Compendial Methods & Pharmacopoeias

Experts Susan J. Schniepp, distinguished fellow for Regulatory Compliance Associates® (RCA), and Steven J. Lynn, executive vice-president of Pharmaceuticals for RCA, discuss the verification of compendial methods.


Q. Are compendial methods considered validated?


A. According to the pharmacopoeias, compendial methods are validated—that’s about as simple as it gets. The United States of Pharmacopeia National Formulary (USP–NF) states,


“…users of analytical methods described in USP–NF are not required to validate the accuracy and reliability of these methods but merely verify their suitability under actual conditions of use”


European Pharmacopoeia


The European Pharmacopoeia (Ph.Eur.) and the (JP) also consider their methods validated. Ph.Eur. states:


“The analytical procedures given in an individual monograph have been validated in accordance with accepted scientific practice and recommendations on analytical validation. Unless otherwise stated in individual monograph or in the corresponding general chapter, validation of these procedures by the user is not required”


Japanese Pharmacopoeia


The Japanese Pharmacopoeia says:


“when an analytical procedure is to be newly carried in the Japanese Pharmacopoeia, when a test carried in the Japanese Pharmacopoeia is to be revised, and when the test carried in the Japanese Pharmacopoeia is to be replaced with a new test according to regulations in General Notices, analytical procedures employed for these tests should be validated according to this document”.




Supporting validation information for pharmacopeia methods is retained by the compendial authorities and not by the users of the methods. However, this does not change the fact that the official methods in these publications are supported by validation information.




regulatory compliance

The methods need to be verified as suitable for use in the user’s laboratory. The USP–NF and the Ph.Eur. both describe the requirements for verification in their respective compendia.


Compendial Procedures


The USP–NF and Ph.Eur. explicitly require that compendial procedures demonstrate suitability under actual conditions of use. This information can be found in General Chapter, Verification of Compendial Procedures <1226> in the USP–NF, and General Notices in the Ph.Eur. (1,2).


On the other hand, the European Directorate for the Quality of Medicines (EDQM) stipulates on their website:


“When implementing a Ph.Eur. analytical procedure, the user must assess whether and to what extent its suitability under the actual conditions of use needs to be demonstrated according to relevant monographs, general chapters, and quality systems.”


In other words, it is the user’s responsibility to transfer the procedure correctly” 




Once a monograph has been established and it is accepted that the published method is validated, users of the monograph need to verify that the method is suitable for determining the product quality. Moreover, the purpose of verification is to establish that the official method is reproducible when used by others.


Lab Equipment


The monograph sponsor proves the method works for its product with the manufacturer’s analysts using the firm’s laboratory equipment. They have already met the basic International Council for Harmonisation (ICH) requirements for reproducibility, repeatability, and intermediate precision. 


The task for the user of the USP monograph is to prove the published method is reproducible. Additionally, any analyst for their company’s product should be capable of testing using the lab equipment.


Test Methodology


There is no absolute guidance for verification requirements. Companies must decide for themselves how they will establish the method is verified and suitable for their product. Lastly, the test methodology verification will depend and fluctuate based on complexity of the test method.




Chromatographic methods should, at a minimum, meet the system suitability requirements defined in the official method. Conversely, other method parameters, such as accuracy and precision, may be considered.




Method performance can be accomplished by using performance characteristics such as blanks in chemistry or un-inoculated media in microbiology. Finally, laboratory control samples and spiked samples for chemistry, or positive culture controls for microbiology to assess accuracy.


Training Records


Technique-dependent methodologies should not require verification. These methods include but are not limited to loss on drying, pH, residue on ignition, etc. Technicians should be trained, and their training records maintained, demonstrating their ability to perform the method regardless of the material being tested.


Lab Procedures


To simplify activities for their analysts, many companies translate monograph instructions into laboratory procedures. Although this practice has its benefits, it can also lead to compliance concerns.


Nevertheless, the author recommends that a baseline comparison be made between the standards and the internal testing documents to minimize this risk. Further, the comparison does not need to elaborate, but should focus on critical parameters for test methods.


System Requirements


Equally important, the reader may also want to consider reference standard usage, system suitability requirements, or other parameters that may help establish equivalency to the compendial methods.


Critical to Quality (CTQ)


Finally, the criteria listed above should not be considered all-inclusive. Establishing an internal method that complies with the official pharmacopeial method is critical to quality (CTQ). After all, many different users may have other requirements to consider for their specific laboratory usage.



regulatory compliance


Article details

Pharmaceutical Technology
Volume 46, Number 4
Page: 58


About RCA’s Pharmaceutical Consulting Services 


Regulatory Compliance Associates (RCA) has helped thousands of pharmaceutical companies meet regulatory, compliance, quality assurance, and remediation challenges. With more than 20 years of experience with FDA, Health Canada, EU and global regulatory agencies worldwide, Regulatory Compliance Associates® offers leading pharmaceutical consultants. We’re one of the few pharma consulting companies that can help you navigate the challenges associated with industry regulations.


Our pharmaceutical consulting firm includes over 500 seasoned FDA, Health Canada & EU compliance consultants and regulatory affairs experts who understand industry complexities. It’s a pharma consultancy founded by regulatory compliance executives from the pharmaceutical industry. Every pharmaceutical industry consultant on the Regulatory Compliance Associates team knows the unique inner workings of the regulatory process. 


Client Solutions


Whether you’re in the product planning, development or pharmaceutical lifecycle management stage or need a remediation strategy for a compliance crisis, Regulatory Compliance Associates will guide you through every pharmaceutical consulting step of the regulatory process and create a customized approach depending on your product and your pharma company’s individual needs. Our regulatory compliance clients include:


  • Companies new to FDA, Health Canada or EU regulations and regulatory compliance
  • Start-up organizations with novel submissions to 510(k) submissions from multi-national corporations
  • Investment firms seeking private equity due diligence for pre-acquisition and post-deal research
  • Law firms seeking pharmaceutical consulting firm expertise in the remediation of warning letters, consent decrees, 483’s or import bans


Regulatory Affairs


Regulatory affairs is Regulatory Compliance Associates backbone. We exceed other pharma consulting companies with industry experts experienced in complexities of the pharmaceutical and biopharmaceutical industries. Our pharma consulting expertise spans all facets and levels of Regulatory Affairs, from Regulatory Support for New Products to Life Cycle Management, to other services like Outsourced Regulatory Affairs, Submissions, Training, and more.


As your partner, we can negotiate the potential assessment minefield of regulatory compliance services with insight, hindsight, and the clear advantage of our breadth and depth of knowledge and regulatory compliance consulting. We offer the following pharma consulting regulatory affairs services for pharmaceutical companies.


  • New Product Support
  • Product Lifecycle
  • Other Regulatory Services
  • Combination Products


Compliance Assurance


The regulations process surrounding pharmaceutical companies can be tricky for even the most experienced industry veteran to understand. Just one misstep could mean significant and lasting consequences for your business. At Regulatory Compliance Associates, we offer the pharma consulting experience and pharma consultants necessary to guide you through the quality compliance process.


  • Assessments
  • Audits
  • Regulatory Agency Response
  • Preparation and Training
  • Inspection Readiness
  • Data Integrity


Quality Assurance


Regulatory Compliance Associates Quality consulting includes assessments, strategy, implementations, staff augmentations, and identification of quality metrics to ensure continuous improvement. Our pharma consultants understand the strategic thinking needed to align your business needs and goals. Regulatory Compliance Associates quality assurance services include quality experts with experience spanning major corporations and start-ups. Our pharmaceutical consulting firm knows firsthand how to achieve, maintain, and improve quality, and we excel in transferring pharma consulting knowledge to your organization.


  • 21 CFR Part 11
  • Data Integrity
  • Manufacturing Support
  • Facility Support
  • Quality Metrics




Regulatory Compliance Associates has significant experience and a proven approach to managing FDA Warning Letters, Consent Decrees, Remediation and other serious regulatory situations. Our pharma consultants know how to partner with executive, legal, and communication teams, and will assist management with a response that will be accepted by the regulatory agency and be realistic to execute. Regulatory Compliance Associates pharma regulatory consultants will develop a comprehensive proof book of documented evidence demonstrating the corrective action taken to remediate non-compliant issues.


In addition, each Regulatory Compliance Associates pharma consulting Expert understands compliance enforcement. We’ll prepare a comprehensive pharma consulting strategy to assist in your remediation efforts, drive continuous improvement, and maintain regulatory compliance with the regulations.


  • Regulatory Action
  • Regulatory Compliance
  • Regulatory Enforcement
  • Warning Letter
  • 483 Observation
  • Oversight Services
  • Risk Management Plan


About Regulatory Compliance Associates


pharmaceutical consultantsRegulatory Compliance Associates® (RCA) provides pharmaceutical consulting to the following industries for resolution of life science challenges:



We understand the complexities of running a life science business and possess areas of expertise that include every facet of R&D, operations, regulatory affairs, quality, and manufacturing. We are used to working on the front lines and thriving in the scrutiny of FDA, Health Canada, MHRA and globally-regulated companies.


As your partners, we can negotiate the potential minefield of regulatory compliance and regulatory due diligence with insight, hindsight, and the clear advantage of our unique expertise and experience.


  • Founded in 2000
  • Headquartered in Wisconsin (USA)
  • Expertise backed by over 500 industry subject matter experts
  • Acquired by Sotera Health in 2021


About Sotera Health


The name Sotera Health was inspired by Soteria, the Greek goddess of safety, and reflects the Company’s unwavering commitment to its mission, Safeguarding Global Health®.


Sotera Health Company, along with its three best-in-class businesses – Sterigenics®Nordion® and Nelson Labs®, is a leading global provider of mission-critical end-to-end sterilization solutions and lab testing and advisory services for the healthcare industry. With a combined tenure across our businesses of nearly 200 years and our industry-recognized scientific and technological expertise, we help to ensure the safety of over 190 million patients and healthcare practitioners around the world every year.


We are a trusted partner to 5,800+ customers in over 50 countries, including 40 of the top 50 medical device companies and 9 of the top 10 pharmaceutical companies.


Commitment to Quality


Our Certificate of Registration demonstrates that our Quality Management System meets the requirements of ISO 9001:2015, an internationally recognized standard of quality.


To begin the Regulatory Compliance Associates scoping process today, please enter your information in the blue form below and click the submit button at the bottom of the webpage. 


Our website uses cookies to give you the best possible experience.

By continuing to use this site, you agree to the use of cookies.