cover under this Q & A are:
“• What prompted development of the Concept of Operations (ConOps)?
• How does this effort relate to the recently announced Program Alignment initiative?
• Are there any additional details available regarding changes in timelines and communications for the specific inspection types?
• Can all facility owners expect final inspection classification communications within 90 days of inspection closing?
• How does FDA communicate the final inspection classification?
• Is the agency updating internal policies and procedural documents to reflect the ConOps?
• Will domestic and international facilities be evaluated differently?
• Will the ConOps help address problems at manufacturing facilities that have impacted approval of drug applications? “
For further reading, refer to the following link.
Reflation on 2021: Guidance and important news published by different regulatory agencies and organizations in the year 2021.
|Agency||Description important updates for pharmaceuticals|
|EU||6 Important Guidelines by EU in 2021|
|MHRA||Several guidelines and 11+ important blog post by MHRA in 2021|
|US-FDA||12 Important Final Guidelines and 8 Draft Guidelines by US FDA in 2021|
|ICH||8 Important updates by ICH in 2021|
Pharma GMP News of the Week: 26-December-2021
Period: December 19, 2021 to December 25, 2021
For the first time, EMA has issued a list of regulatory science topics that need further research to improve medicine development and evaluation to enable access to innovative medicines for patients.
Date of news :December 15, 2021
According to the news, “EMA has identified around one hundred specific topics in the Regulatory Science Research Needs list. These topics, and the initiative itself, emerged from the stakeholder consultations which underpinned the development of the Regulatory Science Strategy to 2025”.
The topics are divided in the following four categories:
“(i) Integration of science and technology in medicines development, (ii) Collaborative evidence generation to improve the scientific quality of evaluations, (iii) Patient-centred access to medicines in partnership with healthcare systems, and (iv) Emerging health threats and availability/ therapeutic challenges”.
According to the Press release by European Commission on EU-UK relations, “Commission delivers on promise to ensure continued supply of medicines to Northern Ireland, as well as Cyprus, Ireland and Malta”
Date of press release: December 17, 2021
As per the press release “The Commission has put forward proposals to ensure the continued long-term supply of medicines from Great Britain to Northern Ireland and to address outstanding supply concerns in Cyprus, Ireland and Malta. In the context of the Protocol on Ireland/ Northern Ireland, this means that the same medicines will continue to be available in Northern Ireland at the same time as in the rest of the United Kingdom, while specific conditions ensure that UK-authorised medicines do not enter the Single Market”.
FDA has publishes draft guideline on “Digital Health Technologies for Remote Data Acquisition in Clinical Investigations”
Date of release: December 22, 2021
According the FDA, “guidance provides recommendations to sponsors, investigators, and other stakeholders on the use of digital health technologies (DHTs) to acquire data remotely from participants in clinical investigations evaluating medical products. DHTs may take the form of hardware and/or software and may be used to gather health-related information from study participants and transmit that information to study investigators and/or other authorized parties to evaluate the safety and effectiveness of medical products”.
MHRA has updated guidance for Update to post-Brexit protocols
MHRA webpage for “New guidance and information for industry from the MHRA” showing guideline updates from Decembers 2021.
Date of news: December 2021
Pharma GMP News of the Week: 19-December-2021
Period: December 12, 2021 to December 18, 2021
FDA publishes draft guidance on “Inspection of Injectable Products for Visible Particulates”
Date of publication: December 16, 2021
The US Food and Drug Administration (FDA) on issued a draft guidance on “Inspection of Injectable Products for Visible Particulates” to help manufacturers set up inspection testing programs to ensure that their injectable drugs are free of visible particles.
The draft guidance provides clarity that meeting an applicable U.S. Pharmacopoeia (USP) compendial standard alone is not generally sufficient for meeting the current good manufacturing practice (CGMP) requirements for the manufacture of injectable products.
The draft guidance provides information regarding the development and implementation of a holistic, risk-based approach to control visible particulate. It describes about product development, manufacturing controls, visual inspection techniques, particulate identification, investigational and corrective actions designed to assess, correct, and prevent the risk of visible particulate contamination.
European Pharmacopoeia (FP) Supplement 10.8 is available now
The European Pharmacopoeia (Ph. Eur.) Supplement 10.8 is now available on EDQM WebStore.
This is applicable for 39 European countries as of 1 July 2022.
This volume is included in the 2022 subscription (10.6, 10.7 and 10.8) to the 10th Edition of the Ph. Eur.
FDA publishes draft guidance on “Referencing the Definition of “Device” in the Federal Food, Drug, and Cosmetic Act in Guidance, Regulatory Documents, Communications, and Other Public Documents”
Date of publication: December 16, 2021
As per the FDA, “FDA is issuing this guidance to clarify how the Agency interprets existing references to section 201(h) of the FD&C Act and how we intend to reference the definitions of “device” and “counterfeit device” going forward. This guidance is intended to provide clarity on references to the terms “device” and “counterfeit device” – as well as references to section 201(h) of the FD&C Act – in guidance, regulatory documents, and other communications and documents for FDA staff, industry, and other stakeholders.
Pharma GMP News of the Week: 12-December-2021
Period: December 05, 2021 to December 11, 2021
FDA publishes draft guideline on “IND Submissions for Individualized Antisense Oligonucleotide Drug Products for Severely Debilitating or Life-Threatening Diseases: Chemistry, Manufacturing, and Controls Recommendations Guidance for Sponsor-Investigators”
Date of publication: December 07, 2021
The objective of this draft guidance is to recommend CMC information require for investigational new drug application (IND) submitted by a sponsor who is developing an individualized antisense oligonucleotide (ASO) drug product for a severely debilitating or life-threatening (SDLT) disease caused by a unique genetic variant where only a small number of individuals are prospectively identified (typically one or two).
FDA publishes “draft guideline on IND Submissions for Individualized Antisense Oligonucleotide Drug Products for Severely Debilitating or Life-Threatening Diseases: Clinical Recommendations Guidance for Sponsor-Investigators”
Date of publication: December 07, 2021
The objective of this guidance provides recommendations for managing the administration of the individualized ASO drug product and conducting clinical assessments of the safety and treatment response during administration of the ASO drug product. The recommendations in this guidance are informed by experience with certain classes of well-characterized ASO drug products and by the ability to anticipate and manage some of the potential adverse events based on this prior experience with the ASO drug classes.
FDA publishes “Considerations for the Use of Real-World Data and Real-World Evidence to Support Regulatory Decision-Making for Drug and Biological Products”
Date of publication: December 08, 2021
The purpose of this guidance is to discusses the applicability of FDA’s IND application regulations under part 312 (21 CFR part 312) to various clinical study designs that utilize Real-World Data. The guidance also clarifies the Agency’s expectations related to clinical studies using Real-World Data submitted to Food and Drug Administration in support of a regulatory decision regarding the effectiveness and safety of a drug.
FDA publishes final guidance on “CMC Post approval Manufacturing Changes for Specified Biological Products To Be Documented in Annual Reports”
Date of publication: December 09, 2021
This guidance provides recommendations to holders of biologics license applications (BLAs) for specified biological products regarding the types of changes to an approved BLA to be documented in an annual report under 21 CFR 601.12. Specifically, the guidance describes CMC post approval manufacturing changes that FDA generally considers to have a minimal potential to have an adverse effect on product quality must be documented by applicants in an annual report.
FDA publishes guidance on its website “Q3C(R8) Impurities: Guidance for Residual Solvents Guidance for Industry”
Date of publication: December 10, 2021
This published guidance gives information for permitted daily exposures (PDEs) for 3 additional residual solvents (RS): (1) 2-methyltetrahydrofuran, (2) cyclopentyl methyl ether, and (3) tert-butyl alcohol. The purpose of this document is to recommend permitted residue for above RS in pharmaceutical for the safety of the patient. The Q3C PDE levels are added and revised as new toxicological data for solvents become available.
FDA publishes draft guidance on “Cover Letter Attachments for Controlled Correspondences and ANDA Submissions Guidance for Industry”
Date of publication: December 10, 2021
This draft document by FDA is published by FDA to assist prospective applicants, applicants, and holders of ANDAs with possible attachments which can be provided along with when preparing cover letters that accompany controlled correspondence to the Office of Generic Drugs, as well as original ANDAs, amendments, and supplements to approved ANDAs. These attachments do not replace the recommendations for the content of cover letters provided in other FDA guidance.
MHRA has published interesting article on its blog on “Global reflections on international inspection transformation: ICMRA remote inspections”
Date of publication: December 10, 2021
In this blog article valuable insight provided about how global regulators have managed to perform regulatory oversight, inspections and assessments during the pandemic to support patients need and business continuity in terms of every aspects.
The article is linked with recently published white paper by ICMRA. ICMRA concluded that the “digital technologies in the remote conduct of inspections, evaluations, and assessments a key business continuity tool for regulatory oversight of certain activities and sites during the COVID-19 pandemic, which has proved valuable in the protection of public health in this emergency situation”.
European Commission’s Medical Devices Coordination Group (MDCG) provided new guidance “MDCG 2021-28: Substantial modification of clinical investigation under Medical Device Regulation”
Date of publication: December 9, 2021
This document has been endorsed by the Medical Device Coordination Group (MDCG) established by Article 103 of Regulation (EU) 2017/745.
The questions and answers describes on requirements related to importers and distributors under Regulation (EU) 2017/745 on medical devices (MDR) and Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR).
Pharma GMP News of the Week: 5-December-2021
Period: November 28, 2021 to December 04, 2021
FDA releases draft guideline: Real-World Data: Assessing Registries to Support Regulatory Decision-Making for Drug and Biological Products Guidance for Industry
Date of news: November 29, 2021
For the purposes of this guidance, a registry is defined as an organized system that collects clinical and other data in a standardized format for a population defined by a particular disease, condition, or exposure.
This guidance provides sponsors and other stakeholders with considerations when either proposing to design a registry or using an existing registry to support regulatory decision-making about a drug’s effectiveness or safety.
MHRA updated guidance on qualified person responsible for pharmacovigilance (QPPV) including pharmacovigilance system master files (PSMF)
Date of guideline update: November 30, 2021
The Medicines and Healthcare products Regulatory Agency (MHRA) of United Kingdom has added guidance on requesting a pharmacovigilance system master file (PSMF) number in it.
Pharma GMP News of the Week: 28-November-2021
Period: November 21, 2021 to November 27, 2021
The International Council for Harmonisation (ICH) met virtually on 17 and 18 November and Further expansion of ICH Membership and Observership
Date of news: November 25, 2021
The ICH has conducted virtual meeting on 17 – 18 November 2021 which was proceeded by ICH Management Committee and MedDRA Management Committee.
As per the ICH website, “the ICH Assembly welcomed COFEPRIS, Mexico as a new ICH Member, in addition to three new ICH Observers: EDA, Egypt, Indonesian FDA, Indonesia and SECMOH, Ukraine, bringing ICH to a total of 19 Members and 35 Observers”.
FDA Updates on possible mitigation strategies to reduce the risk of nitrosamine drug substance-related impurities in drug products
Content current as of: November 18, 2021
FDA site suggests that “the first of these possible mitigation strategies is derived from literature reports showing that commonly used antioxidants such as ascorbic acid (vitamin C) or alpha-tocopherol (vitamin E) inhibit the formation of nitrosamines in vivo based upon data from human gastric luid in vitro studies”.
Further to this, FDA website states that “A second possible approach is based upon the fact that the formation of nitrosamines typically occurs under acidic conditions, whereas, in a neutral or basic environment, the kinetics of these reactions are significantly reduced”.
FDA published An Update to the Resiliency Roadmap for FDA Inspectional Oversight
As per the US FDA update, “since April 1, 2021, FDA conducted more than 600 domestic and more than 200 foreign remote regulatory assessments, which included review of records submitted upon request under section 704(a)(4) authority, as well as review of documents and other information voluntarily submitted upon request where section 704(a)(4) does not apply”.
As per the update, “Between April and September 2021, FDA completed 124 foreign inspections across 23 countries”.
Major update on timelines for CEP applications by EDQM
Date of news: November 26, 2021
On October 1, 2021As per the EDQM started use of a new Information Technology tool for management of CEP applications. As per the update, timelines for evaluation of all CEP applications, revisions or renewal will be specified in business days instead of calendar days.
EMA vision for use of real-world evidence in EU medicines regulation
Date of news: November 24, 2021
As per the vision, “the creation of the Data Analytics and Real World Interrogation Network (DARWIN EU) will be key to delivering this vision”.
As per the EMA website “article explains plans to establish methods and standards for high-quality collection and use of RWE, in cooperation with stakeholders including patients, healthcare professionals, industry, regulatory and public health agencies, health technology assessment bodies, payers, and academia”.
Pharma GMP News of the Week: 21-November-2021
Period: November 14, 2021 to November 20, 2021
FDA conducted a virtual public meeting on November 16, 2021, on enhanced drug distribution security at the package level
Date of last update: November 15, 2021
The purpose of this public meeting was to provide members of the pharmaceutical distribution supply chain and other interested stakeholders an opportunity to provide input to FDA on the implementation of the enhanced drug distribution security provisions of the DSCSA that go into effect in 2023.
FDA requests that stakeholders prepare comments responding to the following questions for one or more of the topics listed below:
• How is implementation of the 2023 enhanced system requirements progressing for your organization?
• What challenges is your organization facing?
• Are the proposed recommendations in FDA’s guidance on enhanced drug distribution security at the package level helpful to achieve compliance with 2023 enhanced system requirements? If not, what additional information would be useful?
• Are there areas in which FDA could provide more clarity?
MHRA has updated the guidance on “How investigators and sponsors should manage clinical trials during COVID-19” with respect to the section ‘Urgent Safety Measures’.
Date of update: November 16, 2021
As per MHRA guidance, “Since 16 November 2021, the notification of USMs to the MHRA should be performed following the standard procedure for USMs notifications as detailed here: Urgent Safety Measures”
Ireland’s Health Products Regulatory Authority (HPRA) posts guide to online controlled drug license system
Date of guideline: November 16, 2021
The National Drug Control System (NDS) allows users for application of import and export licenses for the various schedules of controlled substances in Ireland.
As per the guideline “NDS Web is a highly secure online licence application system for controlled drugs. This system allows users to apply for import and export licences for Schedule 1, 2, 3 and 4, Part 1 controlled substances, and letters of no objection (LONas) for Schedule 4 part 2 controlled substances.
This guidance document outlines the information available on NOS Web and the procedure to apply for an import licence, export licence or LaNa on NDS Web”.
Integration of EudraGMDP and OMS – Questions and answers from the webinar for industry on integration of EudraGMDP and OMS
Date of publication on EMA site: November 16, 2021
As per EMA “The new regulatory framework for veterinary medicines requires several changes to EudraGMDP. The most notable change is the integration of EudraGMDP with EMA’s Organisation Management Service (OMS).
From 28 January 2022, users of EudraGMDP from national competent authorities will no longer introduce organisational data (organisation name and location address details) directly into the relevant fields on the EudraGMDP database. Instead, they will select the relevant organisation name and location address details, including the legally registered address, of the manufacturers/importers/distributors from the Agency’s organisation dictionary (so-called OMS).”
Australia’s Therapeutic Goods Administration (TGA) has published guidance on reclassification medical devices.
Published in: November 2021
As per the TGA, “From 25 November 2021, medical devices that are substances for introduction into the body will be required to meet regulatory requirements demonstrating the safety and performance for
Class IIa (low-medium risk), Class IIb (medium-high risk) or Class III (high risk) devices”.
As per the guidance, “This new classification rule is specific for devices composed of substances, or combinations of substances, that are intended to be introduced into the human body through an orifice or applied to the skin, and to be absorbed by, or locally dispersed, in the human body after introduction or application.
This aligns with EU Regulation 2017/745, rule 21 of Chapter III of Annex VIII”.
Pharma GMP News of the Week: 14-November-2021
Period: November 07, 2021 to November 13, 2021
US FDA Update: Product-Specific Guidances; Draft and Revised Draft Guidances for Industry; Availability
Details as per content updated on FDA site upto November 08, 2021
U.S. FDA provided information on FDA website regarding upcoming new and revised product-specific guidances (PSGs) to support the development and approval of safe and effective complex generic drug products.
The Food and Drug Administration (FDA or Agency) is announcing the availability of additional draft and revised draft product-specific guidances. The guidances provide product-specific recommendations on, among other things, the design of bioequivalence (BE) studies to support abbreviated new drug applications (ANDAs).
Pharmacopoeial Discussion Group (PDG) signs-off on milestone harmonised general chapter on chromatography
Date of news: November 08, 2021
As per the EDQM, “The harmonised general chapter Chromatography was signed-off by the Pharmacopoeial Discussion Group (PDG), which brings together the European Pharmacopoeia (Ph. Eur.), Japanese Pharmacopoeia (JP) and the United States Pharmacopeia (USP), on 28 September 2021. The coordinating pharmacopoeia for this text was the Ph. Eur.”
The scope of this harmonization is applicable for TLC, HPLC, and GC.
For more information, read the following press release.
Concept Papers on the revision of EU-PIC/S GMP Annexes 4 & 5
Date of news: November 10, 2021
As per the news by PICS, “the PIC/S Working Group on Veterinary Medicinal Products (VMP), led by Grégory Verdier (France / ANSES), and the EMA GMP/GDP Inspectors Working Group have jointly developed two concept papers on the revision of Annex 4 (manufacture of veterinary medicinal products other than immunologicals) and Annex 5 (manufacture of immunological veterinary medicinal products) of the EU-PIC/S GMP Guide”.
Pharma GMP News of the Week: 7-November-2021
Period: October 31, 2021 to November 06, 2021
FDA published draft guideline on “Content of Premarket Submissions for Device Software Functions”
Document issued on: November 4, 2021
On November 4, 2021, FDA issues the guidance on “Content of Premarket Submissions for Device Software Functions”. The guideline outlining FDA thinking on the documentation needed to support the agency’s assessment of device software functions for premarket submissions. This draft guidance document is being distributed for comment purposes only.
According to the guideline, it is intended to cover:
• firmware and other means for software-based control of medical devices;
• stand-alone software applications;
• software intended to be operated on general-purpose computing platforms;
• dedicated hardware/software medical devices; and
• accessories to medical devices when those accessories contain or are composed of software.
FDA also provided clarity in terminologies used under this guideline.
As per the guideline “FDA refers to a software function that meets the definition of a device as a “device software function.” For example, a device software function may control a hardware device or be part of a hardware device (i.e., Software in a Medical Device, or SiMD) or be a device without being part of a hardware device (i.e., Software as a Medical Device, or SaMD).”
As per the FDA “the term “function” is a distinct purpose of the product, which could be the intended use or a subset of the intended use of the product. For example, a product with an intended use to analyze data has one function: analysis”.
Link to the Guideline Document: https://www.fda.gov/media/153781/download
Federal Register notice: https://www.govinfo.gov/content/pkg/FR-2021-11-04/pdf/2021-24061.pdf
US Food and Drug Administration (FDA) has released the commitment letter of the Generic Drug User Fee Amendments (GDUFA III) program (For fiscal years 2023-2027)
News of the month: November 2021
As per the FDA, “this document contains the performance goals and program enhancements for the Generic Drug User Fee Amendments (GDUFA) reauthorization for fiscal years (FYs) 2023-2027, known as GDUFA III. It is commonly referred to as the “Goals Letter” or “Commitment Letter.” The Goals Letter represents the product of the Food and Drug Administration’s (FDA or the Agency) discussions with the regulated industry and public stakeholders, as mandated by Congress. The performance goals and program enhancements specified in this letter apply to aspects of the generic drug assessment program and build on the GDUFA program established and enhanced through previous authorizations”.
As per the letter, “New enhancements to the program are designed to maximize the efficiency and utility of each assessment cycle, with the intent to reduce the number of assessment cycles for abbreviated new drug applications (ANDAs) and facilitate timely access to quality, affordable, safe and effective generic medicines. Certain new enhancements are specifically designed to foster the development, assessment, and approval of Complex Generic Products”.
India has issued Draft Policy to Catalyze Research & Development and Innovation in the Pharma – MedTech Sector.
Circular dated: October 25, 2021
Timeline for comments submission declared: November 2, 2021
As per the draft policy “this “Policy to Catalyze R&D and Innovation in the Pharma- MedTech Sector in India” is a commitment to encourage Research & Development (R&D) in pharmaceuticals and medical devices and to create an ecosystem for innovation in the sector in order for India to become a leader in drug discovery and innovative medical devices through incubating an entrepreneurial environment. It acknowledges the need for greater emphasis on encouraging R&D, through indigenously developed cutting-edge products and technologies across the value chain”.
TGA release update on GMP approach to overseas manufacturers of medicines and biologicals during the COVID-19 pandemic.
Date of update: November 01, 2021
In this update, TGA has provided an update on certain temporary measures introduced last year for overseas manufacturers.
It includes details regarding:
• On-going use of Remote Inspections
• GMP Clearance
• Mutual Recognition Agreement (MRA) pathway
EMA encourages companies to submit type I variations for 2021 in November 2021
News released on: October 29, 2021
According to EMA news, “the European Medicines Agency (EMA) is advising marketing authorisation holders to submit type IA and type IAIN variations for 2021 no later than Tuesday 30 November 2021. This will enable EMA to acknowledge the validity of the submissions before the Agency’s closure between 23 December 2021 and 3 January 2022 and within the 30-day timeframe set out in Article 14 of Commission Regulation (EC) No 1234/2008”.
Further to this, agency is advising that “Marketing authorisation holders are advised to submit any type IB variations or groupings of type IBs and type IAs by 3 December 2021 for a start of procedure in 2021. For submissions received on or after 6 December 2021, the procedure may not start until January 2022”.
Pharma GMP News of the Week: 30-October-2021
Period: October 24, 2021 to October 30, 2021
US, Canada, and the United Kingdom – Good Machine Learning Practice for Medical Device Development: Guiding Principles
Date of publication: October 27, 2021
According to FDA website, the U.S. Food and Drug Administration (FDA), Health Canada, and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) have jointly identified 10 guiding principles that can inform the development of Good Machine Learning Practice (GMLP). These guiding principles will help promote safe, effective, and high-quality medical devices that use artificial intelligence and machine learning (AI/ML).
10 Guiding Guiding Principles are as follows:
1. Multi-Disciplinary Expertise Is Leveraged Throughout the Total Product Life Cycle
2. Good Software Engineering and Security Practices Are Implemented
3. Clinical Study Participants and Data Sets Are Representative of the Intended Patient Population
4. Training Data Sets Are Independent of Test Sets
5. Selected Reference Datasets Are Based Upon Best Available Methods
6. Model Design Is Tailored to the Available Data and Reflects the Intended Use of the Device
7. Focus Is Placed on the Performance of the Human-AI Team
8. Testing Demonstrates Device Performance during Clinically Relevant Conditions
9. Users Are Provided Clear, Essential Information
10. Deployed Models Are Monitored for Performance and Re-training Risks are Managed
Great discounts on Amazon during festivals
Pharma GMP News of the Week: 24-October-2021
Period: October 17, 2021 to October 23, 2021
FDA published draft guideline for comments “Data Standards for Drug and Biological Product Submissions Containing Real-World Data” Comments to be submitted by January 21, 2022
Date of draft published: October 21, 2021
The 21st Century Cures Act, signed into law on December 13, 2016, is intended to accelerate medical product development and bring innovations faster and more efficiently to the patients who need them. Among other provisions, the 21st Century Cures Act added section 505F to the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355g). Pursuant to this action, calling for FDA to issue guidance on the use of real-world evidence (RWE) in regulatory decision-making, FDA has created a framework for a program to evaluate the potential use of real-world data (RWD) to generate RWE to help support the approval of new indication(s) for drugs already approved under section 505(c) of the FD&C Act (21 U.S.C. 355(c)) or to help support or satisfy post-approval study requirements (RWE Program).
On ICH’s 30th Anniversary, ICH has published document with an overview of ICH’s history and current work.
Date of news: October 19, 2021
ICH has announceed the publication of a 30th Anniversary document. This follows ICH’s 2020 celebration of 30 years of harmonisation activity. It provides an overview of ICH’s history and current work, as well as views of different stakeholders on how ICH has contributed to better health and ICH’s future directions in the next 10 years.
You can find the publication can be found on following link.
Pharmacopoeial Discussion Group (PDG) prepares pilot for global expansion of membership
Date of news: October 18, 2021
As per thenews by EDQM, the Pharmacopoeial Discussion Group (PDG), which brings together the European Pharmacopoeia (Ph. Eur.), the Japanese Pharmacopoeia (JP) and the United States Pharmacopeia (USP), with the World Health Organization (WHO) as an observer, is preparing a pilot to integrate additional world pharmacopoeias. This is a critical step in the PDG’s commitment to expanding recognition of harmonised pharmacopoeial standards with a view to achieving global convergence.
Since it was founded in 1989, the PDG has successfully harmonised and maintained 29 general chapters, including such important analytical procedures as Dissolution Testing, Sterility and Microbiological Examination. In addition, the PDG has harmonised 46 excipient monographs and has approximately 20 new texts in its pipeline. The aim of the three founding pharmacopoeias is to extend this significant success story to further jurisdictions/regions and to create an inclusive global platform from which to elaborate harmonised pharmacopoeial standards.
Download document for more information: https://www.edqm.eu/sites/default/files/medias/fichiers/PressRelease/press-release-pheur-pdg_prepares_pilot_for_global_expansion-october_2021.pdf
The US House of Representatives passed a following bill on October 19, 2021, H.R. 4369, which promotes advanced manufacturing through the creation of national centers for excellence in continuous manufacturing.
H.R. 4369, the “National Centers of Excellence in Advanced and Continuous Pharmaceutical Manufacturing Act,” was introduced by Pallone and Health Subcommittee Ranking Member Brett Guthrie (R-KY). The bill would amend the 21st Century Cures Act to provide the Food and Drug Administration (FDA) with the authority to designate institutions of higher education that provide research, data, and leadership on advanced and continuous manufacturing for pharmaceuticals as National Centers of Excellence in Advanced and Continuous Pharmaceutical Manufacturing. Such Centers would work with FDA to craft a national framework for advanced and continuous pharmaceutical manufacturing, including workforce development, standardization, and collaboration with manufacturers. The bill passed on the House Floor by a vote of 368-56.
The bill would designate certain universities as National Centers of Excellence in Advanced and Continuous Pharmaceutical Manufacturing, allowing them to work with FDA and industry to further develop and implement advanced and continuous manufacturing technology. The bill would also authorize $100 million in funding to support the effort. Pallone spoke in favor of the bill on the House floor.
European Commission has provided draft Clinical Trial Regulation (Version 4.1 (September 2021) – Clinical Trials Regulation (EU)No 536/2014 Draft Questions & Answers)
Date of release: October 14, 2021
The European Commission has published an updated question and answer guidance on the Clinical Trials Regulation (CTR), which is ready to go into effect this January.
Pharma GMP News of the Week: 10-October-2021
Period: October 3, 2021 to October 9, 2021
News from FDA: S1B(R1) Addendum to S1B Testing for Carcinogenicity of Pharmaceuticals
Date of issue: October 6, 2021
This Addendum is to be used in close conjunction with ICH S1A Guideline on the Need for Carcinogenicity Studies for Pharmaceuticals, S1B Testing for Carcinogenicity of Pharmaceuticals, and S1C(R2) Dose Selection for Carcinogenicity Studies. The Addendum is complementary to the S1 Guidelines.
Download draft guideline: https://www.fda.gov/media/152777/download
ICH published ICH M7(R2) draft Guideline and Addendum reaches Step 2 of the ICH process
Date of issue: October 6, 2021
The ICH M7(R2) draft Guideline and Addendum on Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk reached Step 2 of the ICH process on 6 October 2021 and now enters the public consultation period.
The ICH M7 (R2) Addendum provides useful information regarding the acceptable limits of known mutagenic impurities/carcinogenic and supporting monographs.
7 new compounds have been added in this revision: Acetaldehyde, Dibromoethane, Epichlorohydrin, Ethyl Bromide, Formaldehyde, Styrene, and Vinyl Acetate.
Additionally, a Step 2 Informational Presentation has also been developed by the Maintenance Expert Working Group.
News from ICH: The ICH E8(R1) Guideline reaches Step 4 of the ICH Process
Date of news: October 6, 2021
The ICH E8(R1) Guideline on General considerations for Clinical Studies reached Step 4 of the ICH Process on 6 October 2021.
Clinical studies of medicinal products are conducted to provide information that can ultimately improve access to safe and effective products with meaningful impact on patients, while protecting those participating in the studies. ICH E8(R1) provides guidance on the clinical development lifecycle, including designing quality into clinical studies, considering the broad range of clinical study designs and data sources used.
This modernisation of ICH E8 is the first step towards the Renovation of Good Clinical Practice initiated in 2017. The revision incorporates the most current concepts achieving fit-for-purpose data quality as one of the essential considerations for all clinical trials.
Drug Administration (FDA) has revised its guidance with more flexibility – Hospital and Health System Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act Guidance for Industry
Date of issue: October 6, 2021
This revised draft guidance describes how FDA intends to apply certain provisions of section 503A of the FD&C Act to human drug products that are compounded by state-licensed pharmacies that are not outsourcing facilities for distribution within a hospital or health system. First, the revised draft guidance addresses the requirement that compounding be based on the receipt of a valid prescription order for an identified individual patient (section 503A(a) of the FD&C Act). Second, it addresses the provision concerning compounded drug products that are essentially copies of a commercially available drug product (section 503A(b)(1)(D) of the FD&C Act). This guidance does not apply to human drug products compounded by outsourcing facilities under section 503B of the FD&C Act, compounded drug products that are not distributed for use within a hospital or health system, or drug products compounded for use in animals.
The European Commission’s Medical Devices Coordinating Group (MDCG) on October 04, 2021 issued a guidance to help manufacturers classify their devices under the Medical Device Regulations (MDR) before they are placed on the EU market.
Date of issue: October 04, 2021
The classification of medical devices in use by the EU medical device legislation is a risk-based system taking into account the vulnerability of the human body and the potential risks associated with the devices. This approach uses a set of criteria that can be combined in various ways in order to determine classification, e.g. duration of contact with the body, degree of invasiveness, local vs. systemic effect, potential toxicity, the part of the body affected by the use of the device and if the device depends on a source of energy. The criteria can then be applied to a vast range of different medical devices and technologies. These are referred to as the ‘classification rules’ and are set out in Annex VIII of Regulation (EU) 2017/745 on medical devices (MDR). They correspond, to a large extent, to the classification rules established by the International Medical Device Regulators Forum (IMDRF) in the guidance document GHTF/SG1/N77:20121.
The European Commission (EC) published new document “Good Lay Summary Practice” (“GLSP”), with recommendations on how to prepare, write, translate, and disseminate summaries of clinical trial results in lay language.
Date of publication: October 04, 2021
This is a mandatory requirement laid out in Regulation (EU) No. 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use (“EU CTR”) and a transparency obligation to all trial participants and the interested public.
The Food and Drug Administration (FDA) is issuing a final rule to establish requirements for the medical device De Novo classification process under the Federal Food, Drug, and Cosmetic Act (FD&C Act).
Date of publication: October 05, 2021
This final rule establishes procedures and criteria related to requests for De Novo classification (“De Novo request”) and provides a pathway to obtain marketing authorization as a class I or class II device and for certain combination products. These requirements are intended to ensure the most appropriate classification of devices consistent with the protection of the public health and the statutory scheme for device regulation.
Draft monograph on Oxygen (98 per cent) published for comment in Pharmeuropa
Date of news: October 06, 2021
A new draft monograph, Oxygen (98 per cent) (3098), has been published for comment in this quarter’s issue of Pharmeuropa (33.4), the European Pharmacopoeia (Ph. Eur.) online forum. The deadline for comments on the new monograph is 31 December 2021.
This draft monograph is the outcome of a thorough examination of the substantial response to the request for feedback issued in April 2020 and which prompted lively and constructive discussions with regulatory experts in the field, as well as a series of dedicated Ph. Eur. expert meetings.
Pharmeuropa 33.4 released
Date of news: October 5, 2021
All new European Pharmacopoeia (Ph. Eur.) texts and texts that have undergone technical revisions are published in Pharmeuropa for public consultation. The deadline for comments on Pharmeuropa 33.4 is 31 December 2021.
European Pharmacopoeia Supplement 10.7 available
Date of news: October 04, 2021
The European Pharmacopoeia (Ph. Eur.) Supplement 10.7 is now available and will be applicable in 39 European countries as of 1 April 2022.
This volume is included in the 2022 subscription (10.6, 10.7 and 10.8) to the 10th Edition of the Ph. Eur. Subscriptions for print and/or electronic versions are already available to purchase via the EDQM Store.
Pharma GMP News of the Week: 3-October-2021
Period: September 26, 2021 to October 2, 2021
News from MHRA Inspectorate blog: Updated data integrity requirements for GLP Monitoring Programme members
Date of news: September 27, 2021
The MHRA published the GXP Data Integrity Guidance in March 2018 and has subsequently led the development of an Organisation for Economic Co-Operation and Development (OECD) advisory document on data integrity.
The MHRA GXP Data Integrity Guidance was always intended to sit alongside additional regulatory guidance and should also continue to be used to supplement and support UK GLP facilities as it provides additional guidance primarily associated with the importance of a supportive organisational culture in order to embed and foster a strong data integrity culture within organisations.
The new OECD Data Integrity Advisory Document can be found here:
FDA has published draft guideline on: Real-World Data: Assessing Electronic Health Records and Medical Claims Data To Support Regulatory Decision-Making for Drug and Biological Products
Date of publication: September 28, 2021
FDA states that the 21st Century Cures Act (Cures Act), signed into law on December 13, 2016, is intended to accelerate medical product development and bring innovations faster and more efficiently to the patients who need them. Among other provisions, the Cures Act added section 505F to the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355g). Pursuant to this section, FDA created a framework for a program to evaluate the potential use of real-world evidence (RWE) to help support the approval of a new indication for a drug already approved under section 505(c) of the FD&C Act or to help to support or satisfy postapproval study requirements (RWE Program).
FDA has published draft guideline on “Investigator Responsibilities – Safety Reporting for Investigational Drugs and Devices”
Date of publication: September 29, 2021
As per FDA, this guidance is intended to help clinical investigators comply with the following safety reporting requirements:
Investigational new drug application (IND) studies under § 312.64(b) (21 CFR 312.64(b)
Investigational device exemption (IDE) studies under § 812.150 (21 CFR 812.150)
Recommendations are provided to help investigators identify the following:
1. For drugs — Identify safety information that is considered an unanticipated problem involving risk to human subjects or others and that therefore requires prompt reporting to institutional review boards (IRBs) under § 312.66 (21 CFR 312.66)
2. For devices — Identify safety information that meets the requirements for reporting unanticipated adverse device effects (UADEs) to sponsors and IRBs under § 812.150(a)(1) (21 CFR 812.150(a)(1))
FDA has published draft guideline on “Microbiological Quality Considerations in Non-Sterile Drug Manufacturing”
Date of publication: September 29, 2021
As per FDA, this guidance is intended to assist manufacturers in assuring the control of microbiological quality of their non-sterile drugs (NSDs). The recommendations herein apply to solid non-sterile dosage forms, as well as semi-solid, and liquid non-sterile dosage forms (e.g., topically applied creams, lotions and swabs, and oral solutions and suspensions). NSDs can be prescription or nonprescription drugs, including those marketed under approved new drug applications (NDAs) or abbreviated new drug applications (ANDAs), and nonprescription drugs without approved new drug applications which are governed by the provisions of section 505G of the FD&C Act (often referred to as over-the-counter (OTC) monograph drugs). These recommendations, if followed, will also assist manufacturers in complying with the current good manufacturing practice (CGMP) requirements for finished pharmaceuticals and active pharmaceutical ingredients (APIs).
FDA has published draft guideline on “Benefit-Risk Assessment for New Drug and Biological Products”
Date of publication: September 29, 2021
According to FDA, the intent of this guidance is to clarify for drug sponsors and other stakeholders how considerations about a drug’s benefits, risks, and risk management options factor into certain premarket and postmarket regulatory decisions that the Food and Drug Administration (FDA or Agency) makes about new drug applications (NDAs) submitted under section 505(c) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) as well as biologics license applications (BLAs) submitted under section 351(a) of the Public Health Service Act (PHS Act). This guidance first articulates important considerations that factor into the Center for Drug Evaluation and Research’s (CDER) and the Center for Biologics Evaluation and Research’s (CBER) benefit-risk assessments, including how patient experience data can be used to inform the benefit-risk assessment. It then discusses how sponsors can inform FDA’s benefit-risk assessment through the design and conduct of a development program, as well as how they may…
FDA published final version of Q3B(R) Impurities in New Drug Products (Revision 3) on FDA site
Date of publication: September 29, 2021
This guidance provides recommendations for registration applications on the content and qualification of impurities in new drug products produced from chemically synthesized new drug substances not previously registered in a region or member state. This guidance revises the ICH guidance of the same title that was issued in May 1997 and first revised in February 2003. The first revision clarified the 1997 guidance and included other changes. The revision also provided consistency with more recently published ICH guidances (e.g., Q3A(R) Impurities in New Drug Substances, Q3C Impurities: Residual Solvents, and Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances). This second revision provides clarification to Attachment 2.5
This guidance complements the ICH Q3A(R) guidance, which should be consulted for basic principles along with ICH Q3C when appropriate.
EMA implements new measures to minimise animal testing during medicines development
EMA is putting in place special support to developers to replace, reduce and refine animal use for the development, manufacturing and testing of human and veterinary medicines. The Agency is promoting these three principles — replace, reduce and refine; commonly referred to as 3Rs — through EMA’s Innovation Task Force (ITF). This action will facilitate the development and implementation of New Approach Methodologies (NAMs) that are in line with the European Union legislation on the protection of animals used for scientific purposes.
ITF is a dedicated forum for early dialogue between regulators and developers of medicines to discuss innovative aspects such as emerging therapies, methods and technologies. Set up to ensure coordination across the Agency, the ITF is a multidisciplinary group that includes scientific, regulatory and legal competences. It will provide an opportunity to discuss 3R-compliant methods and facilitate their integration into the development and evaluation of medicinal products.
EU agencies have updated their notice to specify that GMP and GDP certificates, and other time-limited authorizations are extended up to the end of 2022.
Date of publication: September 30, 2021
European regulators announced that good manufacturing practice (GMP) and good distribution practice (GDP) certificates and other authorizations shall be extended upto 2022.
This document provides guidance to marketing authorisation holders of medicinal products for human use (“MAH”) on regulatory expectations and flexibility during the COVID-19 pandemic. The document will be updated to address new questions and to adjust the content thereof to the evolution of the pandemic. For queries related to specific products that are not specifically addressed in this document, MAHs are invited to address the European Medicines Agency (for centrally authorised products) or the relevant national competent authorities (for nationally authorised products).
This document remains valid until further notice. It has been developed in cooperation between the European Commission, the Coordination group for Mutual recognition and Decentralised procedures – human (“CMDh”), the Inspectors Working Group and the European Medicines Agency (“EMA”).
The ultimate responsibility for the interpretation of EU legislation is vested on the European Court of Justice and therefore the content of this document is without prejudice to a different interpretation that may be issued by the European Court of Justice.
FDA issued draft guidance on Electronic Submission Template for Medical Device 510(k) Submissions for comment purposes
Document issued on September 29, 2021.
FDA is issuing this draft guidance document to introduce submitters of premarket notification
(510(k)) submissions to the Center for Devices and Radiological Health (CDRH) and Center for Biologics Evaluation and Research (CBER) to the current resources and associated content developed and made publicly available to support 510(k) electronic submissions to FDA. This draft guidance is intended to represent one of several steps in meeting FDA’s commitment to the development of electronic submission templates to serve as guided submission preparation tools for industry to improve submission consistency and enhance efficiency in the review process.
WHO is requesting input on draft guideline on WHO Biowaiver Project- Preparation for cycle V 5 (2022):
Prioritization exercise of active pharmaceutical ingredients on the WHO Model List of Essential Medicines for solubility determination and Biopharmaceutics Classification System-based classification.
EDQM news: Certification of suitability: revised terms of reference and rules of procedure
Date of news: September 27, 2021
A revised version of the terms of reference and rules of procedure for the Certification of suitability to the monographs of the European Pharmacopoeia (CEP) procedure has been adopted by the Certification Steering Committee and is available on the website of the European Directorate for the Quality of Medicines & HealthCare (EDQM): Terms of Reference and Rules of Procedure (PA/PH/CEP (01) 1, 12 R).
This revision was undertaken to clarify the title and certain working procedures, and to take into account organisational changes in the EDQM Certification of Substances Department.
Pharma GMP News of the Week: 26-September-2021
Period: September 19, 2021 to September 25, 2021
U.S. FDA published very useful guidance “Questions and Answers on Quality Related Controlled Correspondence – Guidance for Industry”
Date of publication: September 20, 2021
This questions and answers (Q&A) guidance provides FDA’s current thinking on quality-related scientific and regulatory topics that appear frequently in controlled correspondence submissions.
Questions covered in the guidance are:
a. Is it acceptable to use a bracketing approach for the manufacture of the exhibit batches of a generic drug product with multiple strengths produced from common bulk granulations (or blends)? Do all of these exhibit batches need to be put into the stability program?
b. If the reference listed drug (RLD) is a sterile injectable drug product packaged in an ampule, can the generic product be packaged in a vial?
c. Should a proposed generic ophthalmic drug product have the same cap color as the RLD when that color is not in line with the American Academy of Ophthalmology (AAO) recommendation?
d. If the dissolution method for a proposed generic drug product is not available in the FDA Dissolution Methods Database or in the United States Pharmacopeia (USP), can the Agency provide the dissolution method for the product?
e. How should a bacterial endotoxins test acceptance criterion be determined for the finished drug product?
f. Is it acceptable to omit bacterial endotoxin limits in the proposed specification for a topical ophthalmic drug product?
g. If an applicant intends to have more than one drug product manufacturing site in an abbreviated new drug application (ANDA), how many exhibit batches should be provided for each site?
h. If the generic drug product is a “for injection” (sterile lyophilized powder), can stability data for exhibit batches be generated using only one orientation?
i. If a product is packaged using blow-fill-seal technology and the container is composed of a single material, can stability data for exhibit batches be generated using only horizontal or upright orientation?
j. Should the three exhibit batches for a generic product be fully packaged in the proposed marketed packaging?
MHRA has updated information about Consultation on the future regulation of medical devices in the United Kingdom
Date of update: September 23, 2021
The Medicines and Healthcare products Regulatory Agency (MHRA) has invited members of the public to provide their views on possible changes to the regulatory framework for medical devices in the United Kingdom (UK).
MHRA wants to develop a future regime for medical devices which enables:
Improved patient and public safety;
Greater transparency of regulatory decision making and medical device information;
Close alignment with international best practice, and;
More flexible, responsive and proportionate regulation of medical devices.
Big News: New EDQM IT tool for the management of CEP activities – Impact for CEP applicants and CEP holders From the beginning of October 2021
Date of news: September 24, 2021
As per the EDQM website, from the beginning of October 2021, the CEP Department (DCEP) of the European Directorate for the Quality of Medicines & HealthCare (EDQM) will use a new IT application for the management of its activities. The implementation of this tool will entail certain changes in the way the EDQM communicates with applicants for Certificates of Suitability to the European Pharmacopoeia monographs (CEPs) and CEP holders.
The news says that the communication with companies in the frame of their CEP applications will be streamlined, and e-mails or automatic notifications will be sent instead of letters in an increasing number of situations, such as reminders and acknowledgements of receipt of responses to deficiency letters and requests for revisions. Companies are therefore strongly advised to provide the DCEP with the name and valid e-mail address of a suitable contact person and to inform the DCEP whenever there are changes to this information.
This new tool will be used to ensure that documents related to CEP applications are shared securely. Applicants will no longer receive documents via e-mail but via the “EDQM DCEP Sharing tool”. Documents will be made available for download for 60 days maximum and will be deleted from the tool afterwards. Designated contact persons will receive a notification from the EDQM DCEP Sharing tool informing them of the automatic creation of their accounts and usernames and inviting them to choose a password. As indicated above, it is highly recommended to inform the DCEP immediately of any changes concerning the name or e-mail of the contact person.
The EDQM Database of Certificates of Suitability (CERTIFICATION Database) will display in real time the reasons why any CEPs are no longer valid (e.g. in case of suspension, withdrawal or expiry).
The implementation of this new IT tool may slow down CEP activities during the initial introductory phase.
Pharma GMP News of the Week: 19-September-2021
Period: September 12, 2021 to September 18, 2021
MHRA launches public consultation on future of medical device regulation: People are being encouraged to contribute their views on changes to how medical devices will be regulated across the UK.
Date of announcement: September 16, 2021
Launched today by the Medicines and Healthcare products Regulatory Agency (MHRA), the 10-week consultation gives everyone the opportunity to draw on their own experiences and contribute to the improvement of the regulatory framework and therefore patient safety in the future.
ISPE published interesting article about Transportable Manufacturing on iSpeak Blog
Date on publishing: 13 September 2021
As per the article, “Transportable or Point of Care manufacturing is a capability that can be readily deployed temporarily in closer proximity to the patient base. This type of manufacturing can take various forms depending on the type of therapy and modality, and different solutions can be implemented depending on the scale and manufacturing requirements. Autonomous cleanroom PODs can be used for the larger footprint processes for clinical and commercial manufacturing. Customized trailers can be utilized for low volume manufacturing or labs as well as for some specific commercial applications. Portable, self-contained process skids can be placed either in a building or potentially on a truck, boat, or airplane. And the ultimate in future portability, suitcase manufacturing, can produce individual doses on demand in the field.”
ISPE published article about Reverse Logistics Planning Can Save Time, Money, and Effort on iSpeak Blog
Date on publishing: September 16, 2021
As per the article “Reverse logistics is the process of planning, implementing, and controlling the efficient and effective inbound flow and storage of secondary goods and related information for the purpose of recovering value or proper disposal. Within the Investigational Product’s Supply Chain, it is an essential element more commonly referred to as the Returns Reconciliation, and Destruction Process.”
ICH published Report of 2021 Implementation Survey on the ICH website on 17 September 2021
Monitoring the progress of international harmonisation and coordinating efforts in this regard is an important ICH focus. In support of this effort, an ICH-driven independent third party survey was conducted in 2021, building on the previous 2019 assessment. The main objective of this survey was to assist the ICH MC in determining whether the Regulatory Members would meet the eligibility criteria for the recent ICH MC elections and to allow participating Observers interested in future ICH Membership to reference the survey findings to confirm their eligibility.
The 2021 Implementation Survey Report and additional information can be found on the ICH Guideline Implementation webpage.
FDA update on Q2B Validation of Analytical Procedures
On September 2021, FDA incorporated Q2B Validation of Analytical Procedures: Methodology (May 1997)(Q2B) on methodology with the parent document Q2A Text on Validation of Analytical Procedures (March 1995)(Q2A) and retitled the combined document Q2(R1) Validation of Analytical Procedures: Text and Methodology (Q2(R1). This guidance consists of the previously published FDA guidances, Q2A and Q2B. It is the same, in substance, as those two guidances, and it is the same, in substance, as the November 2005 ICH Q2(R1) guideline.
FDA released New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 3)
Draft New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 3).”
Date of release: September 17, 2021
This guidance document provides answers to common questions from prospective applicants and other interested parties regarding the Biologics Price Competition and Innovation Act of 2009 (BPCI Act). The question and answer (Q&A) format is intended to inform prospective applicants and facilitate the development of proposed biosimilar products and proposed interchangeable products, as well as describe FDA’s interpretation of certain statutory requirements added by the BPCI Act.
This draft guidance document revises the draft guidance document entitled “New and Revised Draft Q&As on Biosimilar Development and the BPCI Act (Revision 2),” issued December 12, 2018 to retain appropriate Q&As in draft.
Download Guideline: https://www.fda.gov/media/119278/download
FDA published final Questions and Answers on Biosimilar Development and the BPCI Act Guidance for Industry
Date of release: September 17, 2021
This guidance document provides answers to common questions from prospective applicants and other interested parties regarding the Biologics Price Competition and Innovation Act of 2009 (BPCI Act). The question and answer (Q&A) format is intended to inform prospective applicants and facilitate the development of proposed biosimilars and interchangeable biosimilars, as well as describe FDA’s interpretation of certain statutory requirements added by the BPCI Act.
Download Guideline: https://www.fda.gov/media/119258/download
Pharma GMP News of the Week: 12-September-2021
Period: September 4, 2021 to September 11, 2021
U.S. Food and Drug Administration, published Notice on reopening of the comment period for ICH Q12 on post-approval chemistry, manufacturing and controls (CMC) changes for new and marketed pharmaceuticals and drug substances.
The extension was proposed by Request for Extension from Pharmaceutical Research and Manufacturers of America (PhRMA)
The FDA announced on 8 September Federal Register that “reopening the comment period for an additional 30 days from the date of publication of this notice will allow adequate time for interested persons to submit comments without significantly delaying agency decision-making on these important issues.”
U.S. FDA updated guideline “Development of Abbreviated New Drug Applications During the COVID-19 Pandemic – Questions and Answers, Guidance for Industry, April 2021”
The guideline updated on September 8, 2021
As per the FDA, this guidance is issued to provide general recommendations to prospective applicants and applicants of abbreviated new drug applications (ANDAs) related to generic drug product development and regulatory submissions in the form of questions and answers that have been received and addressed by FDA during the COVID-19 public health emergency.
MHRA has updated guidance on “Access to Electronic Health Records by Sponsor representatives in clinical trials”
The guideline updated on September 8, 2021
The guidance has been jointly developed by the Heath Research Authority (HRA) and MHRA, in consultation with the Information Commissioners Office (ICO), on behalf of the UK.
The data collected and analysed during clinical trials are verified and overseen by clinical trial Sponsors via representatives such as Clinical Research Associates (CRAs) or monitors. They will review the medical records to ensure that they match the data collected by the Sponsor, via Source Data Verification (SDV). The trial participants consent to this access of their medical records in writing, as part of the consent to take part in the clinical trial.
Increasingly, medical records are now electronic (Electronic Health Records; EHRs) and this poses the following challenges:
● direct access by the monitor/CRA to these records
● ensuring that access is restricted to only those participants in the trial
● ensuring that records of patients not in the trial, but maintained on the same system, are not accessed by the monitor/CRA
Healthcare Distribution Alliance (HDA) urges the US Food and Drug Administration (FDA) to immediately withdraw its guidance on electronic tracing
The guidance was published to build the electronic, interoperable systems called for in the Drug Supply Chain Security Act (DSCSA), scheduled for implementation on 27 November 2023.
As per the letter from HAD “The enhanced system seemingly contemplated by FDA would pose unacceptable security and compliance risks.” They also described that “We have serious concerns with the Draft Guidance’s assumption that trading partners will open up their proprietary systems for a direct connection with a government authority or with other trading partners. We do not see wholesale distributors or any other trading partners allowing federal or state government officials or other third parties direct, system-to-system connections to their records of every prescription drug product transaction in the U.S. pharmaceutical supply chain.”
Publication of a new general chapter on balances in European Pharmacopoeia Supplement 10.6
At its 168th session (November 2020), the European Pharmacopoeia (Ph. Eur.) Commission adopted a new general chapter: Balances for analytical purposes (2.1.7). This new chapter is included in Supplement 10.6 of the Ph. Eur., published in July 2021.
This addition to section 2.1. Apparatus fills a long-standing gap by setting out clear requirements for a piece of equipment that is the cornerstone of every analytical procedure described in the Ph. Eur. Weighing is one of the most common but also most critical tasks in a laboratory, as even the smallest weighing error can propagate throughout the whole analysis, affecting the accuracy of reported results.
This new general chapter complements existing guidelines for the use and qualification of balances published elsewhere. The principles outlined in it apply to all weighings performed as part of analytical procedures prescribed to establish compliance with a Ph. Eur. text. It is supplemented by the instructions related to “Quantities” given in the recently revised General Notices chapter, which is due to be published in Supplement 10.7 and which now includes a reference to this new chapter.
Rich Dad Poor Dad: What the Rich Teach Their Kids About Money That the Poor and Middle Class Do Not!
Pharma GMP News of the Week: 05-September-2021
Period: August 29, 2021 to September 04, 2021
FDA Guidance on Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency: Guidance for Industry, Investigators, and Institutional Review Boards
Date of release: August 30, 2021
FDA recognizes that the COVID-19 public health emergency may impact the conduct of clinical trials of medical products. Challenges may arise, for example, from quarantines, site closures, travel limitations, interruptions to the supply chain for the investigational product, or other considerations if site personnel or trial participants become infected with COVID-19. These challenges may lead to difficulties in meeting protocol-specified procedures, including administering or using the investigational product or adhering to protocol-mandated visits and laboratory/diagnostic testing.
FDA recognizes that protocol modifications may be required, and that there may be unavoidable protocol deviations due to COVID-19 illness and/or COVID-19 public health control measures.
FDA outlines the following general considerations to assist sponsors in assuring the safety of trial participants, maintaining compliance with good clinical practice (GCP), and minimizing risks to trial integrity.
A. Considerations for ongoing trials:
B. In general, and if policies and procedures are not already in place for applicable trials:
C. For all trials that are impacted by the COVID-19 public health emergency:
The appendix further explains those general considerations by providing about 28 answers to questions about conducting clinical trials that the Agency has received during the COVID-19 public health emergency.
The European Commission seeks stakeholder consultation on the amendments to Commission Implementing Regulation (EU) 520/2012 on pharmacovigilance activities
The Commission Implementing Regulation (IR) on the performance of pharmacovigilance activities was adopted in 2012. It outlines the practical details to be respected by marketing authorisation holders, national competent authorities and the European Medicines Agency (EMA).
As part of the Pharmaceutical Strategy for Europe, the Commission is not only committed to evaluate and review the general pharmaceutical legislation, but also to update and optimise existing implementing measures like the IR. The overall experience with the IR is good. However, following consultation with the EMA and the Pharmacovigilance Risk Assessment Committee, the need for some targeted amendments has been identified to take account of the experience gained and to update certain provisions in view of new technical standards being applied. The aim of this consultation is to inform and consult on those amendments. They focus on the following sections of the IR:
Chapter I – Pharmacovigilance system master file,
Chapter III – Minimum requirements for the monitoring of data in the Eudravigilance database,
Chapter IV – Use of terminology, formats and standards,
Chapter V – Transmission of suspected adverse reactions,
Chapter VIII – Post-authorisation safety studies.
While this consultation primarily seeks the stakeholders’ feedback on those proposed amendments, the Commission welcomes any additional remarks that could improve the application of the IR.
Revised guidance for electronic submissions for CEP applications
As the eCTD format is mandatory for the submission of all applications for Certificates of suitability to the monographs of the European Pharmacopoeia (CEPs), except for applications for the risk of transmissible spongiform encephalopathy (TSE) (PDF format) and for substances for veterinary use (eCTD or VNeeS format), the European Directorate for the Quality of Medicines & HealthCare (EDQM) document “Guidance for electronic submissions for Certificates of Suitability (CEP) applications” (PA/PHCEP (09) 108) has been updated to reflect the current practices to facilitate submissions for applicants.
An important update is that when switching to the eCTD format from another format, it will be mandatory to include any information already assessed and approved previously in a “baseline (full dossier)” to facilitate the lifecycle management of the dossier. This will be implemented at the latest in January 2022. Applicants are invited to do so as soon as possible, however. In addition, based on applicants’ feedback, a number of clarifications are given for specific topics such as the submission of grouped revisions and examples of format issues hindering the receipt of applications.
Blog post on MHRA site about “MHRA and US FDA tackle challenging data integrity”
The second Medicines and Healthcare products Regulatory Agency (MHRA) and US Food and Drug Administration (FDA) joint Good Clinical Practice (GCP) symposium was held in London in February 2020, covering international collaboration, sponsor oversight, electronic source documents, protocol deviations and data quality in novel clinical trial designs.
Paper is published around emerging trends and compliance issues as the COVID-19 pandemic evolved, and the paper evolved with it. The paper discusses both agencies’ considerations on data integrity topics, from decentralised clinical trials, adaptive design trials and management of protocol deviations to real-world data. It was great working on this with our FDA colleagues and keeping up with them throughout the pandemic. The paper was published with the hope to provides a useful insight to readers.
Pharma GMP News of the Week: 22-August-2021
Period: August 15, 2021 to August 21, 2021
FDA published revised draft guideline on “Bioequivalence Studies With Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA Guidance for Industry”
Date of publishing: August 20, 2021
As per the agency, the purpose of revised draft is to clarify the agency’s recommendations regarding BE information submitted in an ANDA submission, provide assistance to potential ANDA applicants, and support access for patients to lower cost, high quality medicines.
The new revision updated a draft originally published in the month of December 2013.
ICMRA released paper on Artificial intelligence in medicine regulation
Month of release: August 2021
The International Coalition of Medicines Regulatory Authorities (ICMRA) sets out recommendations to help regulators to address the challenges that the use of artificial intelligence (AI) poses for global medicines regulation, in a report published today.
AI includes various technologies (such as statistical models, diverse algorithms and self-modifying systems) that are increasingly being applied across all stages of a medicine’s lifecycle: from preclinical development, to clinical trial data recording and analysis, to pharmacovigilance and clinical use optimisation. This range of applications brings with it regulatory challenges, including the transparency of algorithms and their meaning, as well as the risks of AI failures and the wider impact these would have on AI uptake in medicine development and patients’ health.
Pharma GMP News of the Week: 8-August-2021
Period: August 1, 2021 to August 7, 2021
US FDA published guideline on “Development and Submission of Near Infrared Analytical Procedures Guidance for Industry”
Date of publishing: August 6, 2021
This new guidance provides recommendations to applicants to aid the development, validation, and use of near infrared (NIR)-based analytical procedures in evaluating the identity, strength, quality, purity, and potency of drug substances and drug products.
The guidance is applicable for new drug applications (NDAs), abbreviated new drug applications (ANDAs), Supplemental NDAs and ANDAs for small molecule drugs, and Drug substances and drug products covered in Type II drug master files. Scope of biological products will be added in future revision to this guidance.
The guidance is complementary to the PAT guidance published by FDA in September 2004.
The guidance’s concepts of validation can be applied to other process analytical technologies (PATs), including, for example, Raman, focused beam reflection measurement, particle imaging, and X-ray.
This guidance addresses the NIR-specific features that are not addressed in ICH Q2(R1). NIR analytical procedures typically combine the following features:
• Instrumentation elements (e.g., an analyzer consisting of an NIR spectrophotometer, a reflectance or transmission probe, or spectral analysis software)
• Acquisition parameters
• A sample presentation (interface)
• A sampling scheme for process applications
• The composition of spectral datasets
• Spectral pretreatments
• Wavelength ranges
• A chemometric model
For NIR-based process analyzers, Off-line, At-line, On-line, or In-line modes of measurement are commonly used.
The guideline provides detailed information about an application submission. Because of the unique characteristics and complexity of NIR procedures, as compared to conventional analytical procedures, FDA also provided detailed recommendations for reporting post-approval changes to NIR procedures.
MHRA updated a guide to defective medicinal products after 16 years
Month of publishing: August 2021
This guidance is on defective medicines and substances used in their manufacture or packaging which may also be defective. The earlier version of the guide was published in 2005.
The changes are made to reflect the UK’s departure from the European Union.
The document provides guidance to the pharmaceutical industry on handling and investigating suspected quality defects. It also gives details of both, the legal requirements and the
MHRA expectations with regard to product quality related complaints, investigations and recalls.
MHRA has updated its approach to risk classification. It uses National Patient Safety Alert (NatPSA) for defects where Class 1 represents a risk of death or disability. Class 2, 3 and 4 are to categorize lower-risk defects.
Survey of Notified Bodies on Remote Audits: Successful or Unsuccessful?
The survey was conducted by the European Association of Medical Device Notified Bodies (TEAM NB). Out of 52 requests, 46 had participated in the survey with a total of more than 33,000 audit days. The answer to the question “What is your experience with remote audits?” was 90% successful and 10% generally unsuccessful.
Sharing experience is categorized below:
|Decreases travel time and cost||Issues when there is a large time difference|
|Tight focus||Issues with internet connections|
|Easier to take notes||Video does not permit to see and look for as if we were onsite|
|Very effective for non-physical processes (like software) and pure QMS aspects||Generally, the spontaneousness of auditing, i.e. reacting immediately to an issue/sample picking|
|The verification of the quality of records is more accurate than in an onsite audit|
|Remote audits are more successful with established customers|
Download useful information:
FDA grants industry 30-day extension to comment on track and trace guidance under the Drug Supply Chain Security Act (DSCSA)
The US Food and Drug Administration (FDA) has agreed to give the pharmaceutical industry more time to comment on a draft guidance calling for the establishment of electronic systems to track products through the supply chain.
The Pharmaceutical Distribution Security Alliance (PDSA) and the Healthcare Distribution Alliance (HDA) made request for extension.
Registration open for 2021 Seminar on “GMP Assessment Approaches in Post COVID-19 Era”
Date of announcement: August 2, 2021
Deadline for registration: October 3, 2021.
Seminar will be hosted virtually from 9-11 November 2021 are now open (for Medicines Regulatory Authorities only).
The Ministry of Food and Drug Safety (MFDS) of the Republic of Korea is pleased to announce that the 2021 PIC/S Virtual Seminar will be hosted by MFDS from 9 to 11 November 2021.
The Seminar on “GMP Assessment Approaches in Post COVID-19 Era” will consist of presentations, interactive panel discussions, and workshops for GMP Inspectors from around the world.
As the COVID-19 pandemic has put restrictions on GMP on-site inspections, various alternative GMP assessment approaches have been taken by regulatory authorities to ensure the quality of pharmaceuticals. As we face the post COVID-19 era, there is a need to explore the current and future status of these GMP assessment approaches. There is also a need to be prepared for the changes that will likely be seen in post COVID-19. Therefore, in this Seminar, we look forward to valuable presentations and discussions regarding different experiences in distant assessment from regulatory and industry experts; and regarding the status of GMP assessment based on reliance.
The Seminar is open to the participation of Inspectors from medicines regulatory authorities around the world.
For more information, please contact the PIC/S Secretariat.
Pharma GMP News of the Week: 1-August-2021
Period: July 25, 2021 to July 31, 2021
EMA published “Guideline on quality documentation for medicinal products when used with a medical device, dated 22 July 2021”
Month of publishing: July 2021
This guideline describes the information that should be presented in the Quality part of a marketing authorisation dossier for a medicinal product when it is used with a medical device, or device part, and submitted in accordance with Directive 2001/83/EC and/or Regulation (EC) 726/2004.
This guideline focuses on product-specific quality aspects of a medical device, or device part, that may have an impact on the quality, safety and/or efficacy (and hence overall benefit/risk determination) of a medicinal product.
This guideline applies in the following cases:
• Medicinal products where the medical device and/or device part and the medicinal product form an integral product that is not reusable (hereafter called integral) and where the action of the medicinal product is principal,
• Medicinal products placed on the market by the Marketing Authorisation Holder (MAH), where the medical device is packed together with the medicinal product (hereafter called co-packaged), or
• Medicinal products, where the product information refers to a specific medical device to be used with the medicinal product, and the medical device is obtained separately by the user of the medicinal product (hereafter called referenced).
EMA released “Reflection paper on statistical methodology for the comparative assessment of quality attributes in drug development” dated July 26, 2021
Date of publishing: July 26, 2021
This reflection paper identifies specific areas where the quantitative comparative evaluation of drug product quality characteristics plays an important role from the regulatory perspective. This might involve decision making processes potentially leading to marketing authorisation as well as postauthorisation decisions during drug lifecycle.
The document focusses on methodological aspects in relation to statistical data comparison approaches for pre- and post-manufacturing changes, biosimilar development, and generics’ development.
The reflection paper raises open issues from a statistical perspective, and addresses questions related to comparison objectives, sampling strategies, sources of variability and options (or limitations) for statistical inference
This document is targeted at both experts from industry and regulatory assessors. This reflection paper complements other available regulatory guidance where comparative data assessment of quality attributes is discussed for certain contexts, but also provides more detailed guidance of how to actually carry out the comparison task based on empirical sample data.
The guideline also provides protocol requirements for Quality Attributes data comparison.
The International Council for Harmonisation (ICH) on July 27, 2021 issued its Q13 guideline on continuous manufacturing, making a draft available for public comment.
Date of publishing: July 27, 2021
The ICH Q13 Guideline on Continuous Manufacturing of Drug Substances and Drug Products reached Step 2 of the ICH process on 27 July 2021 and now enters the public consultation period.
This guideline describes scientific and regulatory considerations for the development, implementation, operation, and lifecycle management of continuous manufacturing (CM). Building on existing ICH Quality guidelines, this guideline provides clarification on CM concepts, describes scientific approaches, and presents regulatory considerations specific to CM of drug substances and drug products.
This guideline applies to CM of drug substances and drug products for chemical entities and therapeutic proteins. It is applicable to CM for new products (e.g., new drugs, generic drugs, biosimilars) and the conversion of batch manufacturing to CM for existing products. The principles described in this guideline may also apply to other biological/biotechnological entities.
Three different models of continuous manufacturing are described in the draft guideline:
o one includes a combination of approaches in which some unit operations operate in a batch mode while others operate in a continuous mode;
o second is where all unit operations of a drug substance or drug product manufacturing processes are integrated and operate in a continuous mode;
o third is an approach in which the drug substance and drug product unit operations are integrated across the boundary between drug substance and drug product to form a single continuous manufacturing process.
FDA has been encouraging continuous manufacturing for the past decade as a way to improve product quality, minimize product defects, and reduce drug shortages, promoting it as a more efficient process than the more antiquated batch production process. There are 10 approved continuous manufacturing applications in the US, including original applications and supplements.
Food and Drug Administration announced revised Generic Drug User Fee Rates for Fiscal Year 2022 on Jul 28, 2021
Date of publishing: July 28, 2021
The GDUFA fees for FY 2022 announced on the Federal Register pre-publication page. The new fees will be applicable for all submissions submitted on or after October 1, 2021. The FY 2022 fees with a comparison to the FY 2021 fees is provides in the table below.
|Fee category||Fees rates for FY 2021||Fees rates for FY 2022||% Change|
|Abbreviated New Drug Application (ANDA)||196,868||225,712||14.65|
|Drug Master File (DMF)||69,921||74,952||7.20|
|Active Pharmaceutical Ingredient (API)—Domestic||41,671||42,557||2.13|
|Finished Dosage Form (FDF)—Domestic||184,022||195,012||5.97|
|Contract Manufacturing Organization (CMO)—Domestic||61,341||65,004||5.97|
|Large size operation generic drug applicant: >20 ANDAs||1,542,993||1,536,856||-0.40|
|Medium size operation generic drug applicant: 6-19 ANDAs||617,197||614,742||-0.40|
|Small business operation generic drug applicant: 5 or less ANDAs||154,299||153,686||-0.40|
The European Medicines Agency (EMA) on Jul 29, 2021 issued an updated reflection paper specifying the good manufacturing practice (GMP) responsibilities of marketing authorization holders under the European Commission (EC) GMP guidelines and other EU legislation.
Date of publishing: July 29, 2021
The Reflection Paper concerns the responsibilities and activities of MAHs with respect to the European Commission’s Guide to GMP (Parts I, II, and its relevant Annexes) for medicines for human and veterinary use. It also covers the responsibilities of MAHs and Sponsors (where the Sponsor is different from the MAH) with regard to the handling of quality defects with investigational medicinal products.
The scope also extends to certain legislative provisions that have relevance to GMP, such as those stated in the GMP Directives 2003/94/EC and 91/412/EC (as amended), as well as relevant articles in Directive 2001/83/EC and Regulation (EU) 2019/6.
It also applies to holders of Registration and Traditional-use Registrations for herbal/homeopathic medicinal products.
FMD: The relevant provisions of the Falsified Medicines Directive 2011/62/EU and the related Delegated Regulations (including the Safety Features Regulation 2016/161) are also within scope of this Reflection Paper.
ATMP: The reflection paper does not cover some of the advanced therapy medicinal product (ATMP) GMP requirements that are addressed in Part IV of the GMP guide.
GDP Responsibilities: While this Reflection Paper is not intended to address the GDP-related responsibilities that may apply to MAHs, it is considered important to highlight here that MAHs do need to understand the type of interfaces that may need to be in place with the wholesalers they employ or engage.
The main points include:
• Outsourcing and Technical Agreements
• Audits and Qualification Activities
• Communication with Manufacturing Sites (e.g. MA Dossier Information, Variations, Regulatory
• Product Quality Reviews
• Quality Defects, Complaints and Product Recalls
• Maintenance of Supply of Medicinal Products
• Continual Improvement Activities
Pharma GMP News of the Week: 25-July-2021
Period: July 18, 2021 to July 24, 2021
FDA has issued Field Alert Report Submission: Questions and Answers Guidance for Industry
Docket Number: FDA-2018-D-2326
Month of publishing: July 2021
The guidance is issued by: Office of Regulatory Affairs, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research
This guidance provides FDA’s current thinking regarding the requirements for submission of field alert reports (FARs) by applicants of new drug applications (NDAs) and abbreviated new drug applications (ANDAs) and outlines FDA’s recommendations for FAR submissions to help improve their consistency and relevancy. The guidance also addresses certain frequently asked questions.
The question includes following main questions as well other subtopics within these questions.
1. What is a FAR and what triggers its submission?
2. Who is responsible for submitting the FAR?
3. When should I submit a FAR?
4. How do I submit a FAR?
5. Where do I submit a FAR? 6. Should I submit a follow-up or final FAR?
FDA has issued Guidance for Industry: Use of Recycled Plastics in Food Packaging (Chemistry Considerations):
Docket Number: FDA-2020-D-1456
Month of publishing: July 2021
The guidance is issued by: Center for Food Safety and Applied Nutrition, Office of Food Additive Safety
The purpose of this document is to highlight the chemistry issues that FDA recommends that a manufacturer of recycled plastic consider during the manufacturer’s evaluation of a recycling process for producing material suitable for food-contact applications.
This document supersedes the December 1992 “Points to Consider for the Use of Recycled Plastics in Food Packaging: Chemistry Considerations” (1992 “Points to Consider”). The possibility that chemical contaminants in plastic materials intended for recycling may remain in the recycled material and could migrate into the food the material contacts is one of the major considerations for the safe use of recycled plastics for food-contact applications. Other aspects of plastics recycling, such as microbial contamination and structural integrity of the recycled plastic, are also important, but are not discussed in this document.
FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe our current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in FDA guidances means that something is suggested or recommended, but not required. This guidance was revised to include Paperwork Reduction Act information, containing non-substantive formatting or editorial revisions to the guidance, which was originally issued in August 2006. Revisions are noted by date at the end of the guidance.
Revision of USP <857> Ultraviolet-Visible Spectroscopy and <1857> Ultraviolet-Visible Spectroscopy – Theory and Practice
This proposal is based on the version of the monograph official as of January 1, 2020. The proposed revisions, which are in response to stakeholder comments and questions, include the following:
- Clarify that the scope of the chapter does not apply to multichannel plate readers.
- Remove the Xe line reference in Table 2 for control of wavelength by atomic line spectra.
- Remove the Control of Photometric Response section as demonstrating absorbance accuracy over its intended operational range assures proper photometric response.
- Revise for clarity the requirements and procedures for Control of Absorbance, including procedures for absorbance accuracy and precision.
- Clarify the equation in Procedure A for the Estimation of the Limit of Stray Light as determined from the differential absorbance spectrum.
- Replace the term “cell” with “cuvette” throughout.
Further revisions to include appropriate standards for chromatographic detectors and multichannel plate readers are under discussion and may be proposed at a later date.
Additionally, minor editorial changes have been made to update the chapter to current USP style.
Revision of USP <1857> Ultraviolet-Visible Spectroscopy—Theory and Practice
Revision of the chapter includes:
- Changes done in the chapter in line with 〈857〉 Ultraviolet-Visible Spectroscopy
- Multichannel plate reader systems excluded from this chapter
- Replace the term “cell” with “cuvette” throughout.
- Text for Control of absorbance revised as: To establish adequate accuracy, precision, and photometric performance of a given system, it is necessary to verify the absorbance accuracy of a system over its intended operational range by selection and use of the following procedures as appropriate for the wavelength and absorbance ranges required. Demonstrating absorbance accuracy over the system’s intended operational range assures proper photometric response.
- Table 4 “Available CRMs for the Control of Absorbance” revised
The draft chapter <1857> Ultraviolet-Visible Spectroscopy – Theory and Practice is available to refer at this link.
Pharma GMP News of the Week: 18-July-2021
Period: July 11, 2021 to July 17, 2021
WHO has released draft guideline on Good Manufacturing Practices for investigational products:
Document Number: Working document QAS/20.863/Rev1
Month of publishing: July 2021
World Health Organization (WHO) Prequalification Team – Inspection Services (PQT INS) raised the urgency for a revision of the WHO Good manufacturing practices for investigational pharmaceutical products for clinical trials in humans. The Fifty-fifth Expert Committee on Specifications for Pharmaceutical Preparations (ECSPP) concurred with this proposal.
The objective of this update is to bring the guideline in line with current expectations and trends in good practices and to harmonize the text with the principles from other related international guidelines. Investigational products are used for testing purposes; as a reference in clinical trials and field trials; as a placebo; for an unauthorized indication; and to gain further information about the authorized form. In some cases, marketed products which have been re-packaged or modified in some way, are used for investigational purposes.
Source: WHO guideline
PICS released guideline on “COVID-19 Risk Assessment for Routine On-Site Inspections” (PI 055-1)
Document Number: PI 055-1
Date of publishing: 15 July 2021
On 15 July 2021, PIC/S announced adoption of guidance on “COVID-19 Risk Assessment for Routine On-Site Inspections” (PI 055-1). This guidance for inspectorates, which has been prepared by the PIC/S Working Group on Inspectors
Risk Assessment covers announced GXP inspection of national sites. This needs to be completed during the inspection planning phase, in consultation with the site to be inspected, prior to the inspection taking place. The site must confirm that the necessary measures identified in the risk assessment will be implemented Consideration should also be given to Covid testing of Inspectors / Investigators pre and post inspection and may be requested by some sites.
PICS released guideline on “How to Evaluate and Demonstrate the Effectiveness of the Pharmaceutical Quality System with regard to Risk-Based Change Management” (PI 054-1)
Document Number: PI 054-1
Date of publishing: 15 July 2021
This document addresses two fundamental and inter-related elements of the PIC/S GMP Guide – PQS effectiveness and the management of changes. It provides practical guidance for GMP Inspectors in these areas, and the implementation of that guidance has the potential to ultimately lead to the more timely management of risks to product quality and patient safety, as well as better quality and manufacturing performance, continual improvement and innovation. This serves the interest of patients and animals.
In addition to providing guidance for GMP Inspectors, the document provides the pharmaceutical industry with a ready-made solution for addressing a key aspect of ICH Q12 – the requirement to have an effective PQS that can support the risk-based management of post-approval changes when there is more flexible regulatory oversight of such changes in place.
The guideline also covered important aspects and examples of Change Review and effectiveness review with headings “Prior to change closure” and “Prior to or after change closure”.
WHO has released draft guideline on WHO good practices for research and development facilities of pharmaceutical products:
Document Number: Working document QAS/20.865/.Rev1
Month of publishing: July 2021
In view of the need for the development of health products, including the research and development for the treatment of COVID-19 therapies, the World Health Organization (WHO) Prequalification Inspection Services Team (PQT INS) raised the urgency for the development of life cycle appropriate good practices text to address the manufacturing of developmental batches, pilot batches and the sequential stability data that are submitted in product applications (dossiers) for marketing authorization and the prequalification of medical products.
There is currently no other specific WHO guideline which addresses this matter. The data collected from these batches influence the aspects of the product i.e. stability; process validation; and analytical method development and validation.
This guideline is specifically applicable to research and development facilities of pharmaceutical products procedures, processes and data that are intended for transfer and submission for approval in marketing authorization applications, process validation, validation, quality control laboratory activities such as stability testing and development, and validation of cleaning procedures.
The main focus of this document is to provide for GxP in the production and control of pre-clinical and not for human use batches, manufactured in pharmaceutical formulation and development facilities, where these are directly supporting; for example, shelf life claims, animal studies or validation activities. The principles described in this document may be applied in facilities where other products, such biopharmaceutical products, vaccines and medical devices, are manufactured.
Source: WHO guideline
Implementation of the European Pharmacopoeia Supplement 10.6 and Notification for CEP holders to update their applications according to the revised monographs
Date of announcement: July 13, 2021
Supplement 10.6 of the European Pharmacopoeia (Ph. Eur) is now available. CEP holders are invited to update their applications according to the revised monographs that will be implemented on 1 January 2022, and to follow the instructions given below.
According to Directives 2001/83/EC and 2001/82/EC, as amended, it is the responsibility of the manufacturer to comply with the current version of a Ph. Eur. monograph, and therefore to update the specification when a revised monograph is issued. In addition, the European Directorate for the Quality of Medicines and HealthCare (EDQM) ensures that CEPs refer to the most recent version of a Ph. Eur. monograph at any time.
CEP holders invited to comment on draft monographs published in Pharmeuropa 33.3
Date of announcement: July 15, 2021
CEP holders are requested to consult the list of substances for which draft revised monographs of the European Pharmacopoeia (Ph. Eur.) have been published in Pharmeuropa 33.3. The lists of the substances affected by these revisions and for which CEPs have been granted.
Users can register for free for the access to Pharmeuropa on the EDQM website Pharmeuropa, Pharmeuropa Bio & Scientific Notes.
Pharma GMP News of the Week: 11-July-2021
Period: July 1, 2021 to July 10, 2021
Data Integrity Document published by PIC/S: 1 July 2021
There are 14 chapters in the guideline. The document covers important aspects of Data governance system, Organisational influences on successful data integrity management, General data integrity principles and enablers, Specific data integrity considerations for paper-based systems, Specific data integrity considerations for computerised systems, Data integrity considerations for outsourced activities.
Most importantly, it also covered what would be the Regulatory actions in response to data integrity findings and how to remediate the situation of data integrity failures.
Key Points in the guideline:
- Discussed about all activities related to the handling of data, data policy, documentation, quality and security.
- Data management related to Good Manufacturing Practice (GMP) and Good Distribution Practice (GDP). The scope also covers documents related to registration dossier.
- On-site and remote, or desktop, inspections.
- The concept of the data lifecycle, starts from data generation, processing, reporting, checking, data used for decision-making, storage and disposal at the end of the retention period.
- Data governance controls.
- Company culture and its integration with data integrity plan.
- Approach regarding non-hierarchic management structure and top-down structure.
- General data integrity principles and “enablers” that help put the principles into operation.
- ALCOA and ALCOA++ for both, paper and electronic systems.
- Specific elements checking during a record review, and expectations for generation, distribution and control of records.
- Expectations and potential risks in qualifying computer systems.
- System security issues such as user access controls.
- Data integrity within hybrid systems.
- Hybrid systems are discourages to use because of their complexity and potential increased vulnerability to manipulation of data.
- Data integrity related to outsourcing activities.
- Potential regulatory actions that may be taken in response to deficiencies or other data integrity findings.
Providing Regulatory Submissions in Alternate Electronic Format Guidance for Industry issued by US FDA, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research: July 2021
This guidance provides recommendations on an alternate electronic format for submissions covered under an exemption from or a waiver of the requirements of section 745A(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 379k-1). These recommendations pertain to the format of content contained in new drug applications (NDAs), abbreviated new drug applications (ANDAs), certain drug master files (DMFs), certain biologics license applications (BLAs), and certain investigational new drug applications (INDs) submitted to the Center for Drug Evaluation and Research (CDER) or to the Center for Biologics Evaluation and Research (CBER).
Revised general chapter 5.21 Chemometric methods applied to analytical data published for public comment in Pharmeuropa: July 2021
The revised general chapter Chemometric methods applied to analytical data (5.21) has been published in this quarter’s issue of Pharmeuropa (33.3), the European Pharmacopoeia (Ph. Eur.) online forum, for comment. The deadline for comments is 30 September 2021.
This general chapter, published for information, is an introduction to the use of chemometrics and data science techniques. The objective is to provide indications on good practice and requirements for the processing of analytical data.
The chapter is rewritten. Key point includes:
- Updated Section 1. General aspects with a review of parts on Pre-processing (22.214.171.124) and Assessment and validation of chemometric methods (1.3);
- New subsections added:
- Independent component analysis (2.2)
- Decision trees and random forests (2.6);
- Review of sub-sections on:
- Similarity measures (2.3)
- Clustering (2.5)
- Multiple linear regression (2.8)
- Principal component regression (2.9)
- Support vector machines for supervised classification (2.11)
- Artificial neural networks (2.12);
- New section added:
- 3. Related application fields, covering sub-sections on Chemometrics in chemical imaging (3.1)
- Data fusion (3.2);
Pharmeuropa 33.3 released: 05 July 2021
All new European Pharmacopoeia (Ph. Eur.) texts and texts that have undergone technical revisions are published in Pharmeuropa for public consultation.
The deadline for comments on Pharmeuropa 33.3 is 30 September 2021.
Cleaning validation guide (GUI-0028) revised by Health Canada: Published on June 29, 2021
This guide addresses special considerations and issues when validating cleaning procedures for equipment used to fabricate and package of Active Pharmaceutical Ingredients (APIs), Pharmaceuticals,
Radiopharmaceuticals, Biological drugs, and Veterinary drugs.
It covers validation of equipment cleaning for the removal of residues associated with products used in the previous production run, such as active ingredients, breakdown or by-products of concern, intermediates, residues of cleaning agents, and processing agents the control of potential microbial contaminants