Pharmaceutical Deformulation Services
Excipient identification, quantification and Q1/Q2 formulation assessment for pharmaceutical products
What is pharmaceutical deformulation?
Excipient quantification and Identification
Pharmaceutical deformulation is the analytical process of identifying and quantifying the components of a finished drug product to determine what is present, how much is present and, where relevant, which excipient grade or quality may have been used.
Excipia performs pharmaceutical deformulation and excipient analysis for companies developing generic, hybrid or reformulated drug products, investigating failed bioequivalence, comparing reference products or troubleshooting formulation-performance differences.
Our expertise goes beyond basic ingredient identification. Depending on the formulation and excipient, we can investigate excipient quantity, grade, quality, source-related markers and functionality-related characteristics. The results can be combined with Avivia’s formulation, analytical and dissolution expertise to understand whether identified differences may be relevant to product performance.
When Is Pharmaceutical Deformulation Useful?
Deformulation is particularly valuable when the composition of a reference, competitor or existing drug product is unknown or insufficiently documented, or when apparently small formulation differences may affect bioequivalence, stability, manufacturability or drug release. Pharmaceutical companies and researchers approach us for excipient analysis and deformulation for various reasons, including:
- Q1/Q2 formulation assessment for generic development and selected bioequivalence or biowaiver strategies
- Reference product characterization to support formulation matching or product development
- Excipient identification and quantification in complex or poorly documented formulations
- Excipient grade, quality or source investigation, where analytically feasible
- Competitive product analysis and IP-supporting formulation evaluation
- Troubleshooting of stability, manufacturability, dissolution or product performance issues
- Support for Q3/physical characterization, where composition alone is not sufficient
- Understanding a reference listed drug (RLD) before starting formulation development
What Can Pharmaceutical Deformulation Tell You?
| Client question | Typical deformulation output |
|---|---|
| Which excipients are present? | Qualitative excipient identification |
| How much of each excipient is present? | Quantitative excipient profile / Q1/Q2 composition |
| Is the same excipient grade likely used? | Grade or quality assessment, where feasible |
| Are there relevant excipient markers or variability? | Excipient characterization and impurity/quality indicators |
| Does the formulation match the reference product? | Comparative formulation assessment |
| Could differences affect performance? | Recommendation for dissolution, release, stability or formulation follow-up |
| Why did our formulation fail bioequivalence? | Identification of potentially relevant compositional differences and recommendations for follow-up |
| What should we match in the reference product? | Q1/Q2 composition and identification of attributes requiring further characterization |
Why Excipia for Pharmaceutical Deformulation?
Deformulation requires more than running standard analytical methods. Excipients can be difficult to selectively extract, separate and quantify in the presence of an API and other formulation components, and suitable compendial methods are often unavailable.
Excipia combines specialist excipient knowledge with analytical method development to identify and quantify components in complex pharmaceutical formulations. Where analytically feasible, characterization can extend beyond excipient identity and quantity to investigate grade, quality, composition, molecular characteristics or source-related markers.
This is particularly valuable when nominal excipient identity alone does not explain differences between a test and reference product.
Pharmaceutical Deformulation Services: Excipient grade, quality and source assessment
Excipia’s deformulation and excipient characterization expertise can go beyond simple identification and quantification. Depending on the excipient and formulation matrix, we may be able to assess excipient grade, quality and functionality-related properties, and in some cases identify markers that indicate likely excipient source or variability.
These insights can be important when formulation performance, manufacturability, stability or product matching depends on more than the nominal excipient name alone.
Looking to dive even deeper? Learn more about our complementary reverse engineering services, designed to provide a comprehensive understanding of pharmaceutical formulations.
Q1, Q2 and Q3: Where Does Deformulation Fit?
Q1 – What is present?
Identification of the excipients in the reference and test products.
Q2 – How much is present?
Quantification of the excipients and comparison of formulation composition.
Q3 – How is the product structured?
Physicochemical and structural characterization that may be required when composition alone does not adequately describe product performance.
Excipia’s deformulation work primarily provides Q1/Q2 information. For complex products, these data can be combined with Avivia’s analytical, formulation and performance-testing capabilities to investigate relevant Q3 attributes.
Regulatory context: Q1/Q2 assessment in the US and EU
In generic drug development, formulation sameness or similarity can be an important part of the bioequivalence strategy, depending on dosage form, route of administration and product-specific expectations.
Deformulation and Q1/Q2 assessment can help development teams to:
- identify which excipients are present in the reference product;
- quantify excipient levels and compare them with the test formulation;
- assess whether the formulation is aligned with Q1/Q2 expectations;
- identify excipient differences that may create regulatory or development risk;
- determine whether further Q3 or performance characterization may be needed;
- support discussions on bioequivalence strategy, product-specific guidance and formulation risk.
In the United States, FDA product-specific guidances describe the Agency’s current thinking on the evidence recommended to support ANDA approval for specific products. These guidances are issued and revised over time, so Q1/Q2 expectations should always be checked against the relevant product-specific guidance and current FDA requirements.
For some dosage forms, US regulations include specific inactive-ingredient requirements. For example, 21 CFR 314.94 states that ophthalmic or otic drug products generally must contain the same inactive ingredients in the same concentration as the reference listed drug. It also includes specific provisions for parenteral drug products.
In Europe, EMA publishes product-specific bioequivalence guidance after public consultation and CHMP adoption. EMA states that product-specific guidance should be considered together with relevant clinical pharmacology and pharmacokinetics guidance and Q&As.
For complex or locally acting products, formulation composition alone may not be sufficient. FDA’s final Q3 guidance for topical drug products describes how physicochemical and structural characterization can be used to identify dosage form properties that may be critical to product performance and support a bioequivalence demonstration.
Excipia supports this process by providing excipient identification, excipient quantification and Q1/Q2 formulation assessment data. Where needed, deformulation findings can be combined with Avivia’s formulation, analytical and dissolution expertise to support follow-up development decisions.
Recent developments and expectations for Q1/Q2 assessments
Recent regulatory expectations increasingly emphasize a science-based link between composition, structure and performance. For complex generics, FDA continues to publish and update product-specific guidances and provides resources on Q1/Q2 sameness, formulation assessment and complex generic development.
In Europe, EMA also continues to develop and publish product-specific bioequivalence guidance after public consultation and CHMP adoption. These product-specific guidances should be considered together with relevant EMA clinical pharmacology/pharmacokinetics guidance and Q&As.
For topical and other locally acting products, the role of deformulation is particularly important. In these products, small differences in excipient composition, grade, microstructure, viscosity, rheology, particle size, pH, osmolality or release behaviour can affect local availability and product performance. Regulatory expectations therefore often go beyond simple Q1/Q2 composition and may require Q3 physicochemical/structural characterization, in vitro release or permeation testing, and product-specific justification.
This is especially relevant for products such as topical semisolids, ophthalmic and otic products, nasal products, inhaled products, locally acting gastrointestinal products, suspensions and emulsions. FDA’s Q3 guidance for topical ANDA products and EMA’s guidance on quality and equivalence of locally applied, locally acting cutaneous products both reflect this broader focus on linking product composition and structure to performance.
For developers, this means that deformulation is most useful when combined with formulation expertise, analytical method development and, where relevant, dissolution, release, permeation, rheology or other performance testing. This is where Excipia’s deformulation work can connect directly with Avivia’s formulation, analytical and dissolution platforms.
Case study: How Deformulation Helped Resolve a Failed Bioequivalence Study
Fixed dose combination product (example)
A client approached Avivia after failed bioequivalence studies for a complex fixed-dose combination product. Review of the formulation and bioanalytical data indicated that differences between the test and reference formulations could be contributing to the observed performance.
Deformulation demonstrated qualitative sameness but identified important quantitative differences in excipient composition. Based on these findings, the test formulation was adjusted. Improved API release was subsequently confirmed by dissolution testing, and the reformulated product successfully passed the following bioequivalence study.
The case illustrates why deformulation is most valuable when analytical composition data are interpreted together with formulation science and product-performance testing.
Read more about our reverse engineering services.
Fixed dose combination product (example)
A client approached Avivia after failed bioequivalence studies for a complex fixed-dose combination product. After reviewing the formulation and bioanalytical data, the project team recommended deformulation of the reference product and comparison with the test formulation.
Deformulation confirmed qualitative sameness but revealed quantitative differences in excipient composition. The formulation was adjusted, improved release was confirmed through dissolution testing, and the following bioequivalence study was successful.
Read more about our reverse engineering services.
Connecting deformulation data to formulation performance
Deformulation provides the composition and excipient profile. Where needed, Avivia’s formulation, analytical and dissolution teams can help interpret what those findings mean for product performance.
Follow-up work may include dissolution or release testing, formulation screening, excipient compatibility assessment, stability studies or formulation optimization.
Where appropriate, deformulation findings can support formulation redevelopment or prototype reconstruction.
What Is the Difference Between Pharmaceutical Deformulation and Reverse Engineering?
Deformulation answers: What is in the product and how much is present?
Pharmaceutical reverse engineering answers: How is the product designed, why does it perform as it does, and what would be required to reproduce or improve that performance?
Deformulation therefore forms an important part of many reverse-engineering projects, but reverse engineering can additionally include physical characterization, dissolution or release testing, formulation science, process-related assessment and interpretation of product performance.
For broader product understanding, see our reverse engineering services.
FAQ
What is pharmaceutical deformulation?
Pharmaceutical deformulation is the analytical process of identifying and quantifying the components of a drug product, including excipients. It is used to understand formulation composition, support generic development, compare reference products and investigate performance.
What is Q1/Q2 formulation assessment?
Q1 refers to qualitative sameness of inactive ingredients. Q2 refers to quantitative sameness or similarity, meaning the levels of inactive ingredients are aligned with the reference product according to applicable regulatory expectations.
Does Q1/Q2 sameness replace a bioequivalence study?
Not automatically. Q1/Q2 data can support a bioequivalence strategy, but requirements depend on dosage form, route, product-specific guidance and regulatory expectations. Additional Q3 characterization, in vitro testing or in vivo studies may be needed.
What is the difference between deformulation and reverse engineering?
Deformulation identifies and quantifies formulation components. Reverse engineering uses deformulation data together with formulation science and product performance testing to understand how the formulation works.
Welcome to Excipia, a service platform of Avivia, dedicated to the composition, quality and quantity of excipients in medicinal products.
Discover our unique services such as quantitative excipient analysis, identification, selection or specific formulation development support. Don’t forget to check out our case studies.
Feel free to contact us using the “Contact” button or by sending a message to Excipia@avivia.nl.
Menno Wiltink
Founder of Excipia.
