February 4, 2021
Throwback 2020 – A Quick Regulatory Rewind

The year 2020 was a roller coaster for everyone across the world. With the outbreak of the COVID-19, global Health Authorities (HAs) have been working relentlessly to ensure that healthcare professionals and the general public have the best resources to fight this pandemic. A lot of temporary changes have been made to the regulations of various medical, medicinal and cosmetic products, such as vaccines, PPE kits, surgical masks, hand gloves, hand sanitizers, etc., to expedite their approvals and market entry, and to meet their market demand.

As 2020 is coming to an end, let’s rewind the year quickly and take a look at some of the major Regulatory changes that took place throughout the year and changed the landscape of the global life sciences industry. 

Regulatory Updates 2020 – Pharmaceuticals

FDA Guidance: The New and Revised Pediatric Study Plans

To overcome the serious shortage of pediatric drug testing, the FDA has issued final guidance that offers a comprehensive framework for planning and submission of applications for pediatric trials. As per the guidance, The Initial Pediatric Study Plan (iPSP) submission is mandatory for the sponsors who intend to submit a marketing application for the following cases, including an API (Active Pharmaceutical Ingredient)/any new indication except for the one that has orphan status/a new dosage form/a new administration mode. Additionally, with effect from August 18, 2020, an iPSP must be submitted for APIs which come under the PREA’s provision of molecular-based medicine for cancer, regardless of their status of orphan indication.

USFDA Guidance - Nitrosamine Impurities in Human Drugs

In September 2020, the FDA issued guidance for the industry to control the nitrosamine impurities in drugs. The guidance provides recommendations to manufacturers to identify the potential causes of nitrosamine formulations and evaluate the risk of contamination in their APIs and drug products. According to the guidance, the following steps are to be taken by the API and drug product manufacturers to mitigate nitrosamine impurities in their products:

  • Assessment of the nitrosamine impurities in APIs, marketed products, approved products and pending applications.
  • Conduction of confirmatory testing when the nitrosamine impurities are identified
  • Implementation of changes to prevent or reduce the impurities in APIs and drug products must be reported to the FDA

European Pharmaceutical Industry – Regulatory Updates

The COVID-19 pandemic resulted in suspension of the regular on-site inspections. However, as the world is slowly coming out of COVID-19 restrictions, Health Agencies are eying on resuming the on-site inspections. In the same context, Swissmedic (the Swiss Agency for Therapeutic Goods) has resumed regular on-site inspections, the Danish Medical Agency (DMA) of Denmark has extended COVID-19 drug preparedness rules until December 31, 2020, and the European Medicines Agency (EMA) is all set to revise Global Clinical Practice (GCP) guidance are a few of the major Regulatory updates in the European Pharmaceutical Industry.

Brexit-related Guidance for Pharmaceutical Companies

It is a known fact that the UK has officially left the European Union (EU) on January 31, 2020, and is in transition period until December 31, 2020. During the transition period, all the pharmaceutical companies in the UK are required to abide by the EU pharmaceutical law. In March 2020, the EMA also updated Brexit-related guidance for the benefit of the pharmaceutical companies. The marketing authorization holders (MAH) for pharmaceutical products are required to adapt to the suggested processes before the end of the transition period to ensure their products’ continued compliance.

COVID-19: EMA’s GMP and GDP Flexibilities

To support manufacturers during COVID-19, the EMA updated its guidance on the Regulatory expectations for the medicinal products. A new section of temporary flexibilities was added to inputs on good manufacturing practices (GMP) and good distribution practices (GDP). The new development was aimed at responding to the increased demand for medicinal products amid COVID-19.

Mandatory Submissions Through CESP in Cyprus

Being a Member State of the European Union (EU), the Republic of Cyprus through the Department of Pharmaceutical Services has mandated the submission of medicinal products for human use through the Common European Submission Platform (CESP).

The CESP is an initiative available for all the EU Member States, authorization applicants and holders, and for both human and veterinary medicinal products. It is aimed at establishing a single portal for electronic submissions to multiple competent authorities in the context of European registration and post-approval procedures covering, National, Mutual Recognition Procedure (MRP), and Decentralized Procedure (DCP). The implementation of the mandatory submissions through CESP has already begun since January 1, 2020.

TGA Has Announced the New Product Information (PI) Form

The Therapeutic Goods Administration (TGA), the Australian Regulatory authority, has approved a new Product Information (PI) form on November 08, 2017, which was revised on March 8, 2018 following amendments to the Therapeutic Goods Act 1989. The commencement date of the new PI form was January 1, 2018, with a transition period of three years ending on December 31, 2020.

During the transition phase, the PI of any product, including generic and biosimilar products, sold in Australia needs to be reformatted as per the new design. In addition, all the mandatory standard text such as headings, sub-headings must be included in the product information form as specified, according to the TGA.

The EAEU Mandated Electronic Submissions

On August 3, 2017, the committee of the Eurasian Economic Union (EAEU) published the standards for electronic submissions of drug applications. With respect to the same, the Board of the Eurasian Economic Union released the following ‘Decisions’ on the electronic submission format, which mandates the applicants to provide more detailed information.

  • Decision 78 – Decision 78 focuses on providing details and clarification on the content and structure of the submissions. From December 31, 2020, new applicants will no longer be able to file applications as National Procedure. The applications can only be submitted by Decentralized Procedure (DP) or Mutual Recognition Procedure (MRP).
  • Decision 79 – Decision 79 emphasizes the technical compliance of the electronic submissions. The application will require two specific types of XML files:
    • R.017 – Containing information about the applicant company, the product, and the substances
    • R.022 – Containing information about the documents submitted along with each document type’s specific identifiers

Health Canada mandates eCTD format for all new Type I, II, III, IV Master File Submissions

Health Canada (HC) once again postponed the submission deadline for the Drug Master File (DMF) in electronic Common Technical Document (eCTD) format. Referring to the authority’s May 2018 notification, the earlier deadline was Jan 1, 2019 which later got postponed to Sep 1, 2019. Now with the recent notification from the authority, the eCTD format for DMF came into effect from January 1, 2020.

To align with the HC’s new notification, DMF holders must use eCTD format for all the Regulatory activity types as mentioned below.

  • New Type I Master Files – Drug Substance
  • New Type II Master Files – Container Closure Systems and Components
  • New Type III Master Files – Excipients
  • New Type IV Master Files – Drug Products

The TGA Has Introduced New Labeling Requirements for Medicines Supplied in Australia.

The Australian Government Department of Health, the Therapeutic Goods Administration (TGA) has announced new labeling requirements which are effective from 31st August 2016. With the new labeling requirements for Australian Medicines coming after so many years, a four-year transition time was given to the sponsors to ensure compliance with the improved standards. This suggests the Sponsors had enough time for transition, and from 1 September 2020, their new medicine labels must comply with the new improved regulations.

EDQM Mandates eCTD Format for All CEP Applications and Notifications

In July 2019, the European Directorate for the Quality of Medicines and Healthcare (EDQM) has announced that eCTD format shall be mandatory for all Certificate of Suitability to the monographs of the European Pharmacopoeia (CEP) applications including notifications, revisions, renewals and new applications. The announcement was made as part of the revised roadmap (2016-2020) for electronic submissions for CEP applications.

According to the EDQM roadmap, the eCTD mandate came into effect from January 1, 2020, after which the directorate has stopped accepting NeeS submissions for all CEP applications including notifications, revisions and renewals. Although the revised roadmap states that ongoing procedures shall remain unaffected, it also notifies that any changes to existing dossier’s format to eCTD, the conversion process must be treated as a new process.

MHRA’s Post-transition Guidance for PV, QPPV and PSMF

As it is quite inevitable that the transition period for Brexit is not going to extend, numerous Regulatory changes or updates are expected to emerge from the UK’s Medicines and Healthcare products Regulatory Agency (MHRA). In the same context, MHRA has recently issued a guidance on pharmacovigilance procedures and post-transition requirements for Qualified Person Responsible for Pharmacovigilance (QPPV) and Pharmacovigilance System Master Files (PSMF) for the UK authorized products.

Regulatory Updates 2020 – Medical Devices

FDA Expedites Regulatory Pathways for Medical Emergencies

Amidst the COVID-19 pandemic, the United States Food and Drug Administration (USFDA) released a guidance document in March 2020, proposing several tools to expedite the review and approval of a COVID-19 biologic treatment or vaccine, after it emerges. Addressing the unmet medical emergencies in treating serious and life-threatening conditions, the FDA proposed multiple programs to facilitate and expedite the development, review and approval of therapies, including, biologics. If the therapies justify their benefits over the risks, they will be available in the market at the earliest with supportive FDA expedited approval programs like Fast Track Designation, Breakthrough Therapy Designation, Priority Review Designation, Accelerated Approval Pathway, the animal rule and Emergency Use Authorization (EUA).

TGA Standards for Personal Protective Equipment (PPE)

With the abrupt outbreak of Covid-19 pandemic, the demand and need for PPEs’ (face masks, gloves and gowns) increased drastically. This further necessitated an extensive study on the PPEs’, and therefore, the Therapeutic Goods Administration (TGA) designed certain guidelines for PPE manufacturers, consumers and healthcare professionals in April 2020. As per the guidance, supplying the PPEs’ during the pandemic required the manufacturers to meet the following standards, like, the intended purpose of the device, the environment in which it is to be used and the users of the device. The key focus of the guidance was on the criteria of selection, care, use, maintenance, performance, risk-assessments, control methods, penetration and permeation testing for various medical device applications.

TGA Includes Thermometers in ARTG

With the immediate rise in the supply and demand of thermometers due to the COVID-19 pandemic, the sponsors and manufacturers applied to the TGA for the inclusion of thermometers in the Australian Register of Therapeutic Goods (ARTG). Accordingly, to support the manufacturers and the sponsors, the TGA devised a guideline in May 2020, which included a step-by-step process for including thermometers in the ARTG, through a certain set of procedures and Regulatory obligations.

SFDA’s Recognized Standards and Requirements for Ventilators

The wider spread of COVID-19 raised an alarm for ventilators shortage. Pursuant to the situation, in May 2020, the Saudi Food and Drug Authority (SFDA) devised a guidance for quick market entry of ventilators and their accessories, within the Kingdom of Saudi Arabia (KSA). The guidance specified the requirements and recognized standards to obtain the Medical Devices Marketing Authorization (MDMA) for ventilators, ventilator tubing connectors and ventilator accessories, and was applicable to all the manufacturers, importers, authorized representatives and distributors of ventilators and ventilator accessories.      

EMA Accelerated Regulatory Mechanisms for COVID-19 Products

In May 2020, the European Medicines Agency (EMA) established faster scientific advice, rolling reviews and accelerated assessments to expedite the development and approval of medicinal products, amidst the COVID-19 pandemic. With an aim to support the development and marketing authorization of safe, effective and high-quality therapeutics and vaccines at the earliest, the EMA claimed to adapt certain fast-track procedures, like, reduced R&D timeframes, quick review & approval and compassionate use programs, to significantly cut-short the Regulatory timelines for the review of new medicines and vaccines against COVID-19.

HSA Released Guidance for Medical Devices Intended to Decontaminate Used-Respirators

To fight COIVD-19 cases, Singapore’s Health Sciences Authority (HSA) assessed the critical shortage and enormous demand for respirators. Accordingly, in July 2020, the Agency issued a guidance on facilitating access to safe and effective medical devices, intended for decontaminating used-respirators through a provisional authorization pathway. This pathway considers the safety, quality and effectiveness of the decontamination process using the medical devices and verifies that the integrity of the respirators and their ability to achieve their intended functions are maintained following decontamination.

USFDA: eSubmission Formats for Medical Devices

In July 2020, the USFDA issued a new guidance for electronic submission for medical devices. As per the guidance, the FDA interprets the requirements of section 745A(b)(3), which specify the electronic format submissions, timetable and process for implementing the requirements and the criteria for waivers and exemptions from the submissions. The Agency also clarified that all the subsequent submissions to an original submission must be submitted electronically, irrespective of a single-page or a multi-volume submission. 

Medical Devices Registrations during COVID-19 - USFDA Procedures

With an aim to increase the availability of medical devices during COVID-19, in September 2020, the USFDA described the perspective on registering, listing and importing medical devices that have been issued Emergency Use Authorization (EUA). For certain ventilators and Personal Protective Equipment (PPE) devices, the Agency described policies concerning the enforcement of registration and listing requirements for facilities that manufacture, prepare, propagate, assemble, or process these devices during the COVID-19 pandemic.

COFEPRIS Introduced New Electronic Appointment System for Medical Device Registrants

In September 2020, the Mexican Regulatory Authority, COFEPRIS (The Federal Commission for Protection against Sanitary Risk) established a new electronic appointment system for medical device registrants for submitting applications or seeking in-person meetings with the Agency. As required by the Agency, all the users can utilize the new electronic appointment system by adhering to certain key criteria and each executive must wear Personal Protective Equipment (PPE) and the applicants who arrive at the CIS facility must comply with the several provisions, to reduce the risk of coronavirus exposure.

Multiple Function Device Products: FDA’s Pre-market Review Policy and Submissions

The FDA issued a final guidance in the month of September 2020, addressing the review of medical products that contain both, the medical and the non-medical functions (multiple function device products). As an update to a draft that was issued in April 2018, the new guidance specifies how and when the FDA will assess the impact of “other functions” of a product that are not evaluated in a pre-market review. This guidance intends to identify the principles, pre-market review practices, pre-market submissions and policies for the FDA’s Regulatory assessment of such products.  

SFDA Guidance: e-IFU Requirements for Medical Devices

In October 2020, the SFDA (Saudi Food and Drug Authority) issued a guidance to clarify the e-IFU (electronic Information for Use) requirements for medical devices in Saudi Arabia. This guidance was issued in reference to the Essential Principles specified in, “Guidance on Requirements for Medical Device Listing and Marketing Authorization (MDS-G5).” It is applicable for medical devices (including IVD medical devices) supplied to the KSA (Kingdom of Saudi Arabia) market, with IFU in electronic form and is intended for professional users. As per the guidance, the users must provide certain IFU requirements in electronic format and undertake a document risk assessment.

Software as a Medical Device (SaMD) – Decode ANVISA’s Guidance

The Brazilian national Health Authority – ANVISA, has published a guidance in October 2020, dedicated to the software with the intended medical purpose (Software as Medical Device – SaMD). This guidance aims to prevent or mitigate the risks associated with the use of medical software and ensures the safety and performance of the SaMD in the Brazilian market. The software with the intended medicinal purpose designed to operate on non-specific equipment and the special medical software operating medical devices are covered under the scope of this guidance, along with reference to the special international standards, such as IEC 62304: 2006 Software for medical devices.

Regulatory Updates 2020 – Food and Food Supplements

Changes in the FDA’s Nutrition Fact Labels

In 2016, the United States Food and Drug Administration (USFDA) published the final rules for Nutrition Facts Label for packaged food. The FDA established the rule to align the nutrition fact label of food products with the current food habits and practices. As of January 1, 2020, food product manufacturers entering the US market, with annual food sales of more than USD 10 million, are required to comply with the new labeling standards for nutrition fact labels to ensure compliance.

The major changes in the labeling rules are related to the list of food nutrients that are required to be declared on the label of the food product, along with updating the serving size requirements and a change of design.

FDA Released Final Rule for the Labeling of Gluten-Free Products

On August 12, 2020, the United States Food and Drug Administration (USFDA) released the final labeling rule for food products falling under the category of fermented and hydrolyzed food. The labeling rule is applicable for a range of food products that claim to be “gluten-free”. According to the final rule, fermented and hydrolyzed foods manufacturers are required to maintain the following information to adequately substantiate their claims:

  1. The food must comply with the definition of “gluten-free” before being fermented or hydrolyzed.
  2. Manufacturers must thoroughly examine the product for any cross-contact with gluten during the manufacturing process.

The rule came into effect from October 13, 2020.

SFA Released Amendment for Food Regulations

As of August 31, 2020, amendment no. 3 of the Singapore Food Agency’s (SFA) Food Regulations 2020 is in effect in Singapore. The amendment was a part of the SFA’s effort to upgrade the Regulatory provisions pertaining to food products in the country and align them with international standards. The amendment streamlines the usage of new food additives and extends the usage of already existing food additives, along with making the following changes to the Sale of Food Act (Chapter 283) of the SFA:

  • Modification to the definition of food additives such as steviol glycosides, butter and other sweetening agents
  • Amendment to the allowable usage quantity for various Specified Food

Japan Revised Labeling Standards for Food Products

With an aim of streamlining the safe distribution of food products in Japan, the Consumer Affairs Agency (CAA) has revised the labeling standards of these products, effective from July 16, 2020. The new changes in the labeling system emphasize on:

  1. Removal of Certain Terms – The most significant change in the revised labeling system is the removal of terms “artificial” and “synthetic”.       
  2. Classification of Organic Livestock Products – The revision, now, classifies organic livestock products as special raw materials. Thus, these are also subject to the specialized labeling rules and must be underscored on the food product labels.

Although the revised labeling standards are effective from July 2020, manufacturers in Japan have a transition period till March 21, 2022, to modify their labels.

Regulatory Updates 2020 – Cosmetic Products

TGA Established AICIS Replacing the NICNAS

With effect from July 1, 2020, the National Industrial Chemicals Notification and Assessment Scheme (NICNAS) has been officially replaced by the Australian Industrial Chemicals Introduction Scheme (AICIS). Falling under the Industrial Chemicals Act 2019, the AICIS is a Regulatory scheme, which focuses on supporting cosmetic product manufacturers with easy import of new low-risk chemicals to the Australian market. With the AICIS coming into force, many chemicals, which were never deployed industrially and were listed in the NICNAS inventory, are now excluded from the new inventory.

Additionally, manufacturers introducing a new industrial chemical in Australia are required to register their business with the Register of Industrial Chemical Introducers before the chemical is imported/manufactured. The imported/manufactured chemical is now also required to meet the Regulatory requirements of its introduction category, based on the associated risk level.

Cosmetics and the Ban on Usage of Animal Test Data

The global cosmetics industry is now moving towards focusing on cruelty-free products. In line with this global change, starting from July 1, 2020, Australia has also banned testing the cosmetic products on animals. According to the Department of Health of Australia, the ban ensures that the ingredients which are to be used in Cosmetics (either imported or manufactured inside Australia), cannot use information obtained from animal testing to prove the products’ safety.

Health Canada Hand Sanitizer Regulations Updates on Ingredients Usage

During the rise of global pandemic Covid-19, in April 2020, Health Canada (HC) made a temporary update to the hand sanitizer regulations and relaxed the Regulatory requirements for the ingredients used in the sanitizers. The step was taken by HC to ensure that only safe and effective products are distributed in the country.

According to the update, the manufacturers will have to comply with additional labeling guidelines to ensure that the consumers can make the right buying decision. The additional guidelines that manufacturer using technical-grade ethanol in their products are required to:

  • Clearly indicate on their products that technical-grade ethanol is used as an ingredient
  • Mention specific warnings and precautions regarding the product and its ingredients on the packaging and label of the product
  • Manufacturers must mention clear information on how to report any adverse reactions to Health Canada

To conclude, the year 2020 has been quite challenging in terms of changing and evolving regulations, specifically for Covid-19, and the betterment of the life sciences industry. Freyr, as a strategic Regulatory partner, has, as always, been one step ahead in providing manufacturers the latest Regulatory updates through blogs, webinars, newsletter, whitepapers, etc. This year, Freyr went one step ahead with its exclusive Covid-19 platform to ensure that manufacturers are kept abreast with all the COVID-related updates at one single platform.

Keeping in mind the evolving nature of the industry, we can firmly say that 2021 will have a lot more in store for the life sciences industry and its manufacturers to ensure their growth. Till then, stay safe, stay compliant.