Issue 13: Pharmaceutical regulatory roundup




Catch up with the latest news from around the pharmaceutical industry with issue 13 of our regulatory review, curated by Dr Tim Sandle.


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European Pharmacopeia


Supplement 11.3 to the European Pharmacopoeia has been issued, ready for going live on 01 January 2024. A series of supplements will follow up to version 11.8 (by July 2025).


The 12th edition of will follow in July 2025 (effective from January 2026).


For details, see: 




New cleanroom standard for particle sampling


A new part of the ISO 14644 cleanroom series has been published: ISO/TR 14644-21:2023 Cleanrooms and associated controlled environments — Part 21: Airborne particle sampling techniques.


This document discusses the physical limitations of probe and particle counter placement and any tubing that connects the two (particularly in providing representative samples where particles 5 micrometres and greater are of interest).


The document identifies the key factors of sampling performance when classifying and monitoring, as well as good practice to determine and maintain an acceptable compromise between attainable accuracy in counting and feasibility of counting in real-life situations.


This document includes a decision tree, used to identify key considerations when sampling airborne particles, and whether the system requires further assessment. There are also examples provided to illustrate typical application challenges.


The standard is designed to support parts ISO 14644-1 and ISO 14644-2. 


The standard can be purchased from national standards organisations or directly from ISO.




Post-marketing studies and clinical trials


The U.S. Food and Drug Administration (FDA) has announced the availability of a draft guidance for industry entitled “Postmarketing Studies and Clinical Trials:  Determining Good Cause for Noncompliance with Section 505(o)(3)(E)(ii) of the Federal Food, Drug, and Cosmetic Act.” 


The Federal Food, Drug, and Cosmetic Act (FD&C Act) authorises FDA to require certain post-marketing studies and clinical trials for prescription drugs at the time of approval or after approval if FDA becomes aware of new safety information.


The draft guidance describes the factors FDA considers when determining whether an applicant has demonstrated good cause for failure to comply with the timetable for completion of studies or clinical trials required under the provisions.


The draft guidance also provides information on relevant procedures, including how an applicant should communicate with FDA regarding compliance with these required studies and trials and describes actions FDA may take for noncompliance with the requirements.


For details, see: 




Vaccine Safety Net


The Vaccine Safety Net (VSN) is a global network of websites, established by the World Health Organization (WHO), that provide reliable information on vaccine safety.


In recent years, several websites providing unbalanced, misleading and alarming vaccine safety information have been established, which can lead to undue fears, particularly among parents and patients.


Acknowledging the above-mentioned issues and urged by governments, key non-governmental organisations and the United Nations Children's Fund (UNICEF), WHO established the Vaccine Safety Net Project (VSN) in 2003. 


For details see: 




Classification of medicines


The legal classification of a pack of medicine determines the level of control over its supply. In part, classification rests on how much health professional input is needed to diagnose and treat the conditions for which the medicine might be used. Currently, there are three categories that a medicine can be classified within:


  • Prescription-Only Medicine (POM) - must be prescribed by a doctor or other authorised health professional. It must be dispensed from a pharmacy or from another specifically licensed place
  • Pharmacy (P) - an intermediate level of control, can be bought only from pharmacies and under a pharmacist’s supervision
  • General Sales List (GSL) - may be bought from retail stores, such as a newsagent, a supermarket or a vending machine in a shop


The underlying principle for classifying medicines is to maximise timely access to effective medicines while minimising the risk of harm from inappropriate use. The UK government has updated its guidelines for the reclassification of medicines:


To facilitate generic drug product availability and to assist the generic pharmaceutical industry with identifying the most appropriate methodology for developing drugs and generating evidence needed to support ANDA approval, the U.S. FDA publishes product-specific guidances describing the agency’s current thinking and expectations on how to develop generic drug products therapeutically equivalent to specific reference listed drugs.


The agency routinely posts and revises product-specific guidances. FDA always seeks feedback and considers all comments to the docket before it begins work on the final versions of product-specific guidances. The FDA posts plans for issuing new or revised product-specific guidances on the Upcoming Product-Specific Guidances for Generic Drug Product Development web page.


The Product-Specific Guidances database features:


  • Text search of PSGs by active ingredient or by the Reference Listed Drug (RLD) or Reference Standard (RS) application number
  • Filtered search results using a text search box
  • Option to export search results in Excel, CSV, or PDF format
  • Paginated search results, allowing for faster searching


For details see: 




Nitrosamines: Final FDA guidance

The U.S. FDA has produced a final guidance for industry entitled “Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities (NDSRIs).”


This guidance provides applicants and manufacturers of drugs, including prescription and over-the-counter (OTC) drug products, with a recommended framework for predicting the mutagenic and carcinogenic potential of NDSRIs that could be present in drug products and recommends acceptable intake (AI) limits for NDSRIs.


NDSRIs, which are a subcategory of nitrosamine impurities that share structural similarity to the active pharmaceutical ingredient (API) in drug products, typically lack compound-specific mutagenicity and carcinogenicity data to inform safety assessments. 


The guidance provides a recommended methodology for AI determination that uses structural features of NDSRIs to generate a predicted carcinogenic potency categorisation and corresponding recommended AI limit that manufacturers and applicants can apply in their evaluation of potential impurities in their drug products. This guidance is in the absence of other FDA-recommended AI limits.






Hydrogen peroxide


The U.S. FDA has issued the final guidance: “Hydrogen Peroxide-Based Contact Lens Care Products: Consumer Labeling Recommendations - Premarket Notification (510(k)) Submissions.”


This guidance provides recommendations intended to help manufacturers develop labelling with information about specific risks and directions for use of hydrogen peroxide-based contact lens care products in conjunction with a user’s prescribed contact lenses in order to reduce misuse of the product. 


The guidance is also intended to help ensure that consumers are provided with clear information about the benefits and risks associated with the use of these devices, especially in relation to hydrogen peroxide solutions of 3% or greater based on the potential risk to the user if the hydrogen peroxide has not been correctly neutralised.




Mutagenic substances


The U.S. FDA has announced the availability of a final guidance for industry entitled “M7(R2) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk” (M7(R2) Guidance) and two supplemental documents entitled “M7(R2) Addendum: Application of the Principles of the ICH M7 Guidance to Calculation of Compound-Specific Acceptable Intakes” (M7(R2) Addendum) and “M7(R2) Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk Questions and Answers” (M7(R2) Questions and Answers).


The M7(R2) Guidance, M7(R2) Addendum, and M7(R2) Questions and Answers were prepared under the auspices of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).


The guidance and supplemental documents are intended to harmonise the considerations for assessment and control of DNA reactive (mutagenic) impurities.


For details see:


PIC/S GMP incorporate Annex 1

Annex 1 to EU GMP which came into force 25th August 2023 has been incorporated into PIC/S GMP, under the annexes: (as of 23rd August 2023).


PIC/S develops and maintains a GMP guide to be used by its participating authorities, which is its main instrument for harmonisation. This is equivalent to the EU GMP guidelines in terms of GMP requirements. Participation in PIC/S is open to any authority with a comparable GMP inspection system.


This carries important implications, given that the FDA is a member of PIC/S.


New FDA guidance for trading partners (Drug Supply Chain Security Act)


The US FDA has issued a new guidance document titled “Enhanced Drug Distribution Security Requirements Under Section 582(g)(1) of the Federal Food, Drug, and Cosmetic Act - Compliance Policies” (August 2023).


This guidance describes FDA’s compliance policies regarding enforcement of requirements for the interoperable, electronic, package level product tracing (‘enhanced drug distribution security requirements’) under the Federal Food, Drug and Cosmetic Act (FD&C Act). These go into effect on November 27, 2023. 


The compliance policies outlined are designed to aid supply chain stakeholders to develop and refine appropriate systems and processes to conduct interoperable, electronic tracing at the package level, to achieve robust supply chain security under the Drug Supply Chain Security Act (DSCSA), while helping ensure continued patient access to prescription drugs.


Trading partners are required to:


  • Use secure, interoperable, electronic approaches to exchange transaction information. This must include package level product identifiers for each package included in the transaction
  • Have systems and processes in place to verify products at the package level
  • Have systems and processes in place to promptly respond with the transaction information
  • Have systems and processes in place to facilitate the gathering of information needed to produce the transaction information for a product going back to the manufacturer
  • Have systems and processes in place to accept saleable returns under appropriate conditions




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